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Introducing

The Mission:

OPERATION
BREAK FREE!
Empowering Veterans to Break Free from the Prison of PTSD, Major Depression & the Epidemic of Suicide!
Expose on the Negligence of the Veterans Administrations Treatment of Suicide Prevention, PTSD and Depression within the Veteran Community.

Revealing the
Breakthrough Mineral for PTSD, Depression and Suicide Prevention, They Definitely Dont Want You to Know About!

Civilian Soldiers Suicide Rate Alarming

National Guard soldiers who are not on active duty killed themselves this year at nearly twice the rate of 2009.
See USA TODAY 11/26/2010

The New York Times

Suicides Outpacing War Deaths for Troops

Suicide rates have increased by nearly 20% among the nations active-duty military personnel in 2012. See here: New York Times 6/8/2012

Army faces highest monthly total of suicides

The Army experienced a record 38 suicides in July, the highest monthly total since the service began releasing monthly figures in 2009. (Armytimes.com 8/16/2012)

Operation Break Free

is an idea thats time has come!
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Veteran Suicide Breakthrough Operation Break Free Copyright 2012 by Mark Millar D.C. All Rights reserved. No part of this publication may be reproduced except for brief quotations in printed review, without the prior permission of the author. This material may be freely distributed subject to inclusion of this copyright notice and our World Wide Web URL www.opsetthemfree.com. This material may not be duplicated for any profit-driven enterprise or non-profit organization without express permission from the author. This material may not be reproduced in print or on a CD-ROM without written permission from Dr. Mark Millar. Email @ www.opsetthemfree@live.com

STEP ONE! While the author deeply appreciates being compensated for over 7,000 hours of work bringing this book to the market Dr. Mark Millar gives full permission for the free distribution of this E-book to whomever you wish to share it with. If you have freely received this book from someone would you please consider making a minimal contribution by purchasing the complete (250 page) E-book at the website www.opsetthemfree.com. 50% of the net proceeds from the sale of the E-book will be donated to the Veteran Health and Education fund being set up for this mission. Several notable veteran Non-profit groups (soon to be posted on the website) will be overseeing the allocation of the funds raised by this mission for the following purposes.

ATTENTION! Operation Break Free:

1. Advertising and marketing of the mission to veterans and their families. 2. Paying for the clinical research upon veterans to demonstrate to the world the breakthrough solution for the veteran epidemic of PTSD, depression and suicide. 3. Providing this breakthrough solution freely to homeless veterans.

AMERICA WAKEUP!
We are in an emergency situation that requires your immediate assistance and participation.

The suicide rates for the 18-24 year old veterans with a combined diagnosis of depression and PTSD is estimated to be 10-15 times the rate of the general population. (Dr. Mark Millar)

CONTENTS
Introduction 7 Is there really a solution to this suicide epidemic? 9 Lithium: Essential mineral or drug? 10 Does low dose lithium prevent suicide? Is trace mineral lithium in your drinking water? 12 Introducing Lithium Orotate 14 Pharma-lithium vs. Lithium Orotate whats the difference? Orotic Acid is the Key! 16 Medical doctors who are administering Lithium Orotate 19 Call to action for all Americans 24 Chapter One - Harvard Medical School Takes the Lead! The Suicide Breakthrough of Lithium 26 The American Psychiatric Association affirmed the findings of Harvard Medical School 29 Chapter Two - Major Depression, PTSD & Suicide Statistics 32 Chapter Three - Lack of Proper VA Care for Depressed Veterans Exposed 37 What does the American Psychiatric Association say about this? 39 Treatment-resistance: The primary cause of the Veteran Suicide Epidemic! 41 What does the VA leadership have to say about the Lithium-Suicide-Breakthrough? 48 Chapter Four The Calling! 57 Tapping into the Power of Love 58 How to Communicate This to a Veteran 60 Potential Lithium Orotate Benefits for Veterans 62 Is Lithium Orotate the Solution for the Veteran Epidemic of Suicide? 63 The Lithium Orotate MDD/PTSD Study 64 My Personal Short Story 65 The Mission 66 Summation 70 Chapter Five Lithium Orotate Dosing Instructions 71 Response Time to Lithium Orotate Supplementation 73 If You are Already Taking Antidepressants 74 If You are Already Taking Pharma-lithium: Converting Pharma-Li to Lithium Orotate 76 Precautions while supplementing with Lithium Orotate over 40 mg EL 83 Chapter Six - What is causing MDD, PTSD and suicide? 85 Suicide Chemical Imbalances 87 Adrenaline/Noradrenaline 87 Dopamine 88 Cortisol 88 Serotonin 89 Sleep Disorder and Suicide; Noradrenaline, Nightmares and Sleep disorders 89 Lithium is balancing adrenaline, noradrenaline, cortisol, dopamine and serotonin 90 My Lithium Thesis 94 Introducing the Hypothalamic-Pituitary Axis (HPA) Part One 94 Lithiums Effect upon the Hypothalamic-Pituitary Axis (HPA) 94 How does lithium normalize the dysregulated stress hormones? 96 The Hypothalamic-Pituitary-Adrenal Axis (HPAA) 97 The Hypothalamic-Pituitary-Thyroid Axis (HPTA) 97 The Lithium Breakthrough for the Shrinking Brain of MDD and PTSD 100 Lithium to the Rescue; Essential in Maintaining and Restoring Atrophying Brain Mass 102 Lithium is Critically Essential in All Mood Disorders! 104

Chapter Seven - Lithium: The International Treatment of Choice for Depression and Suicide Prevention, a World-Wide Overview of Results. 106 Chapter Eight - PTSD Chemical Imbalances, Over-view Part One 111 Chapter Nine - Diseases Co-occurring with PTSD; Lithium has been demonstrated to benefit 114 Chapter Ten - The Big Lie! - The Pharma-Cartel Lithium Conspiracy 131 Lithium is neither a drug, nor inherently toxic132 What purpose does the Big Lie serve? 133 Is There a Conspiracy to Suppress Lithium Orotate? (1976) 135 Is Lithium Orotate 3 Times or 10 times More Absorbed? (1978) 138 Conspiracy or Ignorance - The Conspiracy to Suppress Lithium Orotate (1979) 139 Comparison of Lithium Orotate (LO) vs. Pharma-Li Carbonate (LC) 143 Chapter Eleven - Dr. Hans Nieper: The Creator of Lithium Orotate! 145 How does Orotic acid function? 146 Diagram of Cell and Transporters Intracellular Locations of Delivery 148 Chapter Twelve - Modern Medical Technology Measuring Intracellular Lithium Concentrations 150 Chapter Thirteen - Veteran Health Administration Treatment of Major Depressive Disorder 152 Antidepressants are no better than a placebo in preventing suicide. 152 Antipsychotics are Controversial for the Treatment of MDD 153 The Antidepressant/Antipsychotic Fiasco 153 With this kind of manipulation of studies, how is a physician to know whether or not an antidepressant is truly effective? 155 Chapter Fourteen - Why Has Lithium Not Been Prescribed to Veterans? 159 Chapter Fifteen - Depression Overview 162 The Symptoms of Major Depression 162 Veteran Depression and PTSD Statistics 163 Rise in PTSD cases from two wars strains resources 164 Chapter Sixteen - How Does Lithium Work in the Brain? The hypothalamic-pituitary axis (HPA) axis Part Two 165 Hypothalamus Functions 165 Hypothalamic Hormones Involved in MDD Dysregulated Hypothalamic Hormones 166 Pituitary Functions 168 Pituitary Hormones Involved in MDD Dysregulated Pituitary Hormones 169 Pituitary Neuropeptides 170 Chapter Seventeen - The Hypothalamic-Pituitary-Adrenal axis (HPAA) & Primary Stress Hormone Imbalances of Major Depressive Disorder (MDD) 171 Lithium Normalizes Primary Hormonal Imbalances of MDD 171 Adrenaline/Noradrenaline 172 Dopamine 173 Cortisol 174 Chapter Eighteen - Hypothalamic-Pituitary-Thyroid axis in MDD 175 Thyroid Hormone Imbalances of MDD 175

Chapter Nineteen - Lithium Normalizes Secondary Chemical Imbalances Associated with MDD 177 Lithium increases the following secondary chemicals found to be reduced in MDD.177 Lithium reduces the following secondary chemicals found to be elevated in MDD. 179 Chapter Twenty - Toxic Heavy Metal Causes of MDD 180 Chapter Twenty One - Posttraumatic Stress Disorder 181 A Classic Story of PTSD Overlooked by the VA 183 The Solution for this Challenge 185 Pharmaceutical Treatment of PTSD 186 Chapter Twenty Two - PTSD Chemical Imbalances Part Two 188 PTSD, Lithium, and their relationship to the Hypothalamic-Pituitary Axis (HPA) 188 PTSD Dysregulated Hypothalamic Hormones & Lithium Effects 192 Circadian Rhythm Altered by a Dysregulated Hypothalamus 195 Hypothalamic Neuropeptides 196 PTSD - Dysregulated Pituitary Hormone 197 PTSD - Dysregulated Pituitary Neuropeptide 198 Chapter Twenty Three - Primary Stress Hormone Imbalances of PTSD Lithium normalizes 199 Adrenaline/ Noradrenaline 199-201 Neuroprotection of Noradrenaline 204 Noradrenaline and the Amygdala 204 Noradrenaline Chronic Stress and Adrenal Fatigue 205 Nightmares - Chemical Imbalance of PTSD 206 Common antipsychotic no help to vets with PTSD. 209 Dopamine 209 Cortisol 210 High/Low Cortisol Levels; Symptoms of Low Cortisol; What causes low cortisol in PTSD? 211 Cortisol Protective Factor 212 High Cortisol and Brain Atrophy 212 Lithium, PTSD and the Hypothalamic-Pituitary-Thyroid Axis (HPTA) 213 Chapter Twenty Four - PTSD & Bipolar disorder, Chemical Imbalance Similarities 218 Chapter Twenty Five Comparison of Brain Scans PET, SPECT, fMRI and MRI Brain Scan Studies; Similarities between Bipolar disorder & PTSD 220 Chapter Twenty Six - Lithium Promotes Neurogenesis 223 The Incredible Shrinking Brain of Post-traumatic Stress Disorder 225 Measuring N-Acetyl Aspartate (NAA) Levels 228 What is Causing This Brain Shrinkage? 229 Chapter Twenty Seven - PTSD Neuro-Chemical Alterations 231 Neurotransmitters: Serotonin, Gamma-aminobutyric acid (GABA) Glutamate and Histamine 231 Neuropeptides & Neurotrophins 233 Miscellaneous PTSD Neuro-Chemical Alterations 235 Enzymes & Signaling Pathways 237 Lithium-Genetic Influence upon PTSD 238 Chapter Twenty Eight Lithium for Miscellaneous Conditions 240 Conclusion 245 Bibliography 246 Index 287

Introduction

Veteran Suicide Breakthrough

&

Operation Break Free

Empowering Veterans to Break Free from the Prison of PTSD, Major Depression and the Epidemic of Suicide!
My name is Dr., Mark Millar and I have dedicated the last few years of my life (5 years and over 7,000 hours) researching and writing the story you are about to read. I reviewed over 10,000 research study documents, reviews and reports to compile this data. After many years of personally experiencing a losing battle with bipolar disorder, depression and suicidal behavior, I was introduced to this life-saving nutrient, which is the basis of this book. Because of the failure of pharmaceuticals to adequately resolve my symptoms and the severe side effects associated with pharmaceuticals, I eventually gave up on them. If I had not been introduced to this incredible trace mineral I might very well have committed suicide. At the very least I would still be a victim of severe mental illness. For me, this miracle mineral has been a total God-send. It has effectively ended my struggle; so I now enjoy life again. Now it is my hope that this message reaches all of Americas veterans.

Eighteen deaths per day among the Veteran population are attributable to suicide.
Dr. Robert Jesse, M.D., PH.D., Principal Deputy Under Secretary for VA Health 2010 See at: (1)

Please do your own research on this subject. Seeing is believing. I have made it easy for you to verify the research studies that are the basis for this book. By reviewing this document on-line you can click on the blue underlined study titles or blue underlined reference numbers and read the evidence for yourself. Example: Click here (1)

As documented by Harvard Medical School research teams and the American Psychiatric Association, there is presently a nutritional solution for the veteran suicide epidemic that reduces all acts of suicide by 80-90% in Major depressive, bipolar and schizoaffective patients. (Tondo et. al., 2001) (Baldessarini et. al., 2003) (Baldessarini et. al., 2006)
(Guzzetta et. al., 2007) (Pompili et. al., 2009) (American Psychiatric Association 2003) Links provided later in this document

Shockingly only 1 in 200 veterans are receiving this nutrient for the treatment of Major Depressive Disorder the largest segment of the suicide epidemic. (Valenstein et. al., 2006)(2) Link provided later in this document
What is more shocking is the fact (discovered in a massive study {244,859 veterans} at a Veterans Administration [VA] medical center) that our nations veterans (who are suffering an epidemic of suicide) have been systematically denied this nutritional solution by the VA for the management of the leading causes of suicide, Major Depressive Disorder (MDD) and (2) treatment-resistant depression (TRD). (Valenstein et. al., 2006) Treatment-resistant depression (TRD) is defined as the failure of pharmaceutical treatment to adequately or sufficiently resolve (cause remission) the patients symptoms of depression. They are also known as poor or partial responders to adequate therapy with a single agent. In other words the patient is still significantly depressed Treatment-resistant depression is also referred to as Refractory depression. Instead of providing nutrients that heal the central nervous system following psychic trauma, our veterans are being prescribed heavily marketed and highly profitable drugs by the pharmaceutical industry. Worse yet, none of these drugs have ever been demonstrated to reduce Major depressive suicides. Source: American Psychiatric Association (APA) Practice Guideline for the Assessment and Treatment of Patients With Suicidal Behaviors (2003) Link provided later Antidepressants (selective serotonin reuptake inhibitors {SSRIs}) for example, have been extensively researched for any evidence that SSRIs reduce suicide rates and yet no such evidence has ever been found, leaving researchers with the undeniable conclusion that, antidepressants are no better than a placebo pill in the prevention of suicide. The following study says it well, by examining the results of studying 48,277 depressed patients. Study title: Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. (Khan, Kolts, & Brown 2003) Northwest Clinical Research Center, Bellevue, Washington Results: Of 48,277 depressed patients participating in the trials, 77 committed suicide. Based on patient exposure years, similar suicide rates were seen among those randomly assigned to an SSRI, a standard comparison antidepressant, or placebo. (Khan, Kolts, & Brown 2003)(3) The VA and its Staff has had equal access to the research cited in this document. They have been aware of this miraculous suicide solution for (at least) 9 years and have not acted on it. WHY? Has the Pharmaceutical Industry deliberately suppressed the needed knowledge and understanding of this suicide solution? If this is the case, why is this occurring? Could it be because this nutrient costs only $10/month and eliminates the need for much of the highly profitable drugs presently used to treat mood disorders? (Much more on this subject later)

Powerful Pharmaceutical Operatives

have conned the VA into an unwinnable situation and the losers are the veterans and their families! Before I reveal the solution to the epidemic of suicide, I must first ask you a question. If a solution for the suicide epidemic really exists, why have we never heard of this solution? The breakthrough Harvard studies (you are soon to see) span over a decade and yet no one in the general public has ever heard of these studies! WHY NOT? The shocking truth: These breakthrough Harvard-Suicide studies have never been featured in the main-stream media! WHY NOT? Simply stated; corporate greed and corruption have been suppressing knowledge of these breakthrough studies.

The Pharmaceutical industry is running the show folks; Its all about the money! (Kevin Trudeau)

Is there really a solution to this suicide epidemic? Absolutely Yes!

The Epidemic Solution: There is a little known trace mineral that dramatically reduces the primary stress hormone imbalances of PTSD, MDD and suicidal patients. This dynamic mineral has been recently clinically demonstrated to balance the dysregulated primary stress hormones (cortisol, adrenaline and noradrenaline) all of which have been shown to be causally related to the primary symptoms of PTSD, MDD and suicide. Additionally this mineral normalizes hyperthyroid, also causally related to PTSD and MDD. Finally this trace mineral has been shown to normalize over 90% of the 40+ individual chemical imbalances of these two illnesses. This breakthrough mineral for mental and neurological illnesses They Definitely dont want you to know about, has been for me, a miracle mineral. After more than 25 years of extreme neurological symptoms and suicidal thoughts, I was Set Free from an illness that I was told that I had to drug and live with. Not only is this nutrient a breakthrough for suicide, but I will show you many studies demonstrating this nutrient is also the #1 best nutritional medicine, as the primary treatment of depression and PTSD.

What is this nutritional medicine?

The nutritional medicine that Harvard Medical School, the American Psychiatric Association and I, plus many medical doctors nationwide and worldwide are referring to is the trace mineral called lithium, not Pharma-lithium. Lithium: Essential mineral or drug?
You may have heard of lithium and believed that lithium is a drug and a dangerous toxic drug as well. It is true the FDA approved the trace mineral lithium as a drug for the treatment of bipolar disorder in 1970; but the truth is lithium is neither a drug nor inherently toxic as They would have us believe. The trace mineral lithium is now considered by many doctors and nutritional experts to be essential for human health. The available experimental evidence now appears to be sufficient to accept lithium as essential; a provisional RDA for a 70 kg adult of 1,000 microgram/day is suggested. (Dr. Schrauzer 2002) 1,000 microgram = 1 mg Remember: Blue underlined reference numbers or study titles will take you to the study with just a click of your mouse. Study title: Lithium: occurrence, dietary intakes, nutritional essentiality. (Dr. Schrauzer 2002)(4) See Dr. Schrauzers full study report at: (Full report) See: (Who is Dr. Schrauzer?) Lithium is an essential trace mineral in the same class (alkali metals) as essential minerals sodium (Na) and potassium (K) and like calcium and magnesium (alkaline earth metals), lithium is metallic in nature. See lithium (Li) element #3, on the Periodic Table of Elements at: (Li)

This is the breakthrough (discovered by Harvard Medical School and confirmed by the American Psychiatric Association) for the veteran suicide epidemic. Furthermore this is the breakthrough for veterans suffering with PTSD and depression.
NOTE: The natural organic lithium product/supplement that I am going to share with you (sold in health food stores across the nation) is not to be confused with the Toxic Pharmaceutical Lithium (Pharma-Li) Compounds. While it is true the massive doses of Pharma-Li commonly prescribed to bipolar and depressive patients can cause intolerable even dangerous side effects; the natural organic lithium product that I am about to present to you has no negative side effects, because the therapeutic doses are 1/10th 1/20th of the Pharma-Li doses.

Pharma-Li toxicity is due ONLY to massive dosing of lithium being prescribed, exceeding the safe maximum therapeutic limits of lithium.
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Natural organic lithium has no inherent toxicity unless the dosage exceeds the maximum safe therapeutic limit, which is true of all mineral supplementation. Furthermore calling an essential trace mineral a drug does not change the fact that it is, in reality, a naturally occurring nutritional element. The pharmaceuticals lithium carbonate and lithium chloride are mined from the ground and sold as is, without the addition of any other active ingredient. Lithium is the only active ingredient. Lithium is not a drug. Lithium is an essential trace mineral.

In 2008 this fact was even stated in an article by the Veterans Administration Research Currents Report.
(Some of the doctors at the VA know what is going on!)

Lithium is NOT technically a drug, but a mineral, similar to salt. VA Research Currents (February, 2008)(5) Jonathan Wright, M.D., author of The Importance of Lithium Supplementation In fact, lithium isnt a drug at all. Its actually a mineral-part of the same family of minerals that includes sodium and potassium.(6) Who is Dr. Wright? (Who is)

Medical doctors are now speaking out about the fact that lithium is an essential trace mineral with incredible therapeutic benefits in low doses.
Emily Deans, M.D., (Harvard trained psychiatrist) author of Feeling Better: A 6-Week Mind-Body Program to Ease Your Chronic Symptoms Could You Have a Lithium Deficiency? Shocking but true Lithium is an essential trace element. (43) Who is Dr. Deans? (Who is) Mark Hyman, M.D., best-selling author of The UltraMind Solution Lithium is an essential micronutrient See at: (7) Who is Dr. Hyman? 5 Time NY Times Best Seller See (Who is) Alice R. Laule, M.D., Lithium is a trace element which has important functions in the brain, including protecting brain cells from various toxins... See at: (8) Who is Dr. Laule? See at: (Who is) Lawrence Wilson, M.D., author of Lithium Lithium is one of the most important elements in the human body. See at: (9) Kerry D. Friesen, M.D., Lithium is an essential micronutrient with some chemical properties similar to calcium and magnesium. See at: (10) Lithium has been proven in animal studies to be an essential trace mineral. When lithium was removed from the diet of farm animals, (rats and goats) they developed numerous, chronic degenerative diseases, such as atrophy of the spleen, development of cysts and tumors, severely depressed immunes systems, inability to conceive offspring (sterilization), and when they did conceive, they produced significantly fewer and smaller pups that had a much lower survival rate. Additionally the mothers quantity of breast

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milk was diminished. (Dr. Schrauzer 2002) report)

(3)

See Dr. Schrauzers full study report at: (Full

Does low dose lithium prevent suicide? You better believe it!
Not only do the extremely low dosages of lithium supplementation (described in this document) prevent suicide; doses one thousand times less than Pharma-Li dosing of depression have been demonstrated (in the following ground-water/drinking-water studies) to significantly reduce suicide rates in the general population by 30-50%. NOTE: Apparently this is not good news at the VA. I sent the VA information about this study via certified mail in November, 2011 and have yet to hear back from them. See my letter to the VA at: www.opgetfree.com

Is trace mineral lithium in your drinking water? Maybe, maybe not.

The trace mineral lithium is naturally occurring in most ground water (in varying amounts) around the world. The amount of the trace mineral lithium found in the ground water supplies that reduced suicide rates (Li-drinking-water content 100 micrograms of elemental Li [EL]) was approximately () one thousand times less than Pharma-Li dosing (100 milligrams EL) of patients with major depression. (Schrauzer and Shrestha 1990)(11) Note: 100 micrograms = 1/10th of one milligram vs. 100 milligrams of Pharma-Li A total of three lithium-water-suicide prevention studies have been conducted and published in Texas, (11) Japan, (12) and Austria (13). Study: Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. (Schrauzer and Shrestha 1990)(11) Study: Lithium levels in drinking water and risk of suicide. (Ohgami et. al., 2009)(12) Study: Lithium in drinking water and suicide mortality. (Kapusta et. al., 2011)(13) All three of these lithium drinking water studies found a similar trend of significant reductions of suicide in the general population. The first published study was conducted in Texas and the researchers found that by analyzing 27 Texas counties, from 1978-1987, it was discovered that the incidence rates of suicide, homicide, rape, drug abuse and felonious acts of crime were about 50% lower in the 27 Texas counties with underground drinking water supplies containing minute amounts of lithium. The lithium water levels ranged from 70-170 micrograms/L. Additionally this study found a significantly reduced rate of arrests the authors noted for drug possession of, opium, cocaine, and their derivatives (morphine, heroin, and codeine) (Schrauzer and Shrestha 1990)(11)

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The significance of these findings cannot be overstated! These findings robustly suggest that low-dose, non-toxic, lithium supplementation prevents suicide.
A Fox News broadcast (2009) reported on this suicide breakthrough of lithium (a naturally occurring trace mineral in municipal ground water). The report confirmed that lithium significantly reduced suicide rates in the general population who consume municipal water that contain minute amounts of the trace mineral, lithium. Never-mind the well-intentioned, albeit misguided souls that fear the government may be adding lithium to the municipal water supply. Apparently they are unaware that lithium (like other essential minerals) is naturally occurring in aquifers all over the planet earth. So as I direct you to this website to view this Fox News video dont be surprised by the article that is attached (NO, the government is not adding lithium to our water supplies). I have yet to see any studies demonstrating that any U.S. Municipal Governments have been found to be putting lithium into the tap water. If you have such a study, please let me know about it. I would love to review it.

Must see Fox News video (45 seconds) See here: (FOX NEWS VIDEO)

Tell Everyone the Good News! You dont have to take Pharma-Li for PTSD, depression and suicide.
Fortunately we have a bona fide, verified and scientifically evaluated natural alternative to Pharma-Li. This organic-lithium-compound-alternative to the inorganic-Pharma-Li is taken in minute dosages (1/10th-1/20th of Pharma-Li doses) to achieve maximal therapeutic results in the management of MDD, PTSD and treatment-resistant depression (TRD) that so often end with suicide. In these minute dosages there are no negative side effects. Would you be shocked to learn that alternative-minded medical doctors have been secretly administering this organic lithium supplement (without a prescription its not necessary) for over 30 years in the U.S., instead of prescribing the poorly absorbed Pharma-Li versions? (I certainly was shocked, when I learned this fact.) This product has been on the shelves of select health food stores for decades. Not only do veterans not need to take high doses of Pharma-Li for the treatment of depression and suicide prevention, they dont need to use Pharma-Li at all.

Allow me to introduce you to the new and improved breakthrough solution for the veteran epidemic of PTSD, depression and suicide.
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Introducing Lithium Orotate!

Lithium Orotate has been scientifically, clinically and laboratory proven to be free of toxicity and negative side effects!

The real breakthrough of lithium supplementation is discovered through the use of an all natural, organic lithium compound known as Lithium Orotate (LO). (Lithium and Orotic Acid were formulated together by Dr. Hans Nieper, an acknowledged German medical doctor and genius.) You will find directions in chapter 5 on how to utilize this nutritional supplement (as recommended by several medical doctors I have consulted with who are now helping many patients) for maximal and rapid recovery from suicidal thoughts, Major Depression, PTSD and many other miscellaneous categories of stress-related illness. This natural organic mineral supplement is sold over-the-counter (no prescription necessary) at select health food stores across this nation and around the world. THIS PRODUCT IS NOT A DRUG! Due to the overdosing of psychiatric patients with Pharma-Li for decades, this must be reemphasized repeatedly; this product is not a drug. Lithium is an essential trace mineral. (Dr. Schrauzer 2002) See at: Lithium: occurrence, dietary intakes, nutritional essentiality. (4) See Dr. Schrauzers full study report at: (Full report)

This is the breakthrough of Lithium Orotate

Lithium Orotate does not require blood tests to establish a therapeutic level, as the prescription forms do, nor is it toxic to the kidneys as the prescription forms are. Prescription lithium is poorly absorbed by the cells, where it needs to be to do its job. (Ward Dean, M.D.) (14) The following diagram demonstrates the mineral transporters (developed by Dr. Nieper) and the different areas that the transporters deliver the minerals within the cell membrane and orotic acid delivering (the mineral) beyond the cell membrane into the cell plasma.

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Pharma-lithium vs. Lithium Orotate whats the difference?

The primary difference between these two lithium salts (Pharma-Li and LO) is how much lithium via each compound a patient has to ingest to get the maximum therapeutic benefits. Pharma-Li is so poorly absorbed (by the brain cells) you have to consume many times more lithium than (should be in the blood stream) to push the lithium through the cell membrane. The defining issue is how much lithium is absorbed within the cells interior, i.e. the cell plasma, as opposed to being stuck within the cell membrane where it is not as beneficial, or stuck within the bloodstream as Pharma-Li is. Pharma-Li is estimated to be absorbed (intra-cellularly) i.e., within the cell plasma, in the range of 5-10%, depending upon the source of the estimate. Lithium Orotate is estimated to be absorbed (intra-cellularly) within the brain cell, in the range of 95-100%, depending upon the source of the estimate. (In-depth analysis provided later).

Orotic Acid is the Key!

This phenomenal rate of mineral absorption is facilitated by Orotic acid (OA) an organic acid shown to be a master mineral transporter, dramatically increasing intracellular absorption of any mineral it is attached to. Study title: Magnesium orotate in myocardial and neuronal protection. (Zeana 1999) Moreover, the orotic acid behaves as a transporter, carrying magnesium into the cells.(15) Orotic acid is an intermediate in the pyrimidine biosynthesis, which is required for DNA and RNA synthesis. It was originally introduced as a vitamin, called vitamin B13, but essentiality has not been demonstrated.(16) Is Orotic acid supplementation safe? Just like lithium, OA is extremely safe within reasonable supplemental limits. Orotic acid is so safe that it is naturally present in large quantities in animal and human mothers milk for newborn babies. It is hypothesized that OA enhances mineral absorption for newborns. Tri-athletes consuming 3,000 mg/day of OA were analyzed and found to be only benefited by this rather large dosage of OA. (17) Typical OA intakes with Lithium Orotate supplementation range between 300-800 mg of OA/day. Orotic acid has been shown to be naturally synthesized within the cells of the breast tissue, (31) liver, heart and skeletal muscle (18) and is believed by some to be produced

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naturally within the intestines via intestinal flora. Orotic acid is ingested from many food sources. See Vitamin B13 (Orotic Acid) (19)

Orotic Acid (OA) supplementation Benefits:

Numerous OA supplemental studies on its effect upon the heart and liver in animals and humans have all shown significant enhancement of function without any signs of dysfunction caused by OA in humans. Orotic acid enhances recovery from heart attacks, reduces hardening of the arteries, and facilitates left ventricular recovery following heart transplant and demonstrates significant anti-oxidant protection. (20),(21),(22),(23) In patients with a form of hyperlipidemia (high blood cholesterol levels) a significant lowering of the serum lipid concentrations has been shown with OA administration. Also Toxic influence on the liver may be reduced by orotic acid. Study title: [Metabolic effects of orotic acid]. (Muller 1984) (24) For an in-depth discussion of Orotic acid please review the best document I have found on this topic by Ed Sharpe. How Orotates Work The Biochemistry of Vitamin B13 Ed Sharpe states; As theorized many years ago by the pioneering German physician Hans Nieper, orotates are a component of a natural system of electrolyte carriers for distributing minerals throughout the body. Either wayvia enhanced diffusion or active transportcomplexing a mineral with orotate results in increased uptake of both components of the complex by cells. (25) Orotic acid is the key to low-dose lithium supplementation while maximizing therapeutic benefits. While mainstream medical doctors routinely prescribe 140-225 mg of elemental lithium (EL) via Pharma-Li (for treatment of Major Depression) alternative medical doctors are routinely administering 1/10th 1/20th of the EL dose (5-20 mg of EL), via Lithium Orotate, for treatment of Major Depression (Ward Dean, M.D.)(14),(26) Lithium like many minerals are not easily absorbed intracellularly, The passive electrochemical handling of lithium disposition across the membrane would predict tenfold higher intracellular concentration due to the cells resting negativity. Therefore, it is clear that lithium concentrations in the brain are not at equilibrium. (Kabakov et. al., 1998)(27) While mainstream psychiatrists routinely prescribe 170-340 mg of EL, (causing numerous negative side effects) via Pharma-Li (for treatment of Bipolar disorder {BD}), alternative medical doctors are routinely administering 1/10 of the EL dose (15-30 mg of EL) for treatment of BD via Lithium Orotate. (Dr. Mark Millar) Why? Because LO has been clinically demonstrated to be effective at much lower doses; due to its apparent superior intracellular absorption. Again, Lithium Orotate (LO) is sold in health food stores as a nutritional supplement no prescription required. LO is sold nationwide in the Vitamin Shoppe stores. Here is the nationwide map of the Vitamin Shoppe store locations for your convenience. If you need LO today go here: (The Vitamin Shoppe Stores) http://www.vitaminshoppe.com

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But I should warn you that you will pay more for LO if you buy from the Vitamin Shoppe. We will ship LO to your door for $16 and change (shipping & handling included) while the Vitamin Shoppe charges over $26, shipping included. But I digress. Because of its high bioavailability, lithium orotate dosages are usually about 1/20 of the dosage of prescription lithium. (Ward Dean, M.D.) See Dr. Deans Q & A comments on Lithium Orotate at: (14) Also see Dr. Ward Deans article The Safe, Unique Mineral with Multiple Uses. See at: (26) Again, Lithium Orotate (LO) is significantly more bioavailable (i.e., absorbable within the brain-cell) than Pharma-Li. The increased absorption of LO is due to Orotic Acid the bodys supreme mineral transporter. (More on Orotic Acid later)

Most Importantly: Lithium Orotate Causes No Negative Side Effects!

Medical doctors have found that doses of Lithium Orotate, 80-90% lower than the orthodox Pharma-Li dosage for MDD patients have shown fair to good response in 50-70% of patients in the treatment of depression. (Jonathan Wright, M.D., Ward Dean, M.D., Shaheen Lakhan, M.D., Stanley Olsztyn, M.D., C Norman Shealy, MD, Ph.D.) Due to concerns over potential FDA persecution (for administering LO) most medical doctors have done so, and continue to utilize it, covertly. A notable exception is Dr. Jonathan Wright. Jonathan Wright, M.D., a well known family practitioner, bestselling author of Guide to Healing with Nutrition and Book of Nutritional Therapy, public speaker and major clinical researcher of Lithium Orotate administration is on record stating that

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Even at a quantity of two low-dose lithium orotate tablets, three times daily (for a total 30 milligrams of EL) patients serum (blood) lithium levels, usually remains in the non-detectable or below therapeutic range, which means that they are very safe. In my 30 years of practice, I have never had a patient report of lithium excess. (Jonathan Wright, M.D.) See at end of article here: (6)

Without lithium excess, there can be no lithium toxicity!

Furthermore, in a recent written communication to me, Dr. Wright, America's top Lithium Orotate (LO) medical expert, declared, After decades of clinical research and laboratory testing of LO on my patients, I discovered that administering Lithium Orotate up to 40 mg per day of EL is completely safe (without negative side effects or toxicity) and absolutely effective in the treatment of numerous mental, neurological and physical conditions. (Jonathan Wright, M.D.) Without negative side effects there is no longer any reason not to utilize LO for all veterans as a primary treatment of major depressive disorder, bipolar disorder, schizophrenia, schizoaffective disorder, borderline personality disorder and Alzheimers disease since these are the major drivers of veteran suicides. I recommend you review Dr. Wrights excellent and vital article, The Misunderstood Mineral: Part one at: (28) Part two at: (29) Many alternative medical doctors are now speaking truth to the power of the Pharma-cartel and declaring that the elemental mineral, lithium, is an essential trace mineral in defiance of the mainstream medical model that implies that lithium is a drug. Just because you call a trace mineral a drug does not make it a drug. Lithium is only mildly irritating when you exceed the safe, maximum therapeutic limit of 100 mg of EL and is moderately toxic at 200 mg EL, but it becomes severely toxic at 400 mg EL (equivalent to 2.0mmol). (Young 2009)(30) Remember: This is the only reason people believe that lithium is a toxic drug. The patients are being prescribed large amounts of Pharma-Li, well in excess of 100 mg of EL. While seemingly rare among mainstream medical doctors, many alternative-minded integrative medical doctors are presently administering LO across the U.S. for major mood disorders such as; MDD and bipolar disorder, PTSD, anxiety disorders, sleeping disorders, other neurological disorders, and those with suicidal ideations. These alternative medical doctors are achieving excellent results with LO, at dosages in the typical range of 10-40 mg of EL, compared to Pharma-Li dosing of all major mood disorders in the range of 100-400 mg of EL, thus causing toxic reactions.

Here follows a few of these alternative-minded integrative medical doctors administering Lithium Orotate: The Essential Trace Mineral.
Shaheen Lakhan, M.D., author of Nutritional Therapies for Mental Disorders Another form of lithium called lithium orotate, is preferred because the orotate ion crosses the

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blood-brain barrier more easily than the carbonate ion of lithium carbonate. Therefore, lithium orotate can be used in much lower doses (e.g. 5 mg) with remarkable results and no side effects. (31) Who is Dr. Lakhan? (Who is) Kerry D. Friesen, M.D., author of Lithium Orotate: Lithium is an essential micronutrient with some chemical properties similar to calcium and magnesium. (10) Al Sears, M.D. Lithium itself is not a drug; its a naturally occurring mineral salt like potassium, and something you need for proper mental and physical health... Lithium Orotate is a safe and simple way to help beat the blues. (32) Who is Dr. Sears? (Who is) Ward Dean, M.D., author of The Unique Safe Mineral with Multiple Uses: The lithium salt of orotic acid (lithium orotate) improves the specific effects of lithium many-fold by increasing lithium bio-utilization. (Ward Dean, M.D.) (26) Lithium orotate has also been used with success in alleviating the pain from migraine and cluster headaches, low white blood counts, juvenile convulsive disease, alcoholism and liver disorders. Lithium Orotate is extremely safe, with no known adverse side effects or drug interactions. (Ward Dean, M.D.) (26) Lithium Orotate does not require blood tests to establish a therapeutic level, as the prescription forms do, nor is it toxic to the kidneys as the prescription forms are (Ward Dean, M.D.) (14) Prescription lithium is poorly absorbed by the cells, where it needs to be to do its job Because it is so poorly absorbed, blood levels need to be fairly high to drive it into the cells. Unfortunately, these therapeutic blood levels are dangerously close to the toxic level. Thats why patients on prescription lithium need to be carefully monitored Successful dosing with Lithium Orotate is measured by clinical effects on the patient, rather than by blood levels. (Ward Dean, M.D.) (14) Lithium Orotate will not cause weight gain, nor will it cause sedation or sleepiness. (Ward Dean, M.D.) (14) Who is Dr. Dean? (Who is) H. E. Sartori, M.D., conducted a Lithium Orotate study titled: Lithium orotate in the treatment of alcoholism and related conditions. Thirty-six of the 42 patients studied had been hospitalized at least once for the management of their alcoholismLithium orotate was given, 150 mg daily Lithium orotate proved useful as the main pharmacologic agent for the treatment of alcoholism. Ten of the patients had no relapse for over three and up to 10 years, 13 patients remained without relapse for 1 to 3 years, and the remaining 12 had relapses between 6 to 12 months. Lithium orotate therapy was safe and the adverse side effects noted were minor, i.e., eight patients developed muscle weakness, loss of appetite or mild apathy. For these patients, the symptoms subsided when the daily dose was given 4 to 5 times weekly. (33) This was an amazing finding; over 50% of the alcoholic patients who completed this study were without relapse for over one year and 25% of them made it over 3 years without a relapse. NOTE: This finding of mild side effects subsiding once the Lithium Orotate

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daily dosage was reduced (33) provides further scientific evidence that lithium has no inherent toxicity when taken in smaller reasonable dosages. C. Norman Shealy, MD, Ph.D. The Shealy Protocol for Treating Depression and Fibromyalgia Lithium Orotate Dosage (20-45mg EL per day) (Page-2) (34) Who is Dr. Shealy? (Who is) Ray Sahelian, M.D., author of Lithium supplement and medication: Available without a prescription. Lithium orotate has been marketed as an alternative to lithium carbonate. As this natural supplement, lithium is joined with an orotate ion, rather than to a carbonate ion. See Dr. Ray Sahelian: (35) Who is Dr. Sahelian? (Who is) Linda Fugate, Ph.D., author of Lithiums Potential Role in Preventing Alzheimers disease lithium orotate is a highly bioavailable form of lithium that is available as an over-the-counter dietary supplement. (36) Dietrich K. Klinghardt, M.D, Ph.D., author of Lyme disease: A Look Beyond Antibiotics: Lithium-orotate in low doses (15 mg/day) has been shown to protect CNS structures from neurotoxin damage (37) Who is Dr. Klinghardt? (Who is) Dr. R Stone, M.D., author of Trace Mineral Salt Lithium Orotate to Treat Many Diseases of the Brain Quantum brain uses Lithium Orotate for the treatment of kleptomania, schizophrenia, migraine, alcoholism, stress-induced memory loss and Alzheimers disease. (38) Phuli Cohan, M.D., author of How I am Treating My Lyme: Lithium Orotate Personal Protocol Lithium Orotate (4.8 mg) 2 pills three times/day (this is not the same as lithium carbonate used in bipolar illness) was also helpful. (39) Garry F. Gordon, MD, DO, MD(H) Dr. Gordons Personal Daily Protocol Lithium Orotate Beyond Lithium (Lithium orotate 4.8 mg) taken once nightly. (40) Who is Dr. Gordon? (Who is) Alice R. Laule, M.D., author of Lithium The form of lithium I have recommended Lithium Orotate primarily Lithium is a trace element which has important functions in the brain, including protecting brain cells from various toxins, and reducing the ill effects in particular of an over abundance of certain neuro-excitatory neurotransmitters which are useful in balanced amounts but harmful in large amounts.(8) Who is Dr. Laule? (Who?) Jeffrey Dach, M.D., author of Beating Depression Naturally. Lithium Orotate, on the other hand, is more bio-available, and safer than the Lithium Carbonate. Who is Dr. Dach? (41) James Howenstine, M.D., author of How to Enlarge Your Brain and Improve Brain Performance (42) Who is Dr. Howenstine? (Who is) Emily Deans, M.D., (Harvard trained psychiatrist) author of Feeling Better: A 6-Week Mind-Body Program to Ease Your Chronic Symptoms Could You Have a Lithium Deficiency? Shocking but true Lithium is an essential trace element. (42) Who is Dr. Deans? (Who is)

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Mark Hyman, M.D., best-selling author of The UltraMind Solution. Lithium is an essential micronutrient It is present in all organs and tissues in the body.(7) Who is Dr. Hyman? 5 Time NY Times Best Seller (Who is) You must see Dr. Hymans book. (The UltraMind Solution) Jonathan Wright, M.D., author of The Importance of Lithium Supplementation. In fact, lithium isnt a drug at all. Its actually a mineral-part of the same family of minerals that includes sodium and potassium. (6) Who is Dr. Wright? (Who is) Lawrence Wilson, M.D., author of Lithium Lithium is one of the most important elements in the human body. (9) Marty Ross, M.D. Lithium Orotate for Lyme disease. See: (video) All of these doctors, plus many more, report that LO is extremely effective and absolutely safe, when taken in reasonable low-dosages. These are a few of the courageous alternative-minded medical doctors who are speaking truth to power and there is no doubt that hundreds, if not thousands, more are administering Lithium Orotate covertly to avoid potential FDA persecution. Many Medical doctors have lost their medical licenses for utilizing vitamins and minerals in their practices. In a recent interview with a Naturopathic doctor, Dr. A. True Ott, (a brilliant researcher and mineral manufacturer), I learned that Dr. Ott had been persecuted by the FDA for his groundbreaking research in the healing properties of lithium and other essential minerals. Dr. True Ott described that he had been specifically ordered by the FDA to discontinue any further research on lithium supplementation. A shocking travesty! Why would the FDA want Dr. True Ott to discontinue his research on lithium, specifically? The pharmaceutical industry (PI) is desperate to keep the public believing that lithium is a dangerous toxic drug. Why? Because the PI cannot compete with the low-cost, high efficacy natural solution for mental and neurological conditions and would prefer the public not discover the healing benefits of the essential trace mineral, lithium. This is why, in my opinion, the PI has rejected the LO alternative to Pharma-Li. Lithium Orotate has no competitors and is truly in a class of its own. Article Title: Is lithium in a class of its own? A brief profile of its clinical use. (Malhi, Adams and Berk 2009). Discipline of Psychological Medicine, University of Sydney, Australia. Arguably, lithium is the only true mood stabilizer and because of its unique properties is in a class of its own. (Malhi, Adams and Berk 2009) (44) Could this be why the PI continues to manufacturer a Pharma-Li compound that is so poorly absorbed by the cells of the brain that massive doses of the trace mineral must be

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administered? In this way the PI controls, in my opinion, the public perception that lithium is a toxic dangerous drug, which obviously it is not. Without exception, all minerals have a supplemental toxic limit. Again, for the most sensitive individuals the supplemental limit for lithium appears to begin at 100 mg of EL per day. Most people however can take up to 150 mg of EL per day without significant side effects. Some people can take up to 200 mg of EL per day without significant adverse side effects but after exceeding 300 mg EL virtually all patients report significant adverse side effects. (Young 2009) (30) This is the breakthrough of Lithium Orotate; therapeutic dosing is typically in the range of 5-20 mg EL for maintenance of depression and 20-40 mg EL for maintenance of PTSD and bipolar disorder. Here are the take away thoughts at this point: Natural lithium in the drinking water significantly reduces suicide rates beginning at dosages of 1/10th of 1 mg. Lithium Orotate effective dosing for depression is typically in the range of 5-20 mg of elemental lithium, 50-200 times greater than the lowest effective dose for suicide prevention discovered in the lithium-drinking-water studies. Therefore, this level of dosing (5-20 mg of elemental lithium) should be more than sufficient to end the suicide epidemic. It has become my profound belief that we have in Lithium Orotate the singular vehicle to end the veteran suicide epidemic if only we can get this information to our veterans. We have created the Veteran Suicide Prevention Team (VSPT) for the purpose of a massive and expedient dissemination of this critical information. Through a committed and purposeful communication effort VSPT members will facilitate a nationwide phone campaign to reach millions of individuals in a short period of time. We invite all who read this to send us an email at opsetthemfree@live.com so we can send you the details of the VSPT actions and objectives. The VSPT will make sure everyone knows about

The Solution that Works: Lithium Orotate!

Reduces suicidal thoughts & actions Reduces MDD and PTSD symptoms Reduces Insomnia and Nightmares Promotes Deep and Still Sleep Veterans may drink alcohol Minimally 1/10th the dose of Pharma-Li 90-100% intracellular absorption No negative side effects No adverse drug reactions No adverse effects on kidneys or thyroid Cost only $5-$15/month Sold in select health food stores & online

Lithium Orotate is the only viable solution to quickly put an end to the veteran suicide epidemic. Thank God for it The time has come for the

Lithium Orotate Revolution! It is time to Set Our Veterans Free!

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Having said all that; I encourage you to order Lithium Orotate, NOW!
(ORDER HERE)

If you are still not convinced read on! I will give much more evidence for the efficacy, essentiality, safety and superiority of Lithium Orotate!

What can we do about this painful situation?

Eighteen deaths per day among the Veteran population are attributable to suicide.
Dr. Robert Jesse, M.D., PH.D., Principal Deputy Under Secretary for VA Health 2010 (1)

Suicides Outpacing War Deaths for Troops

(The New York Times June 8, 2012) National Guard soldiers who are not on active duty killed themselves this year (In 2010) at nearly twice the rate of 2009. (5) (USA TODAY 11/26/10) Veterans with a diagnosis of Major Depressive Disorder [while in the care of VA treatment] have been found to have suicide rates that are seven to eight times the rate of the general population. (Zivin et. al., 2007) See full study at: (10) Sadly, like so many other extremely painful human experiences, most people will turn away from any situation that they feel they have no control over. This is definitely the case with the veteran epidemic of PTSD, depression, suicide and homelessness. Most Americans will almost immediately, emotionally and mentally shut down, the moment I speak with them about this suicidal situation. People just have no idea where to go with this information. They question, What can I do about it? The overwhelming feeling and thus the realization (for an individual American) is I myself can do nothing to help a suicidal veteran or a veteran overwhelmed by depression, PTSD or homelessness. Up until this point the only thing the average American could do is give money to a veteran organization. However today is a new day! We have a nutritional breakthrough that assists veterans in every category of mental, emotional and physical suffering associated with depression and PTSD. Americans that truly care, I mean really care beyond lip service, now have a clear and significant opportunity to make a difference in the life of an individual veteran and for the 23 million veterans as a whole.

This is my call to action for all Americans who really care!

Make the commitment today to join in Operation Set Them Free and become a critical part of the solution to end the veteran suicide epidemic. Take the first step in this mission and add your name to the growing list of members who are part of the Veteran Suicide Prevention Team.

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The Veteran Suicide Prevention Team (VSPT) is committed to playing an integral part of the dissemination of the breakthrough information. If you can envision the potential of this mission to succeed in its promise, we welcome you aboard. The critical element required for the success of this mission is your participation in calling anyone and everyone you may know who truly cares about the welfare of our 23 million veterans and their families. In the simplest of terms all you need to do is pick up the phone and call someone within your circle of influence. If you must, leave a message telling them that you have sent them a critically important email & ask them to call you once they have opened the email. If you don't hear from them please call them again. Unless you speak with them by phone, chances are they will not read the email. Our veterans are counting on YOU! You only need to speak briefly to make the difference of saving a veterans life. You could say something like to following Hey Bob, I just wanted to let you know that I have just sent you an email that you have to see to believe. It appears that a nutritional breakthrough for the veteran suicide epidemic has been discovered by Harvard Medical School. Then simply suggest that your friend review some of the evidence in this email. Thats all it takes! Please review the following videos before you call your family and friends. Dr. John Gray Dr. Marty Ross Fox News see at: www.youtube.com/watch?v=ijMbycw2boM see at: www.youtube.com/watch?v=sR5QegnoKKo see at: www.lovethetruth.com/health/lithium_in_water.htm

Lithium Orotate on Coast 2 Coast with George Noory and guest Dr. John Gray review 5 minute LO discussion; start at 28 minutes - 33 minutes. Follow this link: (Coast 2 Coast)

To receive the prepared VSPT email to forward to your friends, simply go to www.opsetthemfree.com and download the FREE REPORT. Enter your email address and leave the following message in the comments box provided for you: Send VSPT email
If you wish to continue receiving updates on Operation(s) Set Them Free & Break Free just type in the comment section SEND UPDATES. If you prefer not to be sent updates just type in the comment section NO UPDATES and we will respect your request and NEVER share your email address with anyone. We would love to hear from you regarding any questions you may have and especially from those of you who would like to tell us how many contacts you have made. This will give us some idea of how this networking mission is progressing. Email: OpSetThemFree@live.com

Does lithium really prevent suicide?

With such a controversial subject as this, who can we trust on this matter? For starters we can trust the number one ranked, medical research university in America, Harvard Medical School.

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Chapter One

Harvard Medical School Takes the Lead! The Suicide Breakthrough of Lithium
This suicide-breakthrough was determined by Harvard (meta-analysis); defined as the combined analysis of results from several studies that integrates the data, using statistical analysis and thereby reduces statistical error and erroneous conclusions. Harvard Medical School has analyzed over 30 human studies in a meta-analysis and determined that lithium reduces the rate and risk of all acts of suicide (attempts and completed suicides) by 80-90% in patients with Major Depression, Bipolar Disorder and Schizoaffective Disorder. Terms to understand: Affective illness = Mood disorders i.e. Bipolar disorder, Major Depression, Schizoaffective disorder and PTSD. Note: PTSD is not a traditionally considered a mood disorder but I have included it because in my opinion, it should be, as mood is dramatically affected in PTSD. Major Depressive Disorder is also known as Unipolar Depression. Recurrent Major Depression Recurring as if chronic, cyclical or repetitive. A single study or even a few studies on a subject carries far less weight than the meta-analysis of eight studies combined. The Harvard meta-analyses that you are about to read is comprised of eight human studies and thirty-four in the largest Harvard meta-analysis. These numbers (834) make these meta-analyses indisputable in their findings; particularly since Harvard Medical School conducted them.

A meta-analytic study is the gold standard of research analysis.

If all of the following meta-analytic-studies, had not been produced by researchers at the Harvard School of Medicine, I probably would not have believed what I was reading. Study title: Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. (Baldessarini et. al., 2006) Harvard Medical School In 31 studies suitable for meta-analysis, involving a total of 85,229 person-years of riskexposure, the overall risk of suicides and attempts was five times less among lithiumtreated subjects than among those not treated with lithium. (Baldessarini et. al., 2006) (1) The previous abstract quotation from Harvard Medical School illustrates the copious quantity of scientific evidence that has been published on this subject. The combined number of patients

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studied is equivalent to 8,500 patients studied over 10 years = 85,000 person years. This is an unprecedented, extreme amount of evidence for lithium suicide prevention.

Additionally, Harvard researchers discovered in multiple (placebocontrolled) randomized clinical trials (the gold standard of research) the trace mineral lithium had zero suicides while there were 13 suicides in the other drug categories. See: Risk of suicide or attempts in randomized, controlled trials of lithium versus other treatments. See table 3, page 8 of the full study HERE (1)
(Baldessarini et. al., 2006) Lithium Studies Prien et. al., 1974 Greil et. al., 1996, 1997 Bauer et. al., 2000 Bowden et. al., 2003 Calabrese et. al., 2003 Total suicides (Baldessarini et. al., 2006) (1) 0 0 0 0 0 0 Other treatments 2 7 1 1 2 13

Study title: Lithium treatment and suicide risk in major affective disorders: update and new findings. (Baldessarini, Tondo and Hennen, 2003) Harvard Medical School Subjects with bipolar versus various recurrent major affective disorders showed similar benefits (95% vs. 91% sparing of all suicidal acts). (2) Major affective disorders are those mental illnesses which predominantly affect mood and also have an effect on thoughts, behaviors and emotions. They include, but are not limited to, major depression, bipolar disorder and schizoaffective disorder.

Study title: Lithium treatment reduces suicide risk in recurrent major depressive disorder. (Guzzetta, Tondo, Centorrino, and Baldessarini, 2007) Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Lithium reduced the risk of recurrent major depressive suicides by approximately 90%. (3) Eight studies involved 329 MDD patients and exposure for 4.56 years (1,149 person-years) with, and 6.27 years (1285 person-years) without, lithium. Overall risk of suicides and suicide attempts was 88.5% lower with, vs. without lithium. (Guzzetta et. al., 2007) (3)

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Researchers worldwide agree that treatment involving lithium is the best way to protect patients from suicide risk.
(Pompili et. al., 2009, Harvard Medical School) See: Assessment and treatment of suicide risk in bipolar disorders. (4)

If you are wondering, (as I was) why you have never heard of the incredible ability of lithium to prevent suicide, like me, you may be shocked to find out that these Harvard Medical School studies have never been discussed in the main-stream media. How could this be; one of the greatest breakthroughs in Psychiatric medicine discovered in the 21st century and not one whisper of it in the main-stream media? Do you suppose that no one is paying attention to Harvard research? Hardly! Perhaps the world of news, heard about it, but did not believe it? But wait these Harvard reports represent over 30 human studies conducted over three decades, so the preponderance of evidence and validity of the information is beyond dispute, so that cant be it! If you are starting to think like me you have an idea that maybe, just maybe, somebody or something is responsible for this information not being reported in the main-stream media. Can you say Pharmaceutical Industry? We will get into this discussion more in-depth later. The massive scale of these combined research studies (8,500 patients studied over 10 years = 85,000 person years) makes the lithium-suicide-prevention-results indisputable and yet Only 1 in 200 veterans are receiving this nutrient for the treatment of MDD. (Valenstein et al., 2006)

The Veterans Administration has failed to provide our veterans with this breakthrough for suicide prevention! Without question this is actionable intelligence. For the VA to not take action on this is immoral!
Why is the VA not giving our veterans lithium for Major Depression or treatment-resistant MDD - the primary cause of the suicide epidemic? So after reviewing all of these Harvard medical studies on the breakthrough of lithium for the prevention of suicide, you would expect that our beloved veterans who are experiencing an epidemic of suicide would be receiving the best that medicine has to offer, right? Guess again!

Since 2003, year after year the number of veteran suicides continues to climb with no end in sight.
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National Guard soldiers who are not on active duty killed themselves this year (In 2010) at nearly twice the rate of 2009. (5) (USA TODAY 11/26/10)
People often say to me, I just cant believe this is true. If a solution for the suicide epidemic truly existed, those in control and power would utilize the solution, right? Therefore, how can this be true?

Someone once said, The greatest deception the Devil ever pulled on humanity was convincing the world he does not exist.
Whether you believe in God or the Devil, certainly you understand that evil intentions do exist within the human psyche, pharmaceutical industry and every other human organization. Business is War; the pharmaceutical industry is out to win!

The American Psychiatric Association affirmed the findings of Harvard Medical School
This incredible suicide breakthrough discovered by Harvard researchers was published in the American Psychiatric Association (APA) Practice Guideline for the Assessment and Treatment of Patients With Suicidal Behaviors (2003) (6) See: IV. Specific Treatment Modalities: A. Somatic Therapies 1. Antidepressants 2. Lithium The APA stated For suicide, lithium maintenance treatment was associated with an 80%90% decrease in risk, whereas the reduction in suicide attempt rates was more than 90%. (6) Furthermore the APA stated A recent meta-analysis found a highly statistically significant decrease in suicidal acts (i.e., suicide or suicide attempts) of almost 14-fold. (6) Finally, the APA stated There is strong and consistent evidence in patients with recurring bipolar disorder and major depressive disorder that long-term maintenance treatment with lithium salts is associated with major reductions in risk of both suicide and suicide attempts. (6) A 2010 publication by the APA of the Practice Guideline for the Assessment and Treatment of Patients With Suicidal Behaviors has shown no changes in the APA statements regarding lithium and other treatments for the prevention of suicide. (7)

So now we have the two most trusted and authoritative organizations in America (Harvard, the #1 medical research university, and the

29

American Psychiatric Association) on record demonstrating the lithium-suicide-prevention-breakthrough.

So if the management of the VA were doing its job it would have immediately published a strong statement in 2003, to all doctors at all VA clinics demanding that this preventative breakthrough be acted upon immediately! In my opinion, upon receipt of the APA 2003 publication regarding the Harvard studies on Pharma-Li, the following simple statement should have been made and ordered as a matter of treatment protocol by the VA. Attention VA doctors and staff: Harvard and the APA have determined that lithium reduces all acts of suicide by 80-90%! Given the fact that veterans are experiencing an epidemic of suicide, it is critically important that all veterans suffering with PTSD, depression, bipolar and schizoaffective disorders, are prescribed a low non-toxic dose of lithium i.e., 300-450 mg lithium (carbonate, chloride or citrate) immediately and daily. From this minimal dosage (450 mg) of Pharma-Li the veterans would receive 85 mg of EL. At this low dose there are zero significant side effects or patient complaints of lithium toxicity.Therefore patient utilization of lithium would be maximized due to its increased tolerability. Because lithiums suicidal protective effects begin at less than 1 mg of pure EL (proven in 3 aforementioned lithium drinking water studies), I am confident that 85 mg of EL via PharmaLi would have significantly protected the majority, if not all of the veterans who were at high risk of suicide.

This one simple policy act could have saved minimally, over 10,000 veterans lives since 2003!! But, to my knowledge, the VA never published any policy statement ordering the administration of low doses of Pharma-Li to veterans!
What the VA did publish showed either a total lack of understanding of what was going on, or an intention to suppress this breakthrough for those veterans who were at risk of suicide.

Rarely have so many people been so wrong about so much. Never have the consequences of their misunderstanding been so tragic. (President Nixon 1985)
Given the authoritative analysis of Harvard Medical School and peer-reviewed confirmation by the APA of the efficacy of the lithium solution for suicide, you might naturally assume that the VA would be utilizing this breakthrough for its veterans. SADLY THIS IS NOT THE CASE! Very shortly you will review the findings (discovered in a massive study {244,859 veterans} at a U.S. VA medical center) that shows our nations veterans, suffering an epidemic of suicide have been systematically denied this nutritional solution for the management of treatment-

30

resistant depression; the leading cause, quantitatively, of suicide by the Veterans Administration. Treatment-resistant depression (TRD) is defined as the failure of pharmaceutical treatment to adequately or sufficiently resolve (or cause remission) of the patients symptoms of depression. Without relief of severe, treatment-resistant depression, the veteran is too often left with only one way out, SUICIDE! A significant proportion of patients with MDD are treatment resistant or only partial responders to adequate therapy with a single agent. In this situation, one must consider augmentation with another agent. (Dording 2000) (8) To reemphasizeVeterans with a diagnosis of major depression [while in the care of VA treatment] have been found to have suicide rates that are seven to eight times the rate of the general population. (Zivin et. al., 2007) (9)

CLEARLY, THE VA IS FAILING MISERABLY IN SUICIDE PREVENTION!

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Chapter Two

Major Depression, PTSD & Suicide Statistics

Major Depressive Disorder (MDD), a Devastating, Suicidal Mood Disorder! Major Depressive Disorder is one of the most fatal co-occurring medical conditions associated with PTSD; as 70-80% of all suicides occur in depressive states.
Journal Biological Psychiatry (Pfennig et. al., 2005) (1)

Veterans with MDD and PTSD simultaneously have a higher risk of suicide than MDD alone.
(Campbell et. al., 2007) (2)

Veterans of (all ages) with a diagnosis of MDD [while in the care of VA treatment] have been found to have suicide rates that are seven to eight times the rate of the general population.
(Department of Veteran Affairs - Zivin et. al., 2007) (3)

PTSD patients have a 600% increased risk of suicide compared to non-PTSD trauma patients.
(Pietrzak et. al., 2011) (4)

For the youngest off-duty veterans of Afghanistan and Iraq (age 18-24) diagnosed with MDD and PTSD simultaneously, the suicide rate is estimated at least TEN TIMES the rate of the general population.
(Dr. Mark Millar 2012)

Approximately 35% of Vietnam veterans with MDD/PTSD have contemplated suicide, 19% have attempted!
The American Journal of Psychiatry (Hendin and Haas 1991) (5)

In 2010National Guard soldiers who are not on active duty killed themselves this year at nearly twice the rate of 2009.
(USA TODAY November 26, 2010) (6)

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At any given time, approximately 50% of veterans with combat related PTSD are also clinically depressed. Over the course of a lifetime, major depression is experienced by 95% of combat veterans.
The British Journal of Psychiatry (Bleich et. al., 1997) (7)

The suicide rate for the youngest veterans of Afghanistan and Iraq (age 18-29) is 4 times higher than the general population of the (same age).
(This lower suicide rate (4x) averages veterans with MDD and PTSD with veterans who do not have MDD and PTSD diagnoses.) (CBS/AP Veterans Administration, Center for Disease Control 2007) (8)

Stemming the Tide: Suicide Rates for 2011 Continue to Climb

The Army released new data on suicides for May and, continuing the trend from the numbers released in April, they are the highest to date for 2011. (Veteran Journal-Military News, June 24th, 2011) (9)

Veteran Suicides Reach Epidemic Proportions within the U.S.

Over 6,500 Veteran Suicides estimated for 2005 126 Suicides/Week, Approximately 18/day
(CBS News 2008) (10) Must see video at: (CBS Video) (11)

Will 2012 numbers pass 7,000 veteran suicides?

So we have an epidemic of suicide amongst our nations veterans; presently 6800 or more suicides per year, and probably at least five times that amount that are attempting suicide annually. This is over 40,000 acts of suicide annually amongst our veteran population. Seven years since the 2005 suicide estimate the annual veteran suicide rate is now probably well over 7000/year in the U.S. This suicide rate represents all veterans since WWII. The sad fact is that combat veterans frequently have a horrifically difficult time reintegrating into society upon their return from war. This is particularly true if they served on the frontline of combat and now suffer with severe Major Depressive Disorder and Post-traumatic Stress Disorder. Presently there are for more Iraq and Afghanistan veterans dying by suicide than from battle. In recent years, since the VA has come under fire for the mishandling of data for the veteran epidemic of suicide and has been put on the defensive by congressional investigations and

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lawsuits by the veterans groups, Veterans for Common Sense and Veterans United for Truth. The VA has done much since then to deal with a tsunami of veteran suicides. However even with all of their efforts since 2008, the epidemic of suicide amongst our nations veterans is accelerating.

Veteran Suicide Rates on the Rise!

Due to the ongoing wars in Iraq and Afghanistan beginning in 2003 the suicide rate among veterans (from all foreign wars including WWII) was over 540 per month in 2007. (12) This rate is no doubt even higher today since so many veterans have been forced to return for multiple tours of combat duty. According to the Mental Health Advisory Team V, the number of veterans screening positive for mental health problems has more than doubled since the first deployment from 12% to 27% by the third and fourth deployment. (13) The real epidemic of suicide begins after the veterans come home from active duty. As a recent analysis reveals the suicide rate amongst our National Guard soldiers who are not on active duty has nearly doubled from 2009 to 2010. The following excerpt from an article published on the front page of the USA TODAY reveals the sad story.

Civilian Soldiers' Suicide Rate Alarming!

By Gregg Zoroya, USA TODAY 11/26/2010 National Guard soldiers who are not on active duty killed themselves this year at nearly twice the rate of 2009. National Guard soldiers who are not on active duty killed themselves this year at nearly twice the rate of 2009, marring a year when suicides among Army soldiers on active duty appear to be leveling off, new Army statistics show. Eighty-six non-active duty Guard soldiers have killed themselves in the first 10 months of 2010 compared with 48 such suicides in all of 2009. (14)

Senators tell VA to reduce veteran suicides

By Rob Hotakainen, McClatchy Newspapers, Washington Bureau, Wed, May. 25, 2011 Washington - With veterans now accounting for one of every five suicides in the nation, the Department of Veterans Affairs is under pressure from the courts and Congress to fix its mental health services in an attempt to curb the death toll. The suicide rate is out of control. Its epidemic proportions right now, said Paul Rieckhoff, the executive director of the Iraq and Afghanistan Veterans of America. There are very few programs that are effective, and theres a serious lack of national awareness. Senator Patty Murray said that service members and veterans alike continue to take their own lives at an alarming rate she noted that in April, the VAs suicide hotline fielded more than 14,000 calls, or more than 450 per day, the most ever for a single month. (15)

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Finally we examine the continuing increase of active-duty suicides over the past few years. The New York Times published the following statistics in early 2012.

The New York Times

Active-Duty Soldiers Take Their Own Lives at Record Rate

By Elisabeth Bumiller January 19, 2012 See: (NYT Suicide Report) (16)

The New York Times

Suicides Outpacing War Deaths for Troops

By Timothy Williams June 8, 2012. See: (NYT Suicide Report) The military said Friday that there had been 154 suicides among active-duty troops through Thursday, a rate of nearly one each day this year. The figures were first reported this week by The Associated Press. That number represents an 18 percent increase over the 130 activeduty military suicides for the same period in 2011. (17)

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I Repeat! There is presently an epidemic of veterans suicides in America that is presently accelerating!

Approximately 50 percent of suicides among VA health care users are among patients with a known mental health diagnosis.
Dr. Robert Jesse, M.D., PH.D., Principal Deputy Under Secretary for VA Health.2010.(12) The previous statement made by Dr. Robert Jesse is indicative of a systemic stigma problem associated with the diagnosis of a mental disorder, such as major depressive disorder, amongst our nations veterans. Only half of the veteran suicides among VA health care users were known to have a mental health diagnosis. That means, the other half who committed suicide went undiagnosed at the VA for (MDD) a mental illness severe enough that it caused the veteran to take their own life. It appears that half of our veterans are suffering alone in silence unable or unwilling to reach out for help. While only about 50% of patients receive medical care for MDD, only about 40% of those receiving care have an adequate response. The end result is that approximately 20% of 12month (long-term) MDD patients are being adequately treated. (Kessler et. al., 2003) Harvard Medical School (18) These two categories of mood disorder (MDD/PTSD) account for the vast majority of all suicides. Indeed a recent study of suicide attempts in women (non-combat veterans) found that 84% of them had a history of MDD or PTSD. (Cougle et. al., 2009) (19) Suicide is an irreversible permanent solution to an often temporary problem. However, all too often an individual has endured for years with intractable cycles of severe major depression that eventually erodes their will to persevere. There are many factors influencing the final act. Indeed suicidal ideation, attempts and ultimately completed suicides are multifactorial in their causal orientation. The most common factors that trigger the final act are usually a combination of two or more of the following elements: MDD/PTSD, divorce, drug or alcohol abuse, death of a loved one, loss of a job or career, homelessness and incurable degenerative diseases (e.g. Alzheimers, ALS, cancer etc.).

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Chapter Three

Lack of Proper VA Care for Depressed Veterans Exposed

This book is an expose on what I believe we can easily prove to be a grave injustice that has been perpetrated upon the United States veterans.
First lets take a look at the evidence that unequivocally demonstrates that the VA has been negligent in properly treating veterans with MDD and treatment-resistant depression (TRD); which in my opinion, based upon the research of experts in the field of psychiatric treatments, is the primary reason the VA has failed to significantly curtail the veteran suicide epidemic.

As proof I present you with the following landmark study was conducted at a VA medical center.
The question asked by researchers analyzing VA care for MDD; What happened to lithium? is certainly an appropriate question considering the fact that there is presently an epidemic of veteran suicides. Study title: What happened to lithium? Antidepressant augmentation in clinical settings. (Valenstein et. al., 2006) Health Services Research and Development, VA Medical Center, Ann Arbor, MI This landmark study of our veterans was published in The American Journal of Psychiatry, 2006. In this study conducted at the Health Services Research and Development, VA Medical Center, Ann Arbor, MI., the authors (Valenstein et. al., 2006) identified over two hundred and forty thousand (244,859) veteran patients in the Veterans Administration mental health services who had a primary diagnosis of major depression and who received pharmaceutical treatment for depression during the previous year. (1) When veterans failed to adequately respond to antidepressants, known as treatment-resistant depression, (TRD) (with a 22% occurrence rate) they were most commonly given (augmented with) a second antidepressant, antipsychotic or anticonvulsant, but almost never were they given lithium. Approximately 53,807 (22%) of the depressed VA patients treated in mental health settings received antidepressant augmentation Only 1,106 patients received lithium augmentation, approximately 1 in 50. (Valenstein et. al., 2006) See the RESULTS section of the full study. (2)

The first major finding is that the VA is only prescribing lithium to approximately 1 in 200 veterans with major depression. (2)
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The second major finding is that the VA is only prescribing lithium to 1 in 50 veterans with treatment-resistant major depression. What is the big deal regarding treatment-resistant depression (TRD)? TRD patients had more severe depression, more past suicide attemptsOver 60% of patients with MDD do not respond fully to therapy. Half of them eventually will not respond at all and will be referred to as treatment resistant depression (TRD) patients. (Amital et. al., 2008) See at: Serious life events among resistant and non-resistant MDD patients. (3) What is most disturbing about this finding is that the primary cause of the suicide epidemic is MDD and treatment-resistant MDD; and lithium is the only treatment modality ever discovered to significantly reduce suicides associated with major depressive disorder. Remember. Major Depressive Disorder is one of the most fatal co-occurring medical conditions associated with PTSD; as 70-80% of all suicides occur in depressive states. Journal Biological Psychiatry (Pfennig et. al., 2005) (4) Approximately 16% of patients with MDD will eventually attempt suicide! Journal - Biological Psychiatry (Chen and Dilsaver 1996) (5) Approximately 35% of Vietnam veterans with MDD/PTSD have contemplated suicide, 19% have attempted! The American Journal of Psychiatry (Hendin and Haas 1991) (6)

Veteran suicides, obviously, most commonly occur in veterans who have a poor response (treatment-resistance) to pharmaceutical intervention. So clearly this study demonstrates that The VA is missing a critical opportunity to dramatically reduce veteran suicide rates.

Furthermore, those veterans given a second drug; an antidepressant, antipsychotic or anticonvulsant, for major depression or treatment-resistant depression, are in no way significantly protected against suicide.

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What does the American Psychiatric Association say about the suicide prevention efficacy of antidepressants, antipsychotics and anticonvulsants?
THEY DONT PREVENT SUICIDE

American Psychiatric Association (APA) Practice Guideline for the Assessment and Treatment of Patients with Suicidal Behaviors (2003) See section IV. Specific Treatment Modalities A. Somatic Therapies #1, 3 and 4 (7) For antidepressants: The guide indicates antidepressants have not been demonstrated to reduce suicide or suicide attempts. This is based upon a large meta-analysis of 12 antidepressant studies.(7) For antipsychotics: The APA guide provides zero evidence for reduction of completed suicides by antipsychotics in major depression, bipolar disorder or schizophrenia. (7) For anticonvulsants: Anticonvulsants aka antiepileptics (according to the APA suicide guide) are inferior to lithium in the prevention of recurrent mood episodes; they may affect suicidal behavior but the APA provides no evidence of significant reductions in completed suicides in major depressive disorder. The APA states Although treatment with these agents may be associated with some decrease in suicidal behaviors, lithium treatment is still associated with a greater diminution in rates of suicidal acts than treatment with carbamazepine or divalproex There is no established evidence of a reduced risk of suicidal behavior with any other "moodstabilizing" anticonvulsants. (APA Suicide Guide 2003) (7) On the basis of present knowledge about pharmacological interventions and risk of suicidal behaviors, prophylactic (Preventative) treatment with lithium salts of patients with recurrent major affective disorder is supported by the strongest available evidence of major reductions in suicide risk of any currently employed psychiatric treatment. (APA Guide 2006)(8) My search from 2003 2012 has revealed no new significant positive findings of suicide prevention, (particularly for depression) in any of the former three pharmaceutical categories. The lack of efficacy of these drugs to prevent Major Depressive disorder suicides becomes obviously and painfully apparent, when you acknowledge the fact (as stated in the Hearing before the Subcommittee on Oversight and Investigation of the Committee on Veterans Affairs, U.S. House of Representatives, One Hundred Eleventh Congress, Second Session, July 14, 2010.) every day in America, five more veterans commit suicide while in the care of the VA. (9) While the VA has taken admirable steps with the establishment of suicide hot-lines to curb veteran suicides, the horrible fact is

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Veterans, while in the care of the VA are still committing suicide at rates that are higher than the general population. (9) Remember this! Veterans with a diagnosis of MDD [while in the care of VA treatment] have been found to have suicide rates that are seven to eight times the rate of the general population. (Zivin et. al., 2007) See full study at: (10)

So while the VA is supposedly doing everything in their power to reduce veteran suicides they continue to prescribe drugs that provide little to no benefit for preventing completed suicides and deny veterans the only nutritional solution proven beyond a reasonable doubt to shut down the tsunami of completed suicides.
On August 26, 2011, I spoke by telephone with Marcia Valenstein, MD, MS, (Research Scientist, VA Health Services Research and Development/ Serious Mental Illness, Staff Physician Veterans Affairs Ann Arbor Michigan Health System). Dr. Valenstein is one of the researchers (Valenstein et. al., 2006 What happened to Lithium?) that conducted the veteran study that we just reviewed. My intention in speaking with Dr. Valenstein was to inquire about the status of present day lithium administration to veterans. Dr. Valenstein informed me that it appears that there is less lithium prescription in 2011 than 2006 at the VA due to recent published contradictory research that called into question the validity of lithiums indisputable efficacy for the prevention of suicide. It is my determined opinion that the pharmaceutical industry is publishing sham research in an attempt to debunk Lithium Orotate as well as Pharma-Li because of the threat to Pharma-profits. On the surface of it, the picture appears to be that the VA (with its suicide hotlines and various mechanisms to identify veterans at high risk) is doing its best to assist in the suicide epidemic. However just below the surface it is clear that the VA is sadly lacking in effective efforts to end this scourge upon veterans.

"Our ignorance is not so vast as our failure to use what we know."

M. King Hubbert While the VA has done much in recent years to address the epidemic with suicide hotlines for intervention and identification of at risk veterans, the sad reality is

SUICIDE RATES CONTINUE TO SPIRAL OUT OF CONTROL!

U.S. Senator Patty Murray commented on the situation in May, 2011: Senate Veterans' Affairs Committee chairwoman Senator Patty Murray told the story best. Murray said that service members and veterans alike "continue to take their own lives at an alarming rate." She noted that in April, the VA's suicide hotline fielded more than 14,000 calls, or more than 450 a day, the most ever for a single month. The most recent data available indicates the suicide rates are on the rise and the situation continues to worsen. (11)

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The suicide rate is out of control its epidemic proportions right now.., said Paul Rieckhoff, national executive director of the Iraq and Afghanistan Veterans of America. There are very few programs that are effective, and theres a serious lack of National awareness. See U.S. Senator Patty Murray and Paul Rieckoff additional comments at: (11) MDD is one of the most fatal co-occurring medical conditions associated with PTSD, as at least 70-80% of all suicides occur in depressive states. (Phennig et. al., 2005) (12) At any given time, approximately 50% of veterans with combat related PTSD are also clinically depressed. Over the course of a lifetime, major depression is experienced by 95% of our combat veterans. Study titled: Post-traumatic stress disorder and depression. An analysis of comorbidity. (Bleich et. al., 1997) (13) Approximately 35% of all Vietnam veterans have a depressive or PTSD condition. Approximately 35% of Vietnam veterans with MDD and PTSD have contemplated suicide, 19% have attempted! (14) PTSD is frequently comorbid with major depressive episode and their co-occurrence enhances the risk for suicidal behavior. (Oquendo et. al., 2005) See the study titled: Posttraumatic stress disorder comorbid with major depression: factors mediating the association with suicidal behavior. (15) With statistics like these, the question everyone should be asking is; why wont the VA give veterans lithium? Apparently there are some at the VA that are completely aware of the power of lithium even for PTSD. Dr. Fesler, a VA doctor, published the following report.

Clinical studies have demonstrated good results with lithiums use in the treatment of PTSD. Dr. Fesler declared in his report, Anti-kindling agents lithium and carbamazepine have been found effective for PTSD symptoms of intrusive re-experiencing and increased arousal.
(Fesler FA. 1991) See VA article at: (16)

Treatment-resistant depression: The primary cause of the Veteran Suicide Epidemic!

Treatment-resistant depression (TRD) is defined as the failure of pharmaceutical treatment to adequately or sufficiently resolve (cause remission) of the patients symptoms of depression. They are also known as poor or partial responders to adequate therapy with a single agent. In other words, the patient is still significantly depressed. Treatment-resistant depression is also referred to as refractory depression. In my opinion, a broader definition of treatment-resistance includes all of the veterans (treated by the VA) who go off of all medications (including Pharma-lithium), due to the intolerable side effects of these drugs, leaving them extremely vulnerable to suicide.

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Lastly, treatment-resistance includes all the veterans who avoid acknowledging (and taking action upon) their condition due to the stigma attached to the label of mental illness. The previous study by (Valenstein, et. al., 2006) findings of only 1 in 50 veterans received lithium for treatment-resistant depression is massive direct evidence of VA incompetence and potentially, VA liability, for improperly treating in the clinical setting veterans who are most susceptible to suicide, i.e. those with treatment-resistant depression (TRD).

How can I make such a claim?

The veteran most likely to commit suicide is the one whose treatment is not working for the adequate resolution of depressive symptoms, i.e., treatment-resistant depression. Obviously, if the treatment was working and the depressive symptoms were resolved, there would be little, if any, reason to commit suicide. Isn't this logical? Next, we will examine the increased risk of suicide associated with improper handling of treatment-resistant depression; so that everyone will understand how critically important it is that every single veteran with TRD must be given lithium. Treatment resistant patients had more severe depression, more past suicide attempts Over 60% of patients with major depressive disorder (MDD) do not respond fully to therapy. Half of them eventually will not respond at all (Amital et. al., 2008) See at: Serious life events among resistant and non-resistant MDD patients. (3) This finding by (Amital et. al., 2008) points to a very significant risk factor in treating veterans with depression; 30-50% of patients get little if any benefit from antidepressant therapy, i.e. treatment-resistance. Only 35-40% achieve remission from the first antidepressant therapy. Yet in the previous major VA study (Valenstein et. al., 2006), only 22% of the veterans received augmentation with a second drug for treatment-resistance, which suggests that at least half of the veterans are in denial, regarding their degree of suffering, always doing their very best to minimize it, putting on the good face and sucking it up, without realizing how risky their denial is to their future health and life expectancy. This leaves veterans at high risk of suicide as many as half of them give no outward indication of suicidal behavior and they are in deep denial of the severity of their depression. Important note: Severe depression is only the greatest risk for suicide, if the patient is treatment-resistant to therapy. Obviously, if they are NOT treatment resistant, they have responded to therapy and severe depression is no longer an issue (unless they discontinue treatment due to intolerable side effects, a very significant risk factor). Patients who are severely depressed are more apt to be treatment-resistant. Suicide risk is a concern with severely depressed patients; up to 80% will report suicidal ideation. (Kornstein, et. al., 2001) See full study (17)

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Treatment-resistant depressive (TRD) patients are at least 2 times as likely to require hospitalization for severe depression (Crown et. al., 2002) See: The impact of treatment-resistant depression on health care utilization and costs. (18)

The rate of suicide for those hospitalized with severe treatment-resistant depression is approximately 4 times the average rate of suicide among depressed patients, as a whole group. These numbers are a combination of veterans and non-veterans alike. If the analysis was of veterans only, these numbers would be significantly worse. Approximately 13% of patients hospitalized with depression will eventually commit suicide. (Surgeon General) Mental Health: A Report of the Surgeon General (19) The combined lifetime suicide risk of men and women with depression as a whole group is ONLY 3.4%. (Blair-West et. al., 1999) See: Lifetime suicide risk in major depression: sex and age determinants. (20) Thus, it could be said that, severe treatment-resistant depressive patients are potentially at least 400% more at risk of suicide than depressive patients who have had a good response to treatment. Example: See numbers above (3.4 x 400% = 13.6) represents a 400% increased rate of suicide for hospitalized patients (who are twice as likely to be treatment resistant). Another issue for veterans is their natural resistance-to-treatment (another form of treatmentresistant depression). Many resist treatment because of concerns about side effects and taking drugs long term, plus the stigma of not being macho. Fortunately we have the natural nutritional alternative Lithium Orotate, so now all we have to do is educate the veterans about this breakthrough. Here are a few more experts statements on this topic of the serious nature of treatmentresistant depression. Incomplete remission of depressive symptoms is associated withincreased risk of suicide. (Thase 2011) See at: Treatment-resistant depression: prevalence, risk factors, and treatment strategies. (21) Suicide attempts were best explained by a family history ofrecurrence of depression (Hantouche, Angstand and Azorin 2010) See at: Explained factors of suicide attempts in major depression. (22) Treatment-resistant late-life depression increases risk for early relapseand increases the risk for early mortality, including suicide. (Lenze et. al., 2008) See: Incomplete response in late-life depression: getting to remission. (23) Obviously, if you are treatment-resistant (i.e., the treatment is not working for your depression) you are at the highest risk of committing suicide; thats a no-brainer.

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Additionally, treatment-resistant depression is considerably more at risk for brain atrophy of the hippocampus and the prefrontal cortex. (These are defined and explained in the next section.)

Lithium Efficacy in Treatment-Resistant Depression (TRD)

What about lithium response rates in treatment-resistant depression aka refractory major depression? Again treatment-resistant depression (TRD) is defined as the failure of pharmaceutical treatment to adequately or sufficiently resolve (cause remission) the patients symptoms of depression. They are also known as poor or partial responders to adequate therapy with a single agent. In other words the patient is still significantly depressed. What would you guess is the most efficacious, #1 first-choice treatment, most studied and established by international research guidelines as the all-time best treatment of TRD? Antidepressants? No! How about antipsychotics? No! Anticonvulsants? Guess again Lithium? Exactly! Who says this is so? Researchers from around the world have stated this fact and I will give you just a little sample of their findings here. Countries that affirm lithiums superior results (approximately 70% response rates in clinical studies of TRD) are America, Australia, Brazil, Canada, England, France, Germany, Israel, Japan and Portugal to name a few. Typical response rates of patients administered lithium as an add-on (augmenting agent) for treatment-resistant MDD, aka unipolar affective disorder, are in the range of 50-85%; two three times the recovery rate of a placebo. (24-32) Here are just a few of over 30 studies that have been conducted on this subject. TRD is also commonly referred to as refractory depression. Study title: Efficacy and mechanisms of action of lithium augmentation in refractory major depression. (Bschor and Bauer 2006) Department of Psychiatry and Psychotherapy, Jewish Hospital Berlin, Germany. In international treatment guidelines and algorithms, lithium augmentation is considered a first-line treatment strategy for patients with a major depressive episode who do not adequately respond to standard antidepressant treatment. (Bschor and Bauer 2006) (33) Study title: Lithium's emerging role in the treatment of refractory major depressive episodes: augmentation of antidepressants. (Bauer et. al., 2010) Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universitt Dresden, Dresden, Germany More than 30 open-label studies and 10 placebo-controlled double-blind trials have demonstrated substantial efficacy of lithium augmentation in the acute treatment of depressive episodes. CONCLUSION: Augmentation of antidepressants with lithium is

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currently the best-evidenced augmentation therapy in the treatment of depressed patients who do not respond to antidepressants. (Bauer et. al., 2010) (34)

Article title: [Twenty-five years of lithium augmentation]. (Bschor et. al., 2007) Abteilung fr Psychiatrie und Psychotherapie, Jdisches Krankenhaus Berlin, Heinz-GalinskiStrasse 1, 13347 Berlin. Twenty-five years ago the research group of the Canadian psychiatrist Dr. de Montigny reported treating antidepressant-refractory (treatment-resistant) depressive patients successfully (70% response rate) by adding lithium to their antidepressant... Thanks to the sound body of evidence which has accrued in the meantime, lithium augmentation is recommended in most guidelines and treatment algorithms as a main strategy for patients who do not respond to antidepressant monotherapy. (Bschor et. al., 2007) (35) Other clinical researchers have found similar (approximately) 70% response rates. (Mendels 1976) (36) (Inoue et. al., 2006) (37) (Katona 1988) (38) (Baumann et. al., 1996) (39) (Dinan 1993) (40) (Thase 1989) (41) and (Faravelli et. al., 1980) (42) Study title: Antidepressant augmentation and combinations. (Dording 2000) Depression Clinical and Research Program, Massachusetts General Hospital, Boston. A significant proportion of patients with MDD are treatment resistant or only partial responders to adequate therapy with a single agent. In this situation, one must consider augmenttation with another agent. (43) ..lithium augmentation was concluded to be the first-line therapy for depressed patients who failed to respond to monotherapy. (43) Study title: Lithium versus antidepressants in the long-term treatment of unipolar affective disorder. (Cipriani et. al., 2006) University of Verona, Department of Medicine and Public Health, Section of Psychiatry, Policlinico G.B.Rossi, 37134 Verona, Italy. Unipolar affective disorder is aka major depressive disorder. Eight trials involving 475 people were included. Two of the studies included a mixed group of participants with either bipolar or unipolar disorder. Relapse was defined as admission to hospital and when all kinds of relapses were considered (both depressive and manic) there was a statistically significant difference in favor of lithium. (Cipriani et. al., 2006) (44) Why then, if lithium is significantly more effective than antidepressants as the primary treatment of MDD in the prevention of hospitalization and suicide, is lithium NOT included in the primary care of all veterans with MDD? The following study chart compares lithium to some of the other most commonly utilized medicines for treatment-resistant depression.

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Lithium has the highest remission rates of all of them, 57% on average!
Study titled: How best to manage treatment-resistant depression? (Hicks et. al., 2010) (45)
Therapy and # of studies conducted Lithium #5 Thyroid#4 Remission rate 57% avg. 42% avg. Starting dose 600-900 mg 20-50 mcg Ending dose 900-1500 mg same Frequency of side effects over 25% 11-25% Rating A-C A A

Atypical Antipsychotics (listed by Brand name NOT by Trade name, as seen in study) Abilify #4 Symbax #1 Risperdal #3 Seroquel #2 Antidepressant Remeron #1 Alternatives Cognitive therapy #1 Folic acid #1 C SAMe #1 References Lithium 23% 18% 43% NA 15 mg 800 mg NA 30 mg 1600 mg 0-5% 11-25% 50% B B 31% avg. 25% 48% avg. 43% avg. 45% 2-5 mg Fixed 0.25-1 mg 25-200 mg 15 mg 15-20 mg Fixed 0.5-3 mg 100-600 mg 30 mg 16-25% 10-40% 6%-10% over 25% 6-10% ` A A A A B

(46-50) Thyroid (51-54) Abilify (55-56) Symbax (58) Risperdal (59-61) Seroquel (62-63) Remeron (64) Cognitive therapy (65) Folic acid (66) SAMe (67)

Clearly, lithium is the king of the hill in the line-up of commonly prescribed augmenting (add-on) agents in the management of treatment-resistant depression. So why is lithium not being prescribed to veterans? Even though lithium received the best scores overall in this line-up and received the Arating, lithium is usurped by newer drugs that are being promoted as less toxic and more tolerable for patients regarding side effects. This study reported the ending dose for lithium in the 900-1500 milligram range with side effects occurring in over 25% of patients. The truth is at these levels 70-90% of patients are experiencing side effects from these massive doses of Pharma-Li. This Pharma-Li dosage (900-1500 mg) equates to 170 mg - 280 mg of pure EL. There-in we find the problem! These studies are using huge amounts of lithium for their analysis and naturally, over 25% of patients are experiencing intolerable side effects. To reemphasize while mainstream medical doctors routinely prescribe Pharma-Li in the range of (140 mg - 225 mg pure EL) in the treatment of depression, alternative medical doctors are typically administer (520 mg of pure EL) via Lithium Orotate in the treatment of depression and they are reporting fair to good response in 60-70% of cases.

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With the preponderance of international recognition and the compelling evidence of lithium superiority, one would think that American Veterans would be receiving the best of medical management of treatment-resistant depression sadly that is not the case. As previously stated this book is exposing what I believe to be a grave injustice that has been perpetrated upon the American people and their United States veterans. While our heroes are suffering from an epidemic of suicide, the U.S. government, specifically the Veterans Administration (VA), has been found by the United States Court of Appeals for the Ninth Circuit to be severely negligent in caring for them. The following excerpt is from an article published in the editorial section of The New York Times. The New York Times - May 18, 2011

A Victory for Veterans

Court finds government incompetence is leading to thousand of suicides The United States Court of Appeals for the Ninth Circuit ordered an overhaul of the mental health care for veterans, who are killing themselves by the thousands each year because of what the court called the unchecked incompetence of the Department of Veterans Affairs. (New York Times) See this New York Times article: (68) This editorial sheds light on the administrative problems at the VA in recent years. Since the CBS News investigation in 2008, the VA, under civilian pressure to find a solution for the epidemic has set up various panels, task forces, and focus groups to analyze the cause of this epidemic. Since then, the rates of veteran suicides have continued to increase rather than decrease, demonstrating that the VA has failed in its efforts to resolve this tragic epidemic of veteran suicides.

The administrative challenges at the VA are only one aspect of the real problem in failing to prevent suicides.
It is my opinion that the core problem that has completely blocked the VA from ending the suicide epidemic is the VAs obvious failure to provide veterans with the only effective solution lithium.

The question is WHY?

I will go into the various possibilities of why this has happened later in the book but, for now, lets examine some of the published data on what the VAs position is and has been, on prescribing lithium for the prevention of suicide. I believe it appears, the VA is denying our veterans this life saving nutrient!

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What does the VA leadership have to say about the Lithium-Suicide-Breakthrough?

Following the CBS News investigation of 2008 (69) whereby the VA was caught in a cover up of the veteran suicide epidemic, intense political pressure was applied to the VA to come up with a solution. The following VA study is an effort to examine all of the evidence-based solutions for the suicide epidemic. Remember this is six years after the Harvard and APA publications. What follows is the culmination (excerpt) of the VAs effort to examine the viability of the Lithium-Suicide-Prevention-Breakthrough.

What is the VAs current position on the Lithium-Suicide-Breakthrough? Strategies for Suicide Prevention in Veterans January 2009 Department of Veterans Affairs Health Services Research & Development Service Evidence-based Synthesis Program (70)
See: Reviews of mental health interventions See page 40 (Excerpts) I quote, Perhaps somewhat surprisingly given the role of depressive disorders as significant risk factors for suicide, the evidence in support of the use of antidepressants is rather weak.Pooled data from controlled clinical trials of antidepressants have not demonstrated a suicide preventive effect... (70) Some of the best evidence for psychopharmacologic interventions that reduce suicide risk is for lithium in the treatment of bipolar disorder. Baldessarini et. al., (93) reported a meta-analysis of 31 published studies that showed a robust protective effect of lithium for both completed and attempted suicides for both bipolar disorder and other mood disorders. Study title: Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Harvard Medical School (Baldessarini RJ, Tondo L, Davis P, Pompili M, Goodwin FK, Hennen J., 2006) (93)

That is all the VA had to say about the most incredible suicide prevention program ever discovered. No specific mention of lithium prevention of major depressive suicide.
So the previous statement is by far the strongest of all statements by the VA from my search of all VA documents from 2003-2012. This is the only time a document published by the VA has specifically acknowledged even one of the five major Harvard studies published on the lithium-suicide-breakthrough. To the best of my knowledge, never once has the VA publicly acknowledged the 2003 APA publication Practice Guideline for the Assessment and Treatment of Patients With Suicidal Behaviors (2003) (71) .

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Unfortunately the VA follows the previous positive statement with the following outrageous conclusion about the 31 published studies demonstrating the supreme efficacy of lithium in preventing suicide.

Reviews of mental health interventions Conclusions:

There are insufficient studies of suicide prevention programs specfically in veterans to draw conclusions (Grade quality of evidence = Very Low, meaning any estimate of effect is uncertain). (70) See Pg 41, 1st paragraph ARE YOU BLEEPING KIDDING ME! What is going on at the VA? There are insufficient studies to draw conclusions? Who cares that we dont have any veteran-lithium-suicide-prevention-studies specifically for major depression? The 31 published studies totaled 85,000 person years of analysis. Lithiums efficacy proven by Harvard and confirmed by the American Psychiatric Association is beyond dispute! Who would want to dispute this anyway? Does anyone have a better solution for this epidemic of suicide? The only people that are debating this fact are the freaked out pharmaceutical company representatives who are shaking in their boots that this information is going to go public. Do they have something to lose? Are pharmaceutical sales threatened by this supreme essential mineral? HOW MUCH MORE EVIDENCE DOES THE VA NEED TO TAKE ACTION FOR OUR VETERANS WHO ARE COMMITTING SUICIDE, ONE EVERY 80 MINUTES!! In closing the VA states, Further randomized controlled trials and high-quality observational studies are definitely needed. Without waiting for such to be completed, and independent of which program components the VA decides to pursue, there are two supporting initiatives that could be implemented in parallel. The first concerns standardizing vocabulary, and the second concerns electronic medical records. (70) See page 41, last paragraph So thats what the VA proposes to do NOW for the suicide epidemic! Do additional randomized controlled trials; convert to electronic medical records and standardize their vocabulary. Thats BRILLIANT!! DID THEY MISS ANYTHING? Note: Dr. Valenstein informed me that the VA is going to conduct a lithium study but we will have to wait many years for those results! If you are not screaming pissed at this point then I have to assume you lack understanding of the magnitude of the ATROCITY THAT THIS IS! If you dont grasp the meaning of the evidence I have presented here, then I request that you re-read this as many times as you need to, until you see the outrageous nature of what this means.

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Either the individuals responsible for this are asleep at the switch or the VA is intentionally suppressing lithium for our beloved veterans. Perhaps one of the most revealing statements regarding the VA position on lithium was made by Dr. Ira Katz. Next up; a statement from Ira Katz, M.D., PH.D., Deputy Chief Officer, Mental Health Services, Office of Patient Care Services. The following document is the most recent (2010) public statement by a VA official on the subject of VA lithium treatment for suicide prevention.

See at: (72) HOUSE COMMITTEE ON VETERANS AFFAIRS FULL COMMITTEE STATEMENT OF IRA KATZ, M.D., PH.D. DEPUTY CHIEF OFFICER, MENTAL HEALTH SERVICES, OFFICE OF PATIENT CARE SERVICES, VETERANS HEALTH ADMINISTRATION, U.S. DEPARTMENT OF VETERANS AFFAIRS February 24, 2010 (The following is an excerpt of Dr. Katzs statement) Mr. Chairman, Mr. Ranking Member, and Members of the Committee: Thank you for the opportunity to appear today to discuss the Department of Veterans Affairs (VA) response to the mental health needs of Americas Veterans. Findings from other research suggest that lithium, rather than mood-stabilizing anticonvulsants, may be associated with decreased rates of suicide for people with bipolar disorder. End Excerpt (Dr. Katz, Paragraph 13) (72) And thats all Dr. Katz had to say about the greatest suicide prevention nutrient ever discovered for depression. Really Dr. Katz; lithium may be associated with decreased rates of suicide with bipolar disorder. Dr. Katz, have you never heard of the Harvard Medical School studies of lithium for suicide prevention in major depressive disorder, bipolar and schizoaffective disorder, demonstrating 80-90% reductions for all acts of suicide? Have you never read the American Psychiatric Association (APA) Suicide Guide (2003) regarding the amazing breakthrough of lithium for suicide prevention of major depression as well as bipolar disorder, reducing suicide attempts greater than 90%?

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The APA states There is strong and consistent evidence in patients with recurring bipolar disorder and major depressive disorder that long-term maintenance treatment with lithium salts is associated with major reductions in risk of both suicide and suicide attempts. For suicide, lithium maintenance treatment was associated with an 80%90% decrease in risk, whereas the reduction in suicide attempt rates was more than 90%. (APA Suicide Guide 2003) (71) Well I guess I really did not expect anything honorable to come from Dr. Katz mouth considering he was the guy at the VA who stated "There is no epidemic in suicide in the VA,"(69) and who issued the following internal email at the VA. In February, 2007 Dr. Katz sends an e-mail that starts with, Shh! Our suicide prevention coordinators are identifying about 1,000 suicide attempts per month among the veterans we see in our medical facilities. Is this something we should carefully address ourselves in some sort of release before someone stumbles on it? (69) the chief investigative reporter for CBS News, Armen Keteyian, characterized the VAs internal e-mails as a paper trail of denial and deceit, a disservice to all veterans and their families that has rightfully been exposed. (73) Below is the actual copy of this email by Dr. Katz. See this email: (E-mail link)

It appears from all the available evidence that the VA has no intention of immediately utilizing the only proven treatment modality that has been demonstrated to reduce completed (depressive) suicides by 85%. Study title: Lithium treatment reduces suicide risk in recurrent major depressive disorder. Harvard Medical School (Guzzetta et. al., 2007) (74) Finally, I must assert that there is available to you, or your loved one, the over-thecounter, new and improved, treatment modality, Lithium Orotate (LO). LO is the premiere alternative to Pharma-Li for the breakthrough treatment of PTSD, MDD, and for the prevention of suicide in treatment-resistant depression. To reemphasize, LO has been proven in clinical studies (for over 30 years) to provide maximum therapeutic benefit in minute doses (1/10th 1/20th of the Pharma-Li dosage) for the treatment of major depression and bipolar disorder (Ward Dean, M.D.) without side effects, adverse reactions, drug interactions or detrimental changes to the heart, kidneys or thyroid. (Jonathan Wright, M.D.) The only remaining questions are: When will the VA get this non-debatable solution for the never-ending veteran epidemic of suicide? Will the VA spend yet another ten years analyzing and researching Pharma-Li for suicide prevention (as is presently occurring)?

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Lastly, when will the VA acknowledge their failure and the fact that they have no other viable option but to utilize lithium?
For the VA to neglect to take action on this now is not only inexcusable, it is a violation of the veterans rights to receive the best that medicine (nutritional and otherwise) has to offer. It is my profound belief that the only way to end the present epidemic is to systematically provide all veterans (outside of the VA health care system) with low-dose (non-side effect causing) Lithium Orotate to all veterans with MDD and particularly treatment-resistant depression. Additionally we have to reach all veterans outside the VA who suffer with bipolar disorder, schizophrenia, schizoaffective disorder, border-line personality disorder and Alzheimers disease (and all other major categories associated with suicide). Finally, Lithium Orotate should be made available to all veterans within the VA health care system with Major depression, bipolar disorder, schizophrenia, schizoaffective disorder, borderline personality disorder and Alzheimers disease (and all other major categories associated with suicide). In my opinion this action would substantially reduce, or effectively end, the veteran suicide epidemic.

MOST VA DOCTORS WILL RESIST THIS!

Most VA Doctors Will Resist the Implementation of this Breakthrough.

Why in the world would VA doctors resist this? If doctors can reduce suicide attempts by over 90%, why in the world would they not give Lithium Orotate or even Pharma-Li to all veterans who are at high risk (i.e., all veterans with mood disorders and PTSD)? First lets examine the VA doctors resistance to prescribing Pharma-Li. Many doctors at the VA believe that Pharma-Li is a toxic drug that must be prescribed in extreme doses to be effective. Naturally their patients dont want to take Pharma-Li either for this very reason! The following statement by George Opfer, Inspector General of the VA Office of Inspector General (OIG) says it all! The OIG states, In the psychiatric literature, lithium has been reported to have a specific anti-suicide effect for patients with mood disorders. Despite these potential benefits, lithium use in VA and non-VA settings has been declining for several years. Reasons for this are unclear but may be due to concerns about safety, need for monitoring blood levels, tolerability, potential side effects, and stigma. (George Opfer, Inspector General 2007) (75) So there you have it! This entire debacle the veteran epidemic of suicide has unnecessarily persisted for over 9 years because of the misinformed erroneous belief that you have to ingest massive toxic amounts of lithium to benefit depression and

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prevent suicide; thus causing intolerable side effects, concerns about safety and a need for monitoring blood levels. THIS IS A MISTAKE, TOTALLY UNTRUE AND ABSOLUTELY UNNECESSARY! I have researched this topic in-depth and it is absolutely clear that the majority of mainstream medical doctors have been trained (by misleading medical studies) to believe that they must prescribe depressive patients the same toxic, side effect causing, so-called therapeutic dosage of Pharma-Li recommended for the maintenance treatment of bipolar disorder. The best and largest example of this is found in the VA study that we have previously reviewed (Valenstein et. al., 2006). Remember 1,106 veteran patients (0.5%) received lithium for depression and the average dosage was 750 mg of Pharma-Li which contains over 140 mg of EL. (76)

High Dosage Pharma-Li is NOT Required For Treating Depression and Preventing Suicide
Is 140 mg of EL required to get good results in treating depression and preventing suicide? Absolutely NOT! 140 mg of EL, for treating depression is absolutely unnecessary! Remember that pure lithium is referred to as elemental lithium (EL). How can I be so sure of this? This was not an easy question to answer as low dosage Pharma-Li depression studies are almost non-existent. With few exceptions all of the studies for depression have been conducted in the range of 140-225 mg of EL (the standard dosage for bipolar disorder). However three different groups of medical doctors have reported good results in the treatment of depression, with Pharma-Li dosages 40-50% lower, i.e., 75-85mg of EL. Most importantly at this lower dosage no significant side effects were noted. (Jerram and McDonald 1978) (77) (Faravelli et. al., 1980) (78) (Dinan 1993) (79) and (Alevizos et. al., 2010) (80) Dinan confirms this in the following study. Study title: Lithium augmentation in sertraline-resistant depression: a preliminary doseresponse study. (Dinan 1993) The patients received 400mg of Pharma-Li equal to 75 mg of EL. (100 mg of Pharma-Li contains 18.8 mg EL) 65% of patients showed a good response and most importantly, No significant side effects were noted. (Dinan 1993) (79) The most recent example of this fact was published in 2010 during a study of adding lithium to a common antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class known as Effexor. After adding lithium to Effexor, 51% of the patients were much or very much improved. The blood lithium levels were so low that the patients did not require lab monitoring of their lithium levels. The authors reported No troublesome side effects were reported. The lithium levels were 0.33 mEq/L on average. (Alevizos et. al., 2010) (80)

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While orthodox medicine has taught the medical doctor that they must prescribe 140-225 mg/day of EL (the classic bipolar dosage range) for depression, the previous studies and other clinical studies have found that the degree of positive response is not altered by lower Pharma- Li dosages (i.e. 75-85 mg of EL).

The patients receiving 75-85 mg Elemental lithium experienced the same level of recovery as the high end dosed patients. MOST IMPORTANTLY: NO SIGNIFICANT SIDE EFFECTS WERE NOTED.
Without significant side effects there is no longer any reason not to prescribe Pharma-Li to all veterans as the primary treatment of major depressive disorder. Again this is why I submit to you that the VA has completely failed our veterans in this battle against suicide. All the VA has to do is prescribe the minimal non-toxic dose of Pharma-Li to veterans with major mood disorders to significantly reduce suicide rates. Remember that the lithium drinking-water studies (Fox News broadcast) confirmed that the suicide prevention of lithium begins with minute dosages (below 1 mg).

What about the 30-45% of patients that do not feel significant relief of depressive symptoms with lithium? Are they protected from suicide?
Absolutely YES! In the following study it was discovered that lithium reduced suicide attempts by 70%, even in the patients that felt no relief of depressive symptoms. (Ahrens and Mller-Oerlinghausen 2001) Now thats a powerhouse nutrient. Study title: Does lithium exert an independent antisuicidal effect? (81) The basis of the VA decision (to NOT prescribe lithium to all veterans with major mood disorders) MAY BE based upon the erroneous belief that toxic amounts of lithium must be prescribed to effectively treat, depression, treatment-resistant depression and induce the suicide prevention abilities of this breakthrough nutrient. IF THIS IS THE REASON THE VA HAS CHOSEN NOT TO PRESCRIBE LITHIUM FOR THE PREVENTION OF SUICIDE; I HAVE VERY GOOD NEWS FOR THE VA! It is my opinion, based upon over 7,000 hours of research and writing on the topic of lithium administration that the simple act of providing veterans with low dose side-effect free (nontoxic doses) of Pharma-Li (dosage 450 mg) providing 85 mg of EL, would effectively cut the suicide rate within the VA health care system in half. Why only half you ask?

Only half of veteran suicides are known to have a mental health diagnosis.
Approximately 50 percent of suicides among VA health care users are among patients with a known mental health diagnosis. Dr. Robert Jesse, M.D., PH.D., Principal Deputy Under Secretary for VA Health 2010 (82)

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This speaks to the fact that half of the veterans in desperate need of help are in resistance to asking for it. One of the reasons that veterans dont seek help for mental health is because they have a natural resistance to taking mind altering drugs to treat it. This is one of the biggest advantages Lithium Orotate has to offer veterans. With Lithium Orotate you are feeding your brain rather than drugging it. Additionally, while mainstream medical doctors routinely prescribe 140-225 mg of EL via Pharma-Li (for treatment of Major Depression) many alternative medical doctors are routinely administering 1/10th 1/20th of the EL dose (5-20 mg of EL), via Lithium Orotate, for treatment of Major Depression and they are reporting fair to good response in 60-70% of cases. Most importantly, there are no negative side effects at these minute dosages. (Jonathan Wright, M.D., Ward Dean, M.D., Shaheen Lakhan, M.D., Stanley Olsztyn, M.D., C Norman Shealy, MD, Ph.D.)

Lithium Orotate is a breakthrough antidepressant!

Lithium Orotate is also the most exciting novel breakthrough for suicide.

So either way with Pharma-Li or Lithium Orotate the VA could end this epidemic of suicide right now!
So why has the VA not chosen to prescribe Lithium Orotate? Given the evidence of the complete absence of significant side-effects with low-dose Pharma-Li and its proven unequaled ability to single-handedly crush suicide rates; I must ask; why in the world would the VA choose NOT to immediately implement this internationally renowned suicide preventative nutrient? I have an even better idea for the VA. Lets educate all returning combat-veterans about the breakthrough of Lithium Orotate. Lets tell them the truth that they dont have to take drugs for a perceived weakness they may have, all they have to do is feed their brain with an essential mineral for strengthening a nervous system that has endured inhumane levels of stress. Lets tell all of our beloved veterans about the

Breakthrough Nutrient for Suicide, PTSD and Depression They Definitely Dont Want You to Know About.
Researchers worldwide agree that treatment involving lithium is the best way to protect patients from suicide risk. (Pompili et. al., 2009) (83) Harvard Medical School Ideally each and every veteran suffering with a mental, emotional and or neurological disorder (that is potentially a suicidal condition, plus all combat veterans) should be given this preventative nutrient.

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NOTE: Apparently this is not good news at the VA as I sent the VA this information by certified mail in November, 2011 and have yet to hear back from them. (No surprise) See my letter to the VA at: www.opgetfree.com To reemphasize, contrary to the widely held belief that doctors must dose MDD patients at the same extreme levels as bipolar disorder patients, it has been discovered by many alternativeminded integrative medical doctors that low-dose NON-TOXIC Lithium Orotate treatment of MDD is much more effective than high-dose lithium treatment. Lithium Orotate is more effective because patient compliance approaches 100%.

This is the breakthrough of Lithium Orotate

Lithium Orotate does not require blood tests to establish a therapeutic level, as the prescription forms do, nor is it toxic to the kidneys as the prescription forms are. . . . Prescription lithium is poorly absorbed by the cells, where it needs to be to do its job. . . . Lithium Orotate is extremely safe, with no known adverse side effects or drug interactions. (Ward Dean, M.D.) (84),(85) We will not end the veteran epidemic of suicide until all veterans from all foreign wars have heard the truth about Lithium Orotate. You must remember this maxim: Lithium is an essential trace mineral, NOT a drug; lithium is neither a drug, nor is it inherently toxic, as They would have us believe. Lithium is only toxic when the patient is over-dosed! Toxic reactions to Pharma-Li only occur when lithium blood/serum levels exceed the safe, maximum therapeutic level; which is the golden rule of all supplemental vitamins and minerals. Extreme mega-dosing of supplemental nutrients will always lead to side effects once the safe maximum therapeutic limit for an individual has been exceeded. I know of no exception. So what is the safe, maximum therapeutic limit for lithium? As determined by human studies, the maximum (side effect free) level is approximately 100 mg of pure EL/day. At 100 mg the vast majority of individuals will experience little if any significant side effects.

However when you give patients 140 mg of pure EL/day as the VA has been shown to do (Valenstein et. al., 2006) a large number of patients will experience bothersome side effects.
Bothersome side effects will inevitably lead many patients to discontinue utilizing Pharma-Li and leaves the veteran at risk of relapse and suicide. Discontinuation of lithium therapy leaves patients at a much higher risk of suicide. (Tondo et. al., 1998) (86)

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Chapter Four

The Calling
It is with unbridled enthusiasm that I make this call to action for all veterans, veteran families, friends and supporters. Through a massive networking initiative this message will rapidly circumvent this nation coast to coast through the loving and supportive grapevine of communication. YOU ARE THE CATALYST FOR THE RESOLUTION OF THE VETERAN SUICIDE EPIDEMIC. Through Facebook, Twitter and your very own (hopefully video) testimonial (describing your progress) we will begin an avalanche of nationwide participation. We invite and will need your testimonial because thus far none of the male veterans I have worked with are willing to give their real name or picture for their testimonial. Can you say, stigma? Testimonials are beginning to come in and we have posted a few on our website. Operation Break Free is an idea thats time has come and we are confident that Lithium Orotate is the solution that we have all been praying for. This is a God-send! Our Mission: The mission, if you choose to accept it, is speaking truth to deception and power thereby facilitating a breakthrough in our ability to assist our beloved veterans in their struggle to survive the torturous prison of Major Depressive Disorder, Posttraumatic Stress Disorder and, suicidal ideation and behavior. To speak truth to deception you must fully understand that lithium is not a drug. The Pharma-cartel is desperate to keep us all believing that lithium is a toxic dangerous drug. Why? The PI cant compete with Lithium Orotate and insurance companies profit from self-inflicted deaths. Again, lithium is an essential trace mineral that, when taken in small and reasonable doses prevents most suicides. We must shout this truth from the roof tops. If we are to save our veterans from this tragedy, each of us, individually, must draw on our unquenchable spirit of truth and courage to make this paradigm shift. Our ultimate mission is to set the veterans free from being mentally, emotionally and physically forever prisoners of war and take this to the homeless veterans on the streets of America with the battle cry No Man Left Behind. Delivering this powerful nutrient directly to homeless veterans will no doubt assist many of them in their ability to see the way out of their nightmarish situation, empowering them with hope for the future and the promise that is Operation Break Free! The U.S. Department of Veterans Affairs Fifth Annual Report, 2007, suggests (and other authors agree) at least 30 to 40 percent of Iraq veterans will face serious psychological problems associated with PTSD. (1-4)

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Our Challenge: By some estimates, 40-50% of our high-impact multiple-tour combat soldiers between the ages of 18-29 are returning from war with PTSD and/or depression. In actual numbers PTSD cases may be in excess of 600,000. (Veterans for Common Sense 2009) Must see video at: (4) At any given time approximately 50% of patients with combat-related PTSD are also clinically depressed. Over the period of a lifetime major depression is experienced by 95% of combat veterans. (Bleich et. al., 1997) (5) This year alone there will likely be at least 1000 suicides amongst the off-duty and active duty Afghanistan and Iraqi war veterans. We are now losing more veterans to suicide than from battle. The total number of completed suicides of all veterans from all previous wars is expected to be well over 7,000 this year while the numbers of attempted suicides are estimated to exceed 30,000. What can we do about this incredible disaster?

Tapping into the Power of Love They heard it through the grapevine
Moms, Dads, and other loved ones; it is within your power to educate individuals who may (unknowingly) be caught up in the pharmaceutical enterprises hierarchy or network. It takes little effort to request that the emotional conflicts of your loved one be resolved with a low cost nutritional supplement, not behaviorally modified with costly pharmaceuticals. This can only be accomplished through your unbridled participation. Please join us in this winnable battle. The forces we face are powerful and well organized. The pharmaceutical industry and its extensive (willingly) supportive network, some of whom are paid with our tax dollars, are determined to keep this tried and proven nutrient out of the hands of the American people. The willing participants of this (by definition) criminal enterprise care only about protecting, first and foremost, their own interests, followed by the status quo, and (ultimately) the financial interests of those who are responsible and (ultimately) in control of this racket, as well as your loved ones', your and our nation's health/future. On November 15, 2011 we put the Veterans Administration on Notice via certified mail with a complete 25-page outline of this project. The package was addressed to General Eric Shinseki, Secretary of the Department of Veteran Affairs. To date, and not surprisingly, there has been no response from the VA regarding this nutritional breakthrough for MDD, PTSD and ultimately, the prevention of suicide. At this point the VA is simply ignoring this information. There is a saying in medicine regarding challenging the medical establishment, status quo, and dogma with a new a paradigm. It goes something like this. First they ignore you, then they laugh at you, then they attack you, but good science ultimately prevails and finally they integrate and imitate you. Since we are being ignored (STEP 1) we are confident we are on the right path and will ultimately win this battle.

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Because the certified package was received and signed for, someone at the VA read at least the introduction of the 25 page outline of this project. Therefore, in and by law, the aforementioned notice was served (notice to an agent is notice to his principal) and all VA employees have reason to know that there is an alternative remedy for your loved ones condition, IF it is requested. I have no illusions that the VA will take action on this breakthrough any time soon, so we will have to fight together for this paradigm shift to occur. Victory will be ours! It is my belief that once we have a critical mass of veterans young and old describing the awesome healing that they have personally experienced while taking Lithium Orotate we will experience the flash point in this, a chemical reaction of realization; the Lithium Orotate Revolution is an idea thats time has come! At that moment in time Lithium Orotate will become known as the obvious solution for what ails our veteran community. At some point Lithium Orotate will be accepted as the norm and will no longer be misunderstood as something to fear. Until the flash point is achieved we will have to fight a very long and difficult battle against the Pharma-cartel and its representatives who will do anything and everything in their power to defeat this natural healing movement from becoming a reality. Most of our service men and women who are suffering with severe Major Depression, PTSD, and ultimately opt-out through suicide, are so sick they are not even looking for an alternative natural remedy for what ails them; they are compliantly stuck in the horrific spin cycle, of toxic pharmaceuticals. For most of these veterans (and others so afflicted), only their loved ones can speak this truth to them in such a way that it will be heard. This is why I am so urgently Calling for your assistance! When I was most seriously ill with bipolar disorder and living on the edge of suicide and insanity, it was my mother that brought this nutrient to me. No one else could have reached me as she did, because I was in serious denial that I had a problem. My mother saved my life by taking that action. If for any reason you cannot be the one to deliver this message to your father, mother, son or daughter, then it is incumbent upon you to get this information to the individual(s) who can. Our veterans have received the ultimate military training to persevere through all kinds of adversity and this, too often, places them in the inescapable box of denial, forcing them to silently live with devastating medical and emotional conditions or opt-out by suicide. For this mission to successfully educate our tax-paid employees and resolve the life threatening medical and emotional conditions that plague our veterans (and others), effort will be required to access supportive networks with an identified hierarchy where multiple requests for alternative remedy will be heard. This message must be sent across the Grapevine of communication for all to hear and know that internal and external conflicts can be resolved without helplessly standing by as a loved one submits to a protocol whereby his or her behavior is pharmaceutically modified.

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We must begin to assemble and discuss strategies for dissemination of truthful information. Once we reach a critical mass of participation the Hundredth Monkey phenomenon will occur and, at last, all will hear the truth that has been spoken to deception and power! We are calling on all Moms, Dads, and other loved ones who are leaders to give action to this Calling. It will be through mass participation that we will be able to accomplish the seemingly impossible task of ending the epidemic of suicide that plagues our nations veterans. This call goes out to all, to Free Our Veterans from the torture and debilitating prison of Major Depression, PTSD, and the plague of Death by Suicide. Lets educate, protect and defend all those who have willingly protected and defended the men and women our nation, Constitution and country. The Pentagon has published rules for redeploying soldiers who are diagnosed with mental conditions. The rules allow for soldiers to be redeployed while they are dosed with multiple pharmaceuticals. However they are not allowed to be redeployed if they are taking lithium.

Why are soldiers not allowed to be redeployed if they are taking lithium? Lithium is the only remedy for the suicide epidemic. Obviously everything else the VA has tried thus far has failed. General Eric Shinseki, what are you prepared to do about this suicide epidemic that is demoralizing our troops and devastating tens of thousands of veteran families?
Many in our nation are awakening from a deep, intergenerational, feeling of despair. Formerly unable to resolve this suicide nightmare, many have lived with constant fear and anxiety for their loved ones who seem consumed in the black cloud of depression or turbulent cloud of PTSD. By joining with others who have studied the facts and positioned themselves to resolve conflicts with bureaucracy, there is no question, the medical staff at VA Hospitals and Clinics across this nation will ultimately listen, observe and comply, as will the Pentagon. It is my goal to energize thousands of co-creators in this project; individuals that will review much, if not all, of the scientific, irrefutable evidence presented here. It is my vision to create a nationwide coalition of moms, dads, sisters, brothers, and significant others to rally to our troops urgent and critical need. Our beloved veterans have come home from war to a nightmare of psychic pain, dysfunction, and unemployment is presently 20-30% for the 18-24 year olds. Not surprisingly they are killing themselves at unprecedented, record breaking rates that have continued to climb year after year.

How to Communicate This to a Veteran

There is no magic formula to reach a particular veteran with this life-changing product. What I can tell you is this. If you have open communication with the individual you are trying to reach, keep this conversation as simple as possible. If you dont have a good relationship with this person, get this information to someone who can reach out to them.

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Here is how my mother presented this to me. Kay said, Mark I have been doing some research on a nutritional product that is supposed to relax your nervous system and help you sleep, so I tried it and it works, I am sleeping much better. I thought you might be interested in trying the product because I know you have not been sleeping so well lately. Would you like me to send you a bottle to try? I said, Sure what is it? She responded, Lithium Orotate. Thats when all hell broke loose. I said lithium is a toxic drug, Mom. Kay said, I know that honey, but this is not that drug. Long story short, she convinced me to try it and the rest is history. When you present this to a veteran, they will likely tell you they do not want to take another toxic drug! This is where you have to show them the eye of the tiger, as you demonstrate your superior knowledge of the essential trace mineral lithium and the breakthrough of Lithium Orotate. Most importantly you must remember that many veterans are in deep denial that there is something wrong, so dont tell them THEY HAVE A PROBLEM! Remember what my mom told me; she tried it and liked it! Keep it simple. Its all in the delivery, presentation and timing; try the soft sale first (if that doesnt work then tie them down and tube feed them) just kidding, obviously, but dont give up if they are unresponsive the first, second or third time you speak with them. I just recently converted a man to trying Lithium Orotate after almost two years of effort. Remember: This is the essential trace mineral lithium in the same class of minerals as sodium and potassium. This product is nothing like the drug called lithium with regard to side effects and toxicity. You do not have to have your blood lithium levels measured because the blood lithium levels are so low with Lithium Orotate. Additionally, get other family members to try the product so that you can all report on its positive effects without side effects. Remember if at first you dont succeed, try and try again, until you wear them down. If necessary use the Chinese water torture on them! You'll be glad you did. Before we look at the list of conditions most highly benefited by lithium supplementation I just want to give you a look at the overview of lithium healing properties.

Lithium Healing Properties

The biggest threat to the pharmaceutical industry is that lithium has very powerful natural healing (not masking symptoms) properties in virtually every class of medication used to treat mental illness and numerous physical illnesses. Here I present a list of healing lithium properties. These are all explained in my book. Antidepressant Antipsychotic Anticonvulsant Anti-Cancer Anti-Aggressive Anti-Suicidal Anti-Viral Anti-Aging Antibiotic and Anti-microbial Anti-Neurodegeneration Pro-Brain Cell Growth Pro-Neuroprotection

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Potential Lithium Orotate Benefits for Veterans

Lithium Orotate Reduces: Anxiety, depression, headaches, irritability, anger, road rage, restless legs, insomnia, nightmares and consuming excess alcohol and drugs. See the complete list below for other conditions that lithium research shows relief of. The most important step before you share Lithium Orotate with someone you are trying to help is using this product yourself! Remember the instructions from the flight attendant on the airplane, when the oxygen masks come down in an emergency, apply the mask to you first! Hopefully you only have one of the following minor conditions (hope you dont have Alzheimers) that will likely respond in a near miraculous way to Lithium Orotate supplementation. When you can relate the resolution of your symptoms without side effects, by using Lithium Orotate, you will be in an excellent position to share this with your loved ones. This is the partial list of the 100+ diseases/medical conditions highly benefited by lithium supplementation. I left out MDD, PTSD and suicide for obvious reasons.

*Indicates

conditions discussed in Chapter 28, page 240. The other conditions are discussed in Chapter 9, page 114 and throughout the book. ADHD* AIDS Infection * Anxiety disorders* Alcoholism ALS aka Lou Gehrigs disease Alzheimers disease Asthma Back & Hip Pain Bipolar disorder Borderline personality disorder* Bruxism (grinding teeth) * Chronic Fatigue Chronic Headaches Diabetes Mellitus Drug abuse and withdrawal* Epilepsy Fibromyalgia Generalized Anxiety disorder Headaches (all types) Herpes Infection Huntingtons disease Hypercortisolism Hyperthyroidism Inflammatory Bowel Insomnia* Ischemic Heart disease* Liver disease cirrhosis Migraine headaches Multiple Sclerosis* Neck Pain (chronic) Obsessive Compulsive* Osteoporosis* Osteoarthritis Pain syndromes Panic disorder* Paralysis Parkinsons disease* Pathological gambling* Periodic Limb Movement Post-partum Psychosis* Restless Leg syndrome Rheumatoid Arthritis Schizoaffective disorder* Schizophrenia* Sciatic (Hip) Pain Self Mutilation (cutting) * Shingles Shoulder Pain Sleep disorders Social Anxiety/Phobia Spinal Cord injury Strokes Substance Abuse disorder Tinnitus Tourettes syndrome* Transient Ischemic attack* Traumatic Brain Injury Ulcers Violent behavior* Viral Infections

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If you have received this book freely and you appreciate my efforts in preparing this information I would deeply appreciate it if you would make a small contribution by purchasing my E-book available at my website www.opsetthemfree.com. If you do not have one of the listed conditions above, you still must try the product to see how it makes you feel and who knows, Lithium Orotate might just make you feel less stressed, more relaxed, and considerably happier as it does for many others. You must speak truth to deception with your loved one. It is a very powerful and erroneous belief that lithium is a toxic drug! You must be able to say with conviction, LITHIUM IS NOT A DRUG! LITHIUM IS A TRACE MINERAL; A NUTRIENT THAT IS ESSENTIAL TO THE OPTIMAL WELL BEING OF OUR CELLS! You must be able to say that you have tried Lithium Orotate and there are definitely no side effects! Your personal testimonial to your loved one will have a big impact. More importantly you can communicate that you have tried it and felt nothing, but better.

Is Lithium Orotate the Solution for the Veteran Epidemic of Suicide?

Without question, yes! The Harvard Medical School studies and the American Psychiatric Association are absolutely clear on this question and answer. Critics will say that only Pharma-Li has been proven to reduce suicide; so you cant say that Lithium Orotate will do the same; really? Remember, lithium is the active ingredient producing the healing effects. Lithium, a trace mineral, naturally occurring in municipal water supplies around the world, has been demonstrated to significantly reduce suicide rates (approximately 30-50% reduction) amongst the general population. The amount of lithium found in the water was less than 1 mg. Given that suicide prevention by naturally occurring lithium begins below 1 mg (this is a well-documented scientific fact), then we can be confident that giving our veterans 10-20 mg of EL for depression and 20-40 mg EL for PTSD will provide for at least an 85-90% reduction of all acts of suicide. Because 50-80% of psychiatric patient suicides occur while patients are not medicated, usually due to discontinuation from taking their medications, (Mann et. al., 2005) (6) (Lonnqvist et. al., 1995) (7) (Ahearn et. al., 2012) (8) this infers that of the 15% of lithiumtreated patients who were not spared from suicide (most likely due to intolerable side effects and discontinuation of lithium therapy) an additional 12% could be saved by Lithium Orotate, due to dramatic increases in continued, long-term Lithium Orotate (LO) use, i.e., increased patient compliance. If you have not already seen the previous Fox News video on this subject (lithium in the water supply) please do so now or view again!

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Must see Fox News video (45 seconds) See here: (FOX NEWS VIDEO) However achieving this result (ending the epidemic) is dependent upon effectively causing a paradigm shift regarding natural LO supplementation among the entire veteran community. We should not expect any assistance (initially at least) from the VA, or any other governmental agency for that matter. It is completely up to us to deliver this life-saving information to our veterans. The first challenge is getting the veteran to admit he or she has a challenge (in their mind they dont); secondly to get them to seek help; thirdly to educate them that lithium is not a toxic drug; and finally, getting them to take LO everyday! If you are consistent in your supplementation over time you will notice dramatic and continued strengthening of your mood and state of mind will become even more balanced, consistent and enjoyable. For the miracle growth of new brain cells and increasing your brain mass you must take the lithium supplement consistently. Just taking the product when you feel an attack coming on is not sufficient to fully heal and repair your central nervous system. An in-depth discussion of the scientific facts regarding lithiums production of new brain cells and increasing brain-mass is provided later in my book.

The Lithium Orotate MDD, PTSD and Suicide Study

I am seeking veterans from all foreign wars, to participate in this on-line research study, to demonstrate the benefits of supplementing with LO. Protocol for the participants is as follows: The participants will be asked to fill out a health status form detailing all of the symptoms that they are experiencing. We will examine the symptomatic parameters of their present health before and after LO supplementation. For those who are treating at a VA facilitate, and are willing to participate, we ask that they have their doctor at the VA participate with them by doing a blood analysis to measure stress hormone levels and evaluate kidney (GFR and Creatinine clearance tests) and thyroid (hormonal) functions. However, do not be surprised if a VA doctor does not want their patient to participate in this study. Unfortunately, most doctors have no idea what LO does and whether or not it is safe. See page 139; section titled: Conspiracy or Ignorance to see why doctors may be concerned about you consuming LO. By analyzing your stress hormone levels, and kidney and thyroid parameters, we will be able to demonstrate to the world the incredible effectiveness and safety of Lithium Orotate. Tell your friends and families about this critical research project and invite them to help us find the philanthropic donations to fund it. One of the best ways to find the donations is to go on-line and contact any Veterans group or individual who is actively involved with Veterans affairs. From the profits of this project we will fund a double-blind, placebo-controlled, scientific study of the effects of LO upon MDD, PTSD, and other stress-related illnesses. I pledge to donate 50% of the profits of this book, for this purpose.

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Once we have the results from this double-blind placebo-controlled study published, we will be able to demand that the Federal government and the VA educate soldiers about this incredible breakthrough and give them the option of supplementing with LO to de-stress them, bring them out of depression and fatigue, and totally shut down this epidemic of Suicide! We will ask participants to report their results on a weekly basis via email. For those who are willing, we ask that they supply us with their testimonial on the direct benefits they experienced in your recovery with LO. These testimonials will be critical in reaching the hundreds of thousands of veterans returning from Afghanistan and Iraq (and other wars) with PTSD and Major Depressive disorder.

My Personal Short Story Lithium Orotate Saved my Life

My own journey with traumatic brain injury and bipolar disorder began in 1979 when my automobile was struck head-on in an automobile incident in which a drunk driver crossed over the yellow line traveling at a high rate of speed. Our combined rate of speed was estimated to be at 100mph. Upon impact of the automobiles, I sustained a severe closed head injury. Within six months of that incident, I was working in Alaska on the deck of a King crab boat in the Bering Sea, fishing for the Deadliest Catch. Life on the deck of a King crab ship is continuously a life or death situation demanding intense survival like focus and elevated stress hormones. I was in an intense world of survival, experiencing war zone-like levels of adrenaline. After 2 years of fishing I was completely revved up, experiencing super-human levels of adrenaline that only got worse as the years went by. Eventually I was diagnosed with Bipolar disorder, aka Manic-Depression. As you will learn later on, PTSD and bipolar disorder are frequently co-occurring (comorbid) illnesses with virtually identical mental and emotional signs and symptoms of hormonal imbalances as well as similar brain morphological (size and shape) changes. To make a long story short, this illness took virtually everything from me, including my ability to do my job as a Chiropractor and eventually (after 7 years of practice) I voluntarily suspended my own license, due to my inability to function as a professional. Thankfully I have an incredible family that supported me throughout my journey, even when I didnt want the support. The family support, coupled with Lithium Orotate is the only reason I am here today to tell this story. LO has completely set me free from bipolar disorder. I cant promise you a cure (They would drag me into court for that claim) but I will promise you a dramatic improvement in your overall health. It is my joy, passion and mission to bring this great truth, not only to our veterans, but to all who unnecessarily suffer from these frequently debilitating diseases.

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The Mission
You have been called to action in one of the more important missions of your life.

Operation Break Free Is Mission Possible!

Mission statement: The purpose and mission of Operation Break Free, is to empower our veterans in reducing the suffering and severity of MDD, Posttraumatic Stress disorder (PTSD), comorbid (co-occurring) medical conditions and to significantly reduce the number of veteran suicides that has become an epidemic (approximately 7,000/yr) in this country. It is sadly ironic that so many of our troops who have sacrificed for the cause of freedom in foreign nations have come home with MDD and PTSD only to remain forever a prisoner of war; taken hostage by medical conditions that have the potential consequence of suicide. As a retired Chiropractor, I am part of a small (but growing) group of medical and alternative holistic doctors who have discovered Lithium Orotate, a natural, orthomolecular medicine (nutritional remedy) for MDD/PTSD and many other severe neurological and physical disorders. The term "orthomolecular" was introduced by Linus Pauling Ph.D. in "Orthomolecular Psychiatry". In a 1968 article published in the Journal of Science, Dr. Pauling defined orthomolecular medicine to mean

The right molecules, in the right concentration.

Dr. Linus Pauling said "You can trace every sickness, every disease and every ailment to a mineral deficiency." Dr. Pauling is the only individual recipient to ever receive the Nobel Peace Prize twice. In other words his Nobel Prize was undivided (not shared by others). He received his first in 1954, for Chemistry and the second in 1962, for Peace. Dr Pauling was considered by many to be a genius. Dr. Pauling theorized and later proved that chronic degenerative diseases could be ameliorated, even cured by giving the patient, the right nutrients in the right amounts. He was most known in the nutritional field for his research on vitamin C. Today mega-dosing vitamin C is being used to treat cancer and vitamin C deficiency has been scientifically demonstrated to be a primary cause heart disease. The doctor of the future will give no medicine, but will interest her or his patients in the care of the human frame, in a proper diet, and in the cause and prevention of disease. Thomas A. Edison U.S. inventor (1847-1931)

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Orthomolecular Psychiatry began in earnest in the mid 1900s with the introduction of lithium to modern medicine for the treatment of mood disorders, such as bipolar disorder, aka manic depression, major depressive disorder schizophrenia and schizoaffective disorder. This is the first trace mineral in recorded history to be used around the world as true orthomolecular psychiatric medicine. Mainstream medicine has demonstrated that Dr. Paulings theory is scientific fact and the FDAs approved lithium treatment of bipolar disorder is a perfect example of the best that orthomolecular medicine has to offer. Let food be thy medicine and medicine be thy food. Hippocrates, father of medicine, 431 B.C. A large part of this mission, Operation Break Free is to educate veterans on the subject of utilizing vitamins and minerals in larger quantities than are recommended by the RDA (i.e., Recommended Daily/Dietary Allowances). Vitamins and minerals may be highly beneficial in the management or cure of certain illnesses by taking larger amounts that are significantly higher than the RDA. When I speak of a nutritional cure I am referencing the fact that as long as the elevated levels of specific nutrients (recommended and effective for the condition) are maintained, the condition is dramatically resolved or, signs and symptoms of the condition are no longer present. However, when the supplementation is discontinued, the condition will often rapidly return. It appears likely that genetics and stress load play a critical role in determining an individuals unique requirement for larger daily intakes of key nutrients such as lithium. I personally will not tell you that LO will cure your condition for it is against the law to make such claims and furthermore I have no idea what LO will do for each and every individual who uses it. What I can tell you is this: Except for the few times that I neglected to take LO since January of 2006 when I began taking LO on a daily basis, I have not experienced a single manic cycle of bipolar disorder and my chronic major depressive episodes have improved by at least 80%. I can also report to you that without exception each and every individual that has tried Lithium Orotate (with a condition outlined in this book) has reported fair to excellent results. In summary, this mission Operation Break Free is about educating the American veterans as to the truth about lithium/LO. Lithium Orotate is breakthrough orthomolecular medicine for MDD, PTSD and numerous other severe, mental, neurological and somatic (bodily) diseases.

My Qualifications for This Mission

I earned a doctorate of Chiropractic from Parker College of Chiropractic, Dallas, Texas graduating in 1988. Parker College is arguably one of the best colleges in the nation with the most comprehensive education, focusing in every area of alternative health with emphasis on cutting edge, Chiropractic, Homeopathic, and Naturopathic, organic nutritional remedies. My personal passion in my research is the focus on emerging anti-aging, breakthrough orthomolecular medicine. Lithium Orotate is one of the leaders in this field.

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Furthermore, I have invested over 5 years and 7,000 hours of research in this project. I have metaphorically speaking earned a PhD. in the subject of lithium administration. I am committed to this mission in spite of the tactics used by fear-mongering agents of the FDA/Pharma-cartel who wish to defeat the Lithium/Lithium Orotate Revolution in health care. I completely understand what I am up against and the risks I am taking in seeking to expose and illuminate the diabolical nature, of a purely Pharmaceutical medical paradigm for health care. I realize that I will experience personal attacks as I expose this information to the spot light and minds of the American people. Having said that, I look forward to the ensuing challenge to cut away the dogma, lies, machinations and suppression that have been wrapped like a cancerous tumor, around the lithium story. I believe that once a critical mass of participants in the Lithium Orotate Revolution has been met the phenomenon of the Hundredth Monkey Effect will occur. At that moment in time the momentum of expanding the public consciousness regarding the Lithium Orotate breakthrough will begin to grow exponentially and I believe that millions of Americans will begin supplementing with LO. With a little divine providence and a lot of hard work and planning, we just might be able to scientifically demonstrate without any question that LO is in fact absolutely safe in moderate doses up to perhaps 4 mg/10lbs of body weight. At this level 4 mg/10lbs of body weight LO may very well be shown to be a breakthrough Cancer treatment as well. At the rate healthcare lobbyists are promoting legislation, we may not have much time before the FDA, at the behest of the Pharma-cartel, will do everything in its power to take away consumers choice to enjoy LO supplementation without a doctors prescription. If we are quick, determined, and highly efficient in our landmark LO research studies we may just be able to prevent the government take-over of this precious nutrient. Lithium supplementation is an idea thats time has come and we must act now, before They, i.e., corporate interests, bury the fact that lithium is, in fact, the supreme essential trace mineral for overall brain health and optimal neurological function. I thank you in advance for whatever efforts you make to promote the dissemination of this critical information, regarding the breakthrough of the Lithium/Lithium Orotate Revolution. Our nations veterans will be grateful for whatever efforts you make to promote the dissemination of this critical information regarding the scientific breakthroughs of the value of the trace mineral Lithium/Lithium Orotate. Your efforts are sure to assist in revolutionizing preventative health-care in America.

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Publication of this book

Hopefully this E-book will be published in book form by early 2013. In the meantime I am deeply appreciative of those of you who have chosen to purchase my E-book at my website www.opsetthemfree.com.

50% of the net proceeds from the sale of the E-book will be donated to the Veteran Health and Education fund being set up for this mission.
Finally I pledge to donate 100% of the profits from the sale of Lithium Orotate to fund this mission and inspire philanthropists to assist us in this endeavor. Several notable veteran Non-profit groups (soon to be posted on the website) will be overseeing the allocation of the funds raised by this mission for the following purposes. 4. Advertising and marketing of the mission to veterans and their families. 5. Paying for the clinical research upon veterans to demonstrate to the world the breakthrough solution for the veteran epidemic of PTSD, depression and suicide. 6. Providing LO freely to homeless veterans.

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Summation
I provide a summation here for those of you who have no desire to read nearly 250 pages on this topic. If you have made it this far you are one of the troopers and I commend your participation and hope that you will forward this book freely through your email database. The solid foundation of my book rests upon the four granite rock corner posts of this, our Mission: Operation Break Free! 1. The premise that lithium is the only solution for the veteran epidemic of suicide is unshakably grounded in the credibility of Harvard Medical School (Americas leading medical research university) and their analysis of 34 human studies over 85,000 person years. 2. The peer-reviewed confirmation of Harvards lithium studies is unshakably grounded in the credibility of the American Psychiatric Associations (APA) acknowledgement of the lithium suicide breakthrough in the Practice Guideline for the Assessment and Treatment of Patients With Suicidal Behaviors (2003). Furthermore, the findings by the APA that the primary care of veterans with antidepressants, antipsychotics and anticonvulsants, in the treatment of major depressive disorder, do not provide significant protection against, or prevention of, suicide associated with depression. 3. The decades long clinical use of LO for major depression by leading alternative minded integrative medical doctors and their clinical research on the breathtaking efficacy and absolute safety of this breakthrough alternative lithium compound. 4. The landmark study performed [on nearly a quarter million (244,859) veteran patients within the Ann Arbor, VA medical center (Valenstein et. al., 2006)] occurring during the time-line of acute VA urgency to take decisive action, against the tsunami of veteran suicides. This study revealed the negligent treatment of the veterans who are at the highest risk of completed suicides, i.e., those with major depressive disorder and particularly the veterans with treatment-resistant depression.

The findings of only 1 in 200 veterans receiving lithium for major depression and 1 in 50 veterans receiving lithium for treatmentresistant depression is asserted in this document to be the primary reason for the uninterrupted acceleration to date, of the veteran suicide epidemic.

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Chapter Five

Lithium Orotate Dosing Instructions

The recommendations in this document represent Dr. Mark Millars opinion based on over 5 years and 7,000 hours researching and writing about lithium and Lithium Orotate administration. The information in this document is for educational purposes only and any recommendations are not intended to replace the advice of your physician. The information contained in this document has not been evaluated by the Food & Drug Administration. It is not meant to diagnose, treat, cure or prevent any disease. You are advised to seek counsel from a licensed medical professional regarding the application of any recommendations noted within this document with regard to your symptoms or condition. It is important that you do not modify in any way, any medication or treatment without first consulting your physician.

GENERAL INFORMATION FOR ALL CATEGORIES:

Of this 120 mg Lithium Orotate tablet, approximately 5 mg (4.8 actual) of this tablet is pure EL and the rest is orotic acid and miscellaneous binding agents. Most importantly I want to reemphasize just how incredibly safe supplementing with Lithium Orotate (LO) really is. Again thanks to the pioneering work of Jonathan Wright M.D. and his several decades of clinical research on LO, including laboratory testing of kidney and thyroid function. Dr. Wright has demonstrated the absolute safety of LO up to 40 mg of EL/day. He does not have research beyond that dosage because no more than 40 mg was required for his patients to attain the results they were seeking. Here again is what Dr. Wright communicated to me about this issue. In written communication with me Dr. Wright declared After decades of clinical research and laboratory testing of LO on my patients, I discovered that administering LO up to 40 mg per day of EL is completely safe (without negative side effects, toxicity or drug interactions) and absolutely effective in the treatment of numerous mental, neurological and physical conditions. The only potential exception to this rule is if you are already taking antidepressants. Lithium and antidepressants increase serotonin nerve transmission; so if you are going to add LO to your antidepressant prescription please read the Serotonin Syndrome section on this subject before you do so. Additionally the response rate for adding lithium to antidepressants is 65-85% in clinical trials and over 50% in placebo-controlled trials. Chances are very good that you will feel a whole lot better by taking LO. Most importantly your risk of suicide will likely be reduced by 8590%. So far in 10 cases of combat-related PTSD that I have consulted with, every single case has reported dramatic reductions in depressive and PTSD symptoms.

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While it is recommended that you consult with your physician for this process, unfortunately most medical doctors have no experience with LO to draw from to consult you in this process. Worse yet, your doctor may believe that lithium is a toxic drug. Furthermore your doctor may erroneously believe that LO is toxic. If your doctor tells you about the LO study conducted on rats that found kidney inflammation, then you tell your doctor that the researchers used 10 times more LO in that study than humans are typically taking for depression. That study was designed to discourage physicians and their patients from utilizing LO supplementation. Here is that study link for you to see for yourself. Study title: Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate. (Smith and Schou 1979) (1) The measure of the lithium concentration within the blood that caused kidney inflammation was 2.0 mmol (mmol = measure of the lithium concentration within the blood). In relative terms 2.0 mmol would require 400-450 mg of EL in humans to reach this extreme level. With LO, blood levels are typically 10-20 times less than what was used in this study, i.e., 0.1 0.2 mmol derived from 20-40 mg of EL via LO. If your physician is opposed to you doing this, you may have to find another physician to assist you, or you may do this on your own. Naturopathic, Chiropractic and Homeopathic physicians are your best bet for a LO consultation. This is not rocket science and is very safe and simple for you to do. This process is being utilized by medical doctors who are treating their patients with LO. This outline is an amalgamation of the various treatment plans that I learned from medical doctors in interviews with them. Simply choose from one of the following sections 1 - 7 to determine which category you are in. Section 1: Section 2: Section 3: Section 4: Section 5: Section 6: Section 7: Dosing for Major Depression (MDD) only. Dosing for PTSD only. Dosing for Depression and PTSD when they are co-occurring. Dosing for Bipolar disorder (BD) only. Dosing for all three BD, MDD and PTSD when they are co-occurring. Dosing for Schizophrenia or Schizoaffective disorder. Dosing for all other miscellaneous categories.

For all categories the process of finding the right daily dose is the same. Begin with 1 tablet the first day and then add one tablet each day thereafter until you reach the beginning of the maximum dose range recommended for your category. For example if the maximum dose range is 4-6 tabs per day you will stop at 4 tabs and wait a few days before you go higher to determine if the highest dose (6) is of any greater benefit to you. You may take your LO once a day or split into two doses. It does not matter which way you do it. You may also take LO with a meal or without. LO does not bother an empty stomach. If you experience any strange feelings or effects reduce your dosage until you no longer feel anything unusual. As the nervous system integrates the healing power of lithium a

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transition may be felt 1-3 days. After the transition has passed move back to the maximum dosage that feels right for you and wait a week or two to see how you respond before you change your dosage higher or lower. How you feel is your best guide to determine your personal dosage for all conditions. If you are taking too much LO, you may feel too relaxed, a little apathy or reduced appetite. Just reduce your dose by 1 tablet or two to find the right dose. Note: There are no known drug interactions with LO because the EL dosage is so low. If however you are the rare exception to this rule, please discuss this with your physician if you are experiencing any unusual symptoms while taking LO. I would also deeply appreciate hearing from you regarding any unusual experiences you may have with LO. Remember this: The most common reason that LO fails to work for someone is because they failed to go up to the maximum recommended dosage. To achieve maximal relief of your symptoms you have to find your optimal amount. As a general rule taking a minimum of 2 - 4 tabs per day is the best idea for the prevention of Alzheimers disease, to promote the growth of new brain cells and increase your brain mass in the fight against the shrinking brain of MDD and PTSD. (More on this topic in the book) Note: Taking 4-6 LO tabs per day is recommended for adults who want maximum protection against Alzheimers and to maximize the growth of new brain cells.

Response Time to Lithium Orotate Supplementation!

LO may begin to dramatically relieve your depression in just 2-3 days (even the most severe cases of depression) in as little as 1-2 weeks. Sometimes however the dramatic relief is not fully experienced for 2 weeks (sometimes even longer). Factors complicating your full recovery are many and varied and for this reason it is highly recommended that you consult with a medical or alternative doctor to guide you through this process. If you do not feel substantial relief of depression from LO it is still recommended that you take a minimum of 2 tabs per day for suicide prevention, also for prevention of severe depressive relapse, promoting the birth of new brain cells and maintaining your brain mass as well as protection against Alzheimers. Note: 30-40 percent of LO users may get no (or only partial) relief of depressive symptoms, however these individuals should continue taking LO for the prevention of suicide and relapse into severe depression. Also remember that lithium reduced suicide attempts by 70% even in patients who felt little or no relief of depressive symptoms. The LO response time for PTSD and bipolar disorder begins overnight once you reach your ideal dosage. If you are not already taking antidepressants OR Pharma-Li you may jump to page 7 and see the Getting Started section.

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IF YOU ARE ALREADY TAKING ANTIDEPRESSANTS

Caution: If you are already taking antidepressants. Before taking 4 LO tabs per day you must read the next section titled: Serotonin Syndrome. Serotonin Syndrome When too much of an antidepressant is ingested (particularly if two or more antidepressants are taken simultaneously) an excess buildup of serotonin within the brain may occur. When an excess of serotonin occurs within the brain, a condition known as Serotonin Syndrome (SS) may present. The common flu can be confused with a serotonin syndrome. Milder symptoms of too much serotonin are nausea, increased body temperature, excess sleepiness, restlessness and excessive sweating. Severe overdose of antidepressants can cause rapid heartbeat, diarrhea, vomiting and loss of coordination. Chances of SS occurring are very slim but you should be aware of the symptoms. In twenty years of adding lithium to antidepressants, only 19 cases of possible lithium induced SS have been reported in the literature. The chances of SS occurring while taking Lithium Orotate (LO) in low dosages and by itself are zero. This is only a concern if you are taking antidepressants. One of the primary therapeutic actions of lithium in depression is the natural increased production of serotonin and or increased serotonergic neurotransmission by the cells of the brain. This is a very good thing! However if you are taking high doses of an antidepressant, or two or more antidepressants with LO as an add-on, the very rare occurrence of SS may be a possibility. SS with LO may have occurred in one of the veterans that I consulted with. The veteran was taking two (serotonin enhancing) antidepressants, Venlafaxine and Amitriptyline, when she added LO. Instead of following the guidelines for adding LO to antidepressants, the veteran took 4 tablets at the beginning instead of gradually increasing the dosage from one tablet to two tablets etc. When she reduced the (LO) dosage from 4 tablets to 1 tablet the symptoms of nausea and diarrhea and sleepiness immediately resolved. Her depression has been alleviated with one LO tab per day. If you experience these symptoms after you have added LO to your antidepressant regimen you should reduce your dosage to 1 tab or tab until the symptoms resolve and then you may try adding just tab - 1 tab for maximal results. Please discuss this situation with your physician if you experience any of the symptoms of serotonin syndrome. Again I would deeply appreciate hearing from you as well.

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YOU MIGHT CONSIDER ASKING YOUR DOCTOR TO GUIDE YOU IN THE REDUCTION OF YOUR DOSE OF ANTIDEPRESSANTS SO YOU CAN TAKE THE MAXIMUM RECCOMENDED DOSAGE OF LO. I strongly encourage you to ask your physician about reducing your antidepressant dosage so you can take LO. You may be able to quit taking your antidepressant altogether. Obviously it is far better to increase serotonin levels naturally with lithium than to artificially increase serotonin levels by blocking the reuptake of serotonin with a synthetic drug. When you reduce the amount of antidepressant, you should be able to take the maximum dosage of LO without experiencing SS as the following medical doctor observed in the treatment of his patient with Pharma-Li. This patient was reduced from 30 mg to 10 mg of Paxil. See: Serotonin syndrome after lithium add-on medication to paroxetine. (Sobanski et. al., 1997) (2) On a combination of paroxetine (aka Paxil) and lithium the patient developed symptoms of shivering, tremor, agitation, and impairment of focus suggesting a serotonin syndrome. The treating physician indicated that the dosage of paroxetine was reduced to 10 mg/day, and lithium was continued. The patient became symptom-free and the depressive episode attenuated, thus enabling us to discharge the patient. (Sobanski et. al., 1997) (2) So here a medical doctor realized the importance of lithium and reduced the antidepressant instead of eliminating the lithium. This is the right move; lower the antidepressant dosage and maintain your LO regimen! Ask your doctor to consult you on this process. Do not do this without your doctors advice. Slowly reducing your antidepressant while increasing lithium is the definitely the way to go. Again how you feel is your best guide. Serotonin syndrome has presented as a very rare complication of taking Pharma-Li with SSRIs, SNRIs and Tricyclic antidepressants. In 30 years of this practice of adding Pharma-Li to antidepressants only (19) instances of SS with Pharma-Li augmentation of treatmentresistant depression have been published. Here are the drugs that have been shown in rare instances to cause SS when Pharma-Li was added. Antidepressants: Venlafaxine Amitriptyline Paroxetine Fluoxetine Fluvoxamine Clomipramine Other Sumatriptan aka Effexor (SNRI) class aka Elavil (SNRI) class aka Paxil (SSRI) class aka Prozac (SSRI) class aka Luvox (SSRI) class aka Anafranil tricyclic antidepressant

Sulfur drug for migraines

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If you are already taking Pharma-Li

Converting Pharma-Li to Lithium Orotate If you are already taking Pharma-Li and you want to convert to LO (highly recommended) use the following chart as your guide. This will eliminate any side effects you may have with Pharma-Li as you will be reducing your EL dosage by about 80-90%. Please ask your physician to guide you in this process. It is absolutely safe and simple to do this. You can make the switch in a single day, as there is no reason to do this slowly. How you feel is always the ultimate guide. No one can tell you what the right amount is for you. If you feel you need to take more or less do so. This is just a guideline. If your physician is opposed to you doing this you may have to find another physician. It is unfortunately difficult finding a physician who is experienced with LO. Many individuals are forced to do this without physician guidance. The basic conversion rate is this: For every 300 mg of Pharma-Li you will convert to (1) Lithium Orotate (LO) tablet. Each LO tablet contains 120 mg LO. Of this 120 mg tablet, approximately 5 mg (4.8 actual) of this tablet is pure EL and the rest is orotic acid and miscellaneous binding agents. There is 18.8 mg of EL in each 100 mg of Pharma-Li, so 300 mg = 56.4 mg of EL. So we are reducing you from 56.4 EL to 4.8 mg EL with LO. This is a 91% reduction of EL. We are able to do this because LO is believed to be at least 10 times more bioavailable (absorbable by the brain cells). Conversion Table: Pharma-Li 300 mg 600 mg 900 mg 1200 mg 1500 mg 1800 mg 2100 mg 2400 mg to Lithium Orotate (LO) = = = = = = = = 1 tab LO 2 tab LO 3 tab LO 4 tab LO 5 tab LO 6 tab LO 7 tab LO 8 tab LO = approximately 40 mg EL.

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Getting Started
Simply choose from one of the following sections 1 - 7 to determine which category you are in. Section 1: Section 2: Section 3: Section 4: Section 5: Section 6: Section 7: Dosing for Major Depression (MDD) only. Dosing for PTSD only. Dosing for Depression and PTSD when they are co-occurring. Dosing for Bipolar disorder (BD) only. Dosing for all three BD, MDD and PTSD when they are co-occurring. Dosing for Schizophrenia or Schizoaffective disorder. Dosing for all other miscellaneous categories.

This is only a guideline and is not set in stone. You may take more or less and this is entirely up to you, as only you know best what your body needs. Simply how you feel is your best guide. Remember this: The most common reason that LO fails to work for someone is because they failed to go up to the maximum recommended dosage. To achieve maximal relief of your symptoms you have to find your optimal amount. If you are not already taking Pharma-Li you may take LO along with your present treatment program as there are no known drug interactions with anticonvulsants or antipsychotics or any other pharmaceuticals. I would encourage you to talk with your doctor about reducing your dependence on anticonvulsants and or antipsychotics. LO will very likely allow you to reduce the dosage of anticonvulsants and or antipsychotics and sleep aids under the guidance of your physician.

Section 1: Dosing for Major Depression (MDD) only.

A. Dosing for Major Depression if you are already taking antidepressants: General rule is 2 LO tabs per day. Maximum dose range 2 - 6 Note: If you are taking antidepressants it may not be possible for you to take more than 2 tabs per day until you have significantly reduced your dosage of antidepressants. On the other hand you most likely will have no difficulty taking the maximum dosage. Begin with 1 tab and increase by 1/2 tab per day to 3-4 tabs per day and that should be all you need for maximal relief of depression. Here again how you feel is your best guide to determine your personal dosage for depression. If you do not feel substantial relief of depression from LO it is still recommended that you take a minimum of 2-4 tabs per day for suicide prevention, also for prevention of severe depressive relapse, promoting the birth of new brain cells and maintaining your brain mass.

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B. Dosing for Major Depression without antidepressants: General rule is 2 - 4 LO tabs per day. Maximum dose range 4 - 6 tablets Begin with 1 tab and increase by 1 tab per day to 4 tabs. Here again how you feel is your best guide to determine your personal dosage for depression. If you do not feel substantially less depressed you may go up to 6 tabs per day but any higher is unnecessary for depression alone. If you do not feel substantial relief of depression from LO it is still recommended that you take a minimum of 2-4 tabs per day for prevention of severe depressive relapse, for suicide prevention, birth of new brain cells and maintaining your brain mass.

Section 2: Dosing for PTSD only.

A. Dosing for PTSD if you are already taking antidepressants: General rule is 2 - 4 LO tabs per day. Maximum dose range 4 - 8 Note: If you are taking antidepressants it may not be possible for you to take more than 2 tabs per day until you have significantly reduced your dosage of antidepressants. On the other hand you most likely will have no difficulty taking the maximum dosage. Begin with 1 tab and increase by 1 tab per day until you feel a profound sense of calm come over you. You will definitely feel the difference once you reach the right number of LO tablets per day. If you do not experience a profound sense of calm at 8 tablets per day you may need to go up to 10 or 11 tabs per day to find nirvana. This is only a guideline and is not set in stone. You may take more or less and this is entirely up to you, as only you know best what your body needs. Simply how you feel is your best guide. If you do not feel substantial relief of PTSD symptoms from LO it is still recommended that you take a minimum of 2-4 tabs per day for prevention of severe depressive relapse, for suicide prevention, birth of new brain cells and maintaining your brain mass. Note: If you decide to take more than 40 mg EL (8 tabs/day) then be sure and read the section titled: Precautions While Supplementing with LO over 40 mg EL. (See page 15)

B. Dosing for PTSD without antidepressants: General rule is 4-6 LO tabs per day. Maximum dose range 8-11 LO tabs per day. Begin with 1 tab and increase by 1 tab per day until you feel a profound sense of calm come over you. You will definitely feel the difference once you reach the right number of LO tablets per day.

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If you do not experience a profound sense of calm at 8 tablets per day you may need to go up to 10 or 11 tabs per day to find nirvana. This is only a guideline and is not set in stone. You may take more or less and this is entirely up to you, as only you know best what your body needs. Simply how you feel is your best guide. If you do not feel substantial relief of PTSD symptoms from LO it is still recommended that you take a minimum of 2-4 tabs per day for prevention of severe depressive relapse, for suicide prevention, birth of new brain cells and maintaining your brain mass. Note: If you decide to take more than 40 mg EL (8 tabs/day) then be sure and read the section titled: Precautions While Supplementing with LO over 40 mg EL. (See page 15)

Section 3: Dosing for co-occurring depression and PTSD.

A. Dosing for MDD and PTSD if you are already taking antidepressants: General rule is 2-4 LO tabs per day. Maximum dose range 4-8 Note: If you are taking antidepressants taking more than 2 tabs per day may not be possible for you until you have significantly reduced your dosage of antidepressants. On the other hand you most likely will have no difficulty taking the maximum dosage. Begin with 1 tab and increase by 1/2 - 1 tab per day until you feel a profound sense of calm. You will definitely feel the difference once you reach the right number of LO tablets per day. If you do not experience a profound sense of calm at 8 tablets per day you may need to go up to 10 or 11 tabs per day to find nirvana. This is only a guideline and is not set in stone. You may take more or less and this is entirely up to you, as only you know best what your body needs. Simply how you feel is your best guide. If you do not feel substantial relief of your symptoms from LO it is still recommended that you take a minimum of 2-4 tabs per day for prevention of severe depressive relapse, for suicide prevention, birth of new brain cells and maintaining your brain mass. Note: If you decide to take more than 40 mg EL (8 tabs/day) then be sure and read the section titled: Precautions While Supplementing with LO over 40 mg EL. (See page 15)

B. Dosing for MDD and PTSD without antidepressants: General rule is 4-6 LO tabs per day. Maximum dose range 8-11 LO tabs per day. Begin with 1 tab and increase by 1 tab per day until you feel a profound sense of calm come over you. You will definitely feel the difference once you reach the right number of LO tablets per day. If you do not experience a profound sense of calm at 8 tablets per day you may need to go up to 10 or 11 tabs per day to find nirvana. This is only a guideline and is not set in

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stone. You may take more or less and this is entirely up to you, as only you know best what your body needs. Simply how you feel is your best guide. If you do not feel substantial relief of your symptoms from LO it is still recommended that you take a minimum of 2-4 tabs per day for prevention of severe depressive relapse, for suicide prevention, birth of new brain cells and maintaining your brain mass. Note: If you decide to take more than 40 mg EL (8 tabs/day) then be sure and read the section titled: Precautions While Supplementing with LO over 40 mg EL. (See page 15)

Section 4: Bipolar disorder (BD) only

General rule is 4-6 LO tabs per day. Maximum dose range 8-11 LO tabs per day. Note: If you are taking antidepressants it may not be possible for you to take more than 2 tabs per day until you have significantly reduced your dosage of antidepressants. On the other hand you most likely will have no difficulty taking the maximum dosage. If you are already utilizing Pharma-Li for the treatment of bipolar disorder may easily convert to LO. Do not take LO on top of your Pharma-Li dosage. Use the conversion table above on page 7. If you are not already taking Pharma-Li you may take LO along with your present treatment program as there are no known drug interactions with anticonvulsants or antipsychotics or any other pharmaceuticals. I would encourage you to talk with your doctor about reducing your dependence on anticonvulsants and or antipsychotics. Lithium Orotate will allow you to at least reduce the dosage of anticonvulsants and or antipsychotics and sleep aids under the guidance of your physician.

IF YOU ARE NOT ALREADY TAKING PHARMA-Li FOLLOW THESE STEPS:

Begin with 1 tab and increase by 1 tab per day until you feel a profound sense of calm come over you. You will definitely feel the difference once you reach the right number of LO tablets per day. Maximum dose range 8-11 LO tabs per day. If you do not experience a profound sense of calm at 8 tablets per day you may need to go up to 10 or 11 tabs per day to find nirvana. This is only a guideline and is not set in stone. You may take more or less and this is entirely up to you, as only you know best what your body needs. Simply how you feel is your best guide. If you do not feel substantial relief of your symptoms from LO it is still recommended that you take a minimum of 2-4 tabs per day for prevention of severe depressive relapse, for suicide prevention, birth of new brain cells and maintaining your brain mass. Note: If you decide to take more than 40 mg EL (8 tabs/day) then be sure and read the section titled: Precautions While Supplementing with LO over 40 mg EL. (See page 15)

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Section 5: Dosing for all three BD, MDD and PTSD when they are co-occurring.
General rule is 4-6 LO tabs per day. Maximum dose range 8-11 LO tabs per day. If you are already utilizing Pharma-Li for the treatment of bipolar disorder may easily convert to LO. Do not take LO on top of your Pharma-Li dosage. Use the conversion table above on page 7. Note: If you are taking antidepressants it may not be possible for you to take more than 2 tabs per day until you have significantly reduced your dosage of antidepressants. On the other hand you most likely will have no difficulty taking the maximum dosage. If you are not already taking Pharma-Li you may take LO along with your present treatment program as there are no known drug interactions with anticonvulsants or antipsychotics or any other pharmaceuticals. I would encourage you to talk with your doctor about reducing your dependence on anticonvulsants and or antipsychotics. LO will very likely allow you to reduce the dosage of anticonvulsants and or antipsychotics and sleep aids under the guidance of your physician.

IF YOU ARE NOT ALREADY TAKING PHARMA-Li FOLLOW THESE STEPS:

Begin with 1 tab and increase by 1 tab per day until you feel a profound sense of calm come over you. You will definitely feel the difference once you reach the right number of LO tablets per day. If you do not experience a profound sense of calm at 8 tablets per day you may need to go up to 10 or 11 tabs per day to find nirvana. This is only a guideline and is not set in stone. You may take more or less and this is entirely up to you, as only you know best what your body needs. Simply how you feel is your best guide. If you do not feel substantial relief of your symptoms from LO it is still recommended that you take a minimum of 2-4 tabs per day for prevention of severe depressive relapse, for suicide prevention, birth of new brain cells and maintaining your brain mass. Note: If you decide to take more than 40 mg EL (8 tabs/day) then be sure and read the section titled: Precautions While Supplementing with LO over 40 mg EL. (See page 15)

Section 6: Dosing for Schizophrenia or Schizoaffective disorder.

General rule is 2-4 LO tabs per day. Maximum dose range 4-8 Note: If you are taking antidepressants it may not be possible for you to take more than 2 tabs per day until you have significantly reduced your dosage of antidepressants. On the other hand you most likely will have no difficulty taking the maximum dosage. If you are already utilizing Pharma-Li for the treatment of your condition you may easily convert to LO. Do not take LO on top of your Pharma-Li dosage. Use the conversion table above on page 7.

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Begin with 1 tab and increase by 1 tab per day until you feel a profound sense of calm. You will definitely feel the difference once you reach the right number of LO tablets per day. If you do not feel substantial relief of your symptoms from LO it is still recommended that you take a minimum of 2-4 tabs per day for prevention of severe depressive relapse, for suicide prevention, birth of new brain cells and maintaining your brain mass. Note: If you decide to take more than 40 mg EL (8 tabs/day) then be sure and read the section below titled: Precautions While Supplementing with LO over 40 mg EL. (See page 15)

Section 7: Dosing for all other miscellaneous categories.

General rule is 2-4 LO tabs per day. Maximum dose range 4-8 Note: If you are taking antidepressants it may not be possible for you to take more than 2 tabs per day until you have significantly reduced your dosage of antidepressants. On the other hand you may have no difficulty taking the maximum dosage. If you are already utilizing Pharma-Li for the treatment of your condition you may easily convert to LO. Do not take LO on top of your Pharma-Li dosage. Use the conversion table above on page 7. If you are stressed begin with 1 tab and increase by 1 tab per day until you feel a profound sense of calm. You will definitely feel the difference once you reach the right number of LO tablets per day. If you are experimenting with LO for one of the many conditions listed in this text or website it is impossible to say how much you need to take to significantly relieve your symptoms. You may want to increase your dosage at a slower rate to see if your condition responds to a low dosage. If you go quickly to the maximum dosage and do no get immediate relief it is recommended that you allow at least 2-3 weeks at the maximum comfortable dosage to see if your condition improves before lowering the dosage. If you do not feel substantial relief of your symptoms from LO it is still recommended that you take a minimum of 2-4 tabs per day. As a general rule taking a minimum of 2 - 4 tabs per day is the best idea for the prevention of Alzheimers disease, to promote the growth of new brain cells and increase your brain mass in the fight against the shrinking brain of MDD and PTSD. (More on this topic in the book) Taking 4-6 LO tabs per day is recommended for adults who want maximum protection against Alzheimers and to maximize the growth of new brain cells.

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Note: If you decide to take more than 40 mg EL (8 tabs/day) then be sure and read the section below titled: Precautions While Supplementing with LO over 40 mg EL. See next page.

Precautions while supplementing with Lithium Orotate over 40 mg EL.

Rarely in the most severe cases of bipolar disorder and PTSD where the primary stress hormones (adrenaline and noradrenaline) are extremely elevated (as they so often are) it may take up to 10-11 tabs of LO i.e., 50-55 mg/day of EL via Lithium Orotate (LO) to initially achieve the maximum relief you are seeking. This level of dosing is usually only needed for males weighing over 200 lbs. After a month or two of sustained LO usage, you will likely be able to reduce your daily intake to at or even below 40 mg EL. Once the nervous system has time to heal and stabilize, reducing the dosage to 40 mg or below is typical. CAUTION: If however you dont reduce your intake (within 90 days) to 8 tabs (40 mg/day of EL) I must ask request that you see your doctor about testing your thyroid and kidney function for prolonged use above 40 mg EL/day. Why is this important? Because we have no research on the effect of LO at levels over 40 mg/day of EL, I request that you have your kidney functions (GFR and creatinine clearance your doctor knows these tests) analyzed along with a measurement of your thyroid hormone function. I ask you to do this for two reasons. 1. Just to be on the safe side. I am not concerned about your safety, (unless you have preexisting kidney disease then LO may be an issue we just dont know). However, if you are already prone to low thyroid function, it is important for you to know this so you can deal with low thyroid, particularly if LO lowers your thyroid hormones even lower. This is after all one of the great benefits of lithium supplementation. If you are hyperthyroid (which most PTSD soldiers are) lithiums lowering of your elevated thyroid hormones particularly (T3) will bring you dramatic symptomatic relief. If you do have pre-existing kidney disease I insist that you consult with your physician before you begin lithium supplementation. Low dose lithium supplementation will likely be ok for you even with pre-existing kidney disease, but you wont know for sure unless you do the proper testing. In fact low-dose LO, 10-20 EL mg/day may be beneficial for your kidney disease and actually improve kidney function. Remember this: Kidney distress from lithium does not typically begin (for sensitive individuals) until you exceed 120 mg/day of EL. At 20-40 mg you are well below the levels of concern.

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2. I wish to compile definitive research demonstrating that up to 55 mg of EL via LO is completely safe (without adverse effects) for your kidney and thyroid function. So please forward me your laboratory testing so we can show the world just how safe LO is even at 55 mg of EL. Typically kidney and thyroid function is not significantly altered until the daily dosage exceeds 120 mg/day of EL. But if you are that one person perhaps in 1,000 who experiences kidney or thyroid dysfunction while using 55 mg of EL via LO supplementation we want to hear about it. Remember that kidney and thyroid dysfunction occurs without lithium, so it may have nothing to do with your supplementation with lithium. The only way to know for sure is to test it your kidney and thyroid function with and without lithium in your system. If you have a healthy thyroid gland and kidneys, amounts of EL 40 mg and below wont be a problem, but over that level we still have to prove its safety. If you have any other questions regarding dosing with Lithium Orotate please email me at opsetthemfree@live.com.

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Chapter Six

What is causing MDD, PTSD and suicide?

Veterans!
This is important to understand. How is lithium correcting the apparent cause of these conditions?
Combined, there are well over 40 different major and minor chemical imbalances associated with major depression (MDD) PTSD and suicide that scientific medical researchers and I have identified. New minor imbalances are still being discovered. Amazingly, lithium has been demonstrated in animal and human studies to normalize or reduce over 90% of the imbalances identified herein. (Millar 2012) Next we will examine what the scientific evidence suggests may be some of the core primary imbalance of PTSD, depression and suicide. This section is just a small sampling of the discussion and evidence on this subject. For the complete analysis see chapters 16-20 and chapters 22 and 23. PTSD, like bipolar disorder, has the most extreme (abnormally) increased and (sustained) levels of stress hormones and neurotransmitters (adrenaline, aka epinephrine), (noradrenaline, aka norepinephrine) and dopamine, when compared to normal levels. While not as extreme, depression also shows norepinephrine levels that are significantly elevated (at least initially) when compared to healthy, normal populations. The sympathetic nervous system kicks into overdrive, when an individual is in a stressed fight or flight scenario. If this stress response becomes chronic, sustained or unrelenting, as during combat over an extended period of time, then the body experiences the symptoms of depression, PTSD and or bipolar disorder which are commonly co-occurring together in a cyclical fashion. The following are just a few excerpts from the many scientific studies that suggest a direct relationship between excessively high levels of norepinephrine and epinephrine (main controllers of the sympathetic nervous system) and dopamine, with the severity of symptoms of PTSD, depression and suicide. This finding supports prior psychophysiological studies indicating increased sympathetic nervous system activity in PTSD patients. (Kosten et. al., 1987) (1) In Vietnam veterans Dopamine and norepinephrinelevels were significantly correlated with severity of PTSD symptoms (Yehuda et. al., 1992) (2) Depressed patients who had attempted suicide had significantly reduced cerebrospinal fluid (CSF) concentrations of the dopamine metabolite homovanillic acid (HVA) and significantly lower urinary outputs of HVA than patients who had not attempted suicide. (Roy 1994) (3)

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MoreoverNorepinephrine levels strongly and positively correlated with the severity of PTSD symptoms. (Geracioti et. al., 2001) (4) Study title: Sustained urinary norepinephrine and epinephrine elevation in post-traumatic stress disorder. (Kosten et. al., 1987) This study found that the noradrenaline, aka norepinephrine, levels of hospitalized PTSD and bipolar patients were approximately twice the number of other hospitalized patients. PTSD patients also had significantly higher levels of adrenaline compared to bipolar disorder and were 40% higher than the other mental disorders measured. This finding supports prior psychophysiological studies indicating increased sympathetic nervous system activity in PTSD patients. (Kosten et. al., 1987) (1) Study title: Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans. (Yehuda, et. al., 1992) Department of Psychiatry, Mount Sinai Medical School, New York. Epinephrine, norepinephrine and dopamine are referred to as catecholamines. Dopamine, norepinephrine, and epinephrine concentrations were measured in 22 male patients with PTSDThe PTSD inpatients showed significantly higher excretion of all three catecholamines compared with both outpatients with PTSD and normal controls. Dopamine and norepinephrinelevels were significantly correlated with severity of PTSD symptoms (Yehuda et. al., 1992) (2) Study title: CSF norepinephrine concentrations in posttraumatic stress disorder. (Geracioti et. al., 2001) This study found in PTSD males that the noradrenaline levels were 70% higher than the median level of healthy men. MoreoverNorepinephrine levels strongly and positively correlated with the severity of PTSD symptoms. (Geracioti et. al., 2001) (4) Study title: Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. (Strawn and Geracioti 2008) Given the significant involvement of Central Nervous System noradrenaline hyper-activity in PTSD, and its link to intrusive and hyper-arousal symptoms, it is not surprising that interventions directed at this system have therapeutic potential in PTSD. (Strawn & Geracioti 2008) (5)

Clinical studies have demonstrated good results with lithiums use in the treatment of PTSD. Anti-kindling agents lithiumhave been found effective for PTSD symptoms of intrusive reexperiencing and increased arousal. (Fesler 1991) (6)

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Suicide Chemical Imbalances

Increasingly researchers are finding that there is a direct and or indirect relationship between the dysregulated/dysfunctional hypothalamic-pituitary-adrenal axis (HPAA) and the imbalanced stress hormones associated with suicide. The HPAA will be discussed in the upcoming section. Significant chemical alterations/imbalances of primary stress hormones and neurotransmitters (adrenaline, noradrenaline, dopamine, cortisol and serotonin) are the most frequently involved chemical imbalances in suicide patients. These hormones/neurotransmitters are either too high or too low when compared to normals depending on the variables measured. Measurements vary according to variables such as which bodily fluid is analyzed, for example. Most commonly the fluids analyzed are the blood aka plasma, urine, saliva and the cerebrospinal fluid (CSF). Many other variables exist to confound the findings substantially. For the purpose of simplicity I am not going to go into all the variables affecting the various outcomes.

Adrenaline/Noradrenaline
Adrenaline and noradrenaline aka epinephrine and norepinephrine are frequently imbalanced in suicidal patients. Suicide attempts are associated with substantially lower adrenaline and noradrenaline metabolite (MHPG) levels within the cerebrospinal fluid (CSF). (7),(8),(9),(10),(11) Study title: Lower CSF MHPG predicts short-term risk for suicide attempt. (Galfalvy et. al., 2009) Lower CSF MHPG predicted future suicide attempt or suicide (22% increase in hazard for each 10 pmol/ml lower MHPG (Galfalvy et. al., 2009)(9) Urine levels of the noradrenaline metabolite MHPG were significantly higher in patients with suicidal behavior. (12),(13) The ratio of norepinephrine-to-epinephrine levels was significantly lower in the group with a history of suicide attempts. (Ostroff et. al., 1985) (14)

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Dopamine
Depressed suicide attempters had lower dopamine metabolite (HVA) in the cerebrospinal fluid (CSF) when compared to depressed non-attempters.(15),(16) In depressed suicidal patients low concentrations of the dopamine metabolite HVA are associated with suicidality. (Traskman-Bendz et. al., 1989)(17) Depressed patients who had attempted suicide had significantly reduced cerebrospinal fluid (CSF) concentrations of the dopamine metabolite homovanillic acid (HVA) and significantly lower urinary outputs of HVA than patients who had not attempted suicide. (Roy 1994)(18)

Cortisol
Substantially higher levels of cortisol than normal are associated with suicide. Study title: Spiritual well-being, cortisol, and suicidality in Croatian war veterans suffering from PTSD. Results showed that veterans with higher spiritual well-being scores had lower cortisol levels Higher evening cortisol levels were substantially correlated with increased suicidal risk. (Mihaljevi et. al., 2011)(19) Study title: Cortisol in the CSF of depressed and suicidal patients. (Trskman et. al., 1980) The depressed patients had significantly higher CSF cortisol levels than the controls.(20)

Study title: The plasma level of cortisol as a predictor of suicide. The suicide-to-be tends to have a higher mean 8:30 A.M. plasma cortisol level than the suicidal risk with lower suicide potential. If a suicidal risk patient has a plasma cortisol level above 20 ug%, in the absence of other possible causes for such a high level, we recommend he be recognized as having a high potential for suicide (Krieger 1974)(21)

Study title: Cortisol in violent suicidal behaviour: association with personality and monoaminergic activity. Violent suicidal behaviour is associated with increased cortisol secretion (van Heeringen et. al., 2000)(22)

Study title: Life at risk: markers of suicidality in depression. Current hypercortisolism was found in patients that earlier in life had tried to commit dangerous suicides. (Agren 1983)(23)

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Serotonin
The most documented neurotransmitter imbalance associated with suicide is low levels of the serotonin metabolite 5-HIAA within the cerebrospinal fluid (CSF).(24) A review of 27 research reports on the cerebrospinal fluid levels of neurotransmitter metabolites involving 1202 psychiatric patients found strong evidence for the involvement of the serotonin system in suicidal behavior. Attempted suicides, especially those using violent methods, had lower levels of CSF 5-HIAA as compared to psychiatric controls, and those making subsequent suicidal actions also had lower levels of CSF 5-HIAA. (Lester 1995)(24)

Sleep Disorder and Suicide

Nocturnal sleep disturbances, particularly frequent insomnia and recurrent nightmares, were independently associated with enhanced suicidal risk among psychiatric patients. (Li et. al., 2010)(25)

Noradrenaline, Nightmares and Sleep disorders

Horrific images often revisit the soldier, after witnessing acts of war. One of the biggest complaints by veterans with PTSD is the re-experiencing of past psychic traumas both during the day and most disturbingly in the middle of the night through nightmares. 70-90% of PTSD patients have a sleep disorder and as much as 70% of them suffer with recurring nightmares that severely affect their sleep pattern. (26),(27) What is causing the severe unending repetition of nightmares? What is going on within the brain that keeps this maelstrom churning? Could it be that excessive noradrenaline is terrorizing the brain during sleep? The research findings clearly support this hypothesis.

Research strongly suggests that nightmares are caused by a dysregulated norepinephrine system and excessive noradrenaline levels.(26-29)
Study title: Nocturnal/daytime urine noradrenergic measures and sleep in combat-related PTSD. (Mellman et. al., 1995) This study analyzed the noradrenaline levels of combat-veterans with PTSD, while they slept, and found that noradrenaline levels did not come down at night time as they normally should. The authors stated, Our data support a relationship of non-diminished central noradrenergic activity at night, and sleep disturbance, in chronic, combat-related PTSD. (Mellman et. al., 1995)(28)

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In other words the noradrenaline levels remained abnormally elevated throughout the sleep cycle and this demonstrated a causal relationship between noradrenaline and sleep disturbance. Other research groups have found similar results confirming the association of elevated noradrenaline and sleep disorder. (Taylor et. al., 2008) (27) (Taylor et. al., 2008) (29) (Daly et. al., 2005) (30) By far the most effective pharmaceutical treatment of nightmares is prazosin, a drug that blocks the uptake of noradrenaline in the brain cells. Prazosin compared with placebo significantly increased total sleep time by 94 min; increased rapid eye movement (REM) sleep time and mean REM period duration without altering sleep onset latency; significantly reduced trauma-related nightmares... (Taylor et. al., 2008) (29) This treatment is so effective that in a single study that measured the reduction of nightmares, prazosin completely eliminated the nightmares for approximately 90% of veterans in this study. (Daly et. al., 2005) (30) So we see in Prazosin the ultimate proof that much of the suffering through nightmares is apparently caused by excessive noradrenaline and that is good news. As I will show you next, lithium naturally and powerfully normalizes elevated levels of noradrenaline. This is one of the main reasons why lithium is so effective in reducing nightmares and dramatically improving sleep patterns. Every client that I have consulted with has reported significant improvements in their sleep pattern and most report a complete elimination of nightmares through Lithium Orotate supplementation. Next we will look at the evidence supporting lithiums benefits for correcting these stress hormone and neurotransmitter imbalances.

Lithium is balancing adrenaline, noradrenaline, cortisol, dopamine and serotonin.

Lithium effect: Scientific evidence robustly suggests that lithium works at the core of stressrelated illnesses balancing, normalizing and regulating stress hormones and neurotransmitters adrenaline (31,37) noradrenaline (31,36-39) dopamine (40-46) cortisol (47,48) and serotonin.

ADRENALINE
Lithium effect: Lithium has been demonstrated to possess the normalizing dual effect of increasing and decreasing adrenaline levels in mood disordered patients (i.e., bipolar and depressed) (31),(32) while reducing excessive adrenaline effects in humans (33),(34) and animals.(35) In other words lithium has been shown to increase low adrenaline levels and decrease high adrenaline levels. Additional human studies have discovered similar findings. (36),(37)

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In depressed bipolar patients, lithium increased adrenaline metabolite-MHPG and most significantly in those who had the greatest positive response (relief of depressive symptoms) to lithium treatment. See: The effect of lithium on urinary MHPG in unipolar and bipolar depressed patients. (Beckman et. al., 1975) (31) In a study of patients with primary, major depressions lithium significantly reduced adrenaline metabolite (MHPG). (Linnoila et. al., 1983) (32) Acute adrenaline levels causes cardiac arrhythmia and pulmonary edema in rats. Lithium prevents secondary arrhythmia, pulmonary edema and adrenaline induced death in rats injected with high dosage adrenaline. It has been shown that lithium reduces the sensitivity of receptors to adrenaline in rats. (Sobieva et. al., 1981) (35)

NORADRENALINE
Lithium effect: Lithium has been demonstrated to possess the normalizing dual effect of increasing and decreasing noradrenaline levels in mood disordered patients (i.e., bipolar and depressed) When noradrenaline levels are low lithium increased noradrenaline metabolite MHPG in depressed bipolar patients and, most significantly, in those who had the greatest positive response (relief of depressive symptoms) to lithium treatment. (Beckmann et. al., 1975) (31) Furthermore, lithium increased noradrenaline metabolite MHPG in the normal healthy population by an average of 16%. (Manji et. al., 1991) (38) No human-lithium studies available to demonstrate an increase of noradrenaline in unipolar aka major depression. When noradrenaline levels are elevated in patients with affective (mood) disorders lithium significantly reduces noradrenaline. For example, lithium reduced noradrenaline levels associated with the mania of bipolar disorder. (Swann et. al., 1987) (39) Two other studies have demonstrated lithiums reduction of noradrenaline.(36,37)

DOPAMINE

Lithium effect: Lithium has the dual effect of increasing levels of dopamine in bipolar disorder (in patents with manic symptoms) (Fyro et. al., 1975) (40) and decreasing dopamine levels depending on the condition being treated. In depressed bipolar patients lithium carbonate, which stabilized mood in bipolar patients, reduced the urinary output of HVA (dopamine metabolite)and whole-body dopamine turnover. (Linnoila et. al., 1983) (41) Lithium lowers brain levels of dopamine in stress-exposed rats. (Eroglu et. al., 1980) (42) When lithium was injected into rats, lithium reduced the functional activity of brain dopamine neurons and this was attributed to the sedative effects noted in the rats. (Nozu et.

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al., 1976) (43) When lithium was administered to thyroid (T3) treated animals, there was a significant decrease of dopamine and its metabolite, 3,4-dihydroxyphenyl-acetic acid. This suggests that this lithium reduced the synthesis and turnover of dopamine (Rastoge et. al., 1977) (44) and reduces dopamine regulatory mechanisms. (Elphick 1989) (45) In normal rats given lithium an increase of dopamine was noted in the anterior cingulate cortex (CIN), the piriform-entorhinal region (PiEn). Findings of the research suggest changes in the turnover rates of dopamine as well as an action of lithium on dopamine synthesis. (Gottberg 1989) (46)

CORTISOL
Lithium effect: Lithium has been demonstrated to significantly normalize cortisol levels in bipolar disorder (Erolu et. al., 1979) (47) and maintain cortisol levels over the long term. (Smigan and Perris 1984)(48) The following study published in the British Journal of Clinical Pharmacology speaks to one of the most promising functions of lithium in normalizing HPAA dysfunction; the normalization of excessive cortisol levels in patients with mood disorders. Study titled: A study of the relationship between serum lithium and plasma cortisol levels in manic depressive patients. (Eroglu et. al., 1979) The results of partial correlation analysis revealed that there is a strong negative correlation between serum lithium and plasma cortisol levels. (Eroglu et. al., 1979)(47) In simple terms, this study showed that as lithium levels increase in the body, cortisol levels are reduced accordingly. The following study published in the journal Neuropsychobiology, demonstrated further evidence that lithium significantly normalizes cortisol levels and maintains them over the long-term. Study titled: Cortisol changes in long-term lithium therapy. (Smigan and Perris 1984) Patients showed a significant decrease in a.m. serum cortisol levels after 1 year on lithium. (Smigan and Perris 1984)(48)

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Serotonin
Serotonin aka (5HT) Selective serotonin reuptake inhibitors (SSRIs) are the most common medication prescribed for depression and anxiety disorders such as PTSD.(49) Serotonin neurotransmission is most influential in areas of the brain which are involved in mood, memory, regulation of behavior, learning and reducing obsessive disorder.(50) In this study examining serotonin platelet concentrations in suicidal combat veterans it was discovered that serotonin levels were significantly lower in suicidal veterans with PTSD compared to normal healthy controls. These results show that PTSD and suicidal behavior are related to disturbances in the central serotonergic system. See: Platelet serotonin concentration and suicidal behavior in combat related posttraumatic stress disorder. (Kovacic et. al., 2008)(51) Lithium effect: Lithium increases the synthesis and release of serotonin and appears to stabilize serotonin neurotransmission.(Treiser et. al., 1981)(52) Lithium increases serotonin levels in mood disorders, such as bipolar disorder (Fyr et. al., 1975)(53) and major depression, and probably does the very same for PTSD. Lithium increased serotonin synthesis in rat brain by approximately 80%. (Perez-Cruet et. al., 1971)(54)

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My Lithium Thesis
It is my belief that the research herein robustly suggests that lithium is a primary controller-regulator of imbalanced stress hormones via the normalization of the dysregulated and or dysfunctional, hypothalamic-pituitary-adrenal and thyroid axes. As such, lithium may prevent and (on an individual basis) may even be experienced as a cure for many stress-related illnesses such as depression and PTSD. Again I am not promising that Lithium Orotate will cure your condition or any condition for that matter.

Introducing the Hypothalamic-Pituitary Axis (HPA) & Lithiums Effect upon the Hypothalamic-Pituitary Axis (HPA) Hypothalamic-Pituitary-Adrenal Axis (HPAA) & the Hypothalamic-Pituitary-Thyroid Axis (HPTA) in Major Depression, PTSD and Suicide
~PART ONE~
As stated in my thesis, it is my belief that the true power of lithium, to remarkably, often miraculously, promote healing of severe mental and neurological diseases such as bipolar disorder, Major Depression and PTSD, lies in lithiums direct and or indirect normalizing effect upon the dysregulated hypothalamic-pituitary axis (HPA) hypothalamic-pituitaryadrenal (HPAA) and thyroid axes (HPTA). Malfunction of the hypothalamus may give rise to sleep disorder, migraine and tension headaches, mood disorders (i.e. MDD, PTSD, bipolar disorder), anxiety disorders and eating disorders, to name a few of the vast number of stress-related conditions or illnesses, that may originate from a dysregulated hypothalamus. Before we look at the research regarding lithium and the HPA, allow me to give you some basic information about what the hypothalamus and pituitary glands are and what they do for the body. The hypothalamus and pituitary are the primary endocrine (hormonal) glands of the body that are located centrally within the brain. The hypothalamus is that area in the brain located centrally and below the thalamus attaching to the pituitary gland, connecting the endocrine (hormonal) glands to the rest of the central nervous system.

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Below is the hypothalamus and pituitary gland.

The hypothalamic-pituitary axis (HPA) is the neurological connection and coordination between the hypothalamus and pituitary gland. The primary job of the hypothalamus and pituitary gland is to coordinate the functions of all the other endocrine glands within the body; i.e., the adrenal gland, testes, ovaries, thymus, thyroid, stomach, liver and pancreas. The neurological circuitry and control of the hypothalamic-pituitary axis over the adrenal and thyroid glands are referred to as the hypothalamic-pituitary-adrenal axis (HPAA) and the hypothalamic-pituitary-thyroid axis (HPTA). While the thyroid gland is not traditionally thought of as a primary stress hormone endocrine gland; recent findings suggest that the thyroid (Hyper-thyroid) is intimately involved in the abnormal stress-response, of major psychiatric illnesses. These glands (hypothalamus and pituitary) are the two most important hormonal glands as they are primarily responsible for how the body responds to stress, both acute and chronic. Hormonally speaking the HPA is the master control center of the human body. It is from this central command post that all the functions of our stress response are coordinated. The hypothalamus is responsible for sending stimulatory or releasing hormones to the pituitary which in turn produces its own hormones, or stores hormones released from the hypothalamus. Once stimulated by the hypothalamic hormones, the pituitary hormones then travel to the adrenal glands, testes, ovaries, thyroid gland, stomach, liver and pancreas for the

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production of a multitude of primary hormones that control the entire human body in managing homeostasis (balance of bodily functions). If all of these glands are functioning optimally, the body maintains a near perfect balance (homeostasis) allowing for adjustments of all the bodily functions throughout our stressful day. However if there is a dysfunction/dysregulation of these glands, then the entire body will operate sub-optimally at best, or at worst, the body may exhibit numerous hormonal imbalances, stress-related symptoms and multiple degenerative diseases all at once. As you will learn pathologically imbalanced stress hormones are the most common shared finding of MDD, PTSD and suicidal behaviors. However, stress hormones as you will learn are not always too high, but in fact may be pathologically low (i.e., dysregulated). Typically what we find in the stress hormone profile of mood disordered patients are excessive levels of adrenaline, noradrenaline, cortisol, dopamine and thyroid hormones, but there are frequent exceptions to this rule. PTSD is one such condition in which cortisol levels may be significantly lower than the healthy normal population. Significantly low cortisol levels are just one of the many signs of a dysregulated hypothalamic-pituitary-adrenal axis. Medical researchers and medical doctors agree that excessive stress hormones are directly or indirectly related to the majority of disease processes; and it appears that lithium is working directly and or indirectly in the correction of the imbalance or dysregulation of the HPA. The most common finding in the medical conditions that lithium has been shown to assist, e.g. PTSD, is an imbalance of the primary stress hormones.

How does lithium normalize the dysregulated stress hormones adrenaline, noradrenaline, cortisol, dopamine and thyroid?
A preponderance of published evidence points to a lithium effect upon the hypothalamicpituitary axis. As you will see, it is now a widely held belief that lithium is normalizing a dysfunctional or dysregulated hypothalamic-pituitary axis (HPA), between the adrenal and thyroid glands. This is only a fraction of the evidence presented later in the book in Part Two of the hypothalamic-pituitary axis. (See Chapter 16 through Chapter 18; also Chapter 22 and 23)

Following are quotes from various researchers and authors of articles regarding lithium and the hypothalamic-pituitary-adrenal axis (HPAA), the hypothalamic-pituitary-thyroid axis (HPTA) and their relationship to PTSD, Major Depressive Disorder and suicide.
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The Hypothalamic-Pituitary-Adrenal Axis (HPAA)

Study title: The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians. (Varghese & Brown 2001) The data support that HPA axis activation is common in depressed patients. Evidence of HPA axis activation is associated with suicide. (Varghese & Brown 2001) (55) Study title: Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression. (Pfennig et. al., 2005) More than 70-80% of suicides occur in the context of depressive disorders, in which dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most prominent neurobiological findings. (Pfennig et. al., 2005) (56) Considerable evidence suggests that HPA dysregulation is involved in depressive disorders, alcoholism, and suicidal behavior. (Sher 2006) (57) The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behavior. (Jokinen and Nordstrom 2009) (58)

Lithium effect: Lithium has acute and chronic effects on the hypothalamic-pituitary-adrenal gland (HPA) axis that are important (e.g. in the treatment of mood disorders) (Spencer et. al., 2005) (59) Study title: Effects of lithium on the HPA axis in patients with unipolar major depression. (Bschor et. al., 2011) Both lithium monotherapy and lithium augmentation led to significant increase in the HPA axis activity. (Bschor et. al., 2011) (60)

The Hypothalamic-Pituitary-Thyroid Axis (HPTA)

Study title: Thyroid axis activity and suicidal behavior in depressed patients. (Duval et. al., 2010) Our results, obtained in a large sample of depressed inpatients, indicate that various degrees of Hypothalamic Pituitary Thyroid axis dysregulation are associated with the history of suicide. (Duval et. al., 2010) (61)

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Study title: Thyroid hormones and personality traits in attempted suicide. (Sinai et. al., 2009) These results indicate that Hypothalamic Pituitary Thyroid function may be related to Aggressiveness and Detachment in male suicide attempters. (Sinai et. al., 2009) (62) Lithium effect: Study title: The effects of lithium therapy on thyroid and thyrotropin-releasing hormone. (Lazarus 1998) It is probable that the Hypothalamic Pituitary axis adjusts to a new setting in patients receiving lithium. (Lazarus 1998) (63) Study title: Effect of chronic lithium treatment on hypothalamic-pituitary regulation of thyroid function. (Bagchi et. al., 1982) The data also provide indirect evidence that the effect of Lithium is exerted at the Hypothalamus. (Bagchi et. al., 1982) (64)

Following are additional quotes from various researchers and authors of articles regarding lithium and the hypothalamic-pituitary-adrenal axis (HPAA), the hypothalamic-pituitary-thyroid axis (HPTA) and their relationship to PTSD, MDD and suicide.
From the results of this study, it is suggested that the hypothalamus is one area where Lithium exerts its action. (Ozawa 1976) (65) Distorted activity of the hypothalamic-pituitary-adrenocortical (HPA) system is one of the most robustly documented biological abnormalities in major depression. We were able to demonstrate that lithium leads to a significant activation of the HPA system. (Bschor et. al., 2011) (66) Lithium treatment results in increased Hypothalamic Thyrotropin-releasing hormone. (Morley 1981) (67) Neuroendocrine studies in humans on the effects of lithium augmentation on the HPA system showed an unexpected and marked increase in the ACTH and cortisol response in the combined dexamethasone/CRH test. (Bauer and Bschor 2006) (68) Also, a decrease in cortisol level in Lithium responders and an increase in non-responders was observed, suggesting a regulatory effect of Lithium on the hypothalamic-pituitaryadrenal axis activity. (Rybakowski et. al., 1999) (69) Results suggest that lithium augmentation increases HPA system activity, (Baethge et. al., 2003) (70) Chronic administration of Lithium Chloride increased the expression of paraventricular nucleus of the hypothalamus (PVN). (Semba et. al., 2000) (71)

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The evidence was also presented that lithium may alleviate the immune-endocrine component concomitant to an acute affective episode, such as acute phase reaction, cytokine secretion and hyper-activation of hypothalamic-pituitary-adrenal axis. (Rybakowski 2000) (72) Abnormalities of the hypothalamic-pituitary-thyroid axis, some of which may become apparent only during treatment with lithium carbonate (Cowdry et. al., 1983) (73) We may conclude that successful prophylactic lithium therapy against depression is linked to a stabilizing effect on the hypothalamic-pituitary-thyroid axis. (Kjellman et. al., 1980) (74) Both hyper- and hypo-activity of the hypothalamus-pituitary-adrenal (HPA) axis activity are a consistently reported hallmark feature of stress-related disorders, such as major depression and posttraumatic stress disorder (PTSD). (Rohleder 2010) (75) Considerable evidence suggests that HPA dysregulation is involved in the pathogenesis of depressive disorders, alcoholism, and suicidal behavior. (Sher 2006) (76) The hypothalamic-pituitary-adrenal axis and the catecholaminergic (adrenaline/noradrenaline) system are involved in the pathophysiology of post-traumatic stress disorder. (Pervanidou et. al., 2007) (77) From the Center for Military and Veterans Health, comes the following from an article titled: Stress-related musculoskeletal pain. Extensive and chronic musculoskeletal pain may be explained by activation of the hypothalamic-pituitary-adrenal (HPA) axis due to stress. (McFarlane 2007) (78) Based on the concept that PTSD is a disorder of stress response systems, numerous studies have suggested changes in hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary (SAM) system function in patients with PTSD. (Pace and Heim 2011) (79) Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of major depressive disorder. (Boyle et. al,. 2005) (80) In the population studied, psychotic major depression, and non-psychotic major depression patients have distinct profiles of HPA axis dysregulation. (Posener et. al., 2000) (81) Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis is one of the most prominent neurobiological findings in major depressive disorder (MDD). (Aihara et. al., 2007) (82) Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol levels are characteristics of the pathophysiology of major depressive disorder. In the population studied, patients had distinct profiles of HPA axis dysregulation. (Piwowarska et. al., 2009)(83) The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with depression, probably at all levels of the axis. (Meador-Woodruff et. al., 1987) (84)

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Hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation is thought to be related to the development and course of depression. (Appelhof et. al., 2006)(85) HPA axis dysfunction is prevalent in patients with mood disorder, particularly those with psychotic disorders and bipolar affective disorder. (Abraham et. al., 2003)(86) Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has been well-described in mood disorders. (Young 2004) (87) Based on the observations that Major depression with psychotic features patients exhibit marked dysregulation of the HPA axis and elevated cortisol levels (Rothschild 2003) (88) The hypothalamo-pituitary thyroid (HPT)-axis is inhibited in depression.(Swaab et. al., 2005)
(89)

Evidence of a link between recurrent affective (mood) disorders and the hypothalamicpituitary-thyroid (HPT) axis has been frequently reported. (Tollefson et. al., 1985) (90) In the upcoming section we will discuss the SHRINKING BRAIN (atrophy of the hippocampus and other regions of the brain) in Major Depression, PTSD and Alzheimers which I believe may also be related to the dysregulation of the HPA. It appears from a preponderance of published evidence that lithium is a breakthrough remedy for the shrinking brain. The adaptive and maladaptive roles of the hypothalamic-pituitary-adrenal (HPA) axis in stressful conditions and in disorders such as major depression, posttraumatic stress disorder have been the subject of substantial, ongoing study. In particular, HPA disturbances have been associated with memory impairmentsatrophy of the hippocampus, a limbic structure closely associated with declarative memory. See: Therapeutic implications of HPA axis abnormalities in Alzheimer's disease: review and update. (Pomara et. al., 2003) (91) Study title: Clinical and magnetic resonance imaging correlates of hypothalamic-pituitaryadrenal axis function in depression and Alzheimer's disease. (O'Brien et. al., 1996) In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. (O'Brien et. al., 1996) (92)

The Lithium Breakthrough for the Shrinking Brain of MDD and PTSD!
Long-term chronic moderate and severe treatment-resistant MDD is a serious, degenerative brain disease that ultimately causes parts of the brain to shrink, e.g. (bilateral Hippocampus and the front of the brain known as the prefrontal cortex) in those people with recurrent moderate to severe MDD. (Cole et. al., 2010) (93) (Koolschijn et. al., 2009) (94)

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The following picture of the Brain/Hippocampus shows one side of the bilateral Hippocampus.

Smaller hippocampal volumes have been reported in:

Traumatic brain injury Cardiac arrest Dementia Alzheimer's disease Epilepsy Mild cognitive impairment Posttraumatic Stress Huntington's disease Cushing's disease Down's syndrome Bipolar disorder Parkinson's disease Major Depression Schizophrenia Alcoholism Borderline personality Obsessive-compulsive Anti-social personality

The shrinking Hippocampus is involved in memory loss and has been implicated in Alzheimers disease. As you will see, I am quoting from a study conducted in the UK, published in 2010 in the Journal of Affective Disorders. Study title: Subregional hippocampal deformations in major depressive disorder. (Cole et. al., 2010) Hippocampal atrophy is a well reported feature of major depressive disorder in patients with major depressive disorder who were all medication-free and in an acute depressive episode of moderate severity. Both right and left hippocampal volumes were reduced in patients relative to healthy controls.(Cole et. al., 2010) (93) Recent evidence is accumulating that small hippocampal volumes are associated as a risk factor for Alzheimers disease. Study title: The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? (Macqueen and Frodl 2011) Small hippocampal volumes are associated with poor clinical outcome and may be a mechanism through which MDD appears to be a risk factor for Alzheimer's disease. MDD must be re-conceived as a complex illness associated with persistent morphological brain changes that are detectable before illness onset (MacQueen and Frodl 2011) (95) Morphological brain changes refer to changes in size and shape of the brain.

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What about Gulf War veterans with chronic PTSD?

Study title: Hippocampal volume differences in Gulf War veterans with current versus lifetime posttraumatic stress disorder symptoms. (Apfel et al. 2011) Gulf War veterans with chronic PTSD were found to have on average, a (6.5%) smaller hippocampus compared to those who were recovered from PTSD. (Apfel et. al., 2011) (96) Over time, as the brain (Hippocampus) shrinks, the severity of the illness becomes intensely disabling, as the brain functions deteriorate.

When at some point the brain dysfunction becomes unbearably acute for the veteran, the idea to end their life actually offers psychic relief over unrelenting intense psychological pain.

Lithium to the Rescue; Essential in Maintaining and Restoring Atrophying Brain Mass!
NOTE: Lithium is the only known nutritive mineral element to birth new brain cells in animals and increasing brain mass in humans. (Millar 2012) The gray and white matter of the brain atrophies (shrinks) with normal aging and can even be seen in teenagers with depression. (MacMaster and Kusumakar 2004) (97) Lithium effect: In human studies of healthy normal populations, lithium has been shown to significantly increase brain mass in the gray and white matter. (98) Study title: Prefrontal gray matter increases in healthy individuals after lithium treatment: a voxel-based morphometry study. (Monkul et. al., 2007) Lithium treatment resulted in prefrontal regional gray matter volume increases in healthy volunteers, as well as increases in total white matter volume. (Monkul et. al., 2007 (98) A total of nine studies of lithiums effect in increasing brain mass in bipolar disorder have discovered consistent significant increases of brain volume. (98-106) Study title: Enhancement of hippocampal neurogenesis by lithium. (Chen et. al., 2000) The birth of new brain cells (neurogenesis) has been proven to occur in animals. (106) Here is what it looks like, when lithium grows new brain cells, as seen in an MRI image. The first picture is before lithium and the second picture is after lithium was added to the diet of animals. We dont have any human volunteers for dissection of their brain; therefore we dont have human photos showing the same.

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Before Lithium

After Lithium

You can clearly visualize a near doubling of the brain cells, after lithium (dark stain spots) representing new brain neurons (nerve cells). See at: (107) Lithium is the only known nutrient/mineral on our planet that grows new brain cells.
So this is the serious nature of unrelenting treatment-resistant depression high risk of suicide and The Shrinking Brain! And this is just one of the (many) critical breakthroughs of lithium supplementation (growing new brain cells, aka neurogenesis).

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Lithium is Critically Essential in All Mood Disorders!

Mood disorders, aka affective disorders, are those mental illnesses which predominantly (affect) mood and also have an effect on thoughts, behaviors and emotions. They include: Major depressive disorder, aka Unipolar depression and Dysthymia (mild chronic depression) Bipolar disorder aka manic-depression Atypical depression Postpartum disorders ************************************************************************ The conditions listed below are not classically designated mood disorders however they share many similarities, most importantly; they share the common finding of brain atrophy (shrinkage) that lithium has been demonstrated to reverse in many MRS (brain scan) studies of bipolar patients. For this reason alone (there are many others) it is my opinion that lithium should be prescribed to prevent brain atrophy in all the conditions listed below. Schizophrenia Schizoaffective disorder Schizophreniform disorder Anxiety disorders include: Post-traumatic Stress disorder, Agoraphobia, Panic disorder, Social Phobia, Generalized anxiety, and Obsessive Compulsive disorder. Certainly one of the most credible, internationally acclaimed researchers on the topic of lithium treatment for human health is Husseini Manji, MD, formerly the Director of the Mood and Anxiety Disorders Program at the National Institute of Mental Health. He is on record as stating that The use of lithium as a neurotrophic/neuroprotective agent should be considered in the long-term treatment of mood disorders, irrespective of the 'primary' treatment modality being used for the condition. (Manji 2000) (108) What Dr. Manji is suggesting here is that lithium should be utilized in every case of mood disorder regardless of a physicians favorite treatment regimen of mood disorders. From a former director of the Mood and Anxiety Disorders Program at the National Institute of Mental Health this is a rather monolithic decree for Dr. Manji to make. After 5,000 hours of researching the power of lithium to heal and nurture the brain and nervous system, I emphatically agree with Dr. Manji; however, I prefer to go a step further to state that lithium should be considered in the long-term treatment of all mood disorders as well as all neurological conditions with few if any exceptions.

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Because of lithiums unique abilities to prevent brain shrinkage, grow new brain cells, protect against toxic metals and many other neurotoxins I believe that

Lithium is the most powerful essential trace mineral ever discovered for optimal function of the brain and central nervous system. (Millar 2012)
Over-time as the brain (Hippocampus) shrinks, the severity of the illness may become intensely disabling as the brain functions deteriorate. When at some point the pain becomes unbearably acute, the idea to end their life actually offers psychic relief over unrelenting, intense psychological pain. Major depressive disorder is by far the most common psychiatric condition associated with suicide, being present in approximately 70-80% of all suicides. Indeed suicidal ideation, attempts and ultimately completed suicides are multifactorial in their causal orientation. The most common factors that trigger the final act, are usually a combination of two or more of the following elements: alcohol or drug abuse, divorce, death of a loved one, loss of a job or career, homelessness, incurable degenerative diseases (e.g. Alzheimers, ALS, cancer etc.), PTSD and finally, MDD.

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Chapter Seven

LITHIUM: The International Treatment of Choice for Depression and Suicide Prevention, a WorldWide Overview of Results.
Next we will take a deeper look at the world-wide studies and reviews of lithium as the international first-choice, front-line strategy for Treatment Resistant Depression, and we will look to meta-analyses on the subject to see the big picture. Meta-analysis is defined as a statistical analysis of combined (multiple) studies. Combining the results of several studies, allows for a more accurate analysis of research data, thereby reducing statistical errors.

Researchers worldwide agree that treatment involving lithium is the best way to protect patient from suicide risk.
(Pompili et. al., 2009, Harvard Medical School) See: Assessment and treatment of suicide risk in bipolar disorders. (1) Study title: The International Consortium on Lithium Genetics (ConLiGen): an initiative by the NIMH and IGSLI to study the genetic basis of response to lithium treatment. (Schulze et. al., 2010) Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Dept. of Health and Human Services, Bethesda, MD In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic 'fashions', and remains an indispensable element in contemporary psychopharmacology. (Schulze et. al., 2010) (2) Study title: Double-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression. (Bauer et. al., 2000) Neuropsychiatric Institute & Hospital, Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles 100% of patients receiving lithium remained in remission during the length of the doubleblind study period (4 months). None of the 14 patients who received lithium augmentation with antidepressants suffered a relapse during the double-blind phase of the study. (Bauer et. al., 2000) (3) Study title: After lithium augmentation: a retrospective follow-up of patients with antidepressant-refractory depression. (Nierenberg et. al., 1990) Department of Psychiatry, Yale University School of Medicine, New Haven, CT.

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A long term follow-up of 75 patients with treatment resistant depression revealed at 15 months that a total of 71% of patients treated with lithium had a good (48%) or fair (23%) response. (Nierenberg et. al., 1990)(4) Study title: Outcome in refractory depression. (Shergill 1999 ) Institute of Psychiatry, London, UK. We describe a 4-8 year naturalistic follow-up of patients treated with lithium augmentation in two controlled studies of its efficacy in refractory depression. There was a good outcome in 38 (72%) of the patients. (Shergill 1999 )(5) Study title: Lithium therapy for unipolar and bipolar depression among the middle-aged and older adult patient subpopulation. (Lepkifker et. al., 2007) Lithium Clinic, Psychiatric Division, Sheba Medical Center, Tel Hashomer, Israel. Lithium is found to significantly reduce major depression (as a monotherapy) in patients over 60 years of age. We examined the results obtained with long-term lithium maintenance in a group of 60 middleaged and older adult patients (age: 60 years) with unipolar depression and bipolar disorder. A significant reduction was found on all indices during lithium therapy compared to before lithium treatment, attesting to the prophylactic efficacy of long-term lithium in unipolar depression and bipolar disorder. (Lepkifker et. al., 2007)(6) Study title: Lithium augmentation for treatment-resistant depression in the elderly. (Lafferman, Solomon and Ruskin 1988) Dept. of Psychiatry, Lockraven VA Medical Center, Baltimore, MD A total response rate of 71% was achieved in the elderly population; 50% achieved complete remission and an additional 21% showed a fair to moderate response. Lithium augmentation appears to be a promising treatment for geriatric depressed patients who are unresponsive to, or cannot tolerate, other standard therapies. (Lafferman, Solomon and Ruskin 1988)(7) Article title: [Lithium augmentation for mianserin-resistant depression in the elderly]. (Schreiber and Shaley 1992) Dept. of Psychiatry, Hadassah-University Hospital, Ein Karem, Jerusalem. Price et. al., reported that 85% of 12 drug-resistant patients improved, when treated with lithium and mianserin. (Schreiber and Shaley 1992)(8) Mianserin is an antidepressant of the tetracyclic chemical class.

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Article title: [Antidepressive agents in the elderly]. (de Hooge 1990) Deltaziekenhuis, Portugal. Depressive disorders are the most common psychiatric illness in the elderly. Addition of lithium to a cyclic antidepressant can produce a rapid and lasting remission in patients with a major depressive disorder who do not respond to a cyclic antidepressant alone. (de Hooge 1990) (9) Study title: Lithium carbonate augmentation of desipramine in refractory depression. (Dallal et. al., 1990) Department of Psychiatry, Jewish General Hospital, Montreal, Quebec. A significant improvement was found in 13 of the 20 patients (65%) when lithium carbonate was added. (Dallal et. al., 1990)(10) Desipramine aka (Norpramin, Pertofane) is a tricyclic antidepressant that inhibits the reuptake of noradrenaline while lithium has been demonstrated to naturally increase noradrenaline levels when levels are low. Study title: Rapid response to the addition of lithium in iprindole-resistant unipolar depression: a pilot study. (de Montigny, Elie and Caille 1985) Canada All patients showed clinically significant improvement within 48 hours. The authors administered lithium carbonate, 900 mg/day, in an open study to seven patients with a major unipolar depression refractory (treatment resistant) to 3-week treatment with iprindole, 90 mg/day. All patients showed clinically significant improvement within 48 hours. (de Montigny, Elie and Caille 1985)(11) Iprindole aka (Galatur, Prondol, Tertran), is a tricyclic antidepressant. Article Title: Is lithium in a class of its own? A brief profile of its clinical use. (Malhi, Adams and Berk 2009) Discipline of Psychological Medicine, University of Sydney, Australia. Arguably, lithium is the only true mood stabilizer and because of its unique properties is in a class of its own. (Malhi, Adams and Berk 2009) (12) Study title: Lithium augmentation in treatment-resistant depression: clinical evidence, serotonergic and endocrine mechanisms. (Bschor et. al., 2003) Department of Psychiatry and Psychotherapy, Technische Universitt Dresden, Dresden, Germany In international treatment guidelines and algorithms, lithium augmentation is considered a first-line treatment strategy for patients with a major depressive episode who do not adequately respond to standard antidepressant treatment. (Bschor et. al., 2003)(13) Study title: Augmentation strategies for treatment-resistant depression. (Carvalho, Machado, and Cavalcante 2009) Department of Clinical Medicine, Psychiatry Outpatient Clinics, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil

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Lithium and triiodothyronine (T3) augmentation of tricyclic agents remains the best studied strategy. (Carvalho, Machado, and Cavalcante 2009)(14) Study title: Antidepressant augmentation and combinations. (Dording 2000) Depression Clinical and Research Program, Massachusetts General Hospital, Boston. A significant proportion of patients with MDD are treatment resistant or only partial responders to adequate therapy with a single agent. In this situation, one must consider augmentation with another agent. (Dording 2000)(15) ...lithium augmentation was concluded to be the first-line therapy for depressed patients who failed to respond to monotherapy. (15) Article title: [Treatment strategy of refractory depression and its presynaptic mechanism of action]. (Inoue et. al., 2003) Department of Psychiatry, Neural Function, Hokkaido University Graduate School of Medicine, Sapporo, Japan. Although there are only a few studies concerning the mechanism of action of augmentation therapy, recent studies demonstrated that sub-chronic lithium treatment increases basal concentrations of extracellular serotonin in the frontal cortex and hippocampus. Subchronic lithium further increases SSRI-induced increases in extracellular serotonin concentrations, and this effect is suggested to be the mechanism of action for lithium augmentation of antidepressants. (Inoue et. al., 2003)(16) Article title: Augmentation strategies for treatment-resistant depression: a literature review. (Carvalho et. al., 2007) Department of Medicine, Psychiatry Outpatient Clinics, Federal University of Cear, Fortaleza, CE, Brazil. The augmentation therapy with the best evidence was the lithium-antidepressant combination (Carvalho et. al., 2007)(17) Article title: Lithium augmentation therapy in refractory depression-update 2002. (Bauer et. al., 2002) Klinik fur Psychiatrie und Psychotherapie, Charite Campus Mitte Humboldt Universitat zu Berlin, Germany. Lithium is the foremost and most well-documented augmentation strategy in refractory depression. Therefore, it should be considered a first-line treatment strategy in patients with major depression who do not adequately respond to standard antidepressants. (Bauer et. al., 2002)(18) Study title: [Treatment of a refractory depressive episode]. (Bougerol et. al., 1993) Service de Psychiatrie d'Adultes, C.H.U. Sainte-Marguerite, Marseille, France. In some cases, adjunctive lithium leads to improvement of depressive symptoms very quickly, in 2 or 3 days. (Bougerol et. al., 1993)(19)

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Study titled: What to do if an initial antidepressant fails? (McIntyre et. al. 2003) Department of Psychiatry, University of Toronto, Ontario. The best established augmentation strategies are lithium salts. (McIntyre et. al. 2003)(20) Study titled: Lithium augmentation in venlafaxine non-responders: an open study. (Bertschy et. al., 2003) Clinic of Adult Psychiatry, Department of Psychiatry, Geneva University, Switzerland. When lithium was added to venlafaxine aka Effexor approximately 40% of the patients had a significant response while 60% of the responders had a rapid response. Effexor is an antidepressant in the class known as the serotonin-norepinephrine reuptake inhibitors. (Bertschy et. al., 2003)(21) With the preponderance of international recognition of the superiority of lithium treatment of treatment-resistant depression, one would think that American Veterans would be receiving the best of medical interventions; sadly that is not the case. Only 1 in 50 veterans are receiving lithium in the management of treatment-resistant depression. (Valenstein et. al., 2006)

Alternative M.D.S are routinely administering 10-40 mg of EL via LO; 1/10th the EL dosage with superior remission rates due to increased patient compliance and zero negative side effects!

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Chapter Eight

PTSD CHEMICAL IMBALANCES OVER-VIEW ~ PART ONE

What follows here is the complete list that I have compiled after identifying the major chemical pathways of imbalance and chemical molecules associated with PTSD. All totaled I have identified 33 different chemical pathways, or chemical molecules, associated with PTSD including; 11 major hormones, 4 major neurotransmitters, 6 neuropeptides (aka minor neurotransmitters), 2 neurotrophins, 3 enzymes, 2 Cellular Communication (Signaling) Systems and 2 inflammatory chemicals and 3 miscellaneous chemicals. Im sure that there are more than I have identified and I will add them as I find them. References provided in Chapters 22, 23 & 27

The most amazing fact is that lithium has been shown (as having a therapeutic effect) in all but one of the 33 chemical imbalances I have identified that are associated with PTSD.
The one unknown is Orexin-A. Lithiums effect upon Orexin-A has not been analyzed, yet. Lithium has been identified as having a normalizing, neutralizing and or stabilizing effect in 32 of 33 PTSD chemical imbalances.

How could lithium affect virtually all of the major chemical imbalances associated with PTSD?
One possibility is that lithium works from the top down, correcting the dysregulated hypothalamic-pituitary-adrenal and thyroid axes (HPAA/HPTA) and the primary stress hormones; allowing for renewed homeostasis of the entire nervous system. Following is the list of chemical imbalances that lithium has been demonstrated to normalize in animal and human studies. Hypothalamic Hormones Antidiuretic hormone (ADH) aka Arginine vasopressin (AVP) Corticotropin Releasing Hormone/Factor (CRF) Oxytocin Thyrotropin-releasing hormone (TRH) Hypothalamic Neuropeptides Enkephalin OREXIN A No data on lithium at this time. Pituitary Hormone Adrenocorticotropic hormone (ACTH)

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Pituitary Neuropeptides Delta sleep-inducing peptide (DSIP) Neuropeptide Y (NPY) Hypothalamic-Pituitary-Adrenal Axis (HPAA) Hormones Adrenaline Noradrenaline Dopamine Cortisol Hypothalamic Pituitary Thyroid Axis (HPTA) Hormones Thyroid hormones Triiodothyronine (T3) Thyroxine (T4) Miscellaneous Neurotransmitters, Neuropeptides, Neurotrophins, Enzymes and Other Chemical Imbalances Associated with PTSD Neurotransmitters Serotonin aka (5HT) Gamma-aminobutyric acid (GABA) Glutamate (GLU) Histamine Neuropeptides Angiotensin II Neuropeptide S (NPS) Neurotrophins Brain derived neurotrophic factor (BDNF) Vascular endothelial growth factor (VEGF) Enzymes AKT Ca2+/CaM kinase GSK-3beta Cellular Communication (Signaling) Systems Beta-cantenin signaling Protein kinase C signaling

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Inflammatory Chemicals Cytokines Interleukin-6 (IL-6) Miscellaneous PTSD Chemistry N-acetylaspartate (NAA) Cyclic adenosine monophosphate aka Cyclic AMP NMDA receptors
References provided in Chapters 22, 23 & 27

How could there be so many different causal factors of PTSD? Are these individual causes or a matrix of associated causes? I propose that they are neither. I propose that these chemical imbalances are an effect (not the cause) of a trickle down phenomena. In effect they are literally down-stream from the true cause of this condition. My theory is that lithium acts at the core primary cause of these associated imbalances by acting from the top down, inside and out. I believe that the research suggests that the primary cause of PTSD is a dysregulation of the hypothalamic-pituitary-adrenal and thyroid axes and related primary stress hormone imbalances. I believe (and the research demonstrates) the dysregulation of the HPAA and the HPTA are caused/created and sustained by a combination of extreme emotional, mental and physical traumas, coupled with inherent genetic and structural weaknesses, leaving the individual with emotional/mental memories within the brain, and physical cellular memories within the body. Maximal recovery from PTSD I believe can only be achieved by dealing directly with the dysregulated HPA, HPAA and HPT axes via lithium, coupled with cutting edge neuroreprogramming techniques. The horrific memories of severe traumas are burned into the memory and must be released and let go.

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Chapter Nine

Diseases Co-occurring (comorbid) with PTSD that Lithium has been demonstrated to benefit.
Post-traumatic stress disorder has been demonstrated to be associated and co-occurring (aka comorbid) with a wide range of stress-related diseases. In a study of PTSD veterans from the Vietnam War, it was determined that the number of chronic diseases were approximately 40% higher in the veterans with PTSD (67.5% for PTSD veterans opposed to 48.6% of non-PTSD veterans).(1) Most PTSD patients have at least one other psychiatric diagnosis, and large numbers of them have 3 or more psychiatric diagnoses.(2) The scientific research on the cause of these increased levels of chronic disease points to the dysregulated Hypothalamic Pituitary Adrenal axis and the Sympathetic Nervous System commonly referred to as the sympatho-adrenal axes. Dysregulation of these two systems contributes to dysregulated stress hormones adrenaline, noradrenaline dopamine and cortisol. Many studies have confirmed these findings and I will reference a few of them here.(310)

Reduced levels of serotonin also play a role in PTSD especially in the depressive state.(11,12) Chronically elevated levels of adrenaline, noradrenaline, and dopamine appear to be the main offenders in PTSD. Cortisol while initially elevated following traumatic stress may actually fall below normal levels over time causing symptoms of cortisol deficiency. Measurements of the levels of the hormones adrenaline, noradrenaline and dopamine have been consistently shown to be elevated in the urine, blood and cerebrospinal fluid. These changes weaken the immune system, making the body more susceptible to chronic diseases and chronically elevated adrenaline and noradrenaline and sympathetic nervous system activity may lead to higher incidence of arteriosclerosis and heart disease.(13) Here follows a few of the studies demonstrating sustained elevated levels of adrenaline, noradrenaline and dopamine in PTSD. Remember adrenaline is aka epinephrine and noradrenaline is aka norepinephrine. Study title: Sustained urinary norepinephrine and epinephrine elevation in post-traumatic stress disorder. (Kosten et. al., 1987) Urinary norepinephrine and epinephrine levels (microgram/day) were measured at two-week intervals during the course of hospitalization in the following patient groups: post-traumatic stress disorder (PTSD); major depressive disorder (MDD); bipolar I, manic (BP); paranoid schizophrenia (PS); and undifferentiated schizophrenia (US). The mean norepinephrine level during hospitalization was significantly higher in PTSD (76 +/- 10.4 micrograms/day) than in BP

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(60.6 +/- 8.4 micrograms/day), MDD (41.2 +/- 4.7 micrograms/day), PS (33.4 +/- 4.9 micrograms/day) and US (34.3 +/- 5.9 micrograms/day) groups The adrenaline levels were also higher for the PTSD patients than all other groups; PTSD (22.7 +/- 2.4 micrograms/day) BP (21.5 +/- 2.7 micrograms/day) MDD (13.6 +/- 1.7 micrograms/day) PS (14.7 +/- 2.4 micrograms/day) US (18.9 +/- 1.8 micrograms/day). (Kosten et. al., 1987) (3) Study title: Cerebro-Spinal Fluid noradrenaline concentrations in posttraumatic stress disorder. (Geracioti et al., 2001) This study measured noradrenaline levels of PTSD sufferers compared to a normal control group and found once again that noradrenaline levels are consistently and significantly higher than normal control groups. Additionally when noradrenaline normally begins to come down in the late afternoon and even more so during the sleep cycle, combat veterans continue to have elevated noradrenaline levels which appear to be the cause of sleep disorder, insomnia and nightmares. (Geracioti et al., 2001)(4) The graph below details the findings.

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The third study is titled: Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans. (Yehuda et. al., 1992) Catecholamines are the stress hormones adrenaline, noradrenaline and dopamine. Once again wer fine that decades after war, combat veterans are still carrying the disease of war with them. All three hormones were found to be significantly elevated in this group of 22 Vietnam veterans. (Yehuda et. al., 1992)(5) Lithium effect: Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline, dopamine (14-24) and cortisol. (25-28) Lithium has been demonstrated to possess the dual effect of decreasing noradrenaline during the anxiety manic state (14-19) and increasing noradrenaline in the depressed and normal-healthy populations. (20-22) The following data is a list of stress-related illnesses, conditions and symptoms that are commonly associated with PTSD. This is a short list of medical conditions that lithium is beneficial in managing. Included are the probable chemical effects that lithium has upon these illnesses, conditions and symptoms. Alcohol abuse Arthritis Asthma Arteriosclerosis Atypical Psychosis Back pain Bipolar disorder Chronic fatigue syndrome Chronic Pain disorder Depressed Immune system Diabetes Diarrhea/ Colitis Eczema Explosive disorder Fatigue Fibromyalgia Flashbacks Forgetfulness Gastro-esophageal reflux disorder Generalized anxiety disorder Headaches Heart disease Heavy metal toxicity Herpes infection Inflammatory bowel disease Insomnia Irritable bowel syndrome Neck Pain & Spasm Nightmares Osteoarthritis Panic disorder Peripheral Nerve Pain Restless Legs syndrome Rheumatoid arthritis Seborrhoeic dermatitis Shingles Social Anxiety Disorder Spinal Cord Injury Stroke Substance Abuse Traumatic Brain Injury Ulcer

Alcohol abuse Alcohol is a natural self-medicating solution for individuals with PTSD and is a common problem associated with this condition.(29) Once again we find scientific evidence of a relationship between dysregulated stress hormones and alcoholism. The hypothalamicpituitary-adrenal axis (HPAA) and the sympathetic nervous system activation of noradrenaline have been shown to be involved in multiple alcohol studies.(30-32) During alcohol abstinence alcoholics are found to have high levels of noradrenaline and dopamine.(33)
Lithium effect: As previously discussed lithium, is having a significant effect upon most stressrelated illnesses through lithiums influence of the dysregulated hypothalamic-pituitary-adrenal

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axis (HPAA) and the Sympathetic Nervous System, (SNS) sympatho-adrenal axis. Lithiums profound effect of reducing alcohol abuse is most likely due to lithiums stabilizing effect upon the HPAA and the SNS. Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline, dopamine (12-24) and cortisol.(25-28) Lithium may even have the potential to prevent alcoholism from developing in the first place. When lithium is included in their diet, animals also fed alcohol daily, have been prevented from becoming dependent upon alcohol, suggesting, that lithium may have the potential to prevent alcoholism in humans.(34) In a clinical study of the effects of LO in the treatment of alcoholism, it was found that lithium significantly reduced the use of alcohol and dramatically assisted the patients in maintaining abstinence from alcohol. This was a study of severe alcoholics most of whom had been hospitalized one or more times for the illness. Approximately a third of the study participants who remained in the program were without relapse for 1-10 years while another third remained without relapse for 1-3 years and the bottom third remained without relapse for 6-12 months. (35) Future lithium studies found that lithium promotes abstinence from alcohol, delays the time between relapses significantly reduces hospitalization.(36-39) I saved the best for last! Lithium has been demonstrated to prevent brain cell death from alcohol toxicity (in animals).(39,40) Human studies are underway and lithiums effect upon inhibiting GSK-3beta enzyme activity which is one of the keys to human neuro-protection.(41) Assuming the same is true for humans, this is very good news or those of you who insist upon a lifestyle of alcoholic beverages, as you can safely ingest low dose lithium before you drink alcohol and reduce brain cell toxicity and cell death. Be careful however, lithium does not prevent you from becoming drunk, so dont drink and drive.

Arthritis Arthritic conditions are common with PTSD.(42) Osteoarthritis is a common finding
particularly in veterans who have suffered physical injuries.(43,44) COX-2 inhibitors have become a popular therapy for arthritic pain conditions such as osteoarthritis. Rheumatoid arthritis is commonly associated with PTSD. Those suffering with the most severe PTSD symptoms had a rate of RA that was approximately 4 times the rate of those with mild PTSD symptoms.(45) Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to destruction of bone and cartilage. Considerable scientific evidence suggests that excessive production of prostaglandin E2 (PGE-2) (a lipid compound derived from fatty acids) contributes to the cause of RA. PGE-2 inhibitors provide some relief of rheumatoid symptoms. Lithium effect: Lithium is a natural COX-2 inhibitor without the side effects. Lithium has been shown to inhibit the enzyme activity and protein production of cyclooxygenase-2 (COX-2) and Prostaglandin E-2 (PGE-2) in the brain of rats.(46,47)

Asthma Asthma is frequently seen in PTSD.(42) Asthma is due in part to excessive histamine
levels and also appears to be related to brain levels of noradrenaline.(48)

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Lithium effect: In a placebo-controlled human study lithium reduced histamine and bronchial reactivity in airway smooth muscle, improved symptom scores and significantly reduced the use of inhalers.(49) Lithium significantly reduced the contractile effect of histamine on the tissues of the lung and trachea of guinea pigs.(50) Study title: Effect of oral lithium on bronchial reactivity in asthma. (Knox et. al., 1985) These findings suggest a potential clinical applicability of lithium for treating airway hyper-responsiveness. We conclude that lithium reduces bronchial reactivity in airway smooth muscle; this finding raises new therapeutic possibilities for the treatment of asthma. (Knox et. al., 1985) (49) As previously discussed, lithium normalizes levels of noradrenaline in humans and this may be another way that lithium is assisting asthma.

Arteriosclerosis Chronic PTSD is associated with increased risk of coronary artery disease.
(51-52)

Excessive arachidonic acid production may cause inflammation and arteriosclerosis of blood vessels in humans.(53)

Lithium effect: Lithium may prevent calcification of blood vessels in humans. Animals rendered lithium deficient in lab testing developed calcification of blood vessels. Study title: Lithium: occurrence, dietary intakes, nutritional essentiality. (Schrauzer 2002) (54) It has been suggested that lithium deficiency may be one of the causes of atherosclerotic heartdisease.(55,56) Study title: Does lithium depletion cause atherosclerotic heart-disease? (Voors 1969)(56) Lithium reduces excessive levels of arachidonic acid in rat brain. (57,58) Study title: Chronic lithium administration attenuates up-regulated brain arachidonic acid metabolism in a rat model of neuroinflammation. lithium might be considered for treating human brain diseases accompanied by neuroinflammation. (Basselin 2007)(57)

Atypical Psychosis Defined: The DSM-IV definition of atypical psychosis is a psychotic

disorder not otherwise specified. In other words it does not fit into a specific diagnostic class of psychosis. Symptoms may include confusion, agitation, delusional thinking and paranoid ideation. The atypical psychoses fall into two main groups: the schizoaffective and the paranoid (delusional) disorders. In schizoaffective disorder, symptoms of the two major psychoses occur during the same illness. Paranoid disorders are characterized by delusions without other evidence of schizophrenia.(59) Symptoms of psychosis may occur with chronic PTSD.(60,61) Lithium effect: Lithium may have a significant impact upon schizoaffective symptoms of delusional and paranoid ideation. In a study of hospitalized schizophrenics about 50% of the patients responded favorably to lithium.(62,63) Study title: A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients. (Small et. al., 1975) About 50% of the patients treated with lithium showed significant improvement. These results contrast with previous negative reports in the literature and the generally poor prognosis in chronic

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schizophrenic patients. The authors suggest that a trial combining lithium with psychotropic drugs is warranted in schizophrenic patients who do not respond satisfactorily to conventional treatment. (Small et. al., 1975)(62)

Back pain Pain syndromes, particularly back and neck pain are a common problem in PTSD.
Study title: Chronic posttraumatic stress disorder and chronic pain in Vietnam combat veterans. 80% of PTSD veterans report chronic pain. (Beckham et. al., 1997)(64) Elevated stress hormones adrenaline and noradrenaline activate pain syndromes. Excessive stress hormones dramatically increase muscle tension. Multiple studies of workplace stress and back pain have been conducted analyzing the relationship of mental stress, back pain and stress hormone levels. The researchers measured adrenaline and noradrenaline levels associated with work place stress, back and neck pain and discovered that mental stress increased levels of adrenaline/noradrenaline. Elevation of these hormones, adrenaline and noradrenaline was associated with a significant increase of back and neck pain.(65,66) Lithium effect: Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline and dopamine.(14-24) Lithium is not a pain killer in the traditional sense, but it does reduce the frequency and severity of pain episodes by reducing the excessive stress hormone load upon the nervous and musculoskeletal system. Furthermore lithium has been shown to increase dynorphin and enkephalins (naturally occurring opiates in humans) in rat brain. In some patients lithium can provide near miraculous relief for musculoskeletal pain syndromes. No large scale studies exist to give us statistical results however. Most results have been achieved by select physicians utilizing lithium in their clinics. It appears that lithium acts by reducing adrenaline and noradrenaline levels thereby providing pain relief. Robert T. Cochran Jr., author of Understanding Chronic Pain, describes how a patient with intermittent severe back pain found lithium to be an excellent solution to his problem. Lithium thoroughly relieved his often recurring severe back pain. The patient had no history of bipolar disorder.(67) Wise Young, Ph.D., M.D., at the W. M. Keck Center for Collaborative Neuroscience, reports that lithium reduces neuropathic pain.(68) Neuropathic pain is defined as a chronic pain as a result from an injury to the nervous system.

Bipolar disorder The PTSD population is also more likely to present with bipolar disorder.
Both conditions share a virtually identical hormonal profile as well as brain metabolic and degenerative changes. Lithium effect: A comprehensive review of contemporary research conducted in 2010 and published in the Harvard Review of Psychiatry, determined that Lithium is still the gold standard for the treatment of bipolar disorder.(70) In 1977 it was reported that the anti-manic drugs that treated mania all had the same effect of altering the catecholamines, (adrenaline, noradrenaline and dopamine). This is where
(69)

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lithium really shines! Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline, dopamine (14-24) and cortisol.(25-28) Lithium has been demonstrated to possess the dual effect of decreasing noradrenaline during the anxiety manic state (14-19) and increasing noradrenaline in the depressed and normalhealthy populations.(20-22)

Chronic fatigue syndrome (CFS) CFS has been linked to PTSD.(71) Fatigue in general is a
common problem associated with PTSD. Chronic fatigue syndrome like so many other stressrelated illnesses has the classic signs of a dysregulated hypothalamic-pituitary-adrenal axis (72-74) and the Sympathetic nervous system, demonstrating abnormal levels of adrenaline, noradrenaline and cortisol.(74-79) Study title: Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. There is evidence for a hypofunction of the hypothalamic-pituitaryadrenal (HPA) axis in a proportion of the patients with chronic fatigue syndrome (Van Den Eede et. al., 2007) (72) Lithium effect: Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline (14-19) and cortisol.(25-28)

Chronic Pain disorder Combat veterans from Vietnam were assessed for chronic pain syndromes. Of 129 Vietnam veterans with PTSD, 80% reported chronic pain. The most common was limb pain (83%), back pain (77%), torso pain (50%), and headache pain (32%).(66) Lithium has been demonstrated to be beneficial in limb pain.
Lithium effect: Animal studies have demonstrated that lithium is beneficial in the treatment of limb pain due to peripheral nerve and spinal cord injury.(80-81) Study title: [Effect of lithium salts on neuropathological syndromes of spinal origin]. (Grafova et. al., 1985)(81) Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline (14-19) and cortisol.(25-28)

Depressed Immune system In a study (Nikitina et. al., 2010) of 102 combat veterans with PTSD, the immune system was analyzed to ascertain what changes occur with posttraumatic stress. Over 60% of the participants were found to have depressed immune systems (especially lymphocytes) and most frequently infection (53.4%) and autoimmune (17.2%) syndromes.(82)
Lithium effect: Lithium has been discovered to produce profound improvement of immune function by increasing, white blood cell counts of granulocytes, (83) monocytes, natural killer Tcells, and immunoglobulins. Review of lithium effects on brain and blood. (Young 2009) (84) Lithium increases neutrophil production, increases platelet levels and lithium allows for greater chemotherapy dosing by elevating white cell production during chemotherapy.(85) Lithium has profound anti-viral properties against Herpes infections,(86) and significantly reduced the frequency and severity of herpes outbreaks.(87) Lithium decreases bleeding time.(83)

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Diabetes PTSD individuals are more likely to be diabetic.(42)

Lithium effect: Lithium has been demonstrated to significantly assist in the lowering of blood glucose in humans with diabetes mellitus.(88) Blood glucose was measured in Type II diabetic patients who were administered therapeutic dosages of lithium and the plasma glucose response was significantly reduced after lithium between 60 and 180 minutes. Measurement of the insulin/glucose ratios fell 17.3% at 60 minutes.(89) Lithium has been demonstrated to reduce hyperglycemia in bipolar patients.(90) It is suggested that lithium protects insulin-secreting pancreas cells.(91)

Diarrhea/ Colitis Diarrhea is a common symptom associated with PTSD and irritable bowel
syndrome. This is a common complaint amongst returning veterans of Operation Iraqi Freedom/Operation Enduring Freedom.(92) Irritable bowel syndrome (IBS) is associated with activation of the hypothalamic-pituitary adrenal axis and elevated levels of cortisol. IBS was found to have two elevated inflammatory cytokines IL-6 and IL-8. (93) IBS is associated by activation of the sympatho-adrenal system and elevated adrenaline and noradrenaline.(94) Lithium effect: Lithium works at the core of stress-related illnesses such as irritable bowel syndrome balancing the hypothalamic-pituitary adrenal axis and normalizing and regulating stress hormones adrenaline, noradrenaline (14-22) and cortisol.(25-28) Lithium has been shown to reduce inflammatory cytokines IL-6 and IL-8.(95-96) Lithium has also been demonstrated to improve symptoms of colitis and diarrhea in humans.(97-98) Lithium has demonstrated benefit to ulcerative colitis in humans.(98) Lithium is proposed as a new Anti-diarrheal therapy for humans.(99) Lithium appears to be a potential therapeutic for individuals suffering with Irritable Bowel syndrome.

Eczema Skin disorders such as eczema are common amongst PTSD patients. Primary care patients with PTSD were more likely to have had a number of specific medical problems, including anemia, arthritis, asthma, back pain, diabetes, eczema, kidney disease, lung disease, and ulcer. (Weisberg et. al., 2002) (42)
Oral lithium has not been researched for the treatment of eczema however one of my clients had a complete healing of a 20-year long condition of severe eczema over a large area of her body. She discontinued the LO on two separate occasions while traveling and found that the condition began returning within 7-days. On both occasions she resumed her lithium dosing and within 7days the condition vanished once again. She told me that without any doubt the lithium was responsible for the complete elimination of a 20 year condition that no other medication had previously corrected. Her dosage was four LO tabs per day. Now thats a testimonial!

Explosive disorder Intermittent explosive disorder is a potentially severe condition associated with PTSD and is all too common in this disorder. (61) Once again we find that Noradrenaline is elevated in aggressive impulse control disorders such as explosive disorder. (100) Elevation of noradrenaline and dopamine are noted in aggressive ADHD boys.(101) Hormonal levels of adrenaline and noradrenaline levels are significantly increased in aggressive individuals with high blood pressure.(102) 121

Long-standing alterations in the biologic response to stress may contribute to a number of complaints commonly expressed by patients with PTSD. For example, increased sensitivity and sensitization of the noradrenergic system may leave the individual in a hyperaroused, vigilant, sleep-deprived, and, at times, explosive state that worsens over time.(Southwick et. al., 1994) (103) Lithium effect: Lithium has been shown to be effective for explosive disorder and aggression in various populations including prison inmates, bipolar patients, mentally retarded, handicapped and conduct disordered children.(104) Lithium has been shown to be effective in aggression and explosive behavior in multiple studies.(105-108) Lithium works at the core of stressrelated illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline and dopamine.(14-24)

Fatigue Is a common problem amongst returning veterans of Operation Iraqi

Freedom/Operation Enduring Freedom.(92) Alterations of adrenaline levels have been related to fatigue. Feelings of physical fatigue and boredom are associated with low adrenaline levels, while feeling mentally tired is associated with high adrenaline levels.(109) Combined mental and physical stress is the most detrimental form of work stress causing significant effects on adrenaline and cortisol reactivity and recovery.(110) Alterations of noradrenaline levels are most related to tension and irritability associated with fatigue.(111) Fatigue is associated with HPA axis dysfunction and altered cortisol levels.(112) Lithium effect: Lithium works at the core of stress-related illnesses and symptoms of fatigue, balancing, normalizing and regulating stress hormones adrenaline, noradrenaline, dopamine (1424) and cortisol.(25-28) Lithium has been demonstrated to possess the dual effect of decreasing noradrenaline during the anxiety manic state (14-19) and increasing noradrenaline in the depressed and normal-healthy populations.(20-22)

Fibromyalgia PTSD is commonly associated with fibromyalgia.(73) A study of the incidence

and co-occurrence of fibromyalgia with PTSD found that forty-nine percent of PTSD patients, fulfilled the American College of Rheumatology criteria for Fibromyalgia syndrome. (113) Fibromyalgia is associated with a dysfunction in the hypothalamus-pituitary-adrenal axis and altered cortisol levels.(114) Noradrenaline and dopamine levels are imbalanced as well as.(115) Noradrenaline stimulates pain in fibromyalgia and this finding supports the hypothesis that fibromyalgia is a sympathetic nervous system syndrome. Study title: Norepinephrineevoked pain in fibromyalgia. A randomized pilot study [ISRCTN70707830]. (Martinez-Lavin et. al., 2002)(116) Lithium effect: Lithium has been demonstrated in the clinical setting to have a profound effect upon fibromyalgia significantly reducing the frequency and severity of pain.(117) Lithium works at the core of stress-related illness such as fibromyalgia balancing, normalizing and regulating stress hormones adrenaline, noradrenaline, dopamine (14-24) and cortisol.(25-28)

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Lithium has been demonstrated to possess the dual effect of decreasing noradrenaline during the anxiety manic state (14-19) and increasing noradrenaline in the depressed and normal-healthy populations.(20-22)

Flashbacks Are more common in the Gulf war veterans than in previous wars.(118) A study of
U.S. veterans found that (14.6%) of the study participants reported flashbacks in the month prior to examination.(119) Flashbacks are associated with elevated noradrenaline levels. The patients who experienced repetitive and recurring flashbacks had significantly higher plasma noradrenaline levels than those that have only one flashback (120-122) Lithium effect: Lithium reduces noradrenaline levels and this may have a significant effect upon (reducing or eliminating altogether) flashbacks as well as nightmares.(14-19)

Forgetfulness Is a common problem amongst returning veterans of Operation Iraqi

Freedom/Operation Enduring Freedom.(92) Memory problems are often related to the shrinking brain of PTSD. The shrinking of the hippocampus has been implicated in the memory loss of PTSD.(123-124) The combat veterans with PTSD were found to have a significantly smaller (8%) right hippocampus compared to the normal subjects, and this is consistent with deficits/loss of verbal memory.(125) Furthermore abnormal cortisol levels have been identified as a possible cause of this symptom.(124) Lithium effect: Lithium prevents the shrinking brain of the hippocampus and has been shown to restore the hippocampus after it has shrunk. The shrinking hippocampus has been demonstrated in numerous conditions such as bipolar disorder, major depression, schizophrenia and PTSD and lithium has been shown to increase the size of the hippocampus in bipolar disorder. (126) The PTSD/lithium study remains to be conducted. Lithium has also been shown to increase the neocortical gray matter volume in first episode psychosis on average 3.6%.(127) Furthermore a lithium study on healthy individuals found that lithium expanded brain tissue in the gray and white matter of the prefrontal cortex in healthy individuals.(128)

Gastro-esophageal reflux disorder (GERD) aka acid reflux The classic symptoms of GERD are heartburn and acid regurgitation. GERD is frequently associated with PTSD. The frequency of GERD is 3 times higher in anxious and depressed populations.(129)
Some studies have examined the psychological factors such as coping skills and the association with GERD. Coping skills are an important factor in determining responses to stressful events and the illnesses associated with poor coping are classically psychological symptoms (anxiety/depression) and physical conditions such as GERD.(130) It has been hypothesized and verified in research that if a individual is not allowed to express anger or to deal positively with that situation that provoked anger this will frequently lead to physical illness.(131) Lithium effect: Lithium has not been studied in GERD populations however due to the connection of GERD with anxiety and depressive disorders lithium will likely offer some measure of relief as GERD is related to the dysregulated stress hormones of anxiety and depression.

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Generalized anxiety disorder (GAD) GAD is frequently co-occurring with PTSD and may occur in 40% of the PTSD population a rate 12 times that of the general population. (132) According to the National Institute of Mental Health, GAD affects about 6.8 million American adults. GAD is characterized by at least 6 months of frequent worries. Symptoms commonly include poor concentration, irritability, fatigue, muscle tension, restlessness, and unsatisfying sleep.(133) Activation of the hypothalamic-pituitary-adrenal and the sympatho-adrenal axes are involved in this disorder.(134) GAD is associated with abnormal adrenaline, noradrenaline, cortisol and serotonin levels.(135-139)
Health Alert: If you have Generalized Anxiety Disorder you must protect your brain from shrinkage! A 2010 study reveals extreme loss of brain mass. Study titled: Reduced amygdalar and hippocampal size in adults with generalized social phobia. (Irle et. al., 2010) Department of Psychiatry and Psychotherapy, University of Gttingen, Gttingen, Germany. In this study German researchers reveal that patients with generalized social phobia were found to have lost 13% of the volume from the amygdala and 8% from the hippocampus. (Irle et. al., 2010) (140) The amygdala is intimately involved with emotional and memory processing and sends critical signals to the hypothalamus (a major hormonal control center) for the activation of the sympathetic nervous system. The hippocampus plays a critical role in converting short-term memory to long-term memory. The hippocampus controls spatial navigation and is an area affected by Alzheimers disease. Both parts are critical for normal human functioning particularly with regard to memory and emotion. You dont want to lose function of your amygdala or hippocampus. Thankfully lithium is here to save the day. Lithium effect: Bipolar patients taking lithium were found to have significantly increased hippocampal and amygdala volume when compared to bipolar patients not treated with lithium and healthy comparison subjects. This was a large study, a mega analysis of over 300 bipolar patients and over 400 controls.(141) Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline (14-22) and cortisol.(25-28) Lithium increases serotonin levels in patients with mood disorders.(23)

Headaches 32% of Vietnam veterans report headache pain.(142) Of the veterans returning
from Afghanistan and Iraq, 40% report current headache, 10% had a diagnosis of Migraine and 12% a diagnosis of Tension-type headache. Study title: PTSD, combat injury, and headache in Veterans Returning from Iraq/Afghanistan. (Afari el. al., 2009)(143) For veterans over 50 years of age a headache that occurs during sleep known as the Hypnic headache may become a problem. Lithium effect: Lithium has shown in multiple studies to benefit migraines.(144-146) In a study of cyclical migraine nineteen out of 22 patients (85%) responded and showed significant improvement of frequency and severity of migraine headache. 25% of the patients has complete remission of their migraine headaches and the remaining had a 50-75%

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reduction.(147) In cluster headaches (the most severe type of headache) lithium is mentioned repeatedly in the research to be effective and used as a preventative on a daily basis.(148-150) Hypnic headaches have shown to respond well to lithium as a preventative.(150) Tension headache has not been studied with regard to lithium therapy, however the stress hormones (adrenaline, noradrenaline and dopamine) have been demonstrated to be dysregulated in tension headache and lithium normalizes these stress hormones.(14-24) Furthermore serotonin deficiency appears to be a cause of tension headaches and lithium increase serotonin levels.(23) Nitric oxide has been implicated in migraine, tension and cluster headache. Pharmaceuticals that block the production of nitric oxide effectively treat all three types of headache (151) fortunately, animal studies have shown that lithium blocks or reduces nitric oxide.(152,153)

Heart disease PTSD veterans have as significant increased risk of cardiovascular diseases including hypertension, chronic ischemic heart disease and arteriosclerosis.(154) PTSD is associated with a 20% increase in mortality from heart disease.(1) Individuals with a current PTSD diagnosis have higher resting heart rate than trauma-exposed individuals without PTSD and mild elevations in blood pressure.(155) PTSD patients also have a significantly higher risk of circulatory disorders and heart disease.(1,73)
For veterans in the conflicts in Iraq and Afghanistan newly reported hypertension was identified in 6.9% of the group between baseline and follow-up.(156) Rates of hypertension, (high blood pressure) are higher in PTSD patients than non-PTSD populations.(157) Chemical imbalances associated with hypertension (high blood pressure) include (but not limited to) stress hormones adrenaline, noradrenaline, cortisol and atrial natriuretic peptide. A study measuring these stress-hormones (adrenaline, noradrenaline and atrial natriuretic peptide) in hypertensive patients found the adrenaline levels to be approx. 30% higher, noradrenaline 70% higher and atrial natriuretic peptide approx 30% higher when compared to normal subjects (normal blood pressure). The authors suggested that the increased levels of atrial natriuretic peptide were likely compensatory for the vasoconstricting (blood vessel constricting) effects of the elevated noradrenaline levels.(158) Those patients with the highest noradrenaline levels related to heart disease have the worst future outcomes.(159) It is imperative to get the stress hormones, particularly noradrenaline and cortisol normalized as soon as is possible. Lithium effect: Lithium has been demonstrated to prevent calcification of the blood vessels (Arteriosclerosis).(56) Lithium depletion/deficiency has been demonstrated to be linked to atherosclerotic heart-disease in humans. In areas where lithium is contained in municipal water supplies the incidence of atherosclerotic heart disease is reduced. Lithium has been demonstrated to have a beneficial effect on four out of five atherosclerotic-heart-disease risk factors.(57) Lithium has been demonstrated to protect against ischemia (lack of blood flow to the brain, heart and kidneys) areas prone to damage from embolism, blood clots, stroke and heart attack. (160-162)

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High blood pressure is made worse by excessive stress hormones. Lithium normalizes the stress hormones involved in heart disease, adrenaline, noradrenaline (14-22) and cortisol.(25-28)

Heavy metal toxicity is well known to cause numerous psychological disorders such as depression, anxiety and excessive anger.(163) Heavy metals attack the mitochondria (energy factory) of the cell causing severe loss of respiratory function and mitochondrial swelling leading to increased production of free radical damage. Toxic metals are interacting with, and altering major cellular biochemical systems at low dose levels that may not produce signs of obvious metal toxicity.(164) Mercury is perhaps the worst offender causing neurological and psychological symptoms, (163) however aluminum, arsenic, cadmium, lead and uranium also have similar effects upon the nervous system as well.(165)
Lithium effect: Lithium also provides robust protection from heavy metal toxicity. Lithium has been shown to protect cells from aluminum, (166-167) arsenic, (168) cadmium, (169) lead (170) and mercury toxicity.(171-172) Animal studies have shown a wide array of protection by lithium to every single toxic metal analyzed thus far. Lithium protects cells from toxic metal damage via multiple chemical pathways. One of the most impressive protective actions is lithiums blocking of cellular uptake of the toxic metals into the nucleus of the cell where the metals have a genetically mutating effect.(173) One study revealed that lithium actually blocked the uptake of mercury reducing the intracellular concentration of mercury by 45% (171) and another study provided similar results.(172) Furthermore, lithium protects nerve cells from toxic metals by stimulating the production of BCL-2 (a nerve protecting protein), superoxide dismutase (SOD) (a super-antioxidant) and glutathione (super-antioxidant) by nerve cells. Increased production of BCL-2, SOD and glutathione by lithium protects nerve cells from numerous neurotoxins.(174-176) Finally, lithium has been demonstrated to act as a chelating agent (removing toxic metals from the body) in the removal of mercury and aluminum (177-178) and has been used to remove uranium from chemical solutions.(179)

Herpes infection Lithium has profound anti-viral properties against Herpes infections
and significantly reduced the frequency and severity of herpes outbreaks. Study title: Suppression of herpes simplex virus infections with oral lithium carbonatea possible antiviral activity. (Amsterdam et. al., 2012) Overall, lithium treatment resulted in a consistent reduction in the mean number of episodes/month, the average duration of each episode, the total number of infection days/month, and the maximum symptom severity.(87)
(86)

Inflammatory bowel disease (IBD) Crohns disease and ulcerative colitis are diseases of
the inflammatory bowel. Once again we find evidence that the sympatho-adrenal axis and elevated adrenaline and noradrenaline is associated with this stress-related illness.(180) Nitric oxide is significantly elevated in IBD, well over ten times the levels of normal healthy patients and is significantly reduced by effective anti-inflammatory treatment.(181) This buildup of nitric oxide is believed to be part of the chemical cause of inflamed mucosal tissue in the human body.

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Lithium effect: Lithium has anti-inflammatory effects upon the bowel.(182) Lithium has demonstrated benefit to ulcerative colitis in humans.(183) Lithium has been shown to decrease symptoms of IBD in children.(184) Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline and noradrenaline.(14-22) Lithium, a widely used drug in bipolar-affective disorders, plays gastro-protective roles. The effects of lithium on several tissues are mediated through nitric oxide See: Antinociceptive effect of chronic lithium on visceral hypersensitivity in a rat model of diarrhea-predominant irritable bowel syndrome: The role of nitric oxide pathway. (Shamshiri et. al., 2009)

Irritable bowel syndrome (IBS) is a chronic disorder that has been found to be associated
with PTSD and a history of physical and/or sexual abuse. Diarrhea is a common condition associated with PTSD. (124) In a study of irritable bowel syndrome is was determined that 36% of the subjects also suffered with PTSD and 44% had a history of trauma.(185) In a study of female veterans with PTSD, 38% were found to have IBS and 21% suffered with indigestion.(186) Study title: Irritable bowel syndrome and dyspepsia among women veterans: prevalence and association with psychological distress. (Savas et. al., 2009)(186) IBS was found to have two elevated inflammatory cytokines IL-6 and IL-8.(187) IBS is associated with activation of the hypothalamic-pituitary adrenal axis and elevated levels of cortisol.(188) IBS is associated with activation of the sympatho-adrenal system and elevated stress hormones adrenaline and noradrenaline.(189) Lithium effect: Lithium works at the core of stress-related illnesses such as irritable bowel syndrome balancing, normalizing and regulating stress hormones adrenaline, noradrenaline (1422) and cortisol.(25-28) Lithium has been shown to reduce inflammatory cytokines IL-6 and IL-8. (190-191) Lithium has also been demonstrated to improve symptoms of colitis and diarrhea in humans.(191-192) Lithium has demonstrated benefit to ulcerative colitis in humans.(192) Lithium is proposed as a new anti-diarrheal therapy for humans.(193) Lithium appears to be a potential therapeutic for individuals suffering with Irritable Bowel syndrome.

Musculoskeletal complaints 80% of Vietnam veterans with PTSD report chronic pain of
the arms and legs and 77% are living with back pain.(66) Chronic stress-related musculoskeletal pain and stiffness has been linked to alterations of the hypothalamic-pituitary-adrenal (HPA) axis and prolonged activation of the sympathetic-adrenal medullary system (SAM). The dysregulation of the HPA and SAM leads to abnormal levels of adrenaline, noradrenaline and cortisol and these stress-hormones have been demonstrated to cause musculoskeletal pain and stiffness.(68,194-195) Serotonin deficiency may also cause musculoskeletal pain and stiffness.(196) Lithium effect: Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline (14-19) and cortisol.(25-28) Lithium increases serotonin levels.(23)

Neck Pain & Spasm Neck pain and spasm is commonly associated with PTSD.(66)
Lithium effect: Lithium has shown some benefit in neck pain and spasm associated specifically with spasmodic torticollis.(197-199)

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Nightmares Combat veterans are frequently plagued by recurring nightmares. As much as

90% of PTSD patients in general have a sleep disorder and as many as70% of them have nightmares.(200,201) Research strongly suggests that nightmares are caused by a dysregulated norepinephrine system and excessive noradrenaline levels (202-204) The most effective pharmaceutical treatment for the relief of nightmares has been shown to be a drug called Prazosin. Prazosin has been shown to block the neurotransmission of noradrenaline.(204) In a recent study of veteran nightmares, prazosin completely eliminated nightmares for approximately 90 % of veterans.(205) Lithium effect: Lithium works at the core of the cause of nightmares reducing excessive noradrenaline levels.(14-19)

Osteoarthritis (See arthritis above) Panic disorder Panic disorder is frequently co-occurring with PTSD in approximately 6% of
PTSD patients, a rate that is approximately 4 times the general population.(85,164) Panic disorder is a severe complication when it co-occurs with PTSD. 96% of patients with both disorders have nightmares and 100% of them have insomnia.(206) Panic disorder is another stress hormone related condition similar to PTSD in which adrenaline and noradrenaline levels are significantly elevated.(3,207-209) Adrenaline levels were found to be 3 times higher in panic disorder patients and also had elevated levels of noradrenaline, compared to healthy controls.
(210)

Lithium effect: Lithium reduces adrenaline and noradrenaline levels.(14-19)

Peripheral Nerve Pain (PNP) PNP is commonly due to direct injury of nerves in the limbs or spinal cord area and lithium has been demonstrated in animals to be very beneficial in the treatment of PNP due to injury of the nerves.(83,84) Restless Legs syndrome This condition affects approximately 5% of the adult population.
I personally suffered with severe restless legs syndrome until I began taking LO and have experienced a complete remission of this condition. Reduced levels of dopamine are believed to be causing restless legs syndrome. Dopamine drugs are usually the first-line therapy.(211) Lithium effect: Lithium does not block or inhibit the reuptake of dopamine and therefore has no unnatural side effects. Lithium naturally normalizes dopamine levels.(23,24)

Rheumatoid Arthritis (See arthritis above) Seborrhoeic dermatitis (SD) Lithium succinate as a topical cream has been shown to be very effective in the treatment of SD.(212) Low-dose oral lithium may also be helpful. Shingles Shingles are caused by the varicella zoster virus a part of the herpes virus family. Lithium has been demonstrated to suppress the herpes virus and reduce outbreaks caused by the herpes virus. (87) Preventing shingles outbreak with lithium supplementation has not been researched, however patients report significant relief from the pain and itching caused by the shingles outbreak by utilizing Lithium Orotate. 128

Lithium effect: One substance that I have found to be surprisingly effective for shingles is Lithium Orotate. Three-four capsules daily have been reported to help dramatically with these sometimes disabling pains. Lithium Orotate seems to greatly reduce the pain and itiching of post-herpetic neuralgia which can linger for months and years after the lesions of shingles have resolved. (Ward Dean M.D.) See: (Shingles) & (Shingles)

Social Phobia or Social Anxiety Disorder (SAD) SAD is frequently occurring with PTSD
in approximately 17% of cases.(164) Once again we find the activation of the Sympatheticadrenal system, causing a significant rise of adrenaline and noradrenaline related to SAD. Multiple studies have shown this disorder is related to and perhaps caused by, abnormally high levels of circulating adrenaline and noradrenaline.(213-216) A recent article on the effective treatments for SAD (Westenberg 2009) describes SSRIS as the first-line therapy and anticonvulsants as a second-line therapy.(217) These are two chemical pathways that lithium functions well in; serotonin production and anticonvulsant properties. Lithium effect: No studies exist for lithium treatment in SAD however the main chemical imbalances associated with SAD are adrenaline, noradrenaline and serotonin. Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline, noradrenaline (14-19) and the neurotransmitter serotonin.(23)

Spinal Cord Injury Traumatic brain injury and spinal cord injury are pervasive amongst the veteran population and are devastating if not recovered from. There is hope through recent research in how lithium promotes healing of damaged brain, nerve and spinal cord tissue.
The most exciting research being performed in this area is happening at the W.M. Keck Center for Collaborative Neuroscience, by Wise Young PH.D., M.D. Dr. Young reports that this is a very exciting development for those with spinal cord injury and paralysis. His works suggests that lithium promotes the regeneration of traumatized nerve cells and may provide a breakthrough in healing for this crippling condition. Dr. Young reports that lithium reduces neuropathic pain.(68) Neuropathic pain is defined as a chronic pain as a result from an injury to the nervous system. A research team At the Keck Center discovered that lithium stimulates umbilical cord blood cells to grow differentiate and produce neurotrophins which promote regeneration. The idea now is to study umbilical cord blood mononuclear cells and lithium treatment of chronic spinal cord injury in ChinaSCINet. Dr Young points to recent breakthrough research that demonstrated the miraculous ability of lithium to promote (regenerate) the growth of neural stem cells and axonal regeneration in the traumatized spinal cords of rats.(218-220) ChinaSCINet is carrying out the first clinical trials of combination therapies of spinal cord injury, i.e. umbilical cord blood mononuclear cells (UCBMC) and lithium.(221)

Stroke In a study of WWII veterans it was determined that veterans with PTSD had a 70% higher rate of stroke than non-PTSD veterans.(222)

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Lithium effect: Lithium has been shown in animal studies to produce amazing protection against brain cell death due to stroke.(223) The area of tissue death was reduced by 56% by lithium pretreatment.(223) Lithium also promotes remodeling of damaged nerve tissue after stroke.(224) Perhaps the most exciting finding of lithium treatment comes after the stroke occurs. Lithium treatment given after (post-stroke) the stroke has occurred produces amazing recovery of the brain tissue, dramatically reducing brain cell death. Lithium reduces brain damage and produces neurological recovery.(225) Furthermore, lithium promotes the growth of new blood vessels around the stroke area enhancing swift recovery. Lastly lithium enhanced the blood oxygenation levels as well.(226)

Substance Abuse Substance abuse is a significant complication of PTSD. Sixty-to-80% of

patients suffering from PTSD have been found to suffer with substance abuse problems, such as the use of alcohol, cigarettes marijuana, opiates and other central nervous system depressants. (29,227) This is likely due to the fact that PTSD individuals have a hyperactive sympathetic nervous system and these drugs act as depressants of the central sympathetic stress hormones (adrenaline and noradrenaline) activity, thereby temporarily relieving PTSD symptom. In a study of veterans with PTSD it was determined that 48% of veterans with PTSD were heavy smokers (smoking greater than 25 cigarettes a day) as compared to 28% of veterans without PTSD.(228) The compulsivity of addictions appears to be primarily driven by excessive levels of noradrenaline.(229) Lithium effect: Lithium works at the core of stress-related illnesses balancing, normalizing and regulating stress hormones adrenaline and noradrenaline.(14-22)

Traumatic Brain Injury Lithium has been demonstrated to promote nerve cell regeneration
following trauma. (See spinal cord injury)

Ulcer Ulcers are commonly reported in patients with PTSD.(49) This is certainly another
stress-related illness with the classic signs of hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary (SAM) dysfunction; correlating with all the classic imbalances of the primary stress hormones, adrenaline, noradrenaline, dopamine, and cortisol. Levels of these stress hormones have all been found to be excessively high in relapsing ulcer patents.(230) Particularly adrenaline and noradrenaline appear to be the main offenders.(231235)

Drugs that have been found to be effective at reducing ulcers have been found to reduce noradrenaline levels.(236,237) Lithium effect: Lithium works at this core of stress-related illness balancing, normalizing and regulating stress hormones adrenaline, noradrenaline, dopamine (14-24) and cortisol.(25-28) In the study of the lithium response to ulcers in humans, lithium was so effective at healing that it was proclaimed as exceeding the standard anti-ulcerative therapies.(238) When the effect of alcohol upon ulcers was examined in animals receiving lithium, it was discovered that lithium significantly reduced the alcohol-induced hemorrhagic gastritis, aka (bleeding ulcer).(239)

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Chapter Ten

The Big Lie!

(The Pharma-Cartel Lithium Conspiracy)
If you tell a lie long enough, loud enough and often enough, eventually the people will believe it. This is a famous quote by Hitler and his propaganda minister Joseph Goebbels. This has proven to be true of the lie about Lithium. The Big Lie is this. Lithium is a toxic drug. The Pharma-cartel has intentionally programmed the American public with this lie for decades in hopes that we would never discover the truth that lithium is the most powerful essential trace mineral for optimal neurological health. Furthermore, lithium has also been proven to be an essential mineralin animal studies. When lithium was removed from the diet of farm animals they developed numerous chronic degenerative diseases, such as atrophy of the spleen, development of cysts and tumors, severely depressed immunes systems, inability to conceive offspring (sterilization), and when they did conceive they produced significantly fewer and smaller pups that had a much lower survival rate. Additionally the mothers quantity of breast milk was diminished. Study title: Lithium: occurrence, dietary intakes, nutritional essentiality. (Dr. Schrauzer 2002) (1) See Dr. Schrauzers full study report at: (Full report)

The lie that lithium is a drug began to be told soon after it was discovered in 1949 that lithium cured the psychosis of manic depression aka bipolar disorder. The discoverer of lithiums effect upon psychotic patients was an Australian psychiatrist/researcher named Dr. John Cade. Dr. Cade initially indicated that he believed that he had discovered a mineral deficiency disease. Dr. Cade understood that lithium was a mineral, not a drug. I believe that he discovered, through his research, that lithium is an essential mineral for neurological health. For some, as of yet unknown reason, (I will give you my thoughts on this later) the idea that lithium deficiency causes mental illness was dropped. Why was this idea abandoned? Does the Pharmaceutical industry and medical profession want us taking minerals for disease prevention? I dont think so! The knowledge that mineral deficiencies cause disease and the action of individuals taking personal responsibility for ameliorating this fact certainly does not help the pharmaceutical industry sell more drugs! To this day (to the best of my knowledge) there has been no further discussion within the medical community that a deficiency of lithium may contribute to the cause mental illness. I find that very curious; dont you? We know that mineral deficiencies cause numerous chronic degenerative diseases, so why would the same not be true for mental and neurological illnesses?

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I repeat the Big Lie is; Lithium is a toxic drug!

The truth is, Lithium is neither a drug, nor inherently toxic. What is true is that, lithium is given to bipolar patients in such poorly absorbed forms, (carbonate, chloride, or citrate) that the dosage is 10 times over what should ever be in the blood. It is estimated by some doctors and scientists that as little as 5-10 % of the Pharma-Li is absorbed into the interior of the brain cell (plasma) while the rest is either trapped in the outer cell membrane or in the blood stream. But this is the amount required (200-400 mg of EL) of the pharmaceutical version, to stabilize a bipolar patient and is considered to be the gold standard treatment of bipolar illness, within the international medical community. It is critical that you understand this important scientific fact. All nutritive elements and medicines have a toxic limit. I know of no exceptions. When you give a human being 10 times more (of any substance) of the maximum amount of what is good for them, you will inevitably cause a toxic reaction within the body. If this toxicity is continued over a prolonged period of time, this will lead to tissue damage and may ultimately end in organ failure. Such is the case for a minority of bipolar patients who have been forced to take excessive amounts (over 150 mg/day of EL) for years or decades. Science has learned that one to two ounces of alcohol/day is a beneficial medicine for the human body. But that is the maximum that is good for you. However if you ingest 10-20 ounces of alcohol/day, (as we all know) this will eventually cause brain, kidney and liver disease, to say the least. The same is true of drinking too much water. Water drinking contests have killed people. And the same is true of lithium. Twenty to forty milligrams (20-40 mg) of EL/day is a highly beneficial amount of this nutrient for the human body. However doctors are routinely prescribing Pharma-Li to patients in doses of 200-400 mg of EL/day, a toxic amount for the blood. I repeat, over time this leads to toxicity within the cells, causing tissue damage that may ultimately lead to organ failure. Patients, who take over 200 mg of EL via Pharma-Li, frequently express their significant dislike of the toxic side effects. Yet children 12 years and older are routinely administered Pharma-Li at a dose of 200mg of EL/day and adolescents over 250 mg of EL/day to control symptoms of bipolar disorder and violent behavior. This is an FDA approved therapy for children and is generally recognized as safe and is very effective in the treatment of this condition. (2) Through my research on this subject, I believe that the maximum amount of lithium that is good for you (conservatively speaking) is approximately 3 mg/10lbs of body weight. I personally have routinely taken 3.5 mg/10lbs of body weight (up to 60 mg/day) of EL, and the only side effect I have experienced while taking the larger doses, is mild muscular weakness, noted in my grip strength. The trade off is that I am relaxed all the time. I will take a little loss of my grip strength for peace and calm any day of the week. Most of us have heard the stories of super human strength that individuals have displayed in times of emergency. This is due to dramatic increases of adrenaline. As expected, as lithium lowers adrenaline and noradrenaline, as it does naturally, muscular strength declines.

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The side effect of mild muscular weakness is due, I believe, to the direct effect that lithium has upon lowering adrenaline levels. I do not believe this to be a sign of toxicity, and I do not believe this to be a side effect that we need be concerned about. This is one way that lithium may act to significantly slow the aging process. Lowered adrenaline levels leads to slower aging by slowing degenerative metabolic processes. It is a well documented scientific fact that chronically high levels of stress hormones, adrenaline and cortisol, lead to premature aging and disease. For those of us who are experiencing chronic stress, high adrenaline levels, anxiety and panic attacks, lowering adrenaline is a beautiful thing! For as we lower adrenaline-noradrenaline levels the horrific symptoms simply vanish. And oh, what a relief that is!

What purpose does the Big Lie serve?

Simply put the Big lie produces the exact results that the pharmaceutical industry wants! They want us to fear lithium. If we fear lithium as a toxic drug, we will surely not want to take either the drug or, for that matter, the supplement. They would prefer that we not take lithium, but rather one of their counterfeit billion dollar annual income producers. They know that the toxicity and side effects of the Pharma-Li is the reason that most patients soon prefer to discontinue taking lithium and, therefore, excuses the patient and Doctor to try one of the newer more expensive alternatives. This tragedy leads to massive (avoidable) suicides as lithium reduces the risk of suicides in the Bipolar and Major Depression populations of patients by an astounding 80-90%. As much as 15% of bipolar patients will eventually succeed in taking their own lives; (3) yet less than 40% of American Bipolar patients are being prescribed this life saving essential mineral. Furthermore, if patients fear lithium as a potentially toxic drug, they will likely fear lithium the essential trace mineral. They definitely would prefer it not be known that lithium is possibly, overall, the most important mineral for neurological health. You may be wondering? Who are They? They are the Pharmaceutical Companies who are doing the research on this miraculous Essential Trace Mineral, Lithium. What are they doing, researching a mineral you ask? They have discovered the worlds most powerful essential trace mineral for overall health of the central nervous system (brain and spinal cord). From laboratory analysis of lithiums chemical pathways (i.e., its method of action within the human body) They are rapidly creating new and powerful drugs to treat the worst of the degenerative neurological diseases, known to mankind. Degenerative neurological diseases such as Alzheimers, ALS (Lou Gherigs disease) Parkinsons, and Huntingtons show great promise with lithium orthomolecular medicine. The reason They want us to believe lithium is a drug, and a very toxic, potentially deadly one at that, is because They dont want us to know that lithium is in fact an essential trace mineral that ameliorates; i.e., prevents or therapeutically highly benefits, over 100 human diseases including some of the most deadly of diseases, like MDD and PTSD.

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So we must speak truth to power and deception! The truth is that lithium is the most powerful essential trace mineral ever discovered for the balance, health and maintenance of the nervous system. Decades of research now demonstrate that lithium is a powerful preventer of neurodegenerative diseases and perhaps one of the most powerful anti-aging nutrients as well. The invitation I extend to you is that you verify the facts of what I am sharing with you so that you can become an educator of others who are suffering immeasurably from mental and neurological disease. Go to Pubmed.org and pull some of the studies listed herein to verify what I am saying. There is the opportunity is to make a profound difference in the lives of every American who is burdened by mental and or neurological illness. Lithium is a game-changer and all those who try it are forever transformed and eternally grateful. So what is stopping you and others from trying this amazing nutrient? If its fear and lies that are blocking the way, only education can change the paradigm. As I consult with individuals about utilizing the minute dosage of LO, the concern that they are taking a toxic substance is the single most difficult challenge to overcome with them. So I must repeat again and again that LO is given in dosages that are 1/10-1/20th of the concentration of the Pharma-Li. Lithium Orotate is believed to be at least 10 times more absorbable and this is made evident by comparing the typical dosages of each in the treatment of bipolar disorder. LO is typically given to bipolar patients in dosages in the range of 10-40 mg of EL/day. Pharma-Li is typically given to bipolar patients in dosages in the range of 100-400 mg of EL/day; the latter dose only for acute severe bipolar disorder. It does not take a degree in rocket science or pharmacy to see and understand that 1/10th of the dosage of LO is supremely safer and is infinitely more effective. One aspect of the increased effectiveness is due to the fact that patients are happy to continue taking lithium longterm. Patients only report feeling great while taking LO and, to my knowledge and according to Jonathan Wright M.D. and Ward Dean M.D. (experts on Lithium Orotate), there are no known adverse reactions from other medications while taking LO in these low dosages. Furthermore, Dr. Wright has been analyzing the kidney and thyroid function for decades of his patients who are taking LO. Dr. Wright told me that he routinely gave his patients LO in dosages as high as 40 mg (of pure-EL) per day without any detrimental effects noted in lab tests upon the kidneys or thyroid glands, the two most commonly affected organs of Pharma-Li in doses over 150-200 mg of pure EL. This comes as no surprise to me because after 40 years of analyzing lithiums effects in humans, doctors and scientist have come to the conclusion that side effects do not typically

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even begin to appear until the lithium dose reaches approximately 100 mg/day of pure EL. The psychiatrists that I have interviewed have said that about 1 in 100 individuals will show an effect upon the kidneys at this level (100 mg/day{EL}). However the other 99 patients show no effect upon the kidneys or thyroid until higher doses are administered. Most individuals have a lithium tolerance well over 100 mg/day and many over 200mg/day before the side effects become significant or intolerable. From this long history of lithium administration we can surmise that long-term supplementation of LO of up to 40 mg/day (of pure EL) is absolutely safe for all to enjoy. If you have a severe case of anxiety disorder, bipolar disorder, posttraumatic stress or any other condition that requires larger doses initially to maximally benefit your condition, you can also be confident that you are safe from any effect upon your kidneys or thyroid. However, I would ask that you have your kidney function analyzed just to be on the safe side and to provide laboratory results to us so that we can demonstrate to the world that larger doses are also safe. (Please send us your lab results and assist us with the LO Research Project). Most people who have to take larger doses (over 40 mg/day EL) initially will find that their condition stabilizes as lithium heals the nervous system over time and the larger doses will no longer be necessary. This has certainly been the case for me. I used to take 60 mg/day of pure lithium but I now only take 30-40 mg/day to maintain perfect balance of my mental and emotional body with no signs of bipolar disorder at all. I will also continue to take at least 30-40 mg/day indefinitely just for the neuroprotection benefits to prevent Alzheimers and Parkinsons disease. Having had the near-miraculous experience, of a complete elimination of the anxiety and mania of bipolar disorder I am completely and absolutely committed to telling the world the truth, screaming if I have to, speaking truth to power that lithium is not a drug! In deceiving the American public about the true nature of lithium the Pharma-cartel has perpetrated one of the biggest con-jobs ever conceived. They have programmed the world population to believe the Big Lie! Supplemental lithium is an idea thats time has come!

Is There a Conspiracy to Suppress Lithium Orotate? 1976

Everyone I have spoken with about Lithium Orotate, wants to know why they have never heard of Lithium Orotate before. The reason is simple. The pharmaceutical industry does not want us to know about it. I believe that you will agree once you have read this section that They intentionally suppressed this breakthrough with bogus research. Why you ask? The global market for neurological pharmaceuticals has grown to over 80 billion dollars annually! The cost of Lithium Orotate (LO) is $5-$20/month depending how much LO you supplement with. If the truth is told (regarding the healing power of LO) to all who would listen and are in need of this incredible product then LO could seriously disrupt the cash flow of this megalithic, neuro-pharmaceutical machine they have built.

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The following story is how (I believe) They suppressed this incredible mineral compound Lithium Orotate. Before we get into the details of this apparent conspiracy I ask you to consider the present day paradigm that the medical community is promoting with regard to Pharma-Li administration. Not since 1949, when Dr. Cade suggested that he had found a mineral deficiency disease in mentally ill patients, has there been another whisper that bipolar disorder might be due to a deficiency of lithium! 1. The medical community promotes lithium as an effective but toxic, drug therapy. They say that it is essential to ingest 120mg-400mg of elemental lithium to effectively treat bipolar patients. They insist upon laboratory monitoring of blood levels of lithium because it is so toxic, they contend, that it can be a fatal if blood lithium levels get to high. Supposedly numerous deaths have been associated with lithium toxicity due to kidney failure. In my research I discovered that deaths by lithium are extremely rare and only occurred when patients were taking the extreme (overdose) amounts of lithium. Some deaths have been attributed to suicide by lithium overdose. 2. They insist that Pharma-Li is only effective in very high doses and through a very narrow therapeutic range. Unfortunately, they insist that to get the benefits of their drug you must consume amounts so high that 80-90% of the patients experience mild to severe side effects. 3. The medical community has not (yet) declared lithium as an essential trace mineral; this despite animal studies demonstrating that lithium is an extremely essential trace mineral and that lithium is beneficial in the treatment of over 100 human diseases. 4. They have yet to acknowledge that there exists a mineral transporter (Orotic acid) that allows for significantly greater absorption of lithium into the brain cell (intracellular environment) where lithium does its work best. 5. They employed bought and paid for researchers to demonstrate through bogus scientific research that Lithium Orotate was more toxic than Pharma-Li.

They used the very same argument of toxicity associated with Pharma-Li to scare doctors away from prescribing Lithium Orotate.

They used ten times more Lithium Orotate than is administered to patients.
This is how they have gotten away with the suppression of Lithium Orotate! As we investigate the possibility that there is a conspiracy here to cover-up the truth, you may be shocked and outraged to learn that this is a very common occurrence throughout the medical

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research community as the stakes of influence, money and power are so high that it begins to act as a powerful narcotic within the biological belief systems of virtually all who participate. Medical researchers are frequently found to illegally alter research results to promote the passing of FDA approval of new drugs, or, as in this case, suppress powerful, inexpensive, nutrient breakthroughs. If you Google medical research fraud you will find over 10 million citations regarding this epidemic of research manipulation. In 1973, Dr. Hans Nieper, (the inventor of LO) informed the medical community with the announcement that he had discovered that LO was a profound healer of depression, epilepsy and migraines. Approximately 90% of his migraine patients reported significant relief of the frequency and severity of their headaches. He stated emphatically, that he was able to get these results utilizing the unique mineral transporter orotic acid, aka orotate, thus allowing him to administer only minute amounts of lithium to achieve maximum results. See: The clinical applications of lithium orotate. A two years study. (Nieper 1973)(4) Lithium orotate is of truly unparalleled efficiency in the treatment of constitutional migraine, constant headache and hemicranias. Also in the treatment of depression, alcoholism and epilepsy Lithium orotate is effective at uncommonly low dosages and causes no negative side effects. (Nieper 1973)(4) Dr. Nieper explained that orotic acid was a unique organic, natural mineral transporter that efficiently carried virtually 100% of the attached mineral into the intra-cellular environment. His clinical research led him to make the statement that he believed he was able to get these clinical results through maximum absorption, bio-availability, uptake and utilization of virtually 100% of the lithium ion. He believed he had found in orotic acid (OA) the bodys supreme mineral transport system. With regard to treating various medical conditions with LO, he stated that the amount of LO needed to get the same or superior clinical results as Pharma-Li was approximately 7% or 1/14th of the concentration of Pharma-Li for treatment of the same condition. Dr. Nieper was confident that LO was 10-15 times more absorbable than the Pharma-Li. By the mid 1970s, word of Dr. Hans Niepers Mineral Transporters (particularly the MineralOrotates) superior bio-availability and absorption into the interior of the cell had reached the main-stream in America and scientists were wondering if these claims were true. If these claims were true, They (American M.D. & Scientists working with the Pharmacartel) must have wondered, might this change completely the lithium paradigm, of lithium as a toxic drug, to perhaps lithium the essential trace mineral? To the Pharma-suits in the know of how the toxic-drug paradigm was running the show (with regard to the public perception of lithium) They had to be very nervous that this newcomer was about to upset the mainstream applecart and seriously threatened to decrease their profits. Only 3 supposedly independent (of Dr. Nieper) Lithium Orotate absorption studies have been published. Mammalian tests were carried out in 1976, 1978, and 1979.

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The first was performed by Smith D.F. (1976) and published in the British Journal of Pharmacology Study titled: Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats. (Smith D.F. 1976) The pharmacokinetics of the lithium ion administered as lithium orotate was studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride. No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food. The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate. (Smith D.F. 1976) (5) So Smith D.F. states that contrary to what Dr. Nieper has proposed, i.e., Lithium Orotate is many times more absorbed by the cells of the brain, there are No differences between Pharma-Li and LO.

Is Lithium Orotate 3 Times or 10 times More Absorbed?

In our second study of interest regarding comparisons of LO and Pharma-Li we find some very exciting discoveries were reported by researchers (Kling et. al.,1978). These researchers were apparently independent from the sphere of influence of the Pharmacartel in the search for truth about LO and their findings were Earth Shattering when compared to the findings and conclusions of the first study (Smith 1976). Remember that the first study said there was no difference between Lithium Orotate and Pharma-Li in the amount of lithium absorbed within the blood stream; No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride (Smith 1976) (5) The following study was published in the Journal of Pharmacy and Pharmacology. Study titled: Rat brain and serum lithium concentrations after acute injections of Lithium carbonate and Lithium orotate. (Kling et. al., 1978) Eight hours after intraperitoneal injections of 1.0m 2.0m and 4.0m equiv Li+ kg-1, the serum (blood) and brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. Furthermore, the 24 hr brain concentration of lithium after lithium orotate was approximately three times greater that that after lithium carbonate. Additionally this study found that at eight hours there was twice as much Lithium Orotate within the blood.

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Kling et al. concludes: These data suggest the possibility that Lower Doses of lithium orotate (LO) than lithium carbonate (LC) may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations. (6) So what is going on here? Smith DF reported in 1976, absolutely NO difference in the Uptake (absorption) of the orotate ion was observed and yet Kling et al. found dramatic differences in uptake and absorption within the blood and brain. You have some explaining to do here Smith! Again the brain concentration of LO was 3 Times Greater than the lithium carbonate! This is direct evidence suggesting the Superiority of the Uptake, Absorption and Utilization of the lithium in the orotate form. Since this study was conducted upon animals we cannot know for sure if these results apply to humans.

Conspiracy or Ignorance? (The Conspiracy to Suppress Lithium Orotate) 1979

In our 3rd and final study, on the subject of comparing the bio-availability of the Lithium Orotate (LO) to the Pharma-Li, we find some very interesting clues as to the researchers machinations. The conspiracy to suppress the superiority of LO becomes obvious once we compare apples to apples! Here again we find Smith DF, the previous researcher who performed the first study on LO absorption. This time however, he has brought an indisputable authority to the study on the subject of lithium pharmacology. He is seen by many as the Worlds Leading Expert on the use of lithium in psychiatry. His name is Mogens Schou, M.D. I quote Papolo & Papolo, from the book Bipolar Child, (2002): He, (Mogens Schou) is a Danish psychiatrist who became the World Expert on the use of lithium in psychiatry. (7) Smith and Schou have been motivated to perform this 3rd study, by the 2nd study performed by Kling et al. (the independent researchers). As you recall, the Kling et al. study dramatically contradicted the findings of Smith DF in the 1976 study. Remember in the first study that Smith DF reported No differences were noted in the uptake (absorption) of the carbonate, chloride and orotate. Yet Kling et al. found vast differences (3x more) in the uptake of the orotate ion into the brain cells. So who is correct here? Please verify these quotations by clicking on the following blue underlined study title. Study titled: Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate. (Smith and Schou 1979)

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A recent study by Kling et al. (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intra-peritoneal injection (2.0mmol lithium kg-1) The authors suggested that lithium orotate might offer advantages in the treatment of patients. (8) We repeated the experiments of Kling et al. but in addition examined the kidney function of the rats The kidney weight, and the lithium concentrations in serum, kidney and heart were significantly higher after injection of lithium orotate than after injection of lithium carbonate (8) Smith and Schou concludes: it seems inadvisable to use lithium orotate for the treatment of patients! (8) The result of this study and the conclusion drawn from it is based upon using massive toxic amounts of Lithium Orotate. Again the typical maximum therapeutic dose administered to patients with Lithium Orotate is 40 mg of elemental lithium; ten times less than was administered to these lab rats. Lastly, lithium concentrations in the blood/serum of 2.0mmol equivalent to 400 mg elemental lithium dosage in humans automatically causes significant kidney distress and above 2.0mmol can cause permanent brain damage in humans. Here follows a quote from the article; Review titled: Review of lithium effects on brain and blood. (Young 2009) The following is data on toxic levels of lithium. The therapeutic range for lithium carbonate (the pharmaceutical) is 0.6-1.0mmol in serum (blood) and greater than 1.5mM may be toxic. Serum lithium levels of 1.5-2.0 mM may have mild and reversible toxic effects on kidney, liver, heart, and glands. Serum levels of greater than 2.0mM may be associated with neurological symptoms, including cerebellar dysfunction. Prolonged lithium intoxication greater than 2.0mM can cause permanent brain damage. (Young 2009)(9) I repeat! In humans, blood concentrations over 2.0mmol can cause permanent brain damage. So why would Mogens Schou (the worlds leading expert) choose to use such toxic levels, (2.0mmol) of lithium for the purpose of examining the kidney function? I suggest to you that he knew exactly what he was doing and he knew that this would cause kidney dysfunction. Kidney distress is what the Pharma-Li carbonate was already known for due to the extreme dosing! My question: Is not the apparent kidney toxicity due to a natural response to a LO overdose? Did we forget what we were measuring? Did we not expect to find higher intracellular absorption rates with LO to begin with? Of course we did! So, why is this researcher so shocked to find expected results? The Moral of the Story ~ Too much of a good thing can kill you! 10-20 times, too much water can kill you. Eight glasses of water; good thing! But try 80-160 glasses of water and you will not see another sunrise! People have died from water drinking contests. Yes; too much water can kill you!

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Too much daily calcium can apparently kill you as well, men; or so the Pharma-cartel would have us believe Got Prostate cancer? The following study indicates that even the apparently innocuous calcium supplementation can be deadly. Study title: Calcium supplementation in clinical practice: a review of forms, doses, and indications. (Straub 2007) CAUTION: The risk of advanced and fatal prostate cancer has been associated with calcium intakes from food or supplements in amounts greater than 1500 mg/day. (10) Again I repeat! Smith DF & Mogens Schous Conclusion: It seems inadvisable to use lithium orotate for the treatment of patients. This is a very bold conclusion considering (Smith 1976) found no kidney dysfunction when using half the Lithium Orotate dose 1.0mmol in the first study. In the full study Smith and Schou (1979) acknowledge they do not know what caused the lowered kidney function via Lithium Orotate. They state In our previous study of lithium orotate (Smith 1976) there was no evidence of lowered kidney function in the orotate treated rats, but doses were much lower than in the present experiment. So here Smith and Schou acknowledge that lower dosage of Lithium Orotate caused no kidney distress in their first study (1.0mmol) but when they used 2.0mmol (equivalent in humans to 400 mg of elemental lithium) they find a toxic effect upon the kidneys and heart. Never once do Smith and Schou mention that Lithium Orotates recommended dosage is 1/10th of the Pharma-lithium 10-40 mg elemental lithium and that they have obviously given the lab rats a severe Lithium Orotate over-dose that is the cause of the kidney distress. Instead Smith and Schou suggest that Perhaps high doses of orotate exert toxic actions on the kidney. Smith and Schou close with Lithium orotate does not appear to offer pharmacokinetic advantages over other lithium salts. Since the orotate anion may exert toxic action on the kidneys, it seems inadvisable to use lithium orotate for the treatment of patients. Question: What is behind his motivation to measure kidney function? It sounds to me like he has a hidden agenda (causing kidney dysfunction)? It seems obvious to me! Again he uses massive amounts of LO measured at (2.0 mmol lithium kg-1), an extreme toxic amount!

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Remember that levels of (2.0 mmol lithium) in humans is so toxic that it causes neurological side effects; and over 2.0 mmol, potentially causing irreversible brain damage. In the first study he found no difference in the uptake of the orotate form but in this 2nd study he found a significant difference in the uptake of the orotate form! And we might expect a humble conclusion that could sound something like this! In consideration of what has come to light through my 2nd revealing study (Smith and Schou 1979) I recommend that further study of the uptake bio-availability of the LO form be performed to ensure the discovery, revelation and understanding, of what is really going on here. But we did not hear this kind of conclusion from him, did we? Instead we hear a manipulating ego declare, It seems inadvisable to use lithium orotate for the treatment of patients! So I ask you, what was his intent here? Is Mogens Schou an ignorant man making a mistake or is this man an accomplished research scientist (the world expert) who knew exactly what he was doing? Was the funding for his research purposely limited in scope? If so, who authorized the funding for a purpose that limited his scope of research? Is he trying to protect us? I dont think so! In closing on this subject remember this! Kling et al. has already established the fact that Lithium Orotate is a least 3x more absorbable than lithium carbonate. What awaits us is to discover just how much more absorption is possible, in humans through low level dosing with Lithium Orotate! My final conclusion: Lithium Orotate has been clinically shown to provide superior absorption, bio-availability, uptake, and will provide healing benefits at 1/10th of the concentrations used in this sham study. Since 1979 there has not been another single scientific study performed to validate the superiority of Lithium Orotates bio-availability. Today all across LO because of conspiracy has suppressing LO, to put an end to. this great nation doctors and psychiatrists continue to fear prescribing this sham study. It appears that the pharma-industry enterprises been completely effective and has succeeded in its mission of until now! This is a national tragedy that I intend, with your assistance

To fully appreciate the difference of the dosages between Pharma-Li and LO please review the following chart in the next section.

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Comparison of Lithium Orotate (LO) vs. Pharma-Li Carbonate (LC) Therapeutic Blood/Serum Concentration
Once again we review the basic difference between Lithium Orotate and Pharma-Li by looking at the following chart from the perspective of the varying therapeutic dosage between these two modalities. From this perspective it may be easier to see the big picture defing the contrast between LO and Pharma-Li. It has been proposed that patients must ingest 100-400 mg of elemental lithium via Pharma-Li to achieve a Therapeutic Blood/Serum Concentration for lithium to be effective for depressive or bipolar patients. Yet in the world of alternative, complementary and holistic medicine we find that physicians are utilizing approximately 10% of the elemental lithium via Lithium Orotate as a breakthrough alternative to toxic PharmaLi dosing.

Therapeutic Blood/Serum Concentration In mmol (measurement of blood lithium concentration) of Lithium Orotate (LO) vs. (Pharma) Lithium Carbonate (LC) Lithium Orotate (LO) 0.05 0 .25 mmol (typical therapeutic range) equivalent to 10-40 mg of EL 0.50 2.0 mmol (10x more EL used)! equivalent to 100-400 mg of (EL)

Lithium Carbonate

(LC)

What is a mmol? A mole is a measure of a particular amount of a substance. In this case it is the amount of lithium (ions) present in the blood/serum. Remember this: It is completely unnecessary for you to monitor your blood/serum lithium levels with LO as blood levels are way below levels of toxicity. I only compare LO with LC using blood serum levels to help you understand the difference between the two and to assist your physician as well. Pure elemental lithium (EL) amounts in red are shown to give you an approximate estimate of how much pure EL is required to reach a particular blood/serum concentration measured in mmol.
10 - 20 mg EL = 0.05 - 0.10 mmol This level is the typical therapeutic range of blood levels with LO for relief of symptoms associated with major depressive disorder. This level 30-40 mg is typically only seen in dosing of PTSD and bipolar patients with LO. This is the lowest level shown to be therapeutic for (Pharma) lithium carbonate augmentation in treatment-resistant MDD.

30 mg EL = 0.15-0.2 mmol 40mg EL = 0.2-0.25 mmol 75 mg EL = 0.3 mmol 80 mg EL = 0.4 mmol

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100 mg EL = 0.5 mmol 120 mg EL = 0.6 mmol 140 mg EL = 0.7 mmol 160 mg EL = 0.8 mmol 180 mg EL = 0.9 mmol 200 mg EL = 1.0 mmol 220 mg EL = 1.1 mmol 240 mg EL = 1.2 mmol 260 mg EL = 1.3 mmol 280 mg EL = 1.4 mmol 300 mg EL = 1.5 mmol

Mild side effects may begin at these levels particularly in the elderly. Mild side effects begin at this level for most patients

0.80 mmol 1.2 mmol is the therapeutic range of LC for BD. Moderate side effects begin at this level for most patients.

Severe side effects typically begin at this level for most patients. These levels and above are usually only attained during the acute treatment phase of bipolar disorder and typically cause severe side effects in all people.

320 mg EL = 1.6 mmol 340 mg EL = 1.7 mmol 360 mg EL = 1.8 mmol 380 mg EL = 1.9 mmol 400 mg EL = 2.0 mmol

Neurological side effects are usually present at this level.

Levels over 2.0 mmol can cause severe, potentially irreversible brain damage, as well as severe malfunction of the heart, kidneys, liver and thyroid gland. It is here; at these excessively high levels (400 mg of pure EL) of Pharma-Li that lithium has particularly gained its reputation as a heavy duty, toxic drug. However, at 400 mg EL you are 10 times over the maximum amount (40 mg EL) typically prescribed with LO. Most importantly I want you to understand that this toxic level, 400 mg EL/2.0 mmol, was the amount given to the rats in the LO study that showed that LO caused the rats to experience kidney distress. Remember this; all essential minerals have a toxic limit for daily ingestion. Lithium is neither a drug nor inherently toxic, except when such massive doses are administered and the toxic limit has been met. This is true for all nutritive elements; I know of no exception to this rule.

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Chapter Eleven

Dr. Hans Nieper The Creator of Lithium Orotate!

Those of us, who suffer with mental and neurological diseases, owe a great debt to the late Dr. Hans Nieper. His work has made it possible for millions to enjoy life without mental and neurological disease. For me, personally, I would probably be living as a street person if it had not been for the supplement created by Dr. Nieper. With great respect and admiration I present to you Dr. Hans Nieper, the man who created Lithium Orotate! Hans A. Nieper M.D. (1928-1998), an internationally acclaimed internist from Hannover Germany, is best known for the development of mineral transporters that allow for very small amounts of mineral supplementation with maximal absorption and health benefits. His creation of four mineral transporters, 2-AEP, Arginates, Aspartates and Orotates, have been shown in scientific studies to be highly effective and in the case of orotates, (orotic acid), far superior to the most common Pharma-Li mineral (carriers), the carbonates, citrates, and chlorides. I have referred to them as carriers because they are ineffective mineral transporters, and in my opinion, should not be referred to as such. It is a fact that minerals can be difficult to absorb within the cell and mineral transporters, particularly the orotates, make nearly, 100% intracellular absorption a reality. Of all the mineral transporters, Dr. Nieper seemed to be most interested in the orotates, particularly the unique ability of orotic acid to pass through the cell membrane transporting the mineral ion into the interior/nucleus of the cell. He made a very important discovery and distinction about the other mineral carriers of lithium. He discovered that the other carriers were not able to transport lithium across the cell membrane; instead the lithium became trapped within the cell membrane. Dr. Nieper was also known for his alternative treatments of cancer. He was successful in assisting President Ronald Reagan in the treatment of his cancer. He also treated many world celebrities including; Princess Caroline of Monaco, Anthony Quinn, John Wayne and Yul Brynner. Dr. Nieper treated thousands of patients with his unique mineral transporters. Dr. Niepers transporters have had outstanding success in diseases where other treatments had failed. His most exciting cancer study was conducted over a four year period with 3300 normally healthy patients. He supplemented their diet with one of his mineral transporters, 2-AEP, and calcium. None of the study participants contracted cancer during the 4 year study. In the general population we would expect to see approximately 2-3 cases of cancer/year for every 1000 patients. So over 4 years we would have expected to see 24-40 cases (depending on the average age of the group studied) of cancer develop and yet, there were none.

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How does Orotic acid function?

The mineral-orotates are the mineral salts of orotic acid. Orotic acid is a natural organic substance produced within the human intestine and is also ingested from certain fruits and vegetables, even milk. The orotates are part of the bodies natural mineral transport system. Study title: Recalcification of bone metastases by calcium diorotate. (Nieper 1970) (1) The orotates are perhaps the bodies supreme mineral transport system as they pass through the cellular membrane intact, delivering the mineral ion into the interior of the cell. This is the most exciting aspect of Orotic Acid transportation because it directly transports lithium through the cell membrane into the cell plasma, nucleus and mitochondria where the genetic material (DNA and RNA) is produced and stored within the human body. Lithium miraculously protects our genes (genetic material DNA/RNA) from mutation. This may be one of the reasons that lithium is being shown in cancer research to slow growth of certain malignant tumors. (2-5) According to Dr. Nieper, intra-cellular absorption is the key to benefitting from mineral supplementation. Based upon his observations of cultured cells, Nieper concluded that minerals attached to orotic acid pass through cell membranes intact without dissociating (breaking apart) into their component ions, and therefore release their ions only at specific membrane sites within the cell.(1,6) Further Nieper concluded that the orotates were specific in their delivery of minerals to specific cellular organelles, such as the mitochondria, nucleus, lysosomal membranes and endoplasmic reticulum; through specific metabolic (pentose) pathways.(6,7) See The clinical applications of lithium orotate. A two years study. (Nieper 1973) (7) The mineral carriers (carbonates, chlorides and citrates) are ineffective, at best, at providing nutrition into the cell (intra-cellular absorption). Most of the minerals attached to carbonates, citrates, and chlorides, simply pass through and out of the body without ever entering the cell. It is widely believed that absorption of calcium carbonate, for example, may be absorbed as little as 10-30% intracellularly depending upon a persons biochemical individuality. This is also true of Pharma-Li-carbonate. This is why the pharmaceutical industry is poisoning patients with toxic amounts of lithium; so little is absorbed. Modern technology through the MRI-like Magnetic Resonance Spectroscopy (MRS) brain scan has verified that Pharma-Li is only partially absorbed within the cell with a near majority simply passing through the body. With Pharma-Li, so little is absorbed into the cell plasma (cells interior) that excessive amounts of lithium must be ingested to achieve the therapeutic dose for bipolar disorder. Such a small amount of the Pharma-Li is absorbed into the interior of the cell (most is trapped in the outer-cell membrane and blood stream) that some (approximately 30%) of bipolar patients do not experience relief from Pharma-Li. Additionally, approximately 80% of patients who receive Pharma-Li treatment for bipolar disorder experience debilitating side effects due to the massive dose of lithium in their blood stream.

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Dr. Nieper discovered that when lithium was attached to orotic acid, he was able to achieve remission of bipolar disorder with doses at approximately 1/10th of the EL concentration when compared to Pharma-Li carbonate.(7,8) The passive electrochemical handling of lithium disposition across the membrane would predict tenfold higher intracellular concentration due to the cells resting negativity. Therefore, it is clear that lithium concentrations in the brain are not at equilibrium. (Kabakov et. al., 1998) (9) Niepers lithium results were further confirmed in a study of alcoholics who achieved substantial remissions of alcoholism. As well, functional improvement was demonstrated in liver, cardiovascular, thyroid and immune systems. Cluster headaches, manic symptoms, migraines and seizure disorder were also seen to improve in this study. Lithium orotate in the treatment of alcoholism and related conditions. (Sartori 1986)(10) Toxic treatments do more harm than good in the long run. The best physician is your own body. We must strengthen, no weaken, its defenses. Hans A. Nieper, M.D. Mineral Transporters: Excerpt from New Dynamics of Preventive Medicine 1974 Hans Nieper, M.D. (6) I think a few of you have already heard of the concepts of active mineral transport in directed therapy. I will give you a tour of horizons of what active mineral transport is and what it can do and how it is to be explained. Late in the 1950s it was discovered that cells of the female breasts becoming malignant are going to lose magnesium so we thought why not conceive of an extra-active transport principle to take magnesium into these cells with the help of phenylalanine and paraminobenzoic acid. At the same time, Hans Selyes book on the prevention of myocardial necrosis with the help of potassium and magnesium chloride was published and so we developed, in fulfilling the requirements of more active transport of potassium and magnesium into the cell, the potassiummagnesium aspartate in 1957-1958. This became quite successful world-wide as a medicament of the protection of myocardial necrosis, enhancement of liver functions and the detoxification of digitalis. Since this has been so successful, we followed this concept of active mineral transport and we changed as well the mineral which had to be transported as also the molecules which are suitable to transport the mineral into a cell by means of artificially created active transport. So the most important transporters we have today are aspartic acid, 2-aminoethylphosphoric acid and orotic acid. 2-aminoethylphosphoric acid (AEP) is a substance which plays a role as a component in the cell membrane and at the same time has the property to form a complex with minerals. You may replace the calcium by magnesium, potassium, iron or whatever. This substance goes into the outer layer of the cell membrane and is decomposed there incorporated into the cell membrane and releases the ion upon metabolization.

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Diagram of Cell and Mineral-Transporters Locations of Delivery

The second substance, the aspartates, especially the L-aspartate, goes to the inner layer of the outer cell membrane and there, upon metabolization releases the mineral to become the ion. The third substance which interests us enormously is orotic acid which forms a high complex salt with any mineral and which has no metabolic affinity to the outer cell membrane but penetrates the outer cell membrane even in the form of a complex salt and is only

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metabolized at the site of the membranes of the mitochondria and of the structures found in the cell plasma. Only here the mineral will be released to the form of an ion. So we have three different kinds of transporters: The AEPs (outer layer of the outer cell membrane), the aspartates (inner layer of the outer cell membrane) and the orotates (cell plasma organelles). All three substances are officially on the market in Germany and they play an important role in cardiology and hepatology for the aspartates. In the prevention and the treatment of multiple sclerosis, for the AEP, calcium, potassium, and magnesium AEP is officially declared in Germany as the only active substance in the treatment of multiple sclerosis. The myelin is a multilayer of cell membrane and AEP goes there, fits as a membrane component in the damaged membrane in the case of multiple sclerosis, releases the calcium at the same time which shields against aggression by antibodies. The orotates are officially on the market for the treatment of numerous diseases, especially decalcification and aggression toward the cell. Now here I have to stress a little bit the aspects of the transport by the orotates. The orotic molecule is mostly taken up by mesenchymal tissue and by bradytrophic tissue, especially be cartilage tissue and also by the vessel walls, by the blood-brain barrier and by the matrix of the bone. The orotic acid plays a very important role to so-called pentose pathway metabolism which accounts for the metabolism in cartilage tissue and especially for all organs which account for aging. End excerpt (Dr. Hans Nieper) (6) Many scientists and doctors have repeatedly attacked Niepers assertions and theorys attempting to debunk his work and marginalize the power of LO. Time however was on Niepers side. Modern clinical and laboratory research is proving Niepers theories correct. Nieper made many assertions in his writings about the role of lithium in the healing process of diseased cells. One of the important physiological effects of lithium asserted by Nieper was normalizing excess sodium within the cell. (3) Decades later modern research confirmed Niepers theories on lithium intracellular sodium normalization. This is the first demonstration that lithium can normalize abnormally elevated intracellular sodium levels. This may be an important mechanism of lithium action. Lithium normalizes elevated intracellular sodium. (Huang, Lei, El-Mallakh, 2007) (11) Until recently there has been little independent research conducted upon the orotates ability to transport minerals. However a recent look at magnesium orotate in the treatment of heart disease showed significant clinical improvement. These results were published in 1998 in the journal Cardiovascular Drugs and Therapy. See: Metabolic supplementation with orotic acid and magnesium orotate. (Rosenfeldt 1998) (12) Next we will examine the scientific evidence proving that Pharma-Li is poorly absorbed by the brain cells of humans.

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Chapter Twelve

Modern Medical Technology Measuring Intracellular Lithium Concentrations

The MRI-like (magnetic resonance imaging) studies of Pharma-Li absorption within the human brain cell; referred to as MRS (magnetic resonance spectroscopy) have demonstrated that only half (approximately 50%) of the Pharma-Li is absorbed from the blood/serum into the cellular membrane and not into the interior of the cell plasma known as the true intracellular environment. See: Brain lithium concentration by 7Li- and 1H-magnetic resonance spectroscopy in bipolar disorder. (Kato et. al., 1992) (1) This is the most essential, take away message, understanding, and distinction with respect to the superiority of LO; it is the difference of the intra-cellular absorption, bioavailability, cellular uptake and compound solubility when compared to the pharmaceutical versions of lithium; carbonate, chloride and citrate. Mary Elvira Weeks, the author of Discovery of the Elements, states; Unlike sodium carbonate, lithium carbonate is only sparingly soluble. (2) With low solubility comes low intracellular absorption. This is the precise reason that the pharmaceutical versions of lithium administration are considered toxic drugs. They are so poorly absorbed within the cell that the blood/serum levels must be pushed to toxic extremes to achieve the therapeutic intracellular concentrations of lithium which will facilitate the remission of symptoms, particularly symptoms of severe bipolar disorder. The blood/serum (extracellular) concentration of lithium achieved during the therapeutic use of lithium (for bipolar disorder) is in the range of 0.8-1.2 mM. However, intracellular concentrations of lithium are the essential measurement for achieving physiological effects. Intracellular lithium concentrations in the brain have been difficult to evaluate. (Lam and Christensen, 1992) (3) Most people are now familiar with MRI scans, because MRI scans are very useful at visualizing soft tissue structures of the human body and are commonly utilized. A version of the MRI scan called Magnetic Resonance Spectroscopy (MRS) can be utilized for measuring intracellular lithium concentrations. Here follows some of the quotes from recent MRS studies, regarding intracellular lithium concentrations. Magnetic Resonance Spectroscopy (MRS) is a novel non-invasive approach for investigation of in vivo (in vivo defined: within the living body) brain neurochemistry. Measurement of in vivo brain lithium concentrations may have clinical relevance. (Soares, Krishnan and Keshavan 1996) (4) I find it amazing that as late as 1996 researchers were still saying; Measurement of in vivo brain lithium concentrations may have clinical relevance. Really? The intracellular lithium brain concentration (in my opinion) is the most clinically relevant matter, and the main point to

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understand. This is what Dr. Hans Nieper was explaining in his papers as far back as the late 1950s. Gyulai et. al., (1991) states; The average brain/serum lithium concentration ratio was 0.47. The hypothesis is advanced that the minimal effective concentration of brain (cell) lithium concentration for maintenance treatment of bipolar disorder is around 0.2-0.3 mmol. (5) This low blood/serum level of lithium concentration, 0.2-0.3 mmol, is the typical maximum amount ever utilized with LO. Lithium brain concentrations measured by MRS in 10 lithium-treated bipolar patients were at the half level of those measured in serum (blood). (Kato et. al., 1992)(1) Two other studies conducted since the early 1990s confirm that the lithium intracellular concentration is approximately half (50%) of levels in the blood/serum. Relaxation times and concentrations of 7Li in the brain of patients receiving lithium therapy. (Kushnir et. al., 1993) (6) (Komoroski and Pearce 2008)(7) These studies, however, did not differentiate between intracellular lithium within the cell plasma and the lithium trapped in the outer cell membrane. So we know from these MRS studies that Pharma-Li is poorly absorbed into the brain cells showing only half as much lithium in the brain tissue compared to the blood/serum levels. What has not yet been measured, however, is exactly how much Pharma-Li is actually making it through the outer-cell membrane and passing into the critical area of the inner cell plasma where the all important cell organelles such as the mitochondria, nucleus, lysosomes and endoplasmic reticulum are located. It is upon these cell organelles that lithium interacts and provides its near miraculous benefits. This is the critical distinction to understand. LO is able to pass through the outer cell membrane fully intact delivering 100% of the lithium to the cell organelles and the nucleus where DNA and RNA genetic transcription (duplication) and building of new genetic material is happening. This is where the power of lithium is demonstrated, INSIDE THE CELL PLASMA! This is the beauty of Orotic acid! Orotic acid allows for virtually 100% absorption of lithium into the interior of the cell; where lithium does its most profound healing of the human body. At these low LO dosages even the most severe psychosis can be dealt with, without suffering the side effects associated with excessive blood/serum levels of lithium carbonate. Sadly I do not yet have a localized 7Li magnetic resonance spectroscopy study of LO to share with you. It is coming very soon! As soon as I have the study I will post it for all to see.

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Chapter Thirteen

Veteran Health Administration Treatment of Major Depressive Disorder

Prepare yourself to have your eyes opened wide by incontrovertible evidence that there is something missing within the Veterans Health Administration system for the treatment of Major Depressive Disorder. As previously disclosed by VA researchers (Valenstein et. al., 2006) it was found that the most common drugs being prescribed our veterans for major depression (MDD) are antidepressants, antipsychotics and anticonvulsants, and lithium is being prescribed to only 1 in 200 with MDD, and only 1 in 50 of our veterans with treatment-resistant MDD. (1) You might be thinking, whats the big deal with prescribing antidepressants for MDD? Everybody knows that antidepressants are prescribed for depression, but did you know that

Antidepressants are no better than a placebo in preventing suicide.

(Khan et. al., 2003) The American Journal of Psychiatry (2) As the following article reveals, FDA reports demonstrated that antidepressants do not reduce suicide rates and are comparable to placebo rates. Remember that the most common antidepressants being prescribed in America today are selective-serotonin reuptake inhibitors (SSRIs). Study title: Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. (Khan et. al., 2003) Northwest Clinical Research Center, Bellevue, Washington. Results: Of 48,277 depressed patients participating in the trials, 77 committed suicide. Based on patient exposure years, similar suicide rates were seen among those randomly assigned to an SSRI, a standard comparison antidepressant, or placebo. (2) So if antidepressants are no better than a placebo pill for the prevention of suicide, then why arent our veterans being augmented with lithium for MDD? Wait, it gets worse! The age group of combat veterans experiencing the highest suicide rates, at 4 times the rate of the general population of the same age, is 18-24 years of age. Antidepressants have been demonstrated in some patient groups (young adults 18-24) to actually increase the risk of suicide. (FDA Black Box Warning)(3) Lithium was found to be statistically and significantly superior to, antidepressants in reducing MDD hospitalization (Cipriani et. al., 2006) (4) as well as treatment resistant depression.

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How is it that while our nations veterans are experiencing an epidemic of suicide because of the co-occurrence of MDD and PTSD they are being denied (1) the only nutrient-essential-tracemineral (Lithium) ever discovered and scientifically proven to reduce the risk of suicide (80-90% reduction) associated with treatment-resistant MDD?

Antipsychotics are Controversial for the Treatment of MDD

Antipsychotic treatment of major depression is a controversial one as the FDA has not approved antipsychotics for the primary treatment of MDD. Seroquel and Abilify have FDA approval as an add-on, aka an augmenting agent, in the treatment of treatment-resistant depression. Furthermore, the additional benefit of adding an antipsychotic augmentation to an antidepressant for treatment-resistant depression falls far short of the rates of response that lithium achieves. Antipsychotics achieved measurable results in treatment-resistant depressive cases in a range of 47-57% of cases (Papakostas et. al., 2007) (5) while lithium has a response range of 50-85%.(6-14) While lithium is significantly more effective than antipsychotics in achieving remission of MDD symptoms, the biggest advantage lithium has over antipsychotics is the 80-90% risk reduction of suicide. My research of the benefit of antipsychotics for the prevention of suicide revealed that

Antipsychotics have not been demonstrated to reduce the risk of suicide associated with MDD.
In some groups of patients (e.g. Schizophrenics, Bipolar patients) antipsychotics have actually been scientifically demonstrated to increase suicide rates. (15),(16) How could this be happening at the VA medical centers? Antidepressants, antipsychotics and anticonvulsants are the drugs of choice for veterans with MDD and treatment-resistant depression (the condition most at risk of suicide) and yet none of these drugs have any measureable effect of suicide prevention; while lithium, has been virtually abandoned. The only logical and rational answer is the powerful influence of the Pharmaceutical industry upon the VA and the Pharma-cartel is calling the shots.

The Antidepressant/Antipsychotic Fiasco

In a skeptical analysis of the FDA antidepressant/placebo studies (Kirsch, Scoboria, Nicholls & Moore 2002) and (Kirsch 2009) antidepressants were found to provide a partial improvement in approximately 50% of the most severe cases of MDD. Responses to mild and moderate cases of MDD were found to be essentially the same as the placebo response.(17),(18) Summary excerpts are presented from the following study.

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Study titled: The Emperor's New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration. (Kirsch et. al., 2002) This article reports an analysis of the efficacy data submitted to the U.S. Food and Drug Administration for approval of the 6 most widely prescribed antidepressants approved between 1987 and 1999. Approximately 80% of the response to medication was duplicated in placebo control groups and the mean difference between drug and placebo was approximately 2 points on the 17-item (50-point) and 21-item (62-point) Hamilton Depression Scale. Improvement at the highest doses of medication was not different from improvement at the lowest doses. (17) Worse yet, careful analysis revealed that the pharmaceutical companies are routinely dropping the studies that show no benefit to their drugs. A follow-up meta-analyses study by (Kirsch 2009) demonstrates similar findings once again. Study titled: Antidepressants and the placebo response. (Kirsch 2009) Department of Psychology, University of Hull, United Kingdom. Results: Most trials failed to show a significant advantage of SSRIs (selective serotonin reuptake inhibitors) over inert placebo, and the differences between drug and placebo are not clinically significant for most depressed patients. Documents obtained from the U.S. Food and Drug Administration (FDA) revealed an explicit decision to keep this information from the public and from prescribing physicians.(18) The following study published in the New England Journal of Medicine, exposed the fact that most pharmaceutical studies demonstrating a negative or low-response rate, were systematically eliminated from publication. Here are excerpts from the abstract of that study. Study title: Selective publication of antidepressant trials and its influence on apparent efficacy. (Turner et. al., 2008) Department of Psychiatry, Oregon Health and Science University, Portland, OR. We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. Results: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published was associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. (Turner et. al., 2008) (19)

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With this kind of manipulation of studies, how is a physician to know whether or not an antidepressant is truly effective?
The following article on this topic was published in 2008, in the Journal of Psychiatry, (Edgmont). Article title: More depressing news on antidepressants: should we panic? (Feifel 2008) A recent article appearing in the January issue of the New England Journal of Medicine has created quite a controversy. The paper titled, Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy has cast a shadow on the efficacy of antidepressant medication in depression. The authors obtained and reviewed the results of all Phase II and Phase III randomized, placebo-controlled studies of drugs for the short-term treatment of depression registered with the US Food and Drug Administration (FDA). They then compared these registered studies with those in the literature and found that only 69 percent of the studies on file with the FDA were published, and the studies deemed to have clearly positive outcomes were much more likely to be published (37 of 38) compared to those resulting in a negative or equivocal (uncertain) outcome (14 of 36). (Feifel 2008) (20) Sadly this expose on the lack of efficacy of antidepressants in the treatment of MDD would not be widely told until 2010. Newsweek January 28, 2010, (21) published a story on the article published by the Journal of American Medical Association (JAMA, Jan. 2010). Antidepressant drug effects and depression severity: a patient-level meta-analysis. (Fournier et. al., 2010)(22)

Major internet websites that have featured the findings of the JAMA article include the WebMD, USA TODAY and the Guardian Unlimited.(23-25)
Newsweek: WebMD: The Guardian: USA TODAY: The Depressing News About Antidepressants. (21) Antidepressants No Better Than Placebo? (23) Prozac, used by 40m people, does not work say scientists (24) Study: Antidepressant barely better than placebo (25)

As previously stated, in some sub-groups of patients, (e.g. young adults age 18-24) antidepressants have been shown to actually increase suicide rates in the treatment of MDD. (FDA Black Box Warning) (26)

This age group 18-24 years of age is the age-group of combat veterans with the highest rates of suicide in the U.S.
A CBS/AP article revealed the following data from the VA. The VA calculated the numbers using Centers for Disease Control and Prevention numbers from 16 states. In 2005, the rate per 100,000 veterans among men ages 18-29 was 44.99, compared with 56.77 in 2007. (27)

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This is over a 25% increase in suicides in this age group and represents a number that is approximately four times the rate of suicide for the general population of the same age group. The suicide rate for non-veteran men ages 18-24 in the U.S. in 2007 was approximately 16/100,000, compared to 56.77/100,000 for veterans age 18-24.(28) To calculate the actual number of suicides of non-veteran men you must subtract 20% from the general population data, accounting for suicides by veteran males. In 2007, the general population suicide number was 20/100,000 20% = 16/100,000. The suicide mortality data files, from which this data is derived, are maintained by the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention. (28) This suicide rate of 56.77/100,000 in 2007 is an average of combat veterans with support troops, therefore, the suicide rate for the front-line (high-impact) combat troops only is, potentially, 90+/100,000 troops, a rate that is approximately six times higher than the general population. Furthermore, since 2007, the suicide rates for off-duty (inactive civilian soldiers) have dramatically increased. As previously stated in the USA TODAY story published in 2010, the suicide rate for inactive, off-duty civilian National Guard soldiers more than doubled from 2009 to 2010. So at this very moment, as you are reading this book, our beloved younger combat veterans ages 18-24 are experiencing a massive epidemic of suicide, with no end in sight. Sadly, many veteran bipolar patients are not being prescribed lithium either; this despite the fact that lithium remains the international standard of comparison for the treatment of bipolar disorder.(29,30) No other pharmaceutical treatment has ever been shown to be superior overall to lithium for the treatment of bipolar disorder.(29) Lets not forget the most important fact, bipolar disorder has the highest rates of suicide of all mood disorders and lithium is the only remedy that significantly reduces the risk of suicide associated with bipolar disorder by 80+% (7) A recent study of VA records (Sajatovic et. al., 2007) discovered, by analyzing the VA's National Psychosis Registry, that the prescription rate of lithium for the treatment of veteran bipolar patients, that of the 44,637 patients analyzed, only 16,962 (38%) were given prescriptions for lithium.(31) Instead, many of them are being prescribed antipsychotics, which have been shown to have potentially deadly consequences. For veterans being treated for bipolar disorder with antipsychotics, the data is stunning. In a review of 405 veterans with bipolar disorder, attempted suicide events were over 9 times greater for the veterans receiving only antipsychotics, compared to veterans prescribed only a mood stabilizer such as lithium. Even more telling perhaps, of the danger of antipsychotics, is the fact that suicide attempts were 3.5 times greater in bipolar patients when antipsychotics were combined with a mood stabilizer as opposed to a mood stabilizer alone (monotherapy). (Yerevanian et al., 2007) (32)

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In other words the veterans were far better off taking a mood stabilizer all by itself, rather than adding an antipsychotic to the regimen.
The use of antipsychotic medications for veterans appears to be increasing and dangerously so. A recent analysis (2009) of the Off-label prescriptions (Off-label use is the practice of prescribing pharmaceuticals for an unapproved medical condition) written for antipsychotics to veterans, published in the Psychiatric Services (Washington D.C.), reveals some very disturbing statistics. Sixty percent (60%) of veterans receiving antipsychotics had no record of a diagnosis for which these drugs are approved.(33) The study follows here: Off-label use of antipsychotic medications in the department of Veterans Affairs health care system. (Leslie et. al., 2009) Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA. Given that these drugs are expensive, have potentially severe side effects, and have limited evidence supporting their effectiveness for off-label usage, they should be used with greater caution. (Leslie, Mohamed and Rosenheck 2009) (33) The most common mental illness diagnoses among patients given prescriptions for antipsychotics off label were posttraumatic stress disorder (PTSD, 41.8%), minor depression (39.5%), major depression (23.4%), and anxiety disorder (20.0%). (Leslie et. al., 2009) (33) Prescribing antipsychotics off-label is good for pharmaceutical profits but evidence is lacking that it is good for patients. The following article was published in 2007 by the Department of Health & Human Services' (HHS) Agency for Healthcare Research and Quality. Review title: Evidence Lacking to Support Many Off-label Uses of Atypical Antipsychotics Some newer antipsychotic medications approved to treat schizophrenia and bipolar disorder, are being prescribed to millions of Americans for depression, dementia, and other psychiatric disorders without strong evidence that such off-label uses are effective, according to a new analysis by the Department of Health & Human Services' (HHS) Agency for Healthcare Research and Quality (AHRQ). (34) The following study was published by the by the Department of Health & Human Services' (HHS) Agency for Healthcare Research and Quality (AHRQ). Study titled: Efficacy and Comparative Effectiveness of Off-Label Use of Atypical Antipsychotics [Internet]. (Shekelle et. al., 2007) Findings: For Major Depression, For Serotonin-Reuptake-Inhibitor (SRI), antidepressantresistant patients, with major depressive disorder, combination therapy with an atypical antipsychotic plus an SRI antidepressant is not more effective than an SRI alone at 8 weeks. For PTSD, Strength of evidence is low for risperidone and olanzapine (antipsychotics) for combat-related PTSD due to sparse data. (35)

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A further disturbing fact revealed in another VA study (Yale School of Medicine Mohamed, Leslie and Rosenheck 2009) found that of the veterans receiving antipsychotics for MDD, 43% of them received higher doses than is recommended for schizophrenia, an approved condition for antipsychotic drugs.(36) So it appears that overall the evidence of the benefits of prescribing antipsychotics for MDD and PTSD is weak and when compared to the evidence for prescribing Pharma-Li for MDD, there is no comparison. Antipsychotics have never been shown to reduce suicide rates; on the contrary they have only been shown to increase suicide rates. So who or what is driving these trends for prescribing antipsychotics for MDD? You guessed it, the pharmaceutical companies. These second-generation (atypical) antipsychotics are big money makers and as long as they are patent protected these trends will continue until they become generic. At the point in time when antipsychotics become generic, we will no doubt hear that they are no better than placebo (as we are hearing now about antidepressants) in the treatment of MDD. Given the increase of antidepressant prescriptions provided to the public for the treatment of major depression, you would expect that there would be a significant drop in the rates of suicide if antidepressants were having any effect at all. However, the rates of completed suicide have remained unchanged as the following article illustrates. Article title: A stubborn behaviour: the failure of antidepressants to reduce suicide rates. (Van Praag 2003) Department of Psychiatry and Neuropsychology, Academic Hospital, Maastricht University, the Netherlands. Over the past decades the rate of completed suicide has remained quite stable, that of suicide attempts even seems to have increased (to the extent it has been studied in defined regions). These are puzzling observations, since depression is the major suicide precursor and since antidepressants over the years have been increasingly used in the treatment of depression. (37) With all of the evidence proving that antidepressants dont reduce suicide rates but in fact may increase suicide rates is it any wonder that the VA has failed miserably to reduce suicide rates? Who will hold the VA accountable for this failure. Will we have to go all the way to the court of appeals to win this victory? Will the Veterans for Common Sense fight and win another battle in court like the following article illustrates.?

A Victory for Veterans (New York Times 5/18/2011) (See article here)
Court finds government incompetence is leading to thousand of suicides
The United States Court of Appeals for the Ninth Circuit ordered an overhaul of mental health care for veterans, who are killing themselves by the thousands each year because of what the court called the unchecked incompetence of the Department of Veterans Affairs. (Excerpt)

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Chapter Fourteen

Why Has Lithium Not Been Prescribed to Veterans?

The most obvious reason, lithium is not being prescribed at the VA for MDD, is simply there is no pharmaceutical promotion of lithium, as there is no money to be made in doing so. Secondly remember this point, the studies conducted at the Harvard Medical School, Boston, MA that produced the revelation that lithium reduces the risk of suicide (2 STUDIES) by 100% and 88.5% in major depressive disorder, were not published until 2003 and 2007. Up until that point physicians were only aware that lithium prevented suicide in bipolar disorder. It generally takes many years for a medical breakthrough in understanding to become a mainstream practice. So regardless of the past practices of the VA we have to give them the benefit of the doubt. We also have a responsibility to our nations veterans to hold the VA accountable to change their future practices and begin to end the epidemic of suicide amongst our nations veterans.

Thirdly, and I believe the main reason that Pharma-Li is not prescribed to veterans for MDD is the common physician belief, a misconception that extremely high doses of lithium must be given to achieve a therapeutic blood level of 0.7mmol - 1.0mmol, about (140-200 mg of pure EL) to be an effective treatment for MDD. (1) This is simply not true.
What is a mmol? What is mEq/L? Just know this; a mole or mEq/L, is a measure of a particular amount of a substance. In this case it is the amount of lithium (ions) present in the blood/serum. The truth is much lower doses (approximately 1/2 the dose, 75-85 mg of EL) of Pharma-Li, have been demonstrated to be highly effective, in the augmentation (add on) treatment of treatment-resistant MDD.(Faravelli et. al., 1980) (1) (Dinan 1993) (2) Amounts at 75-85 mg of EL, generate lithium blood levels, of approximately 0.30 0.40 mmol and as such generates little if any side effects for the patient. At blood/serum lithium levels over 0.5 mmol, = approximately 100 mg of pure EL, some veterans begin to feel the side effects of excessive levels of lithium in their blood stream. As the lithium levels climb from 0.50 mmol to 0.7 mmol, (100 mg -140 mg EL) the side effects are felt by almost all the veterans and the general feeling is that something is wrong with this socalled drug. This is the biggest reason veterans dont want to take lithium. At lithium levels above 0.5 mmol (over 100 mg of EL) the veterans are told that they must have their blood levels monitored periodically by the lab so as to ensure that their lithium levels do not

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get too high. This fact alone is a likely deterrent to prescribing veterans Pharma-Li. Who in their right mind wants to receive a medicine that may be toxic to them? Significant side effects do not generally begin to appear with Pharma-Li until amounts over 100 mg/day of pure EL are ingested. The fourth reason; at high lithium blood levels, (1.0 mmol, 200 mg EL), the veteran is told by his physician not to drink alcohol with the lithium medication, as the alcohol dehydrates them and thus may push the blood lithium levels even higher, potentially causing significantly elevated lithium levels, blood toxicity and side effects.(3) For this reason alone (not being able to drink alcohol) the veteran will likely choose not to take any medicine that interferes with his social drinking with his or her comrades in arms. This concern for alcohol/lithium toxicity is simply overblown as an analysis on the topic showed very mild interaction between alcohol and lithium. The following study on the topic sheds light on the reality. Study title: Effect of acute alcohol consumption on lithium kinetics. (Anton et. al., 1985) Acute alcohol had no effect on lithium absorption, elimination, distribution, or clearance. Alcohol did, however, increase the peak serum lithium level in nine of 10 subjects, from a mean of 0.62 mEq/L in the placebo condition, to 0.70 mEq/L in the alcohol condition. Our data suggest that alcohol has limited effects on lithium carbonate kinetics. (4) This increase of lithium levels from 0.62 - 0.70 mEq/L, while drinking alcohol, is just slightly over a 10% increase of lithium levels and hardly represents a life threatening situation. This increase of 10% might temporarily cause a patient (with extreme lithium blood levels over 1.5 mEq/L) to feel a transient increase of already bothersome side effects. The good news for Lithium Orotate users is that blood lithium levels rarely go over 0.2 mEq/L (compared to 1.0 mEq/L for Pharma-Li; 5 times more lithium in the blood). At this low LO blood level, 0.2 mEq/L, there is absolutely no reason why a user of LO cant drink alcohol responsibly. Finally, the reason our veterans are not being given low dose Lithium Orotate (LO) for the treatment of MDD and the prevention of suicide is because most medical doctors are completely unaware of this all natural, organic, alternative lithium product, and that (unlike prescription lithium) LO is fully absorbed by brain cells. Remember this important fact about lithium therapy: With regard to the therapeutic response to lithium, its not how much lithium is in the blood thats important; it is how much lithium makes it into the interior of the cell (intra-cellular absorption) thats important. LO has been shown to be absorbed at least 3 times more into the brain cells of animals when compared to Pharma-Li. (Kling et. al., 1978)(5) Dr. Nieper, the inventor of LO, hypothesized that LO was at least ten times more absorbed by the interior of the cell due to his cultured cell experiments and the results he achieved with his patients in the clinical setting. The fact that he was able to achieve therapeutic clinical

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results for migraine headaches, epilepsy, manic depression (bipolar disorder) and alcoholism with amounts that were approximately 7% of the dosage of Pharma-Li, led Dr. Nieper to the conclusion that LO was 10-14 times more bioavailable than the Pharma-Li. I have learned through my research that Dr. Nieper theory of greater absorption via Lithium Orotate is true. However, the actual intracellular-absorption differential between the orotate and pharmaceutical version has not been absolutely, scientifically determined and I believe more research will need to be done, even if I have to do it. The best evidence we have is from all of the patients that have converted from taking Pharma-Li to taking LO suggesting that LO absorption is ten-times greater than that of Pharma-Li. Time and time again we see patients are getting excellent results from LO with approximately 1/10th of the EL dosage. To recap: Why Has Lithium/Lithium Orotate Not Been Prescribed to Veterans? Regretfully, this failure to give our veterans either the organic nutritional mineral solution (LO) or Pharma-Li is driven by pharmaceutical influence, money, power, politics and ignorance. In my estimation (based upon over 5,000 hours of research, my personal experience with Lithium Orotate and a complete recovery from over 25 years of bipolar disorder) by giving veterans natural organic LO, we would easily reduce the need for 50% of the pharmaceutical prescriptions written for our veterans suffering with PTSD, Major Depression, Sleep Disorders, and many other neurological conditions. Lithium Orotate costs approximately $10-$20/mo. Pharmaceuticals for veterans mental and neurological conditions cost several hundreds of dollars per month. Pharmaceutical companies cant make money on Pharma-Li ($20-$40/mo.) or LO and, obviously, money is driving the choices and options for veteran care. The loss of annual revenues to the pharmaceutical industry, due to the power of LO to replace other expensive mental and neurological drugs, would easily run into the billions annually. The pharmaceutical industry is not likely to allow this loss of revenue and will continue to do whatever is required to suppress the truth about LO. Some have advised me not to take on the pharmaceutical industry by divulging this revolutionary information about LO; they fear for my life. Hopefully they wont shoot the messenger.

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Chapter Fifteen

Depression Overview
Depression, aka MDD, aka unipolar depression, is the most common of the mood disorders and one of the most common illnesses co-occurring with PTSD among combat veterans as well as the general public.(1,2) Distinguishing bipolar, unipolar and major depressive disorders - The terms bipolar depression and unipolar depression, aka major depressive disorder, are distinguished from one another by the occurrence of mania (hyperactivity) preceding, bipolar depression. Unipolar depression, aka MDD, refers to depression with no history of mania (intense hyperactivity) or hypomania (mild to moderate hyperactivity). Major Depression is the third leading cause of disease burden worldwide according to the World Health Organization; Global Burden of Disease 2004 Update.(3)

The Symptoms of Major Depression

Major depression is defined by a low mood or an inability to experience pleasure (anhedonia), or both, for more than 2 weeks. Furthermore there are several symptoms relating to loss of brain function (loss of cognitive function/impairments) combined with anxiety and distress. (4) Symptoms of MDD include very low or depressed mood, confusion, desperation, hopelessness, irritability, fatigue, low self esteem and a lack of participation in normally enjoyable activities (reclusiveness). While most veterans prefer to suffer in silence rather than admit they are depressed, they are commonly unable to suppress the irritability that so commonly accompanies MDD. Chronic irritability may be the only sign that the veteran is unable to hide, particularly, from family members. A 2010 study conducted by the Department of Psychiatry, Massachusetts General Hospital, analyzing rates of irritability as a major symptom of MDD found that approximately 50% of the patients with 12-month MDD were significantly irritated. (Fava et. al. 2010) (5) In the cases of MDD lasting a period of at least 12 months, approximately 10% of reported cases are mild, 38% moderate, 38% severe and 12.9% very severe. While about 50% receive medical care for MDD only about 40% of those receiving care have an adequate response. The end result is that only about 20% of 12-month MDD patients are being adequately treated. (Kessler et. al., 2003) Harvard Medical School(6) The other 80% of those patients who are not receiving adequate care for MDD are left to their own devices which, I believe we can agree from the results leads too often to deadly results. Severe MDD has a crushing effect upon all intimate relationships and a deleterious effect upon productivity at work and home. The overall impact of MDD is often quite severe and is often

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associated with increased rates of co-occurring; mental, emotional, physical and psychiatric health problems.

Severe chronic MDD all too often (16% occurrence) results in the individual attempting to end their life. (7)

Veteran Depression and PTSD Statistics

The diagnosis rate for veteran depression is 14%, according to the National Alliance of Mental Health.(8) However studies show that Major Depression and PTSD are under-diagnosed in the veteran population. Due to the stigma attached to it, men (in particular) frequently do not seek help for depression or PTSD. Our troops are extensively trained to resist mental weakness. According to a report from the veteran Mental Health Advisory Team (MHAT) V, 2008, approximately 20 percent of the troops who screened positive for a mental health challenge said they avoided seeking care for it because my leaders discourage the use of mental health services.(9) Furthermore the VA Special Committee on PTSD (2005) reported that as many as 20% of the Iraq and Afghanistan veterans are at risk for significant symptoms, short of full diagnosis but severe enough to cause significant functional impairment.(10) As veterans avoid being completely open and honest about their condition with the VA, they often seek outside care for mental illness symptoms; 56% of the active duty, 60% of reserve component and 76% of retired/separated service members say they have reported mental health symptoms to a health care provider according to The Presidents Commission on Care for Americas Returning Wounded Warriors, Final Report, July 30, 2007.(11) This report suggests that the number of veterans who are actually suffering with symptoms of depression, anxiety and sleep disorders is likely twice the number of those who are diagnosed as such at VA medical centers. I mention the following PTSD statistics here because of the fact that PTSD and MDD are intimately related. At any given time approximately 50% of patients with combat-related PTSD are also clinically depressed. Over the period of a lifetime major depression is experienced by 95% of combat veterans.(12) As documented by the PTSD Research Quarterly National Center for PTSD(13): Of the troops returning from Afghanistan and Iraq the diagnosis of Post-traumatic Stress is being applied to as many as 18% of them.

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Critics of the VA contend that PTSD rates are much higher perhaps as high as 40% or more. Is the VA trying to minimize the PTSD problem or is the problem a stigma issue that keeps the veterans from reporting honestly about their situation? Read on to find out. The VA is finally coming clean with the actual numbers of veterans who are suffering with PTSD. For the longest time the VA minimized the numbers of veterans affected by PTSD on their return from the war in Iraq and Afghanistan. In the most recent article by Greg Zoroya of USA TODAY (the most prolific journalist on the subject) Zoroya reveals that the VA acknowledges that the problem is likely twice as bad as the VA had indicated in the past. Previous reports by the VA were that only 10-15% of combat veterans were coming home with PTSD. Now the VA is acknowledging that the actual number is potentially over 30%. The following article excerpt tells the story.

Rise in PTSD cases from two wars strains resources

By Gregg Zoroya, USA TODAY November 30, 2011 Since the Iraq and Afghanistan wars began, 211,819 combat veterans have been treated by the VA for post-traumatic stress disorder (PTSD) about 16% of the 1.3 million who fought. But the VA says it sees only about half the veterans from the two wars, because hundreds of thousands seek care elsewhere or not at all.(14) The following resources reported that veterans PTSD is as high as 30%. Epstein (2005) reported as many as 30% of veterans who fought in Korea, and are still alive today, may have symptoms of PTSD. More than 30% of the Vietnam veterans have suffered with symptoms of PTSD (Kukla et. al., 1990).(15,16) The U.S. Department of Veterans Affairs Fifth Annual Report (2007) suggests at least 30 to 40 percent of Iraq veterans will face serious psychological problems associated with PTSD.(17) The average risk of recurrence of MDD is 85% within 2-3 years.(18)

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Chapter Sixteen

How Does Lithium Work in the Brain? The Hypothalamic-Pituitary Axis (HPA)
PART TWO
As stated in my thesis, it is my belief that the true power of lithium, to remarkably, often miraculously, promote healing of severe mental and neurological diseases such as bipolar disorder, MDD and PTSD lies in lithiums direct normalizing effect upon the dysregulated hypothalamic-pituitary axis (HPA), hypothalamic-pituitary-adrenal (HPAA) and thyroid axes (HPTA). The pituitary gland is called the "master gland" of the body. It is called the master, because of its critical control, of all the major hormones within the human body. The pituitary gland may be the master, but the real culprit in mood disorders appears to be the hypothalamus.

Hypothalamus Functions
The hypothalamus is responsible for the production of many neuro-hormones that activate the pituitary gland, to produce further hormones that target specific endocrine (hormonal) glands, i.e., (thyroid, thymus, adrenal glands, pancreas, ovaries and testes) throughout the body. The hypothalamus has many different functions, to name a few it regulates hormone production, body temperature, hunger, thirst, digestion, immune system, mood, emotions and sexuality. Most importantly, for sleep disordered individuals the hypothalamus regulates circadian cycles, aka biochemical and hormonal rhythms within the body, that have a huge impact on the quality, and quantity of sleep that one gets. This is just one area where lithium has been proven to have a normalizing effect; lithium has been demonstrated to normalize the dysregulated circadian rhythm of the human body (Maurizi 1984) (1) as well as animals and other living creatures. It is now widely recognized amongst the psychiatric community that sleep disorders inevitably lead to a diverse group of other comorbid (co-occurring) psychiatric illnesses; fix the sleep disorder and you will find that many of the symptoms of comorbid psychiatric illnesses dramatically improve or vanish altogether. Lithium corrects the psychosis by inhibiting adenylate cyclase and slowing the circadian rhythm. (Maurizi 1984) (1)

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Hypothalamic Hormones Involved in MDD Dysregulated Hypothalamic Hormones

For the purpose of this discussion, Dysregulation refers to the state of the body being unable to normalize stress hormone levels required to maintain the balance or homeostasis of human biochemistry; specifically in this instance the loss of normal hypothalamic-pituitary hormones and primary stress hormone levels. Main Teaching Point: There are 4 major hypothalamic hormones involved in the cause and/or treatment of MDD and PTSD and Lithium has been demonstrated to adjust, normalize or regulate all 4 of them.They are the Antidiuretic hormone (ADH), Corticotropin Releasing Factor/hormone (CRF) and or (CRH), Oxytocin and Thyrotropin-releasing hormone (TRH). Antidiuretic hormone (ADH) aka Arginine vasopressin (AVP) Is a hormone that controls the reabsorption of molecules in the kidneys and the regulation of water. ADH plays a critical role in glucose, and salts in the blood and maintaining homeostasis. It appears that increased AVP is involved with MDD as well as PTSD. (de Kloet et. al., 2008) (2) These human data support the hypothesis of increased AVP release and receptor function as pathogenetic (potentially causal) characteristics of major depression. (Goekoop et. al., 2010) (3) Stress alters the secretion of one or more of the hypothalamic factors which interact at the pituitary Patients with bipolar disorder show a (abnormal) biphasic secretion of AVP. AVP might be responsible for an increased catecholamine activity; i.e., increased adrenaline, noradrenaline and dopamine levels. (Scantamburlo et. al., 2001) (4) Mean plasma AVP concentrations were higher in the group of depressed patients than in controls. A subgroup of 16 patients showed very high levels of plasma AVP (van London et. al., 1997) (5) Lithium effects: Lithium appears to be a blocker of excess AVP. (6,7) Lithium is listed as a diuretic and is useful in the treatment of (water retention due to AVP dysregulation) associated with chronic heart failure. (6) Lithium therapy is known to reduce the kidney responsiveness to AVP. (7) Additional Arginine vasopressin hormone information: AVP is a hormone that controls the reabsorption of molecules in the kidneys and the regulation of water. ADH plays a critical role in glucose, and salts in the blood and maintaining homeostasis. Corticotropin-releasing hormone (CRH) Excessively high levels of CRH are associated with higher risk of depression. A number of clinical investigations and postmortem brain studies have provided evidence that excessive corticotropin-releasing hormone (CRH)

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secretion and neurotransmission is involved in the pathophysiology of depressive illness (8) Too much CRH release and there may be a cascading effect downstream, creating an excess release of stress hormones (particularly cortisol) leading to a variety of stress-related mental and neurological illnesses. Dysfunction of the hypothalamic CRH systems has been reported in patients with major depression and post-traumatic stress disorder (9-12) Evidence of dysregulation of CRH in bipolar disorder has been verified as well. (13,14) Considerable evidence exists from cerebrospinal fluid studies, postmortem tissue receptor measurements, and CRH stimulation test studies to support the hypothesis that CRH is hypersecreted in depression, resulting in both pituitary-adrenal axis hyperactivity and certain signs and symptoms of depression, e.g., decreased libido, insomnia, and decreased appetite. (Nemeroff 1992) (15) Lithium effects: The findings of a study conducted in 2003 suggest that the therapeutic actions of lithium may be in part a direct result of lithiums actions on central CRH nerve systems.
(16)

Lithium administration decreased CRH (1) mRNA expression in both the amygdala and frontal cortex of rats. (16) In a study of stressed adult rats, lithium reduced the CRF-like immunoreactivity in the hypothalamus. (17) This action by lithium, of decreasing CRF, may be one of the key mechanisms for its therapeutic value to MDD and PTSD victims as they have also been found to have a hyperactive central CRH system. (18) Additional Corticotropin-releasing hormone information: Corticotropin-releasing hormone, aka corticotropin-releasing factor (CRF), is a hormone produced by the hypothalamus. CRH has been shown to be one of the most commonly imbalanced hormones in the anxiety, mood and stress-related disorders. CRF plays a critical role in integrating and coordinating the endocrine, (glandular) and behavioral responses to stress. CRH is a primary regulator of the HPA, i.e., the final common pathway in the stress response. (19) Oxytocin Oxytocin appears to be altered with in postpartum depression, in patients with a history of traumatic stress and actually shows a significantly larger increase when individuals are stress challenged in those with a traumatic stress history than those without a traumatic history, i.e. normal individuals.(20) This action of Oxytocin increase may be a protective response, adaptation or compensation to stress. Increased Oxytocin levels have been demonstrated to reduce the effects of acute stress in mammals and low oxytocin levels appear to be associated with the severity of postpartum depression. Oxytocin warrants further study as a therapy for the treatment of anxietyrelated disorders. (21)

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Lithium effects: Lithium has been demonstrated to increase levels of Oxytocin in the blood stream of rats (human studies unavailable) and may be useful in withdrawal from marijuana in humans. (22) Oxytocin known as the love hormone is increased by lithium and for good reason. Oxytocin as a healer of the nervous system is now being investigated for the treatment of depressive and anxiety disorders. Additional Oxytocin information: Oxytocin is best known for its release in large amounts after distension of the cervix and uterus during labor. Scientist are now investigating oxytocin's role in anxiety disorders such as PTSD and depressive disorders such as postpartum depression Thyrotropin-releasing hormone (TRH) Dysregulation of TRH may be involved in MDD and PTSD. Therapies that increase TRH have demonstrated a rapid improvement of MDD symptoms. Thyrotropin-releasing hormone (TRH) has been known anecdotally to produce antidepressant effects since the 1970s. Recent clinical reports have shown that intrathecal administration of TRH can more reliably induce remissions of major depression that last for 2-3 days. (23) Ten women with major depression were given a single injection of thyrotropin-releasing hormone (TRH) and a single injection of saline in a double-blind, crossover comparison. TRH precipitated a rapid, brief improvement in depression without significant sideeffects.(24) Lithium effect: In a study of rats (no human study available) lithium was found to increase TRH. Lithium treatment results in increased hypothalamic TRH.(25) This effect of lithium upon TRH may be one of the ways that lithium reduces symptoms of MDD.

Pituitary Functions

The pituitary gland secretes hormones that directly control the following processes in the body; blood pressure, growth, water regulation, thyroid gland hormone production, and adrenal gland hormone production, influencing the metabolism of proteins, glucose and fats, as well as sex organ functions; to name a few. Perhaps one of the most compelling findings of the critical and essential nature of lithium for the normal function of the pituitary gland is the fact that when animals are subjected to laboratory-induced lithium deficiency, the pituitary gland maintains normal lithium levels within the tissue of the pituitary (as well as adrenal glands) while other tissues in the body are found to have as much as 50% reduction in lithium levels. This finding was reported in the following study published the Journal of the American College of Nutrition.

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Study titled: Lithium: occurrence, dietary intakes, nutritional essentiality. Gerhard N. Schrauzer, PhD, CNS, FACN, Biological Trace Element Research Institute, Chula Vista, CA A key result of this study was that the mature, Li-deficient rats retained Li at control (normal) levels in the pituitary and adrenal glands, suggesting that these organs require Li for some functions. In other tissues, including blood, cerebrum, liver, kidney, spleen, heart and bone, a 20% to 50% reduction in lithium contents compared to the controls occurred, and all soft tissues contained less Li than the endocrine tissues. (Schrauzer 2002) (26)

Pituitary Hormones Involved in MDD Dysregulated Pituitary Hormones

Adrenocorticotropic hormone (ACTH), aka Corticotropin - Elevated ACTH levels are a common finding in human depression. Elevated ACTH has been noted in cases of major depression, (27-31) and depressed drug addicts. (32) Excessive levels of ACTH have also been demonstrated to cause psychosis. (33) Lithium effect: The effects of excess levels of ACTH aka corticotropin are neutralized by lithium. In a human study lithium has been shown to prevent the psychosis and anxiety associated with acute excess levels of ACTH. (33) Intranasal administration of ACTH stimulates secretion of adrenaline and noradrenaline. (34) Lithium significantly reduces adrenaline and noradrenaline. Additional studies have demonstrated a relationship between lithium, ACTH, MDD and bipolar disorder in humans. (35-37) Study titled: Lithium prophylaxis of corticotropin-induced psychosis. Published in the Journal of the American Medical Association, (Falk et. al. 1979) In none of the patients treated with lithium did a psychotic reaction occur, although in a comparable group of 44 patients previously treated identically with corticotropin (aka ACTH) but without lithium, six (14%) became psychotic. (33) Additional information on ACTH: Stimulates synthesis and secretion of adrenocortical hormones (cortisol, androgens, and aldosterone) which affect the metabolism of glucose, proteins, and fats. Secretion of cortisol is controlled almost entirely by ACTH. ACTH has been implicated in MDD and PTSD. Luteinizing hormone (LH) Stimulates ovulation and estrogen and progesterone synthesis in ovaries; stimulates testosterone synthesis within the testes. Stress causes significant changes to LH, estrogen levels (estradiol) and testosterone. Stress and corticotropin-releasing hormone inhibit the reproductive axis. The half-life of luteinizing hormone was significantly shorter in women with depression than in their matched controls the blood level of estradiol (estrogen hormone) was significantly

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lower. The mean plasma estradiol level was 30% lower in the follicular phase in women with depression than in their matched controls: Estradiol is known to affect a number of neurotransmitter systems in the brain. (Young et. al., 2000) (38) Lithium effect: - In a human bipolar study lithium increased Luteinizing hormone levels. (39)

Estrogen: Lithiums effect upon the estrogen hormone (estradiol) was found in (an animal study) to increase the estrogen hormone-estradiol.(40) Increased levels of estradiol have been reported to be effective in perimenopausal depression. Testosterone: Lithiums effect upon testosterone (in bipolar patients) is to raise levels into the normal range of healthy individuals and maintains normal levels even after 5 years of examining the hormone levels. (41)

Pituitary Neuropeptides
Neuropeptides are one way the brain cells communicate with each other and in this way neuropeptides are regarded as minor-neurotransmitters (signaling molecules) neuromodulators (affecting the health and function of neurons {brain cells}). Neuropeptides are very small protein molecules that have been discovered to affect brain functions such as learning, memory and mood. Neuropeptide Y (NPY) - NPY has been demonstrated to be significantly reduced in many patients with MDD. I quote from the abstract of the MDD, NPY study (Heilig 2004); A robust suppression of NPY levels in (MDD) patient cerebrospinal fluid (CSF) was found. Our present findings are in line with an extensive animal literature, and further support the notion that impaired NPY function could contribute to depressive illness. (42) Additionally the abstract from the study (Widerlov et.. al., 1988) states; The finding of reduced CSF concentrations of NPY in patients with major depression may reflect disturbed synthesis, turnover or degradation of the peptides. (43) Lithium effect: Lithium has been found to increase NPY in human cerebrospinal fluid and rat brain. (44,45)
(44)

Lets review the hypothalamic and pituitary hormones that have been identified to be dysregulated in MDD. The hypothalamic hormones are the Antidiuretic hormone (ADH), Corticotropin Releasing Factor/hormone (CRF),(CRH), Oxytocin and the Thyrotropinreleasing hormone (TRH). The pituitary hormones are the Adrenocorticotropic hormone, Luteinizing hormone and Neuropeptide Y.

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Chapter Seventeen

The Hypothalamic-Pituitary-Adrenal axis (HPAA)

& Primary Stress Hormone Imbalances of Major Depressive Disorder (MDD)
My research has led me to one conclusion: Lithium is a master nutrient for the normalization of stress-related hormonal function via interaction with the hypothalamic-pituitary-adrenal axis (HPAA) and the hypothalamic-pituitary-thyroid axis (HPTA). Excessive and or dysregulated hormone production from the hypothalamus, pituitary, adrenal and thyroid glands are consistently involved with the symptoms of MDD/PTSD. The HPAA is a complex neuro-hormonal network of communication between the hypothalamus, pituitary and the adrenal glands.

If this system (HPAA) is dysregulated, abnormal levels of the primary stress hormones (adrenaline, noradrenaline, dopamine and cortisol) occur and stressrelated illnesses such as MDD/PTSD may result. (Millar 2012)
The dysregulation of the hypothalamic and pituitary axis hormones followed by the imbalanced primary stress hormones (adrenaline, noradrenaline, dopamine and cortisol), are the first of a chain reaction of chemical imbalances to occur in response to severe life threatening/traumatic events. These chemical imbalances frequently become permanently embedded, and statically fixed, within the central nervous system. This permanent fixation of elevated or reduced (perhaps fatigued) stress hormones in MDD or PTSD is a particular problem for combat veterans who are subjected to life and death situations on a recurring daily basis. Identifying the primary stress hormone imbalances of MDD goes a long way in understanding the causal elements of this devastating illness. Here I present what I believe are the main (primary) stress-hormone/neurotransmitter imbalances associated with MDD and that lithium, to a significant degree, normalizes. The dysregulated (HPAA) leads to (I believe the research shows) abnormal levels of the primary stress hormones, adrenaline, (1-4) noradrenaline, (8-11) dopamine (11,13-15) and cortisol, (23,24) all of which are a common finding in MDD.

Lithium Normalizes Primary Hormonal Imbalances of MDD

MAIN TEACHING POINT: Lithium has a normalizing effect upon the imbalanced stress hormones adrenaline, (3,5-7) noradrenaline, (3,12) dopamine, (17-23) cortisol.(26,27) Levels of the primary stress hormones in MDD are typically significantly lower than the normal healthy population; however, in certain sub-groups of depressed patients, these stress horm-

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ones may also be abnormally high. The common finding in depression is that the primary stress hormones are either too high or too low; in other words dysregulated. Here is a look at a few of these studies. Remember there are three catecholamine-primary stress hormones, they are; adrenaline, noradrenaline and dopamine. Study titled: Catecholamine measures for diagnosis and treatment of patients with depressive disorders. (Schatzberg et. al., 1980) Measurements of catecholamines (adrenaline, noradrenaline and dopamine) show certain statistical patterns with three types of depression; bipolar depression, major depression and schizophrenia/shizoaffective depression. (Schatzberg et. al., 1980) (1)

Adrenaline
Adrenaline levels have been shown demonstrated, to be either too high or too low, comparing depressed, to normal subjects or other subgroups of depression. Fortunately lithium has been demonstrated to (normalize) move adrenaline in both directions depending on the condition being treated. In other words lithium has been shown to increase low adrenaline levels and decrease high adrenaline levels. Measurements of stress hormones are taken from blood, saliva, urine and cerebrospinal fluid (CSF) Study titled: Do concentrations of neurotransmitters in lumbar CSF reflect cerebral dysfunction in depression? (Gjerris et. al., 1988) Journal - Acta Psychiatrica Scandinavica. Adrenaline levels were measured in the cerebrospinal fluid and found to be significantly lower in depressive patients than the control group (Gjerris et. al., 1988) (2) Lithium effect: In depressed bipolar patients, lithium increased adrenaline metabolite MHPG and most significantly in those who had the greatest positive response (relief of depressive symptoms) to lithium treatment. (Beckman et. al., 1975)(3) No human studies available to demonstrate an increase of adrenaline in unipolar aka major depression. Abnormally high levels of adrenaline may also be found in different phases or sub-groups of depressed patients. Forty-five percent of the depressed patients excreted markedly elevated levels of urinary adrenaline and(adrenaline metabolite)metanephrine (MET), while only 5% of healthy controls did so. (Davis et. al., 1988) (4) Lithium effect: In a study of patients with primary, major depressions lithium significantly reduced adrenaline metabolite (MHPG). (Linnoila et. al., 1983) (5) In humans lithium has been demonstrated to reduce the adrenaline-induced rise in Cyclic AMP. (6) Acute adrenaline levels causes cardiac arrhythmia and pulmonary edema in rats. Lithium prevents secondary arrhythmia, pulmonary edema and adrenaline induced death in rats injected with high dosage adrenaline. It has been shown that lithium reduces the sensitivity of receptors to adrenaline in rats. (Sobieva et. al., 1981) (7)

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Noradrenaline
Some of the newer antidepressants are noradrenaline reuptake inhibitors, designed to assist in low noradrenaline levels, found in major depression. Noradrenaline is frequently measured by its metabolite, MHPG. Patients with depressive spectrum disorder (DSD) have low levels of the norepinephrine metabolite, MHPG. (Garvey & Tuason 1996)(8) Additional studies have found low noradrenaline (MHPG) levels in major depression. (Muscettola et. al., 1984)(9) (Karege et. al., 1991)(10) (Lambert et. al., 2000)(11) Lithium effect: Lithium increased noradrenaline metabolite MHPG in depressed bipolar patients and, most significantly, in those who had the greatest positive response (relief of depressive symptoms) to lithium treatment. (Beckmann et. al., 1975) (3) Furthermore, lithium increased noradrenaline metabolite MHPG in the normal healthy population by and average of 16%. (Manji et. al., 1991) (12) No human-lithium studies available to demonstrate an increase of noradrenaline in unipolar aka major depression.

Dopamine
Some studies or sub-groups of patients have demonstrated low cerebrospinal fluid dopamine levels in depression. In the present study including 24 depressed patients and 10 controls, we found significantly increased concentrations of total CSF dopamine in depressed patients. This finding suggests a dysfunction in central dopamine turnover in depression. (Gjerris et. al., 1987, 1988) (13, 14) Plasma measurements of dopamine levels have revealed a significant correlation to depression severity scores. (Hamner and Diamond 1996) (15) Major depression is also associated with dopamine receptor sensitivity. Patients with major depression, alcohol dependence and neuroleptic medication displayed a reduced sensitivity of central dopamine receptors compared to control subjects. (Schmidt 2001) (16) Lithium effect: Lithium has the dual effect of increasing levels of dopamine in bipolar disorder (in patents with manic symptoms) (Fyro et. al., 1975) (17) and decreasing dopamine levels (Linnoila et. al., 1983) (18) depending on the condition being treated. In depressed bipolar patients lithium carbonate, which stabilized mood in bipolar patients, reduced the urinary output of HVA(dopamine metabolite)and whole-body dopamine turnover. Lithium lowers brain levels of dopamine in stress-exposed rats. (Eroglu et. al., 1980) (19) When lithium was injected into rats, lithium reduced the functional activity of brain dopamine neurons and this was attributed to the sedative effects noted in the rats. (Nozu et. al., 1976) (20) When lithium was administered to thyroid (T3) treated animals, there was a significant decrease of dopamine and its metabolite, 3,4-dihydroxyphenyl-acetic acid. This suggests that this lithium reduced the synthesis and turnover of dopamine (Rastoge et. al., 1977) (21) and attenuates dopamine regulatory mechanisms. (Elphick 1989) (22)

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In normal rats given lithium an increase of dopamine was noted in the anterior cingulate cortex (CIN), the piriform-entorhinal region (PiEn). Findings of the research suggest changes in the turnover rates of dopamine as well as an action of lithium on dopamine synthesis and/or storage in the nigrostriatal and mesocortical systems. (Gottberg 1989) (23)

Cortisol
Excessively high levels of the primary stress hormone cortisol, a core component of HPAA dysregulation, appears to be a primary driver in the cause of depressive symptoms, as well as a significant decline in overall brain functions, which are so common in mood disorders. (Young 2004) (24) The reported results are in line with prior research on hypothalamus-pituitary-adrenal (HPA) axis dysregulation in patients suffering from high cortisol levels in depression. (Ehlert et. al., 2005)(25) Therapeutic mechanisms which lower circulating cortisol levels hold promise for relieving symptoms of depression and restoring or improving brain function. (Young 2004)(24) Lithium effect: Lithium has been demonstrated to significantly normalize cortisol levels in bipolar disorder (Eroglu et. al., 1979)(26) and maintain cortisol levels over the long term. (Smigan and Perris 1984)(27) The following study published in the British Journal of Clinical Pharmacology speaks to one of the most promising functions of lithium in normalizing HPAA dysfunction; the normalization of excessive cortisol levels in patients with mood disorders. Study titled: A study of the relationship between serum lithium and plasma cortisol levels in manic depressive patients. (Eroglu et. al., 1979) The results of partial correlation analysis revealed that there is a strong negative correlation between serum lithium and plasma cortisol levels. (Eroglu et. al., 1979) (26) In simple terms, this study showed that as lithium levels increase in the body, cortisol levels are reduced accordingly. The following study published in the journal Neuropsychobiology, demonstrated further evidence that lithium significantly normalizes cortisol levels and maintains them over the long-term. Study titled: Cortisol changes in long-term lithium therapy. (Smigan and Perris 1984) Patients showed a significant decrease in a.m. serum cortisol levels after 1 year on lithium. (Smigan and Perris 1984)(27)

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Chapter Eighteen

The Hypothalamic-Pituitary-Thyroid Axis (HPTA)

Thyroid Hormone Imbalances of MDD

The thyroid gland is not traditionally thought of as a primary stress hormone endocrine gland; however recent findings suggest that hyperthyroidism maybe intimately involved in the abnormal stress-response, of major psychiatric illnesses including MDD and PTSD. When the primary stress hormones adrenaline, noradrenaline, dopamine and cortisol are imbalanced, the thyroid gland maybe hyper-functioning as well. In one study of hyper-thyroidism, approximately 50% of the patients were depressed (Sender et. al., 2004) (1) suggesting, perhaps, a strong link between hyperthyroidism and MDD. Other studies have also found a link between depression and hyperthyroidism at rates of 30-40%.(2-5) Dysregulation of the hypothalamus-pituitary-thyroid axis (HPTA) leading to hyperthyroidism is also a common finding of combat veterans with PTSD. To keep this discussion simple, I will mention the two major thyroid hormones, triiodothyronine, (T3) and thyroxine (T4), with regard to the lithium effect in MDD and PTSD. Lithium effect: Lithium rapidly and robustly reduces pathologically elevated thyroid hormones, triiodothyronine, (T3) thyroxine (T4). (6-13) Lithium has been demonstrated in numerous human studies to normalize hyperthyroid hormones in major depression, Graves disease, Toxic Goiter and bipolar disorder. Major Depression - In a long-term study (3.5 years) of lithiums effect upon patients with MDD it was discovered that lithium maintained normal thyroid levels over the long-term. Quote from the abstract; All hormones were also measured in 41 healthy controls matched for age and gender. Patients on lithium had normal serum concentrations of TSH, T4, fT4 and T3 only the levels of rT3 were elevated. The efficacy of the lithium prophylaxis was significantly correlated to the serum concentrations of T3, i.e., the higher the patients' serum levels of T3, the shorter was the overall duration of recurrences of depression within the 3.5-year period. (Baumgartner 1995)(14) Hyperthyroid (Graves disease) Studies of lithiums effect upon hyperthyroid conditions, consistently demonstrate major regulation of thyroid hormones, triiodothyronine, (T3) and thyroxine (T4). The most common cause of hyperthyroid hormones is Graves disease. In a study of lithiums effect upon Graves disease it was determined that lithium reduced T3 by 42% and T4 by 28%. These amazing changes occurred in just 7 days. (Eigenmann and Burgi 1978)(6)

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Diffuse Toxic Goiter (DTG) DTG is a thyroid condition that displays elevated triiodothyronine (T3) and thyroxine (T4). In a study of 22 patients with DTG, the lithium response was evaluated in a therapeutic dose of 900-1800 mg/day for a period of 4-6 weeks. Lithium produced a significant reduction in thyroid hormones T3 and T4. (Pimenov 1982)(7) Similar findings have been demonstrated in multiple studies of lithiums effect upon Hyperthyroid hormones T3, T4.(9-14) Bipolar disorder - Eight manic patients were examined before and after lithium treatment, 6001,200 mg daily, for four weeks. Slight reduction in the plasma levels of thyroxine T4, were seen following lithium treatment.(15) Lithium alters the response of cultured cells to thyrotropin-releasing hormone (TRH) and stimulates DNA synthesis. Lithium inhibits thyroidal iodine uptake. It also inhibits thyroid hormone secretion. It is probable that the hypothalamic pituitary axis adjusts to a new setting in patients receiving lithium. (Lazarus 1998)(16) Lithiums powerful normalizing influence upon the hormones of the dysregulated hypothalamic-pituitary-adrenal and thyroid axes, primary stress hormones (adrenaline, noradrenaline, dopamine and cortisol), and thyroid hormones (T3 & T4) makes lithium, in my understanding of mood disorders, the single most powerful remedy for mood disorders ever discovered. Add to this, the amazing fact that lithium increases brain mass in mood disorders and now lithium truly has Hollywood star power! However, this is only the tip of the iceberg of the wide range of chemical imbalances that lithium restores in major depressive disorder and all the other mood disorders. There are dozens of different secondary chemical imbalances that I have been able to identify in MDD and I am sure there are many more. Lithium has been demonstrated, in scientific animal and human studies, to normalize approximately 80% of these identified secondary chemical imbalances of major depression. (Millar 2011) Next I will share a portion of the other 80%, that we have evidence in human and/or animal studies demonstrating the balancing effect of lithium.

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Chapter Nineteen

Lithium Normalizes Secondary Chemical Imbalances Associated with MDD

Lithium has been shown in animal and or human studies, to normalize the following beneficial chemical compounds, that are frequently found to be significantly reduced, or dysregulated, in MDD. Important note: The studies noted herein are not studies of MDD: They are studies of miscellaneous lithium effects in different scenarios. So we dont know with absolute certainty that lithium would have the same exact effect in MDD chemical imbalances. These findings are simply good clues as to what lithium may be doing in MDD. I suspect that many of these secondary chemicals become imbalanced, or dysregulated, in response to chronically dysregulated primary stress hormones as a consequence of the dysregulated hypothalamic-pituitary-adrenal (HPAA) and thyroid axes (HPTA). Stated differently, these secondary chemical imbalances are driven by the primary HPAA and HPTA dysfunction. Because no lithium human studies exist for the secondary imbalances, I have included the animal studies. Lets begin with the secondary chemical imbalances that have been found to be reduced in depression and that lithium has been shown to increase. In the following animal and human studies lithium has been demonstrated to provide the following beneficial effects:

Lithium increases the following secondary chemicals found to be reduced in MDD.

Increasing AKT cellular communication (signaling) - Reduced AKT cellular signaling (communication) is a proposed chemical pathway (cause) of depression.(1-3) Lithium increased AKT in mouse brain.(4) Increasing Adenosine Triphosphate (ATP) - Lithium has been demonstrated to lead to an increase in ATP production in rat brain (hippocampus). (Wilot et. al., 2004)(5) ATP is a pure cellular energy storage molecule. The depressed brain possibly has a defective neuronal ATP production caused by defective brain glucose (and lactate) transport. (Pereira et. al., 2011)(6) Increasing BCL-2 - B cell lymphoma protein-2 (Bcl-2) protects nerve cells from death from numerous toxic reactions and promotes brain cell growth. Cell death is present in major depression particularly in the hippocampus. BCL-2 appears to protect the brain from cell death in stress-related mood disorders, such as major depression. Repeated unpredictable stress reduces BCL-2 levels.(7) Lithium significantly increases BCL-2 in the brain. Lithium significantly increases cell growth of the hippocampus. lithium-induced increases in bc1-2 are also observed in cells of human neuronal origin and are observed in rat frontal cortex at lithium levels as low as approximately 0.3 mM. (Manji et. al., 2000)(8,9)

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Increasing Brain-derived Neurotrophic Factor (BDNF) - BDNF is part of the neurotrophic family of proteins produced in the brain that promotes the growth of brain cells and significantly protects brain cells from stress-induced, premature death. BDNF may also be a positive factor in maintaining cell growth in the hippocampus, an area degenerating in MDD. (10) Lithium has been demonstrated to triple the levels of BDNF in the blood of psychotically depressed patients.(11) Lithium significantly increased the expression of BDNF in the hippocampus, frontal cortex and temporal cortex of rats.(12) Increasing Delta sleep-inducing peptide (DSIP) - Decreased DSIP is correlated to sleep disturbances. (13) Lithium elevated DSIP in patients with mood disorder. (Regnell et. al., 1988) (14) Increasing Docosahexaenoic acid (DHA) metabolism - DHA has anti-inflammatory properties that appear to be highly beneficial to major depression. MDD is shown to have increased levels of interleukin 1 (IL-1), an inflammatory cytokine. (15) This study demonstrates, for the first time, that lithium can increase brain 17-hydroxy-DHA formation, indicating a new and potentially important therapeutic action of lithium. (Basselin e.t al., 2010) (16) Increasing the omega-3 fatty acid DHA may help prevent or treat Alzheimer's disease. (17) Increasing Estrogen - Lithiums effect upon the estrogen hormone (estradiol) was found in an animal study to increase the estrogen hormone-estradiol.(18) Low levels of estradiol have been implicated as potentially causal in depression. Increasing estradiol levels diminished a mouse model of depression.(19) Increasing GABA - Lithium increased GABA in the rat brain (cerebellum and mid-brain). GABA is a neurotransmitter that benefits memory. (20) GABA has been demonstrated to be significantly reduced in MDD. (21) Increasing Glutathione & Glutathione S-transferase (GST) - Lithium increases GST and GST increases glutathione levels. (22) Glutathione and GST are powerful antioxidants that prevent free-radical damage of brain cells and may prevent cancer by protecting DNA damage (mutation).(23, 24) GST levels have been found to be significantly reduced in MDD. (25) This is just one of several ways that lithium protects the brain from free-radical damage and degeneration. Increasing Mitochondrial Respiration Mitochondrial respiration was found to be reduced in an experimental model of depression in rat brain.(26) Disturbances in metabolic networks, e.g., mitochondrial respiration are implicated in the pathophysiology, brain volumetric changes, symptomatic expression (e.g., neurocognitive decline), and medical comorbidity in depressive disorders. (McIntyre 2007)(27) Numerous experimental models suggest mitochondrial respiration dysfunction in development of depression and affective (mood) disorders.(28) Lithium increases mitochondrial cellular respiration.(29) Increasing Testosterone - Lithium increased testosterone in bipolar men and maintained normal levels even after 5 years of study. (30) Low testosterone has been implicated in psychological symptoms.(3l) Increasing immune functions of Natural Killer cells - Major depression can have severe effects upon the immune system particularly lowering natural Killer cell cytotoxicity. (32-35) Natural killer (NK) cells are lymphocytes that are involved in defense against various forms of stress, such as infection with parasites malignancy, viruses, or bacteria. Lithium increases lymph-

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ocyte natural killer cell counts and natural killer cell cytotoxicity and may be very effective in the fight against cancer. (36-38) N-acetyl aspartate (NAA) Reduced NAA levels indicate dying or degenerating brain cells. Lithium has been shown to cause a significant increase in total brain NAA concentration. NAA concentration increased in the frontal, temporal, parietal, and occipital lobes brain regions following lithium treatment. (39) Significant reductions of NAA have been noted in depression, by MRI/MRS scans. (40,41) Increased Allopregnanolone & Pregnenolone (Natural Brain Neurosteroids) - These two Neurosteroids have been demonstrated to provide powerful brain cell protection and growth stimulation to brain cells. Baseline levels of Allopregnanolone & Pregnenolone are significantly reduced in major depression.(42) Lithium significantly increased Allopregnanolone & Pregnenolone in lithium treated rats.(43) Many neuroactive steroids (NS) demonstrate neurotrophic and neuroprotective actions. Allopregnanolone levels are significantly elevated in lithium-treated rats. Pregnenolone levels also tend to be higher following lithium treatment. NS induction may be relevant to mechanisms contributing to lithium therapeutic efficacy and neuroprotection. (Marx et. al., 2008) (43) Increased Neurotrophin 3 - Lithium increases the expression of Neurotropin-3 (NT3). NT3 is an interesting protein that regulates neuronal survival, synaptic plasticity, and neurotransmission. Animal studies have shown that it also modulates the neurotransmitters, serotonin and noradrenaline, which are essential in the development and treatment of depression. (44) Reduced levels of NT-3 mRNAs have been found in patients with MDD. (45)

Lithium reduces the following secondary chemicals found to be elevated in MDD.

Reduced Arachidonic acid (AA) AA is a omega six inflammatory fatty acid. Increased levels of AA have been implicated as a causal factor in major depression. (46,47) Lithium decreases arachidonic acid turnover in rat brain.(48) Reduced Glutamate Glutamate is a neurotransmitter that when overproduced can cause severe brain cell damage, even cell death. Referred to as glutamate excitotoxicity, this reaction may be causal in major depression.(49) Animal research has demonstrated lithiums ability to significantly reduce glutamate excitotoxicity cellular damage. (49-51) Reduced Monoamine oxidase A (MOA-A) - This may be the main reason that lithium so powerfully elevates low levels of monoamines, aka noradrenaline, dopamine and serotonin in the brain. Monoamine oxidase A is the enzyme primarily responsible for reducing these hormone-neurotransmitters. It was recently discovered in major depression that MOA-A is highly elevated (average 34%) in every brain region assessed. The authors concluded: The sizable magnitude of this finding and the absence of other compelling explanations for monoamine loss during major depressive episodes led to the conclusion that elevated MAO-A density is the primary monoamine-lowering process during major depression. (Meyer et. al., 2006) (52) Lithium reduced MAO-A cellular activity in primary depression and bipolar depression. (53,54)

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Chapter Twenty

Toxic Heavy Metal Causes of MDD

Heavy metal toxicity is well known to cause numerous psychological disorders such as depression, anxiety and excessive anger. (1) Heavy metals attack the mitochondria (energy factory) of the cell causing severe loss of respiratory function and mitochondrial swelling leading to increased production of free radical damage and premature cell death. Toxic metals are interacting with and altering major cellular biochemical systems at low dose levels that may not produce signs of obvious metal toxicity. (2) Mercury is perhaps the worst offender causing neurological and psychological symptoms; (1) however, aluminum, arsenic, cadmium, lead and uranium also have similar effects upon the nervous system as well. (3) Lithium effect: Lithium provides robust protection from heavy metal toxicity. Lithium has been shown to protect cells from aluminum, (4,5) arsenic, (6) cadmium, (7) lead (8) and mercury toxicity. (9,10) Animal studies have shown a wide array of protection by lithium to every single toxic metal analyzed thus far. (Millar 2011) Lithium protects cells from toxic metal damage via multiple chemical pathways. One of the most impressive protective actions is lithiums blocking of cellular uptake of the toxic metals into the nucleus of the cell where the metals have a genetically mutating effect. (11) One study revealed that lithium actually blocked the uptake of mercury reducing the intracellular concentration of mercury by 45% (9) and another study provided similar results. (10) Furthermore, lithium protects nerve cells from toxic metals by stimulating the production of BCL-2 (a nerve protecting protein), superoxide dismutase (SOD) (a super-antioxidant) and glutathione (super-antioxidant) by nerve cells. Increased production of BCL-2, SOD and glutathione by lithium protects nerve cells from numerous neuro-toxins. (11-14) Finally, lithium has been demonstrated to act as a chelating agent in the removal of aluminum and mercury. (15-17) Lithium chelation has potential for removing toxic metals from the body although studies upon humans have not yet been conducted.

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Chapter Twenty One

Posttraumatic Stress Disorder

Clearly the true cost of this war in human suffering is beyond anything we could have imagined.
76% of retired/separated service members say they have reported mental health symptoms to a health care provider according to The Presidents Commission on Care for Americas Returning Wounded Warriors, Final Report, July 30, 2007. (1) Note: The most recent publicized report (Fox News May 18, 2012) puts the PTSD rate over 40% for returning veterans of Afghanistan and Iraq. This is confirmation that the Veterans for Common Sense estimates of PTSD exceeding 600,000 troops, is likely the truth of this desperate situation. With the returning veterans, from the Afghanistan and Iraq war, comes a tsunami of human suffering; returning home to a continued fight to survive, with a traumatized central nervous system that has been severely abused by protracted acute and chronic stress. Indeed PTSD has become the new epidemic for our returning troops. Since the war began in 2001 about 2.5 million U.S. troops have deployed to the wars in Afghanistan and Iraq with many serving in 3-5 tours. This has exposed the combat veterans to prolonged periods of combat-related stress and multiple traumatic events. It appears now that the psychological cost of this protracted deployment is excessively higher than the physical injuries from the war. Many times more troops will die by suicide than were killed in the war. According to a 2008 RAND Corporation study, one in five Afghanistan and Iraq veterans are suffering from PTSD or Major Depression. As of 2008 about 300,000 veterans have reported symptoms of post traumatic stress disorder or major depression.(2) Additionally researchers found 19 percent (about 320,000) of returning veterans report that they experienced a traumatic brain injury while they were in battle. Traumatic brain injury refers to the spectrum of brain injuries from mild concussion to severe open-head wounds.(2)

In 2012 numbers, we are talking about 600,000 - 800,000 veterans are devastated by war.
Critics of the VA point to another alarming statistic. Only slightly more than half of the veterans are seeking medical care for their condition, possibly due to the stigma attached to the diagnosis or other miscellaneous concerns. Critics further suggest that the problem is at least 50% greater than has been reported by the VA due to veteran resistance to reporting a problem for fear it will affect their careers or fear they will be labeled as someone trying to milk the system for a disability payment as this has been widely reported.

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There is much discussion and conjecture amongst the VA, concerning the heavy numbers of veterans who are claiming that they suffer with PTSD and the wide range of symptoms associated with this condition born out of inhumane stress levels. There is also widespread rumor that the VA is denying veterans the PTSD diagnosis to avoid making disability payments to veterans. There are those within and without the VA that suggest soldiers are seeking a permanent disability PTSD diagnosis, so the soldiers can remain on the government payroll for the rest of their lives. This is absurd and definitely the exception rather than the rule. While many are saying that these veterans are making this stuff up so that can milk the system, I suggest to you that just the opposite situation going on. I suggest that the numbers of veterans suffering with PTSD symptoms is easily 2 times what the VA is acknowledging. To receive a PTSD diagnosis, a soldier must be at the extreme of suffering with this disorder and then and only then will the VA give them the diagnosis and make the soldier eligible for disability payments. Furthermore, the veteran must be willing to admit severe weakness by taking on the PTSD diagnosis. The stigma attached to this diagnosis is huge. Most of the veterans, are likely minimizing their suffering so as not to appear weak and/or to appear to be working the system for a disability payment. The stigma attached to the diagnosis of PTSD is huge and, I believe from my own experience with mental illness that, most of them are minimizing their degree of suffering so as not to be labeled as a liar, or a weak individual. I believe that most veterans would rather suffer in silence than admit they are weak with this mental illness. Most soldiers are trained beyond our understanding to endure, without complaint, degrees of stress and suffering that goes infinitely beyond what normal humans can endure without expressing their pain. A recent analysis reveals Veterans are seeking care at the VA more than ever before. Since 2009 approximately half of the troops that have been discharged from active duty from the Iraq and Afghanistan wars have sought help from the VA. Of those Veterans who used VA care, 48% were diagnosed with a mental health problem. (U.S. Department of Veterans Affairs) (3) However, many Veterans who are suffering with mental health problems have not come in for treatment. Reasons that some Veterans have given for not seeking treatment include:

Concerns about privacy Concern over being viewed as weak Relying on family and friends is preferred Worried that others would lose confidence in them Concern about being treated differently They dont believe treatment is effective Worry about side effects of treatments Challenges with access, such as cost or location of treatment (U.S. Department of Veterans Affairs) (3)

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A Classic Story of PTSD Overlooked by the VA

This is a must read story! See here: (4)

After war, an Air Force pilot's life spirals out of control - CNN.com
By Ed Lavandera , February 15, 2011 CNN.com

The Air Force ordered Maj. Chad Bushman to have no contact with his wife and children for almost two years. STORY HIGHLIGHTS

Pilot faces military inquiry that may result in being discharged His wife detailed years of abuse upon her husband's return from duty Military may have missed the early signs of PTSD Board to determine whether it's in best interest of Air Force to keep the pilot in its ranks

This Situation is Preventable

In this story of Major Chad Bushman we see the classic difficulty that service men and women face as they deal with PTSD. These dedicated men and women of armed forces are trained to extreme degrees to deal with the horrific stress and strain of combat-related, life and death situations. Each and every one of them is psychologically programmed to suppress the normal human emotions of terror during life and death situations and carry on in their duties, without showing the normal human emotions of vulnerability and the weakness of human emotion that naturally occurs during those near-death experiences.

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Regardless how tough they are and successful in their suppression of emotions regarding combat-related experiences these individuals still have central nervous system reactions that cause the stress-related hormones to skyrocket to inhumane levels. These extreme stress hormone reactions all too often cause the central nervous system to become imprinted (permanently programmed) to function at diseased and dysregulated levels that may become fixed and unrelenting once the service member returns to civilian life. If the military fails (in this case for 4 years) to identify obvious cases of PTSD or worse downplays the occurrence of such cases, denying the veteran a diagnosis of PTSD to limit disability payments, the service member is forced to deal with the condition in less than favorable ways. Self-medication, domestic abuse and numerous other detrimental psychological compensatory behaviors result, leaving the veteran and family to deal internally with this potentially life threatening illness. Furthermore, even if the veteran is assessed, the service member naturally resists telling the VA the extremity of their illness for fear that it will mark the service member as weak, potentially ruining their reputation and future career with the military or civilian job opportunities. There is also the pressure to maintain secrecy about this disorder from other veterans as it is seen as weakness by fellow veterans who too often will turn away from relationship from those who admit they have a problem. The stigma of receiving a PTSD diagnosis is huge and about half of the service members who acknowledge symptoms of PTSD refuse mental health services from the VA (according to the 2008 RAND Corp. study) choosing instead to rely upon their own devices to survive with the illness. When asked by the RAND survey why they dont follow up with mental health services offered by the VA, veterans respond that they feared that seeking treatment would lead bosses or colleagues to lose respect for them and that this could severely damage their careers. Other said that the cost of therapy or fears about the side effects from the drugs was a deterring factor. While the RAND study has identified approximately 20% of service members as having PTSD or depression or both, how many more service members are suffering in silence rather than admit there is a problem. I suggest to you that the actual number of combat troops suffering with PTSD symptoms along a spectrum of severity from mild to severe is more likely 40-50%. The stigma attached to admitting there is a problem is so great that I believe that the majority of veterans are not being honest about their struggle with PTSD symptoms. While some in the VA have suggested that many veterans are fraudulently seeking a diagnosis of PTSD so the veteran can go on permanent disability and receive disability payments I believe this is the rare exception rather than the rule. The stigma of the PTSD diagnosis is great and the majority of our veterans are far too proud and strong to admit they need our help. I believe the story of Major Chad Bushman is all too often the end result of the stigma of this illness. We must and can do more to reach out and educate these service men and women that there exists natural nutritional remedies that are supremely efficient at managing the dysregulated stress-hormone response that they are forced to live with. If we fail to reach them, we condemn many of them to a never ending tumult that curses their daily life and interns them, to forever live as prisoners of war.

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The Solution for this Challenge

We must insist that the VA administer the stress-hormone tests to all combat veterans (upon their return from combat) to determine whether or not the central nervous system has been significantly impacted by combat or military service near the front lines. It is only through the examination of the primary stress-hormone levels and thyroid hormones that we will see the true effects of war upon our veteran population. This would set a new standard of assessment and transform the discovery process, ensuring that all veterans receive proper care for these hormonal imbalances. Lab testing of stress hormones has confirmed dysregulated hormones, adrenaline, noradrenaline and cortisol many years after war in veterans with PTSD. We now know from thyroid hormone testing of WWII veterans that those who suffer with PTSD still have abnormally elevated thyroid hormones 50 years after the war and this is an absolute confirmation that PTSD is a lifetime illness with devastating health consequences over a lifetime. Please join me in this campaign to bring the truth of essential nutrients to our troops who so desperately need it at home and for those who are still in the battlefield!

PTSD Diagnosis and Symptoms

A formal diagnosis of PTSD requires that the symptoms last more than one month and cause significant impairment in social, occupational, or other important areas of functioning.(5) The most common signs and symptoms of Posttraumatic Stress are as follows: Hypervigilance/Hyperarousal Isolation Depression Nervousness Irritability Hostility Aggression Sleep disorder up to 90% of combat veterans with PTSD (6) Re-experiencing the trauma through nightmares

Lithium has been demonstrated to provide significant relief for all of these stressrelated-symptoms.

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Pharmaceutical Treatment of PTSD

The power of the lithium breakthrough for PTSD is clearly visible through the examination of the pharmaceutical treatments of the disorder. The most commonly prescribed pharmaceuticals for the treatment of PTSD are Selective Serotonin Reuptake Inhibitors (SSRIs).(7) Antidepressant medications affecting serotonin re-uptake are better than those, affecting noradrenaline reuptake. (8) As you will learn veterans with PTSD do not need more noradrenaline! Treatment options for PTSD include antidepressants, anxiolytics, (anxiety reducing) anticonvulsants, and mood stabilizers. (9) Lithium is actively involved in all four categories of orthodox treatment options for PTSD. Lithium is the number one choice for augmenting antidepressant treatment in treatment resistant depression.(10) Lithium reduces anxiety via increased serotonin synthesis and secretion (11) and by reducing adrenaline and noradrenaline levels.(12) Lithium possesses anticonvulsant aka antiepileptic properties (13) and lithium is the leading mood stabilizer.
(13, 14)

With all these healing properties of lithium associated with pharmaceutical treatment of PTSD, you might assume that there would be extensive research documenting lithiums effects in the treatment of PTSD. Surprise! Just the opposite is true. Lithium has been completely overlooked in randomized double-blind placebo-controlled clinical trials for the treatment of PTSD. So why am I writing this book you ask? If I dont have solid research studies proving that lithium is highly beneficial for PTSD, what am I writing about? For starters some doctors at the VA have known for decades that lithium is very effective in the treatment of PTSD as is demonstrated in the following VA article published in the Journal of Clinical Psychiatry. Article titled: Valproate in combat-related posttraumatic stress disorder. (Fesler 1991) Psychiatry Service, Department of Veterans Affairs Medical Center, Seattle, WA The symptoms of posttraumatic stress disorder (PTSD) suggest sympathetic nervous system hyperarousal and hyper-reactivity. Pathophysiology of this condition may include stressactivated limbic kindling. Anti-kindling agents lithium and carbamazepine have been found effective for PTSD symptoms of intrusive reexperiencing and increased arousal. (15) What I am writing about is the apparent cover up or near complete dismissal of what I believe the scientific research shows is the most powerful nutrient medicine for our suffering veterans. Furthermore, the scientific evidence for the overwhelming benefit of lithium for PTSD is revealed by examining all the chemical (pathways) imbalances that are dysregulated in PTSD. It was

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there that I discovered the incontrovertible evidence of lithiums efficacy for this horrific condition. I believe that I prove this hypothesis beyond a reasonable doubt. If you choose to read the book in its entirety I am sure you will agree that the evidence for lithiums essentiality in maintaining homeostasis (balance) of the human body (central nervous system) is overwhelmingly compelling and incontrovertible. Those who bring an open mind, a willingness to learn and authentic intellectual honesty to this subject matter will come away from this conversation, absolutely blown away by the evidence. I believe that lithium has a unique place in the hall of fame as the supreme neurological nutrient for optimal function of the central nervous system and in the treatment of PTSD. So what direct evidence do I have for the lithium PTSD connection? I could only find a few references regarding lithium treatment for PTSD. The articles indicated that lithium may be useful in the treatment of PTSD. (16,17) An article published in 2008 discussed one of the most exciting areas in which lithium is potentially most beneficial to PTSD. That emerging area of research is in the area of growing brain tissue in the atrophying hippocampus. The shrinking hippocampus is seen in a variety of psychiatric and neurological disorders e.g. post-traumatic stress disorder, recurrent depression, schizophrenia and bipolar disorder. (18) A large study conducted in 2005 at the St Andrew's Hospital, Northampton, UK, reviewed of 249 patient files; 75 of the patients (30.1%) were receiving one or more mood stabilizers, e.g. lithium for conditions of aggression, mood swings, schizophrenia and PTSD. However, lithium was infrequently prescribed. (19) Thats no surprise! Lithium has been placed on the side lines by newer profitable drugs and is being prescribed less and less every year by main-stream medicine. Finally an article published in 2000 stated that, regarding multiple suicides within a single family, the immediate concern is to prevent a PTSD-like syndrome amongst surviving intimate family members and lithium is highly recommended in that situation. (20) So while there is some data on lithium and PTSD, it is sparse. To write this book I perused the Pubmed database and local medical school library, reviewing hundreds of studies, reviews and articles, to discover all the various chemical imbalances associated with PTSD. What I discovered blew my mind and made me a believer that lithium is indeed the right choice for recovery from PTSD. Next, I will show you an overview of the chemical imbalances that have been scientifically demonstrated to be at least related, if not causal, to this stress-induced illness.

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Chapter Twenty Two

PTSD CHEMICAL IMBALANCES

PART TWO

All totaled I have identified 34 different chemical pathways, or chemical molecules, associated with PTSD and we will examine all of them in the upcoming chapters. The most amazing fact is that lithium has been identified (as having a therapeutic effect) in all (but one) of the 34 chemical imbalances associated with PTSD. How could lithium affect virtually all of the major chemical imbalances of PTSD? My theory is that lithium acts at the core primary cause of all of these associated imbalances by acting from the top down, inside and out. I believe that the research suggests that the primary cause of PTSD is a dysregulation of the hypothalamic-pituitary-adrenal and thyroid axes and related primary stress hormone imbalances. I believe (and the research demonstrates) the dysregulation of the HPAA and the HPTA are caused/created and sustained by a combination of extreme emotional, mental and physical traumas, coupled with inherent genetic and structural weaknesses, leaving the individual with emotional/mental memories within the brain, and physical cellular memories within the body. It appears that maximal recovery from PTSD can only be achieved by dealing directly with the dysregulated HPA, HPAA and HPT axes via lithium. So lets take a look at the chemical imbalances within the brain of PTSD patients.

PTSD, Lithium and their relationship to the Hypothalamic-Pituitary Axis (HPA)

Teaching points: 1. The hypothalamus and pituitary glands control the stress hormones that are produced by the adrenal gland. The adrenal gland produces adrenaline, noradrenaline dopamine and cortisol. 2. Posttraumatic stress disorder has consistently been shown to have abnormally high stress hormones, adrenaline and noradrenaline and dopamine. All three hormones have been shown to have a direct correlation with the severity of PTSD symptoms. Lithium normalizes adrenaline, noradrenaline and dopamine levels and has been demonstrated to relieve PTSD symptoms.

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3. Cortisol is found to be either too high or too low in PTSD. Lithium normalizes cortisol levels. Cortisol levels have been shown to have a direct correlation with the severity of PTSD symptoms. 4. Lithium has been demonstrated in numerous human studies to normalize all of the primary stress hormones discussed herein. I believe the key to understanding PTSD is to know the hormonal systems that are dysregulated and deal with them in a natural nutritional way. Recent brain imaging studies such as MRI have demonstrated alterations of fear circuitry within the brain. I believe that PTSD is a fear circuitry disorder that directly disrupts the hypothalamicpituitary-adrenal axis (HPAA) and the hypothalamic-pituitary-thyroid axis (HPTA) and thus throws the primary and many secondary stress hormones and neurotransmitters into disarray. The following study review was published in the Journal of Traumatic Stress (2009) Study titled: Is posttraumatic stress disorder a stress-induced fear circuitry disorder? (Shin and Handwerger 2009) Department of Psychology, Tufts University, Medford, MA. Neuro-imaging studies of posttraumatic stress disorder (PTSD) have reported functional abnormalities in brain regions involved in fear conditioning, extinction, and emotion regulation. In this review, the authors summarize the results of functional neuro-imaging studies and conclude that there is a strong argument for characterizing PTSD as a stressinduced fear circuitry disorder. (Shin and Handwerger 2009) (21) My research has led me to one conclusion: Lithium is a master nutrient for the normalization of the hormonal function via the hypothalamic-pituitary xis (HPA), the hypothalamic-pituitary-adrenal axis (HPAA) and the hypothalamic-pituitary-thyroid axis (HPTA).

Excessive and or dysregulated hormone production from the hypo-thalamus, pituitary, adrenal and thyroid glands are consistently involved with the symptoms of PTSD.

Following are quotes from various authors, researchers and articles regarding Lithium and the HPA, HPAA, HPTA and their relationship to PTSD.
Posttraumatic stress disorder (PTSD) has been associated with dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis as well as of the hypothalamus-pituitarythyroid (HPT) axis. (Olff et. al., 2006) (22) The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behavior. (Jokinen and Nordstrom 2009) (23) These results indicate that Hypothalamic Pituitary Thyroid function may be related to Aggressiveness and Detachment in male suicide attempters. (Sinai et. al., 2009) (24)

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Based on the concept that PTSD is a disorder of stress response systems, numerous studies have suggested changes in hypothalamic-pituitary-adrenal (HPA) axis function in patients with PTSD. (Pace and Heim 2011) (25) Under certain conditions of severe and prolonged stress, the hypothalamic-pituitary-thyroid axis may become activated (Prange 1999) (26) Findings support research associating PTSD with hypothalamic-pituitary-adrenal (HPA) axis changes (Tucker et. al., 2010) (27) Both hyper and hypo-activity of the hypothalamus-pituitary-adrenal (HPA) axis activity are a consistently reported hallmark feature of stress-related disorders, such asposttraumatic stress disorder (PTSD). (Rohleder 2010) (28) Hypothalamic-Pituitary-Adrenal axis alterations in men are associated with trauma exposure during adulthood, also in the absence of psychopathology. (Klaassens et. al., 2010) (29) The hypothalamic-pituitary-adrenal axis and the catecholaminergic (adrenalinenoradrenaline) system are involved in the pathophysiology of post-traumatic stress disorder. (Pervanidou et. al., 2007) (30) Another relevant finding in PTSD is the hypersensitivity of the hypothalamic-pituitaryadrenal (HPA) axis feedback. (Jovanovic et. al., 2010) (31) These alterations reflect an enhanced negative feedback inhibition of the hypothalamicpituitary-adrenal (HPA) axis in PTSD. (Yehuda et. al., 1996) (32) From the Center for Military and Veterans Health, comes the following from an article titled: Stress-related musculoskeletal pain. Extensive and chronic musculoskeletal pain may be explained by activation of the hypothalamic-pituitary-adrenal (HPA) axis due to stress. (McFarlane 2007) (33) From the results of this study, it is suggested that the hypothalamus is one area where Lithium exerts its action. (Ozawa et. al., 1976) (34) It is probable that the Hypothalamic Pituitary axis adjusts to a new setting in patients receiving lithium. (Lazarus 1998) (35) The data also provide indirect evidence that the effect of Lithium is exerted at the Hypothalamus. (Bagchi et. al. 1982) (36) Lithium treatment results in increased Hypothalamic Thyrotropin-releasing hormone. (Morley et. al., 1981) (37) Neuroendocrine studies in humans on the effects of lithium augmentation on the HPA system showed an unexpected and marked increase in the ACTH and cortisol response in the combined dexamethasone/CRH test. (Bauer and Bschor 2006) (38)

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Also, a decrease in cortisol level in Lithium responders and an increase in non-responders was observed, suggesting a regulatory effect of Lithium on the hypothalamic-pituitaryadrenal axis activity. (Rybakowski et. al., 1999) (39) Lithium has acute and chronic effects on the hypothalamic-pituitary-adrenal gland (HPA) axis that are important for both therapeutic (e.g., the treatment of mood disorders) (Spencer et. al., 2005) (40) Results suggest that lithium augmentation increases HPA system activity, (Baethge et. al., 2003) (41) Chronic administration of Lithium Chloride increased the expression of paraventricular nucleus of the hypothalamus (PVN). (Semba et. al., 2000) (42) The evidence was also presented that lithium may alleviate the immune-endocrine component concomitant to an acute affective episode, such as acute phase reaction, cytokine secretion and hyper-activation of hypothalamic-pituitary-adrenal axis. (Rybakowski 2000)
(43)

PTSD Dysregulated Hypothalamic Hormones & Lithium Effects

Main Teaching Point: There are 4 major hypothalamic hormones involved in the cause and/or potential treatment of PTSD and Lithium has been demonstrated to adjust, normalize or regulate all 4 of them. They are Antidiuretic hormone (ADH), Corticotropin Releasing factor/hormone (CRF), (CRH) Oxytocin and Thyrotropin-releasing hormone (TRH). The hypothalamic hormones are referred to as releasing and inhibiting hormones which stimulate the Pituitary to take action, or cease and desist. Arginine Vasopressin (AVP) AVP is a hormone that controls the reabsorption of molecules in the kidneys and the regulation of water. AVP plays a critical role in glucose, and salts in the blood and maintaining homeostasis. AVP has been implicated in PTSD. Study titled: Elevated plasma arginine vasopressin levels in veterans with posttraumatic stress disorder. (de Kloet 2008) Department of Military Psychiatry, Central Military Hospital, Magnus Institute of Neuroscience, Utrecht, The Netherlands. It appears that elevated AVP levels are specifically related to PTSD and the results suggest that AVP is a causative factor in anxiety. Plasma AVP levels were higher in PTSD patients compared to both healthy controls and trauma controls. (de Kloet 2008) (44) Lithium effect: Lithium appears to be a blocker of excess AVP. (45) Lithium is listed as a diuretic and is useful in the treatment of water retention associated with chronic heart failure. Lithium is

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listed as an antagonist (blocker) of the action of AVP. (46) Lithium therapy is known to reduce the kidney responsiveness to AVP. (47) Corticotropin-releasing hormone (CRH) CRH levels are found to be significantly elevated in combat veterans compared to normal subjects. (48) Study title: Serial CSF corticotropin-releasing hormone levels and adrenocortical activity in combat veterans with posttraumatic stress disorder. (Baker et. al., 1999) Psychiatry Service, Cincinnati VA Medical Center, OH, USA. Mean cerebrospinal fluid (CSF) CRH levels were significantly greater in PTSD patients than in normal subjects (Baker et. al., 1999)(48) In a study of suicide victims with a diagnosis of major depression it was discovered that CRH neurotransmission was elevated in the brainstem and that these findings support the hypothesis of a relationship between CRH, depression and suicide in men. (Austin et. al., 2003)
(49)

Furthermore, the neuroendocrinology of PTSD appears to be unique, in that patients have hyperactive central CRH systems with under-activity of the pituitary-adrenal axis. (Kasckow et. al., 2001) (50) In a study of Vietnam combat veterans CRH hormone measurements were significantly higher, (approximately 40%), than the comparison subjects. (Bremner et. al., 1997) (51) unexplained health symptoms and PTSD in Gulf War veterans are associated with relatively greater hypothalamic-pituitary activity which may reflect increased CRH activity and is evident only in consideration of deployment effects. (Golier et. al., 2009) (52) The higher the levels of CRH, the higher the chances of severe psychosis associated with PTSD. (Sautter et. al., 2003) (53) CRH dysregulation or imbalance is a common finding of PTSD and major depression. (50-54) Evidence of dysregulation of CRH in bipolar disorder has been verified as well. (Raadsheer et. al., 1994) (54) (Schmider et. al., 1995) (55) Studies measuring CRH in individuals with PTSD have shown increased levels of corticotropin-releasing hormone within the cerebrospinal fluid. I quote from an article published in 2010, titled, Neuroendocrinology of post-traumatic stress disorder. (Pervanidou and Chrousos 2010) Dysregulation of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis and the (noradrenaline) sympathetic nervous system is involved in the pathophysiology (abnormal chemistry) of post-traumatic stress disorder (PTSD), an anxiety disorder that develops after exposure to traumatic life events. Neuroendocrine studies in individuals with PTSD have demonstrated elevated basal cerebrospinal fluid corticotropin-releasing hormone (CRH) concentrations(Pervanidou and Chrousos 2010) (56)

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A study conducted at a VA medical center showed that PTSD patients given 1 hour of traumarelated audiovisual stimulation showed a significant change in CRH and adrenaline and noradrenaline levels. Interestingly the CRH levels actually went down (compared to the control group) following the experiment (possibly due to a dysregulation of the hypothalamus). I quote, the decline in cerebrospinal fluid CRH levels is surprising and could be due to audiovisual stress-induced increased uptake of cerebrospinal fluid CRH into brain tissue, increased CRH utilization, increased CRH degradation, or to an acute stress-related inhibition or suppression of CRH secretion. (Geracioti et. al., 2008) (57) A study examining corticotropic releasing hormone (CRH) found the following; There is also evidence for an involvement of CRH in the pathophysiology of anxiety disorders. Considerable evidence exists To support the hypothesis that CRH is hyper-secreted in depression, resulting in both pituitary-adrenal axis hyperactivity and certain signs and symptoms of depression, e.g., decreased libido, insomnia, and decreased appetite. (Nemeroff 1992) (58) Study title: Elevated plasma corticotrophin-releasing hormone levels in veterans with posttraumatic stress disorder. (de Kloet et. al., 2008) Altrecht Institute for Mental Health Care, Zeist, the Netherlands. A study of CRH levels in veteran PTSD patients found, Plasma CRH levels were higher in PTSD patients compared to controls. This led to our conclusion, that elevated plasma CRH levels are specifically related to PTSD and not to exposure to traumatic stress during deployment. (de Kloet et. al., 2008) (59) Lithium effect: Fortunately, lithium appears to have diverse regulatory effects upon CRH. The findings of an animal study conducted in 2003 suggest that the therapeutic actions of lithium may be in part a result of lithiums actions on central CRH nerve systems. Lithium administration decreased CRH (1) mRNA expression in both the amygdala and frontal cortex of rats. (Gilmor et. al., 2003) (60) In the hypothalamus, lithium tended to decrease CRH- like immunoreactivity. (Husum et. al., 2002) (61) This action by lithium of decreasing CRH may be one of the key mechanisms for its therapeutic value to PTSD victims as they have been found to have a hyperactive central CRH system. (Kasckow, Baker and Geracioti 2001) (62) Oxytocin Increased Oxytocin levels have been demonstrated to reduce the effects of acute stress in mammals. Oxytocin warrants further study as a therapy for the treatment of anxietyrelated disorders. (Cohen et. al., 2010) (63) Oxytocin appears to have anti-anxiety properties that are related to the exaggerated startle and hypervigilance typically seen in PTSD patients. Oxytocin reportedly decreases anxious feelings in humans and may therefore have therapeutic value for anxiety disorders, such as post-traumatic stress disorder. (Missig, Ayers, Schulkin and Rosen 2010)(64)

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PTSD is challenged by abnormalities of anxiety, social functioning and stress regulation. Oxytocin has been recently proposed for the treatment of PTSD in conjunction with Cognitive Behavioral Therapy for Oxytocins ability to provide the patient with a feeling of safety. Oxytocin has multiple effects upon the nervous system that promote a sense of safety and for this reason oxytocin is a good candidate for treatment of patients with PTSD. Given that PTSD is marked by deficits in anxiety/stress regulation and in social functioning, and that oxytocin is implicated in both of these areas, oxytocin seems a likely candidate for treatment of patients with PTSD. (Olff, Langeland, Witteveen and Denys 2010) (65) Oxytocin appears to be altered with a history of traumatic stress and actually shows a significantly larger increase when individuals are stress challenged in those with a traumatic stress history than those without a traumatic history, i.e. normal individuals. (Pierrehumbert 2010)(66) This action of Oxytocin increase may be a protective response, adaptation or compensation to stress. Lithium effect: Lithium has been shown to produce a significant elevation of oxytocin levels in the peripheral blood of rats. This has been demonstrated to be a therapeutic effect for marijuana withdrawal syndrome. Study title: Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation. (Cui et. al., 2001)(67) Lithiums effect upon oxytocin in morphine dependent rats suggests that lithium might inhibit the physical dependence on morphine as well as psychological dependence in rats, and that this inhibitory effect of lithium on the development of morphine dependence might be associated with oxytocin systems in the central nervous system. (You et. al., 2001) (68) Oxytocin known as the love hormone is increased by lithium and with great benefit; oxytocin is a healer of the nervous system, now being investigated for the treatment of anxiety disorders, such as PTSD. Thyrotropin-releasing hormone (TRH) Stimulates the pituitary to secrete thyroid stimulating hormone (TSH). Patients with PTSD have a blunted (reduced) TRH response to desipramine (a tricyclic antidepressant) and the authors stated that These findings support a link between PTSD and affective (mood) illness. (Kaufman et. al., 1987) (69) Lithium effect: Lithium treatment results in increased hypothalamic TRH. (Morley et. al., 1981) (70) Both bipolar patients in remission and healthy controls showed an increase of TSH response to TRH when treated with lithium in comparison with the testing before lithium administration. (Grof et. al., 1984) (71) Chronic lithium treatment increased TRH binding in the nucleus accumbens and amygdala about two-fold in both Wistar and WKY rats but no change was observed in pituitary binding. Both acute injection and chronic treatment with Lithium Chloride decreased TRH and TRH-related peptide levels in the entorhinal cortex. The present results are consistent with a component role for TRH and related peptides in the moodaltering effects of lithium administration and withdrawal frequently observed during treatment for depression and bipolar disorder. (Sattin, Senanayake and Pekary 2002) (72)

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Circadian Rhythm Altered by a Dysregulated Hypothalamus

The circadian rhythm is the master biological and chemical system that coordinates and regulates the human sleep cycle as well as many other biological functions within the body. Circadian rhythm of sleep-wakefulness is controlled by the master clock located in the hypothalamus of humans. Dysregulation of the circadian rhythm has been shown to cause hormonal imbalances that reportedly may cause varied psychiatric conditions such as PTSD, depression, and sleep disorders.(73,74) When the hypothalamus is dysfunctional or dysregulated, this may disturb the circadian cycle aka circadian clock and poor sleep may be a result.(75) Veterans returning from Operation Iraqi Freedom/Operation Enduring Freedom are suffering with sleep disorder.(76) An average of 80% of patients who suffer from posttraumatic stress disorder experience sleep disorder. These patients have nightmares in which the traumatic event is re-experienced, and they also have difficulty in falling or staying asleep. (Miller 2008)(77) This disturbance has been related to a dysfunctional circadian rhythm located in the hypothalamus. Fortunately lithium resets or influences the (circadian clock) and does so in all mammals and humans. Lithium treatment (of mood disorders such as PTSD and bipolar disorder) influence circadian rhythms and therefore indicates that biological clocks play a role in the causation of these disorders. (Schulz and Steimer 2009) (78) Lithium is a powerful treatment of sleep disorders and this is one of the many areas that lithium has been an absolute miracle for me. I frequently slept only 2-3 hours at a time with horrific restless leg syndrome and now I can sleep a solid 8 hours uninterrupted. Every client that I have consulted with regarding LO and their sleep patterns has reported dramatic improvements of their sleep quality and quantity. Ironically high-dose Pharma-Li is widely known by Psychiatrists to cause insomnia and restless legs. (79) As is the case with many other mineral deficiencies or over-doses of minerals, both situations often cause the same set of symptoms and lithium is no exception.

Hypothalamic Neuropeptides
Neuropeptides are small protein molecules used by nerve cells to communicate with each other. They are in essence minor-neurotransmitters, also known as neuromodulators as they modify the actions of neurons (brain cells).

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Enkephalin Enkephalin is an endorphin, a morphine-like protein, (opioid neuro-peptide) having opiate qualities that occurs in the brain and spinal cord. Low levels of enkephalin may have some effects upon PTSD. Animals with an endogenous deficit in enkephalins might be more sensitive to PTSD-like aversive stimuli and elicit stronger anxiety and depressive PTSD symptoms, suggesting an oversensitivity hypothesis of enkephalin deficit-induced PTSD. (Kung et. al., 2010) (80) Lithium effect: Lithium increases brain enkephalin in rat brain. Increases in brain enkephalin content, were found after rats consumed lithium in the diet for 2-3 weeks. Not only were brain enkephalin levels increased after this treatment, but some signs of basal analgesic responsiveness also suggested that the elevated levels of enkephalins were functionally significant. (Bloom et. al., 1983) (81) Orexin A Orexin A is a neuropeptide produced by the hypothalamus. Orexins have been implicated in the influence of, the sleep-wake cycle, and control of the cardiovascular system, pain, stress, addiction, as well as psychiatric disorders such as anxiety, depression and panic. (Bonnavion and de Lecea 2010) (82) Orexin A (OA) has just recently (2010) been implicated in PTSD. OA has been shown to be low in the cerebrospinal fluid and blood plasma of combat veterans. The study findings Suggest low central and peripheral orexin-A activity in patients with chronic PTSD are related to symptom severity and raise the possibility that orexin-A is part of the pathophysiological mechanisms of combat-related PTSD. See: Low cerebrospinal fluid and plasma orexin-A (hypocretin-1) concentrations in combat-related posttraumatic stress disorder. (Strawn et. al., 2010) (83) Lithium effect: discovered. Lithium effects in relation to OA and anxiety disorders remain to be
(84)

Neuropeptide Y (NPY) NPY is produced in the hypothalamus humans.

and the adrenal gland in

Clinically, lower plasma NPY levels have been correlated with greater psychological distress, increased symptoms of dissociation, and poorer performance among active duty military personnel. (ClinicalTrials.gov) (85) Baseline blood/plasma NPY levels in combat veterans with PTSD are reduced compared to normal subjects. The low levels of NPY commonly persist in veterans long after the war and may cause anxiety hyper-arousal, excessive startle reactions. NPY has been shown to inhibit the release of norepinephrine (usually excessive in PTSD) from sympathetic noradrenergic neurons. Combat stress-induced decreases in plasma NPY may mediate, in part, the noradrenergic system hyper-reactivity (noradrenaline hyperactivity) observed in 97combat-related PTSD. (Rasmusson et. al., 2000) (86) Increased levels of NPY appear to reduce anxiety and psychological distress. (Morgan et. al., 2002) (87)

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Lithium effect: Lithium has been found to increase NPY in human cerebrospinal fluid. (Mathe et. al., 2007) (88) Lithium has a profound effect upon the hypothalamic hormones and neuropeptides restoring balance and assisting in regulating normal hormonal and neurotransmitter function within the human body and appears to be a master regulator of hypothalamic dysfunction. After reviewing all the hypothalamic hormones that lithium influences, the evidence is overwhelming that lithium is influencing the hypothalamus in a normalizing fashion. I have to agree with researchers who have come to the conclusion that lithium appears to be a regulator of the hypothalamus. Next we will examine the Pituitary involvement.

PTSD - Dysregulated Pituitary Hormone

Adrenocorticotropin hormone (ACTH) aka corticotrophin ACTH stimulates synthesis and secretion of adrenocortical hormones (cortisol, androgens, and aldosterone) which affect the metabolism of glucose, proteins, and fats. Secretion of cortisol is controlled almost entirely by ACTH. Intranasal administration of ACTH stimulates secretion of adrenaline and noradrenaline. (89) Excessive levels of ACTH may be a driver of excessive secretion of adrenaline and noradrenaline, two of the primary stress hormones consistently shown to be involved in PTSD. In a stress-test study ACTH levels were found to be significantly higher in the anxiety disorder group than the normal control group. (Gerra et. al., 2000)(90) The ACTH response to corticotropin releasing factor (CRF) is abnormal/blunted in PTSD. The blunted ACTH response to CRH in PTSD patients is similar to that seen in other psychiatric disorders, such as depression, panic disorder, and anorexia nervosa. (Smith et. al., 1989) (91) Excessive levels of ACTH have been demonstrated to cause psychosis. See: Lithium prophylaxis of corticotropin-induced psychosis. (Falk et. al., 1974)(92) Excessive ACTH levels may precede the acute mania of bipolar disorder. (93) Lithium effect: The effects, of excess levels of ACTH, are apparently neutralized by lithium. Lithium has been shown to prevent the psychosis and anxiety associated with acute excess levels of ACTH. (Falk et. al., 1979) (92)

PTSD - Dysregulated Pituitary Neuropeptide

Delta sleep-inducing peptide (DSIP) Research suggests that DSIP is produced in the pituitary as well as the adrenal gland.(94) As the name implies, DSIP is involved in sleep regulation and sleep disorder. DSIP has been shown in human studies to reduce anxiety and assist in the withdrawal from alcohol and opiates. When DSIP was administered to 107

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inpatients, the signs and symptoms of withdrawal disappeared, or significantly improved in 97% of the opiate addicts and 87% of the alcoholics. (95,96) DSIP has not been examined in PTSD; however, it is a likely imbalance due to the sleep disorder associated with PTSD. Low levels of DSIP are associated with depression and schizophrenia and these low levels related to sleep disturbances. 98(97) Low levels of DSIP are also associated with bipolar disorder. (98) Lithium effect: Lithium has been shown to significantly increase DSIP in affective (mood) disorders such as bipolar disorder and PTSD. See: Delta sleep-inducing peptide in CSF of patients with affective illness is elevated by lithium treatment. (Regnell et. al., 1988) (98)

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Chapter Twenty Three

Primary Stress Hormone Imbalances of PTSD & the Hypothalamic-Pituitary Adrenal Axis (HPAA)
Lithium Normalizes the Primary Hormonal Imbalances of Posttraumatic Stress Disorder
Lithium works at the core of stress-related mood disorders such as bipolar disorder, major depression and PTSD, balancing, normalizing, and or regulating neurotransmitters and stress hormones, adrenaline, (11-16) noradrenaline, (25-28) dopamine, (52-58) and cortisol.(61, 62 ) Posttraumatic stress disorder is not classically thought of as a mood disorder. However the fact is that mood is significantly altered in PTSD and the chemical imbalances are virtually identical to the imbalances of bipolar disorder and MDD. This is why I am referring to PTSD as a mood disorder. Furthermore I should be clear that while lithium normalizes the chemical imbalances of bipolar disorder we do not have direct evidence that lithium does so in PTSD as that research has not been conducted yet.

Adrenaline aka Epinephrine

Adrenaline is a catecholamine. Catecholamines adrenaline, noradrenaline and dopamine are the fight or flight primary stress hormones, and research demonstrates that all three are involved in the symptoms of PTSD. When a sufficient stressor occurs, the (autonomic) sympathetic nervous system (SNS) stimulates the release of adrenaline and noradrenaline from the adrenal gland and noradrenaline and dopamine from the brain, to regulate the biological responses, permitting the body to cope with difficult psychological, physiological and environmental stressors. It stimulates both the alpha- and beta- adrenergic (adrenaline) systems, stimulates the heart, dilates lung bronchi and cerebral blood vessels as well as controlling systemic vasoconstriction and gastrointestinal relaxation. High levels of adrenaline immediately following a traumatic event are associated with an increased risk of PTSD symptoms later on. (Delahanty et. al., 2005) (1) As just stated excessive adrenaline levels are present in PTSD (2 ) but also bipolar disorder. (3)

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Adrenaline levels run extremely high in PTSD and levels are virtually identical to Bipolar disorder. In a study of hospitalized patients with affective (mood disorders) PTSD, bipolar disorder, major depressive disorder and paranoid schizophrenia, adrenaline and noradrenaline levels were measured and found to be significantly elevated in all patient groups. (4) However PTSD and bipolar disorder were found to have levels of both hormones that were approximately twice as high as the other conditions demonstrating the level of intensity of PTSD and bipolar disorder. This is yet another similarity of these two conditions. (4) Study title: Sustained urinary norepinephrine and epinephrine elevation in post-traumatic stress disorder. (Kosten et. al., 1987) the journal of Phsychoneuroendocrinology. Compared to patients with MDD and bipolar disorder the authors state, The mean norepinephrine (aka noradrenaline) level during hospitalization was significantly higher in PTSD The mean epinephrine (aka adrenaline) level during hospitalization was also significantly higher in PTSD (Kosten et. al., 1987) (4) In states of mania associated with bipolar disorder, adrenaline levels are extreme and directly associated, with the severity of manic symptoms. In other words the higher the levels of adrenaline the more severe the symptoms associated with the manic state. Adrenaline levels were measured in 19 hospitalized manic patients. Adrenaline levels were significantly elevated and correlated with the severity of the core manic syndrome, anxiety, and hostility. The findings of studying this relationship between excess adrenaline and severity of manic symptoms suggest that the adrenal gland is directly or indirectly involved in the symptoms of mania. (Swann et. al., 1991) (5) The following study analyzed adrenaline aka epinephrine (catecholamine) levels in Vietnam combat veterans. Remember the catecholamines are; adrenaline, noradrenaline and dopamine. Study titled: Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans. (Yehuda et. al., 1992) Department of Psychiatry, Mount Sinai Medical School, New York. This study demonstrated that excessively high levels of catecholamine (adrenaline, aka epinephrine) are present in combat-related PTSD. Dopamine, norepinephrine, and epinephrine concentrations were measured in 22 male patients with PTSD (14 inpatients and eight outpatients) and in 16 nonpsychiatric normal males. The PTSD inpatients showed significantly higher excretion of all three catecholamines compared with both outpatients with PTSD and normal controls. (Yehuda et. al., 1992) (2) Pathological aggression and hostility is often associated with PTSD. Here again adrenaline is a driving force. In a study assessing aggression, hostility and adrenaline levels it was discovered that the higher adrenaline levels naturally increased aggressive states. (6)

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Adrenaline levels are often measured by the urinary excretion of the adrenaline metabolite, (metanephrine). Excessive levels of metanephrine in the urine are a classic sign of abnormally high levels of adrenaline circulating through the system. High metanephrine levels are seen in PTSD. (7) When Vietnam combat veterans are shown films of combat they experience a dramatic rise in adrenaline levels as well as symptoms of anxiety and increased blood pressure. (8) So it appears that the emotion of fear is driving the excessive stress hormone responses of combat-related PTSD and PTSD in general. The following study discusses this phenomenon. Study titled: Fear potentiation is associated with hypothalamic-pituitary-adrenal axis function in PTSD. (Jovanovic et. al., 2010) Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA This study demonstrated that impaired fear inhibition is associated with alterations in HPA feedback. The inability to suppress fear, even in safe conditions is a core problem of PTSD. PTSD patients are continually re-traumatized by their memories and cannot inhibit their conditioned fear. So it could be said that PTSD is associated with the hypersensitivity of the hypothalamic-pituitary-adrenal (HPA) axis feedback. (Jovanovic et. al., 2010)(9) Fortunately Lithium normalizes excess levels of Adrenaline. Lithium effect: In a study of lithium effect upon adrenaline it was discovered that lithium significantly reduced adrenaline in patients with primary, major depressions.(10) Additional human studies have discovered similar findings. (11-13) Lithium has been demonstrated to reduce the adrenaline-induced rise of Cyclic AMP in human studies.(14) It has been shown that lithium reduces the sensitivity of receptors to adrenaline. Acute adrenaline levels causes cardiac arrhythmia and pulmonary edema in rats; lithium removed the secondary arrhythmia and pulmonary edema.(15,16)

Noradrenaline (NA) aka Norepinephrine

Dysregulation of the stress-response system, including the hypothalamic-pituitary-adrenal (HPA) axis and the norepinephrine-sympathetic nervous system (SNS), is a primary cause of chemical imbalance associated with posttraumatic stress disorder (PTSD). Noradrenaline (NA) is a precursor of adrenaline and is produced and secreted by the adrenal gland acting as a primary stress hormone. NA is also produced in the brain arising from the locus ceruleus area and by nerve cells throughout autonomic (sympathetic) nervous system. The excessive level of noradrenaline is a consistent finding in PTSD and is certainly a major player in the symptoms associated with combat-related PTSD. In my opinion, the evidence reviewed thus far emphatically demonstrates that excessive noradrenaline levels are a primary driver of many PTSD symptoms.

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Noradrenaline aka norepinephrine is significantly and pathologically elevated in PTSD and has been demonstrated so in numerous recent studies.(17-20) This next study measured noradrenaline levels of male combat-veteran, PTSD sufferers, compared to a normal control group and found, once again, that noradrenaline levels are consistently and significantly higher than normal control groups even in a non-stressed environment. Additionally, when noradrenaline, aka norepinephrine, normally begins to come down in the late afternoon and even more so during the sleep cycle, combat veterans continue to have elevated noradrenaline levels which appear to be the cause of sleep disorder, insomnia, nightmares, and hyperarousal.(17) Study titled: CSF norepinephrine concentrations in posttraumatic stress disorder. (Geracioti et. al., 2001) Mental Health Service, Veterans Affairs Medical Center, Cincinnati, OH Cerebrospinal fluid (CSF) norepinephrine (aka noradrenaline) concentrations were significantly higher in the men with PTSD than in the healthy men. Moreover, CSF norepinephrine levels strongly and positively correlated with the severity of PTSD symptoms. (Geracioti et. al., 2001) (17) The graph below details the findings.

Blood/plasma levels of noradrenaline have also been found to be elevated in PTSD patients.(18) Noradrenaline acts as a peripheral vasoconstrictor that causes constriction of arterial and venous beds via its alpha-adrenergic action. Too much noradrenaline can cause a significant loss of circulation and oxygenation (via arterial constriction) to the brain and this can lead to numerous brain disorders. It appears from the most recent research on PTSD, that noradrenaline may be one of the most influential hormonal imbalance of this disorder and Given the significant involvement of Central Nervous System noradrenaline hyperactivity in PTSD, and its link to intrusive and hyper-arousal symptoms, it is not surprising that interventions directed at this system have therapeutic potential in PTSD. (Strawn and Geracioti 2008) (19)

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Increased noradrenaline promotes enhanced memory performance; however, excessive noradrenaline levels may be responsible for the persistent memories of trauma associated with PTSD as noradrenaline is associated with memory recall. (20) In a study of hospitalized PTSD patients, noradrenaline aka norepinephrine, was found to be extremely high and was higher than all the other disorders that it was compared to, i.e. Bipolar disorder (BD) MDD and Schizophrenia. I quote: The mean norepinephrine level during hospitalization was significantly higher in PTSD (76 +/- 10.4 micrograms/day) than in Bipolar disorder (60.6 +/- 8.4 micrograms/day), Major Depressive disorder (41.2 +/- 4.7 micrograms/day), Paranoid Schizophrenia (33.4 +/- 4.9 micrograms/day) and Undifferentiated Schizophrenia (34.3 +/- 5.9. (Kosten et. al., 1987) (4) Bipolar disorder like PTSD is characterized by excessively high levels of noradrenaline. In a study of bipolar patients, lithium significantly reduced noradrenaline levels in the cerebrospinal fluid and in the urine. The authors determined that mania is associated with high noradrenaline levels and the severity of the symptoms is also associated with noradrenaline levels. (21) In another similar study low levels of noradrenaline were seen in the depressive phase of bipolar disorder when compared to the manic phase. The authors concluded that the elevated noradrenaline levels preceded the onset of mania. (22) Fortunately for those of us suffering with disorders such as PTSD and bipolar disorder, Lithium significantly reduces noradrenaline levels! Even more amazing is the fact that Lithium adjusts/normalizes Noradrenaline in both directions up and down as required by the individual illness that lithium is being used for. Here again we see the amazing homeostatic (balancing) power of lithium to move imbalanced chemical processes in both directions (up or down as needed) towards optimal levels and function. Lithium effect: When noradrenaline levels are elevated in patients with affective (mood) disorders lithium significantly reduces noradrenaline. For example lithium reduced noradrenaline levels associated with the mania of bipolar disorder. (Swann et. al., 1987)(21) Two other studies have demonstrated lithiums reduction of noradrenaline.(13,14) Lastly, I would like to share the study that demonstrated that lithium significantly increased the levels of noradrenaline in the normal population. Most normal individuals are suffering from a lack of mental energy, even if it is minor and subtle. Most individuals will respond, if asked, that their number one goal for pursuing wellness is to increase their energy levels. As you will see from the following study lithium does exactly that. Lithium increases noradrenaline levels in the healthy/normal population.

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Study title: The mechanisms of action of lithium. I. Effects on serotoninergic and noradrenergic systems in normal subjects. (Manji et. al.,1991) Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, Md. In this study, conducted at the National Institute of Mental Health, it was discovered that lithium increases noradrenaline levels in the normal healthy population. The effect of lithium carbonate administration was measured in 11 normal volunteers. The Lithium effect on Norepinephrine (noradrenaline) levels was to show a increase of 16% on average. (Manji et. al., 1991)(23) This finding suggests that most individuals are running a little low on noradrenaline levels and lithium is a natural solution to this deficit. The action of lithium, increasing noradrenaline levels in those of us who are running a deficit is a premiere benefit of lithium as noradrenaline has been discovered to be a critical neuroprotective hormone for the brain.

Neuroprotection of Noradrenaline
Neuroprotection is the ability of certain chemicals to protect nerve cells from a wide variety of neurotoxins and noradrenaline is one of the hormones that provide neuroprotection to brain cells. Increasing low levels of noradrenaline (NA) is a significant and important finding for lithium because of the fact that noradrenaline possesses properties of Neuroprotection. So while too much NA is a big problem, too little NA is not a good thing either. Optimal NA levels are associated with increased neuroprotection of brain cells. Neuroprotection will be discussed in greater detail in the neuroprotection chapter. Noradrenaline (NA) has been demonstrated to protect brain cells of rats from many types of chemical insults e.g. (Amyloid-beta-induced damage seen in Alzheimers) (24,25) and also methamphetamine. NA has also been demonstrated to increase cell survival.(26) In diseases such as Major Depressive disorder where there is a chronic deficiency of NA over long periods of time it has been hypothesized that NA play a critical role in the progression of Parkinson's disease (PD) and Alzheimer's disease (AD).(27)

Noradrenaline and the Amygdala

What parts of the brain are affected in PTSD? The answer is many areas of the brain are affected including the HPA and this further complicates the clinical and symptomatic picture of PTSD. One area of particular interest is an area known as the Amygdala. The Amygdala function is in the processing and memory of emotional reactions such as the anxiety reaction or 'flight or fight' response.

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Multiple studies show that noradrenaline system and the amygdala are intimately connected in the causal relationship of PTSD. These two relate to one another in responding to fear signals and hyper-function of both is related to stress-related illnesses, PTSD and anxiety disorders in general.(10, 28)

Noradrenaline Chronic Stress and Adrenal Fatigue

When humans are exposed to stress the production and secretion of noradrenaline increases to meet the demand. However with age and chronic stress noradrenaline levels may fall below normal,(29) as is seen with adrenal fatigue leaving the individual vulnerable to conditions associated with low noradrenaline levels e.g. migraine and tension headaches.(30)

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Nightmares - Chemical Imbalance of PTSD?

Nightmares may be one of the most horrible aspects associated with combat-related PTSD and PTSD in general. Chronic nightmares are one of the most common and debilitating symptoms of PTSD. Approximately 70-90% of PTSD patients in general have a sleep disorder and as much as70% of them have nightmares.(31,32) In a study of veterans with mild traumatic brain injury returning from Afghanistan and Iraq it was found that over 50% of them suffer with sleep disorder.(33) There are few things more disturbing than being awakened by a scene of horror in the middle of the night. For veterans this is certainly the most nightmarish aspect of this disorder (no pun intended). What is causing the severe unending repetition of nightmares? Research strongly suggests that nightmares are caused by a dysregulated norepinephrine system and excessive noradrenaline levels.(17,32,34-40) Normally, stress hormones drop off at night, so normal sleep can ensue, however with PTSD, noradrenaline levels remain excessive during sleep as well and it appears certain from recent research of Vietnam veterans, that this is what is causing the pathological nightmares of combat veterans. (Mellman et. al., 1995)(34) Study titled: Nocturnal/daytime urine noradrenergic measures and sleep in combatrelated PTSD. (Mellman et. al., 1995) Miami Veterans Administration Medical Center, Psychiatry Service, Miami, FL. Our data support a relationship of non-diminished central noradrenergic activity at night, and sleep disturbance, in chronic, combat-related PTSD. (Mellman et. al., 1995)(34) In other words the noradrenaline levels remained abnormally elevated throughout the sleep cycle and this demonstrated a causal relationship between noradrenaline and sleep disturbance. Horrific images can come after witnessing acts of war. What is going on within in brain that keeps this maelstrom churning? Could it be that excessive noradrenaline is terrorizing the brain during sleep? The research findings clearly support this hypothesis. By analyzing the most effective pharmaceutical for the treatment of nightmares associated with PTSD we find the chemical imbalance that is responsible for this severe aspect of PTSD. It appears that the main offender within the brain chemistry during sleep disorder and nightmares is Noradrenaline!

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Study titled: Clinical case series: the use of Prazosin for combat-related recurrent nightmares among Operation Iraqi Freedom combat veterans. (Daly et. al., 2005) Department of Psychiatry, Madigan Army Medical Center, Tacoma, WA. Veterans returning from Iraq were treated with prazosin for chronic nightmares; an astounding 87% had complete elimination/resolution of their nightmares. (Daly et. al., 2005) (35) In other words a drug that works by blocking excessive noradrenaline in the brain almost completely cured 90% of the veterans with chronic nightmares! An 87% response rate is unheard of for virtually any condition. An 87% complete elimination response is what some call a cure! As seen in the bipolar studies, mania is preceded and driven by, excessive levels of noradrenaline. Lithiums significant reduction of noradrenaline levels and the correlation between that reduction and the minimizing the severity of symptoms in the bipolar studies demonstrates I believe one of the primary actions of lithium. Lets look at the chemical pathway to understand how Prazosin does what it does for nightmares. Prazosin works by blocking the action of excessive noradrenaline at the receptors. See: Effect of prazosin on norepinephrine concentration and turnover in rat brain and heart. (Fuller et. al., 1978)(36) Additionally prazosin works by relaxing and expanding the blood vessels, thereby improving blood flow. This is especially important for the excess noradrenaline causes chronic constriction of the blood vessels of the brain and this may lead to hypoxia and acidosis of brain tissue. Prazosin belongs to a group of drugs called alpha-adrenergic blockers. Alpha-adrenergic blockers are drugs or other substance that blocks the chemical reaction pathway at alphaadrenergic receptors. These are the receptors that facilitate the action of adrenaline and noradrenaline. By blocking the excessive action of this hormone/neurotransmitter, the brain can be relieved of the symptoms associated with excessive levels of the noradrenaline hormone, aka as a neurotransmitter. The results from the following study suggest this very thing. High levels of stress hormone noradrenaline and (noradrenergic activity) is responsible for sleep disorders of PTSD. The most common symptoms of excessive noradrenaline during sleep are severe nightmares, distressed awakenings, awakening to a panic attack with a racing heart. In a study of PTSD patients treated with the drug Prazosin (a blocker of noradrenaline) the frequency and severity of nightmares was dramatically reduced. Prazosin compared with placebo dramatically increased total sleep time by 94 min and increased rapid eye movement (REM) sleep time. (37) In a comprehensive review (conducted in 2007) of the effects of Prazosin on combat-related PTSD, it was clear in every study that this drug was highly effective (and well tolerated) at relieving chronic severe nightmares. See study: Prazosin for treatment of nightmares related to posttraumatic stress disorder. (Taylor et. al., 2008) (32)

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Prazosin is also found to be very effective at reducing overall daytime symptoms of PTSD. Specifically prazosin has been demonstrated to significantly reduce symptoms of reexperiencing, avoidance/numbing, and hyperarousal. (Raskind et. al., 2003)(39) Consistently the research on prazosin, and nightmares has come to the conclusion that increased brain noradrenaline is a contributor, if not the cause of nightmares and that elevated noradrenaline correlates with the severity of PTSD symptoms. Given the success rate of Prazosin (complete elimination of nightmares in 87% of PTSD veterans), significant improvement of daytime symptoms of PTSD coupled with the fact that side effects are minimal (its well tolerated), you might expect that it would be prescribed to every veteran suffering with PTSD and nightmares. In fact, in the area that prazosin was developed (within the vicinity of the Veterans Affairs Puget Sound Health Care System, Tacoma, Washington) 37.6% of veteran patients with PTSD are treated with Prazosin. Tracing the flow of knowledge: geographic variability in the diffusion of prazosin use for the treatment of posttraumatic stress disorder nationally in the Department of Veterans Affairs. (Harpaz-Rotem and Rosenheck 2009)(41) However analyzing prescribing patterns at other VA centers around the country the prescription rate of Prazosin for veterans with PTSD averages around 9% and is as low as 1-2% of veterans in some areas. (Harpaz-Rotem and Rosenheck 2009)(41) Why is Prazosin not being prescribed to every veteran with PTSD and nightmares? SIMPLY PUT THERE IS NO MONEY IN IT! Prazosin is a $4 generic prescription at major pharmaceutical retailers. Like lithium, prazosin will never reach super-star status for the relief of veteran PTSD unless you and I tell them about it! This is outrageous that our veterans are being denied low-cost high-result medicines for what ails them. Instead they are being prescribed newer high-profit drugs that are not as effective and do not protect them against suicide. Thats the end of the prazosin story folks. We cant blame the VA exclusively for the lack of prescribing lithium and Prazosin. The VA is working with and for the Pharma-cartel and the choices that the VA makes are based upon what the Pharma-cartel tells them. The Pharmaceutical industry would collapse if doctors only prescribed generic drugs (like Prazosin) and natural remedies (like Lithium) for the treatment of disease. The system demands that doctors continue to prescribe the latest patented drugs, even if they are no more effective (in some cases with no effect, e.g. antipsychotic Risperdal), and are more dangerous, e.g. antipsychotics (may increase suicide rates). Recent analysis of antipsychotic risperdal, aka risperidone, discovered that the drug is providing no benefit (to veterans), only to pharmaceutical profits.

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The following headline reported on Aug 3, 2011, Reuters Health, by Frederik Joelving

Common antipsychotic no help to vets with PTSD.

"We know there are large numbers of veterans who have been getting risperidone for a long time, and our study suggests that it is not helpful" said Dr. John H. Krystal of the Veterans Affairs Connecticut Healthcare System in West Haven.(42) By raising the VA and consumer awareness to this problem we can make a change. We can demand that the VA do a better job of education our veterans regarding the benefits of LO supplementation for the prevention of suicide and PTSD. The good news is that lithium is extremely effective at lowering the excessive levels of noradrenaline believed to be causing chronic nightmares. The veterans I have worked with thus far report dramatic reductions in the frequency and intensity of their nightmares.

Dopamine
Dopamine is produced in the brain, the kidneys and tissue of the abdomen. Dopamine is a primary stress hormone and a neurotransmitter. Excessively high levels of dopamine are reported in combat-related PTSD. Dopamine is a catecholamine. Study titled: Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans. (Yehuda et. al., 1992) Department of Psychiatry, Mount Sinai Medical School, New York. This study of 22 Vietnam veterans discovered that dopamine levels were excessively high when compared to normal individuals. Dopamine levels were significantly correlated with severity of PTSD symptoms (Yehuda et. al., 1992) (2) Another common finding with PTSD is migraine headaches. A study measuring the dopamine metabolite (DOPAC) levels associated with migraine headaches found a positive correlation with increasing dopamine levels increasing the intensity of migraine headaches. Patients with migraine headaches had DOPAC levels 3-4 times higher than the control group. (43) Lithium effect: Lithium has the dual effect of increasing low levels of dopamine (44) and decreasing elevated dopamine levels.(45) Lithium lowers brain levels of dopamine in stressexposed rats.(46) When lithium was injected into rats, lithium reduced the functional activity of brain dopamine neurons and this was attributed to the sedative effects noted in the rats.(47) When lithium was administered in thyroid hormone-treated animals there was a significant decrease of dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid. This suggests that this lithium reduced the synthesis and turnover of dopamine (48) and reduces dopamine regulatory mechanisms. (49) In normal rats given lithium an increase of dopamine was noted in

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the brain-anterior cingulate cortex (CIN), the brain-piriform-entorhinal region (PiEn). Findings of the research suggest changes in the turnover rates of dopamine as well as an action of lithium on dopamine synthesis and/or storage in the brain (nigrostriatal and mesocortical systems). (50)

Cortisol
Cortisol is produced by the adrenal gland in response to release of ACTH from the pituitary gland. Cortisol is released in excessive levels in response to acute stress and chronic stress. Cortisol has been consistently shown to be dysregulated in PTSD. Cortisol is either too high or too low in PTSD patients. (Pervanidou and Chrousos 2010)(51) High levels of cortisol associated with HPAA dysregulation have been demonstrated in PTSD, often many years after the trauma. I quote from an article published in 2010. Article titled: Biological correlates of direct exposure to terrorism several years postdisaster. (Tucker et. al., 2010) Department of Psychiatry and Behavioral Sciences, University of Oklahoma College of Medicine, Oklahoma City, OK Eleven survivors with posttraumatic stress disorder (PTSD) had significantly higher cortisol levels than did both non-PTSD survivors and controls; 6-7 years after the Oklahoma City bombing. Findings support research associating PTSD with hypothalamic-pituitaryadrenal (HPA) axis changes. (Tucker et. al., 2010)(52) Lithium effect: Lithium has been demonstrated to significantly normalize cortisol levels in bipolar disorder (53) Lithium has been demonstrated to maintain cortisol levels over the long-term in mood disordered patients. (54) The following study published in the British Journal of Clinical Pharmacology speaks to one of the most promising functions of lithium in normalizing HPAA dysfunction; the normalization of excessive cortisol levels in patients with mood disorders. Study titled: A study of the relationship between serum lithium and plasma cortisol levels in manic depressive patients. (Eroglu et. al., 1979) British Journal of Clinical Pharmacology The results of partial correlation analysis revealed that there is a strong negative correlation between serum lithium and plasma cortisol levels. (Eroglu et. al., 1979) (53) See full study here: (53) In simple terms, this study showed that as lithium levels increase in the body, cortisol levels are reduced accordingly. The following study published in the journal Neuropsychobiology, demonstrated further evidence that lithium significantly normalizes cortisol levels and maintains them over the long-term.

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Study titled: Cortisol changes in long-term lithium therapy. (Smigan and Perris 1984) Patients showed a significant decrease in a.m. serum cortisol levels after 1 year on lithium. (Smigan and Perris 1984) (54)

High Cortisol Levels

Excessive cortisol levels cause numerous health problems. Signs and symptoms include but are not limited to: Upper body obesity, high blood pressure, fatigue, musculoskeletal pain, bone pain, fatigue, headaches, anxiety and depression.

Low Cortisol Levels

It is a confusing finding with PTSD that we often find low cortisol levels with this condition. Typically it is expected that you will find high cortisol levels in those who suffer with stressrelated illness, but this is often not the case with PTSD. The findings from numerous studies of PTSD have shown that cortisol levels may be normal, higher, or lower than normal, in cases of PTSD. The direction of cortisol levels is controlled by the HPA axis and cortisol may be too high or too low depending on various factors such as genetics, age, type of trauma, chronicity of trauma, depression, and alcohol and/or drug abuse. (Pervanidou and Chrousos 2010) (51)

Symptoms of Low Cortisol

Some of the more symptoms of low cortisol are depression, fatigue, irritability, confusion, headaches, muscle weakness, dizziness, nausea and diarrhea.

What causes low cortisol in PTSD?

The answer is we just dont know, yet. However it does appear that the dysregulation of the hypothalamic-pituitary-adrenal axis (HPAA) is a very likely core component of this mystery question. For some, as of yet unknown reason, it appears likely that the body responds erroneously to severe traumatic stress from the outset in some individuals. The findings from a study by (Mcfarlane et. al., 2010) found evidence for dysregulation of the HPAA and that this dysregulation was associated with a dramatic increased risk of PTSD. Comments from that study follow here.

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The low levels found in chronic long-term cases of PTSD may be due to a unique dysregulation of the HPA axis. The following quote is from (Mcfarlane et. al., 2010). A lower rise in cortisol at 08.00h on day 2 was associated with an increase in risk of PTSD. The findings support a hypothesis that dysregulation of the HPA axis and suppression of cortisol are established early in the disease process. (Mcfarlane et. al., 2010) (55) Furthermore decreased basal cortisol levels have been reported in combat veterans with PTSD. There is a sure sign of dysregulation of the HPA axis in PTSD. Decreased adrenal gland responsiveness may be involved with low cortisol in PTSD. (Kanter et. al., 2001)(56) Chronically low cortisol findings among PTSD subjects may indicate that These alterations reflect an enhanced negative feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD or possibly adrenal gland insufficiency. (Yehuda et. al., 1996)(57) Another possibility for a low cortisol response to stress may be adrenal fatigue. Many chronically stressed out individuals are suffering from adrenal fatigue due to years of excessive stress hormone output that eventually may cause the adrenal gland to atrophy, (shrink) thereby perhaps reducing the adrenal glands ability to secrete cortisol and other hormones to effectively respond to stressful traumatic experiences.

Cortisol Protective Factor

Cortisol also may act to protect the nervous system from overstimulation from noradrenaline during acute stress overload. In a hospital (emergency room) environment it has been shown that PTSD symptoms arising from intense emergencies, i.e. life and death situations, are actually made worse when there is a low cortisol response during the stressful experience. Study title: Post-traumatic stress disorder in somatic disease: lessons from critically ill patients. (Schelling 2008) When cortisol is administered to patients during emergency room situations the symptoms of PTSD are significantly reduced. This can possibly be explained by a cortisol-induced temporary impairment in traumatic memory retrieval that has previously been demonstrated in both rats and humans. (Schelling 2008)(58) So it appears that Cortisol may actually be essential in protecting the nervous system from overstimulation from excessive acute stress hormones (adrenaline/noradrenaline). Cortisol is part of the control of excessive hormone production from the hypothalamic-pituitary axis and acts to reduce the hyperactivity of these glands in response to stressors.

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High Cortisol and Brain Atrophy

Abnormally high levels of cortisol have been directly linked to brain atrophy and are linked to cognitive decline in older people.(59) Brain atrophy of the cerebral cortex is a common finding in PTSD as the following study demonstrates. Study title: Cerebral cortical atrophy and silent brain infarcts in psychiatric patients. (Avdibegovi et. al., 2007) Cerebral cortical atrophy was more frequent in patients with PTSD in comorbidity with depression (43%), PTSD (39.0%), Complex PTSD (26%) (Avdibegovi et. al., 2007) (60) So that ends our review of the dysregulated stress hormones of the hypothalamic pituitary adrenal axis (HPAA). Again I say the research shows that lithium is acting directly and or indirectly upon adrenaline, dopamine, noradrenaline, and cortisol to normalize these imbalances. This is the amazing effect of lithiums action upon the hypothalamic-pituitary-adrenal axis (HPAA), normalizing dysregulated stress hormones. Lithium has been shown to increase and or decrease stress hormones (depending on the condition) associated with the HPAA. This is a very powerful dual effect of lithium.

Lithium, PTSD and the Hypothalamic-Pituitary-Thyroid Axis (HPTA)

The thyroid gland is not traditionally thought of as a primary stress hormone endocrine gland; however, recent findings suggest that hyperthyroidism maybe intimately involved in the abnormal stress-response, of major psychiatric illnesses including MDD and PTSD. To keep this discussion simple I will mention the two major thyroid hormones triiodothyronine, (T3) and thyroxine (T4) with regard to the lithium effect in PTSD. Dysregulation of the HPTA has been discovered to be a consistent finding of combat-related PTSD and has been identified in veterans going all the way back to WWII. (Wang and Mason 1999) (61)

The WWII veterans suffering with combat-related PTSD showed significant elevation of thyroid hormone, triiodothyronine (T3), 50 years after the war.
Study titled: Elevations of serum T3 levels and their association with symptoms in World War II veterans with combat-related posttraumatic stress disorder: replication of findings

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in Vietnam combat veterans. (Wang and Mason 1999) National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, Veterans Administration Connecticut, West Haven. WWII veterans with combat-related PTSD showed elevations of serum total and free T3 with no elevations of free T4 and TSH compared to control subjects, replicating the results of our previous studies. A significant positive relationship between total and free T3 and PTSD symptoms, specifically hyperarousal symptoms, was also replicated in the total WWII group. This study supports the observation that the thyroid system is altered in chronic combat-related PTSD. The observed alterations of thyroid function along with PTSD symptoms appear to be chronic, detectable 50 years after the war. (Wang and Mason 1999) (61) Clinically speaking PTSD overtakes normal thyroid function and simulates a condition of hyperthyroidism. However this is not a classic hyperthyroid scenario. Classic hyperthyroid is primarily due to an autoimmune disease called Gravess disease. This disease is due to an overproduction of thyroid hormones triiodothyronine (T3), thyroxine (T4) and thyroxine-binding globulin and presents with and enlarged thyroid gland. However the classic cause, auto-immune dysfunction of hyperthyroidism is not present in combat-related PTSD. So what is causing this combat-related hyperthyroidism? Once again we dont know for sure what is causing hyperthyroidism in PTSD, but it appears likely that the body has compensated in some way, perhaps to draw on the energy resource that the thyroid hormones have to offer combat veterans who are demanding extraordinary amounts of energy from the body to meet the demand of chronic life and death situations. Lets review the findings of two more combat-related studies conducted at the National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, Veterans Administration West Haven, Connecticut. The first study of 1994 analyzed the thyroid hormones of a total of 96 male combat veterans and compared hormone levels to 24 male control subjects. What they found was significantly elevated thyroid hormones, triiodothyronine, (T3) thyroxine, (T4) and thyroxinebinding globulin. Study title: Elevation of serum free triiodothyronine, total triiodothyronine, thyroxinebinding globulin, and total thyroxine levels in combat-related posttraumatic stress disorder. (Mason et. al., 1994) National Center for Posttraumatic Stress Disorder, Veterans Affairs Medical Center, West Haven, Conn. The PTSD groups all showed a marked and sustained elevation in levels of bothT3 and free T3, as well as elevated T3/T4 ratios. These findings demonstrate an unusual pattern of thyroid alterations, featuring substantial elevations in total T3, free T3, and T4-binding globulin levels, in combat-related PTSD that differs from established endocrinopathies, such as classic hyperthyroidism, T3 thyrotoxicosis, or chronic T4-binding globulin elevation. (Mason et. al., 1994) (62)

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The next study conducted in 1995 examined the same parameters again in 65 male Vietnam veterans. Study title: Relationships between thyroid hormones and symptoms in combat-related posttraumatic stress disorder. (Wang et. al., 1995) National Center for Posttraumatic Stress Disorder, Veterans Affairs Medical Center, West Haven, Conn. The same elevated levels of triiodothyronine, (T3) thyroxine, (T4) were seen again and this time, were shown to have a significant positive correlation to the severity of PTSD symptoms, namely hyperarousal. (Wang et. al., 1995) (63) Most recently in a study of Croatian Soldiers with PTSD, T3 levels were found significantly elevated as well and the T3 levels correlated with the number of traumatic events the soldiers had experienced as well as the intensity of hyperarousal symptoms. (Karlovic et. al., 2004) (64) Hyperthyroidism is frequently associated with anxiety, related PTSD. (61-64)
(65)

and is a classic finding in combat-

Fortunately, lithium rapidly and significantly normalizes/reduces excessive levels of triiodothyronine, (T3) thyroxine, (T4). Thyroid hormone functions as a regulator of the speed at which the metabolism of the body proceeds. If there is an excess of thyroid hormone, the cellular functions and metabolism will significantly speed up. Therefore, the symptoms of hyperthyroidism are anxiety, heart racing, irritability, nervousness, increased perspiration, hand tremors, hyperarousal and difficulty sleeping, to name a few. Hyperthyroidism may also cause acute psychiatric illness. Elevated thyroid hormones are also associated with major psychiatric disorders such as schizophrenia and major depression and the research data shows that elevations of T4, FT4I, T3, and FT3I are a common finding among psychiatric inpatients, especially at the onset of the psychosis. Furthermore the levels of thyroid hormones are correlated with severity of psychiatric symptoms. See: Thyroid hormone elevations during acute psychiatric illness: relationship to severity and distinction from hyperthyroidism. (Roca et. al., 1990) (66) Elevated thyroid hormones are also found in bipolar disorder.(67) This is a most interesting aspect of combat-related PTSD in that this disorder uniquely hijacks the function of the thyroid gland, (permanently in the case of PTSD, WWII veterans) and utilizes the thyroid for a unique purpose. It appears that purpose is to maintain a chronic state of hyperarousal aka hypervigilance. Combat troops are under immense fear-related stress and the body compensates by hyping up the thyroid gland to maintain extreme alertness. It has been something of a mystery as to what has been the cause of the increased sustained production of thyroid hormones, T3 and T4 in these veterans. Why have these hormones become locked into hyperactivity (for decades) long after the war is over?

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The following theoretical discussion on this topic was published in the journal of Psychosomatic Medicine, March, 1999.

Article titled: Thyroid axis sustaining hypothesis of posttraumatic stress disorder. (Prange 1999) Published in the journal Psychosomatic Medicine. The authors well referenced review of the evidence on this topic suggests that the elevated thyroid hormones are likely a result of combat. (Prange 1999) (68) Prange suggests that the thyroid might be capable of quick responses to the horror of war and thus through thyrotropin/TSH hormone from the pituitary, draws on the fast-acting thyroid hormone, triiodothyronine (T3). T3 promotes noradrenergic (noradrenaline) neurotransmission. As you may remember noradrenaline is associated with hyperarousal, anxiety etc. Thus it is postulated that elevated T3 may be a compensatory mechanism or a product of the arousal stimulus-response and may actually be perpetuating the chronic hyperarousal. Prange further hypothesizes that under severe long-lasting combat stress the hypothalamicpituitary-thyroid axis may become sufficiently over-stimulated as to slightly overproduce the pituitary hormone thyroid stimulating hormone that drives T3 to adversely affect certain brain structures, thereby perpetuating continual hyper-function of the thyroid and sustaining in a chronic fashion, hyperarousal/hypervigilance. (Prange 1999) (68) Could it simply be the terrorizing indelible memory (permanently imbedded) of the horrors of war?

Fortunately Lithium Reduces & Regulates Hyperthyroid Hormones T3 & T4!

Once again, however, we will have to look at other than the PTSD patient populations, to see the effects of lithium, upon this hormonal imbalance. Lithium is used in the treatment of hyperthyroidism aka /Graves disease, diffuse toxic goiter, and bipolar disorder. Lithiums beneficial adjustments to hyperthyroid hormones are far reaching. It is probable that the hypothalamic pituitary axis adjusts to a new setting in patients receiving lithium. (Lazarus 1998). (9) Lithium effect: Lithium rapidly and robustly reduces pathologically elevated thyroid hormones triiodothyronine, (T3) thyroxine (T4). (70-77) Hyperthyroid (Graves disease) Studies of lithiums effect upon hyperthyroid conditions, consistently demonstrate major regulation of thyroid hormones, triiodothyronine, (T3) thyroxine (T4). The most common cause of hyperthyroid hormones is Graves disease. In a study of lithiums effect upon Graves disease it was determined that lithium reduced T3 by 42% and T4 by 28%. These amazing changes occurred in just 7 days. (Eigenmann and Burgi 1978)
(70)

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Diffuse Toxic Goiter (DTG) DTG is a thyroid condition that displays elevated triiodothyronine (T3) and thyroxine (T4). In a study of 22 patients with DTG, the lithium response was evaluated in a therapeutic dose of 900-1800 mg/day for a period of 4-6 weeks. Lithium produced a significant reduction in thyroid hormones, T3 and T4. (Pimenov 1982) (71) Similar findings have been demonstrated in multiple studies of lithiums effect upon hyperthyroid hormones T3, T4. (72-78) Bipolar disorder - Eight manic patients were examined before and after lithium treatment, 6001,200 mg daily, for four weeks. Slight reduction in the plasma levels of thyroxine T4, were seen following lithium treatment. (Takahashi1975)(78)

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Chapter Twenty Four

PTSD & Bipolar disorder, Chemical Imbalance Similarities

An ever increasing number of studies have found that bipolar disorder and posttraumatic stress disorder are frequently co-occurring. Studies of bipolar patients have documented elevated rates of PTSD. Based on our review, representing 1214 bipolar patients, the mean prevalence of PTSD in bipolar patients is 16.0% (95% CI: 14-18%), a rate that is roughly double the lifetime prevalence for PTSD in the general population. (Otto et. al., 2004) (1) Researchers are beginning to examine the common neurotransmitters involved in these two disorders. Dr. Freeman has identified the following: Dopamine, noradrenaline, gamma-aminobutyric acid (GABA) and serotonin. (Freeman et. al., 2002) (2) Having now done a near-complete analysis of the chemical imbalances of the two disorders, I would like to show you the similarities between bipolar disorder and posttraumatic stress disorder. Clearly these two disorders are virtually identical in their chemical equations of dysfunction. Lithium is the gold standard of care for bipolar disorder (BD) and now you know, this is likely true for PTSD as well. List of hormonal and chemical imbalances found in each illness. Hypothalamic Hormones Antidiuretic hormone Corticotropin Releasing Hormone Oxytocin Thyrotropin-releasing hormone Hypothalamic Neuropeptides Enkephalin Orexin A Neuropeptide Y Pituitary Hormone Adrenocorticotropic hormone Pituitary Neuropeptides Delta sleep-inducing peptide Yes No Yes Yes Yes Yes Yes Yes Yes Yes BD Yes Yes Yes Yes PTSD Yes Yes Yes Yes

References for the PTSD chemical imbalances provided throughout the book.

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The Hypothalamic-Pituitary-Adrenal Axis (HPAA) Hormones Adrenaline Noradrenaline Dopamine Cortisol Yes Yes Yes Yes Yes Yes Yes Yes

Hypothalamic-Pituitary-Thyroid Axis (HPTA)Thyroid hormones Triiodothyronine (T3) Thyroxine (T4) Miscellaneous Neurotransmitters Serotonin Gamma-aminobutyric acid Glutamate Histamine Miscellaneous Neuropeptides Angiotensin II Neuropeptide S (NPS) Miscellaneous Neurotrophins Brain Derived Neurotrophic Factor Vascular Endothelial Growth Factor Enzymes AKT Ca2+/CaM kinase GSK-3beta Cellular Communication Systems Beta-cantenin signaling Protein kinase C signaling Inflammatory Chemicals Cytokines - IL-2, IL-4, IL-6, IL-8, TNF-alpha Miscellaneous PTSD Chemistry N-acetylaspartate Cyclic adenosine monophosphate NMDA Receptors Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No data Yes YES Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

References for the PTSD chemical imbalances provided throughout the book.

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Chapter Twenty Five

Comparison of Brain Scans PET, SPECT, and fMRI Brain Scan Studies Similarities between Bipolar disorder & PTSD
The following chart examines the areas of the brain that are demonstrating either increased or decreased metabolic activity changes in both bipolar disorder (BD) & PTSD; to demonstrate the common areas of brain involvement within these two disorders. As you can see these two disorders have much in common in the areas of the brain affected.

BD Amygdala (1)(11)(17) Anterior Cingulate Gyrus (2)(4)(6)(12)(15) Basal Ganglia (7)(16) Cerebellum (2)(3)(4) Frontal Cortex (4)(10) Hippocampus (1)(4)(6)(17) Insula
(4)(17)

PTSD Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

Occipital lobe (2)(4)(9) Orbitofrontal Cortex (5)(17) Parietal Lobe

(6)(8)(9)(15)

Prefrontal Cortex (1)(4)(6)(7)(8)(9)(10)(13) Temporal Lobes (2)(3)(4)(8)(9)(10)(15) Thalamus (2)(10)(11)(14)(17)

See different types of metabolic brain scans: Positron Emission Tomography scan (PET SCAN) fMRI: Functional Magnetic Resonance Imaging (fMRI Scan) Single Photon Emission Computed Tomography scan (SPECT SCAN) See: (Veteran PTSD SPECT Scan Video) Learn about: Eye Movement Desentization Reprocessing (EMDR) & (Traumatic Brain Injury SPECT Scan) & ( Anxiety Scan)

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Comparison of Brain MRI Studies between Bipolar Disorder (BD) & PTSD
Following is a list of the regions and sub-regions of the brain that have been identified as atrophying/shrinking in PTSD and Bipolar disorder (BD) and that have also been shown to regenerate in BD, following lithium administration. The following chart examines the areas of the brain that are demonstrating volumetric changes (reductions/increases) in both BD & PTSD. They are paired together to demonstrate the common areas of brain involvement within these two disorders. A YES indicates that the area is experiencing atrophy, shrinking, shape or volumetric changes. Unknown means that the studies have yet to be conducted. As you can see these two disorders are basically identical in the areas of the brain affected. When lithium has been shown to increase the size and or normalize the shape of brain cells in the region described, I will illustrate that fact by placing a red Y for yes, in front of the brain region listed. If no change is noted, an N will be listed. If no study exists I will indicate with a U for unknown. Common areas of brain involvement in BD and PTSD as determined by MRI brain scans and areas lithium has shown therapeutic effect

Main regions of brain listed in red. All other listings are various sub-regions of brain. Lithium effects Y- Amydala (6-10,38) Y- Anterior Cingulate (1-5,38) Y- Basal Ganglia (11,12,34) Y- Brain stem (13) U- Cerebellum (?) Y- Frontal Lobe (12,14) Y- Gray Matter (2,3,14-21,38) Y- Habenula (22 ) Y- Hippocampus (7,23-30,38) Y- Lateral Ventricles (31) U- Nucleus Accumbens (? ) BD Yes (3,7,6,8) Yes (1,2,3,4) Yes (3,11) Yes (35,42) Yes (35,41,42) Yes (35) Yes (20,21,43,44) Yes (22) Yes (7,24, 29,30,35,36) Yes (7,35) Yes (35) PTSD Yes (47,63-67,72) Yes (6,47,52,60) Yes (68-70) Yes (61) Yes (55,56) Yes (61) Yes (52,53,60,73-79) Unknown Yes (47,48,49-53,60) Yes (57,58) Unknown

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Y- Occipital Lobe (34) Y- Orbiofrontal Cortex (34) Y- Parietal Lobe (34) U- Pituitary gland (?) Y- Prefrontal Cortex (4,14,34) U- Putamen (?) Y- Temporal Lobe (5,21,34) Y- Thalamus (32) Y- White Matter (4,31,33)

Yes (46) Yes (37,42) Yes (35) Yes (38,39) Yes (7,43,45) Yes (7) Yes (7,21,35,42) Yes (32,35) Yes (33,43,44)

Yes (59,62,84) Yes (47,51,53) Yes (61,77) Yes (82) Yes (59) Yes (70) Yes (53,54,59,61) Unknown Yes (54,75,80,81)

So this is all very impressive data. However, the skeptics are saying, This data is all well and good but wait a minute, are these effects of brain cell growth limited to bipolar patients only? How do we know that lithium is doing the same for other medical conditions? Well, as previously stated, lithium increases the mass of gray and white matter brain tissue in healthy individuals so it is possible that lithium promotes the growth of brain mass in everyone. More research will have to be conducted to be absolutely sure though.(4) Considering these amazing brain cell growth boosting effects by lithium prompted researchers in Italy to conduct a lithium study on Lou Gehrigs disease patients, aka Amyotrophic Lateral Sclerosis (ALS). ALS is severe and fatal progressive neurodegenerative disease of the motor neurons in the brain and the spinal cord. Motor neurons extend from the brain to the spinal cord and connect to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually kills the motor neurons of the brain and spinal cord. Without regeneration of the motor neurons the ability of the brain to initiate and control muscle movement is lost. The average life span of an ALS patient is 3-5 years from the day of diagnosis. Researchers gave therapeutic dosages of Pharma-Li to patients with near end-stage ALS (Lou Gehrigs disease) along with Riluzole, the pharmaceutical used to delay ALS. What they discovered was truly earth-shaking. Lithium was found to delay the progression of ALS. No other treatment has shown such a powerful effect upon this paralytic disease which affects some 30,000 Americans. At the end of the 15-month study about 30 percent of the patients that only took Riluzole had died, while all those given lithium had survived. Allow me to restate that. In other words while 30% of the patients died on the pharmaceutical alone, not one patient died on lithium. Furthermore, none of the lithium patients were forced to go on life support. (85) Additionally, researchers found in animal studies that lithium facilitated other miraculous results, I quote; In particular, the effects induced by lithium can be summarized as follows: The removal of altered mitochondria and protein aggregates; the biogenesis of well-structured mitochondria; the suppression of glial proliferation; the differentiation of newly formed neurons in the spinal cord towards a specific phenotype. (Fornai et. al., 2008) (86) This is why lithium is now the hottest research topic in the search for the cure of neurodegenerative diseases.

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Chapter Twenty Six

Lithium Promotes Neurogenesis

Neurogenesis defined: The birth and development of new brain cells and nervous tissue. Teaching Points: 1. Lithium grows new brain (hippocampus) cells in rats, (Neurogenesis) and all the scientific evidence points to the same lithium effect in humans. (1-3) 2. 11 regions and sub-regions of the brain have been shown to be atrophying, degenerating and shrinking in PTSD. The brain areas that are degenerating in PTSD are virtually identical to Bipolar disorder. 3. Lithium has been shown to increase brain mass (brain cell growth) in bipolar patients, in 10 of the 11 areas that are atrophying in PTSD. This fact has been verified in numerous MRI studies of bipolar patients. 4. Neurogenesis is the hottest topic in the research for the cure of neurodegenerative diseases such as ALS, Alzheimers, Bipolar disorder, Huntingtons, Parkinsons, PTSD and many others. 5. Even healthy individuals have been found to have shrinking brains and lithium has been shown to cause brain mass increases of the gray and white matter in healthy individuals. 6. Over 20 human studies have verified the fact that lithium increases brain cell volume, i.e. brain mass, in bipolar patients, (4) and have even been demonstrated in normal healthy adults. MRI brain scans have discovered that the brain is shrinking in the normal healthy population as we age. (5) 7. A 2007 UCLA MRI study, demonstrated an increase of approximately 15%, in select regions, of the brain cortical gray matter, in bipolar patients taking lithium. Greater cortical gray matter density in lithium-treated patients with bipolar disorder. (Bearden et. al., 2007 ) (6) Nowhere in the scientific literature is there a greater preponderance of compelling evidence for the essentiality of lithium than in the study of Neurogenesis (the birth of new brain cells). Neurogenesis and the power of lithium to grow new brain cells is the hottest topic in the search for a cure in the neurodegenerative diseases such as Alzheimers, ALS, Bipolar disorder, Parkinsons and PTSD. Lithium has even been proven to significantly slow the degeneration of brain and spinal cord (motor neuron) cells, even when there is a genetic disease that kills those cells. Now, thats a powerhouse nutrient! See: A systematic study of brainstem motor nuclei in a mouse model of ALS, the effects of lithium. (Ferrucci et. al., 2010) (7) No other mineral element on this planet has been demonstrated to birth new brain cells like lithium does.

Lithium stands alone as the supreme mineral nutrient for the regeneration of brain cells and nervous tissue. (Millar 2012) 223

For those of you who have been busily destroying your brain cells at an unprecedented rate through consumption of alcohol, cigarettes, drugs (recreational & pharmaceutical) and junk food laden with nerve cell destroying chemicals, this is really good news. Until just recently scientists believed that brain cells did not regenerate, nor were any new ones being created. Now with lithium we know that this is not true.

This is a recent scientific breakthrough in the understanding just how amazing critically essential lithium is for brain regeneration. The first studies documenting this amazing fact were first published in 2000.
Since that time dozens of studies and articles have been published documenting this incredible scientific discovery. Does lithium increase brain mass in everyone, even healthy individuals? It appears so! Study titled: Prefrontal gray matter increases in healthy individuals after lithium treatment: a voxel-based morphometry study. (Monkul et. al., 2007) Department of Psychiatry, The University of Texas Health Science Center at San Antonio, TX, USA. This is an emerging area of research so the data is just beginning to come out. A study conducted at the Department of Psychiatry, University of Texas Health Science Center published in 2007, found that healthy individuals had expanded brain tissue in the gray and white matter of the prefrontal cortex following lithium treatment.. (Monkul et. al., 2007) (5) At first some scientists speculated that the measured growth of brain tissue visualized on MRI scans, may only be due to an effect of hydration of cells by lithium. In other words the lithium might have been causing the cells to be better hydrated (not a bad thing) causing them to swell a little. Lithiums hydration of cells may be a component of neurogenesis, but animal autopsy studies absolutely confirmed that lithium directly stimulates the birth of new neurons (nerve cells) within the brain (hippocampus). (1-3) This visualization (via autopsy) in humans, of new brain cells being birthed, has not been accomplished yet. As you can imagine no one is volunteering to have their brain dissected to see if lithium is growing new brain cells. However over 20 published human studies have demonstrated lithium-induced brain mass growth (via MRI scans) of multiple regions within the brain; these areas have been identified as atrophying, in many different mental and neurological illnesses. Read next what internationally acclaimed neurological researcher, Wise Young, Ph.D., M.D. has to say about the miraculous benefits of lithium. Dr. Young points out that lithium stimulates the growth and production of stem cells in the brain and spinal cord. He is conducting research upon spinal cord trauma utilizing stem cells and lithium. Review titled: Review of lithium effects on brain and blood. (Wise Young, Ph.D., M.D. 2009) W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University

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Lithium has been reported to be beneficial in animal models of brain injury, stroke, Alzheimers Huntington's, and Parkinson's diseases, Amyotrophic Lateral Sclerosis (ALS), spinal cord injury, and other conditions. A recent clinical trial suggests that lithium stops the progression of ALS. The stimulation of endogenous neural stem cells may explain why lithium increases brain cell density and volume in patients with bipolar disorders. (Wise Young, Ph.D., M.D. 2009) Lithium also remarkably protects neurons against glutamate, seizures, and apoptosis (cell death) due to a wide variety of neurotoxins. Lithium is still the most effective therapy for depression. It "cures" a third of the patients with manic depression (Young 2009)(8) How about that folks? Lithium rocks the house!

The Incredible Shrinking Brain of Post-traumatic Stress Disorder

I repeat! Lithium prevents the shrinking brain! Not only that, but lithium prevents the shrinking brain in healthy individuals as well! (5) We are all under-stress that shrinks the brain prematurely and this has even been seen in teenagers; the shrinking brain targets young and old! See study titled: Stress predicts brain changes in children: a pilot longitudinal study on youth stress, posttraumatic stress disorder, and the hippocampus. (Carrion et. al., 2007)(9) The ravages of combat-related stress and war upon the shrinking brain are abundantly obvious, particularly from the perspective of the MRI brain scan, measuring various regions and subregions of the brain. One of the shrinking areas of the brain most commonly affected by stressrelated illnesses such as PTSD is called the Hippocampus.

There are two pieces of the hippocampus (mirror imaged) on the right and left side of the brain. The hippocampus is a part of the limbic system and plays a critical role in long-term memory and spatial navigation and orientation. This is one of the critical brain areas also involved in Alzheimers disease as well as PTSD.

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The bad news: In PTSD, this hippocampal shrinkage, aka atrophy/degeneration, may lead to signs of early dementia (loss of cognitive function and memory). See: Insular cortex involvement in declarative memory deficits in patients with post-traumatic stress disorder. (Chen 2009) (10) Hippocampal function during associative learning in patients with posttraumatic stress disorder. (Werner 2009) (11) This may occur if the hippocampus is allowed to degenerate without proper nutritional preventative care.

The good news is that lithium appears to be that nutritional preventative care.
As you will see in the studies herein, lithium not only protects against that shrinkage, but lithium can restore the hippocampus volume even after it has been reduced in size. (Yucel 2007)(12) See: Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Decades of research have now confirmed that the hippocampus is shrinking in numerous degenerative brain diseases such as Alzheimers, Bipolar disorder, Depression, Huntingtons disease, Parkinsons disease, Posttraumatic Stress disorder, Schizophrenia to name a few. Study titled: MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. (Geuze, Vermetten and Bremner 2005) Department of Military Psychiatry, Central Military Hospital, Utrecht, Rudolf Magnus Institute of Neuroscience, in the Netherlands! After the authors of this study reviewed over 400 patient records, it was discovered that there are many different conditions in which the hippocampus is shrinking. The hippocampus is shrinking in PTSD, as well as the following conditions. (Geuze, Vermetten and Bremner 2005)
(13)

Smaller hippocampal volumes have been reported in:

Traumatic brain injury Cardiac arrest Dementia Alzheimer's disease Epilepsy Mild cognitive impairment Posttraumatic Stress Huntington's disease Cushing's disease Down's syndrome Bipolar disorder Parkinson's disease Major Depression Schizophrenia Alcoholism Borderline personality Obsessive-compulsive Anti-social personality

Following are studies demonstrating shrinking of the hippocampus in Combat Veterans!

Study titled: MRI-based measurement of hippocampal volume in patients with combatrelated posttraumatic stress disorder. (Bremener et. al., 1995) Department of Psychology, Yale University School of Medicine. The combat veterans with PTSD were found to have a significantly smaller (8%) right

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hippocampus compared to the normal subjects, and this is consistent with deficits/loss of verbal memory. (Bremener JD et. al., 1995) (14) Study titled: Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. (Gurvits et. al.,1996) Research Service, VA Medical Center, Manchester, NH Seven Vietnam veterans with PTSD were compared with seven combat veterans without PTSD and eight normal civilians. The veterans had significantly smaller right & left hippocampi, when compared to the other two groups. (Gurvits et. al., 1996) (15) Study titled: Smaller right hippocampus in war veterans with posttraumatic stress disorder. (Pavic et. al., 2007) Radiology Department, University Hospital Dubrava, Zagreb, Croatia. In a study measuring hippocampal volumes in 15 war veterans compared to 15 matched normal controls. Veterans with PTSD had significantly smaller hippocampal volume (9.4%) compared to those without PTSD. Furthermore the right hippocampus was smaller than the left (on average7.9%) in all the PTSD patients. (Pavic et. al., 2007) (16) Lithium prevents hippocampal atrophy and promotes neurogenesis (birth of new brain cells) within the brain (hippocampus).(17-19) Study titled: Enhancement of hippocampal neurogenesis by lithium. (Chen et. al., 2000) Wayne State University School of Medicine Detroit, Michigan USA. Increasing evidence suggests that mood disorders are associated with a reduction in regional Central Nervous System volume and nerve cell atrophy or loss. Lithium has been shown to significantly increase the levels of Bcl-2 (a neuroprotective protein) in areas of rodent brain and in cultured cells. The present study was conducted to examine the lithium affects on neurogenesis in the adult rodent hippocampus. Mice were treated with lithium, over 12 days and cell counting revealed that lithium produced a significant 25% increase of the cells in the dentate gyrus (part of the hippocampus). (Chen et. al., 2000)(17) Study titled: Increased volume of the amygdala and hippocampus in bipolar patients treated with lithium. (Foland et. al., 2008) University of California, UCLA School of Medicine. The effects of lithium upon the growth of the hippocampus in PTSD has not been measured yet, however we do have results from bipolar subjects who share the same chemical and hormonal imbalances and share the same areas of the brain affected as is seen in PTSD. This study examined a total of 49 MRI scans of bipolar subjects who were currently being treated with and without lithium to compare the effects of lithium upon the hippocampus. The results were clear and the bipolar patients being treated with lithium had significantly larger hippocampal volumes than the patients not treated with lithium. (Foland et. al., 2008)(18) In yet another study of 12 bipolar patients treated only with lithium, researchers found that lithium not only increased hippocampal volumes but also appeared to enhance verbal

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memory performance over the 4-year period of measurement as assessed by the California Verbal Learning Test. Study title: Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. (Yucel 2007)
(19)

Lithium prevents amygdala and hippocampal atrophy and promotes neurogenesis within the hippocampus. (Savitz et. al., 2010) (20) (Beyer et. al., 2004) (21) (Bearden et. al., 2008) (22) Amgydala bottom green stem Hippocampus

Measuring N-Acetyl Aspartate (NAA) Levels

One of the key chemical measurements that indicate the overall health of brain tissue and the number of nerve cells (cell volume) in tissue is called N-acetyl aspartate (NAA). The healthier nerve tissue will have higher NAA levels than the diseased brain. When NAA levels are low (this is a sign of cell death and or degeneration of cells) that indicates that the nerve cell numbers/volume are also low in that brain area. When NAA levels are normal that indicates that nerve cell number are healthy/normal as well. Bipolar disorder has been shown to have reduced NAA levels.(23) Reduced NAA levels were first discovered in adult bipolar disorder but recently it has been shown in children as well.(24) Most recently reduced NAA levels have been demonstrated in PTSD as we would naturally expect due to the atrophy of the PTSD brain. Study titled: Abnormal N-acetylaspartate in hippocampus and anterior cingulate in posttraumatic stress disorder. (Schuff et. al., 2008) Center for Imaging of Neurodegenerative Diseases, DVA Medical Center, San Francisco, CA. When the NAA levels were measured in the hippocampus of patients with PTSD, it was discovered that NAA levels were significantly lower in PTSD patients than the normal controls. Furthermore, these decreases, indicative of nerve cell loss, (cell death) in the hippocampus were seen in both the right and the left hippocampus. (Schuff et. al., 2008)(25) This indicates that PTSD patients are experiencing nerve cell death, at a faster pace than the re-birth of new nerve cells.

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More Good News!

Lithium increases NAA levels in the adult (human) hippocampus demonstrating that lithium is promoting the birth of new neurons (nerve cells) in the region. (26-30 )
Study titled: Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2's neurotrophic effects? (Moore et. al., 2000) Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan. Lithium treatment increased NAA concentration in all brain regions investigated, including the frontal, temporal, parietal, and occipital lobes. This study demonstrates for the first time that Li administration at therapeutic doses, increases brain NAA concentration. These findings provide intriguing indirect support for the contention that chronic lithium increases neuronal viability/function in the human brain, and suggests that some of Li's long-term beneficial effects may be mediated by neurotrophic/neuroprotective events. (Moore et. al., 2000)(27)

WHAT IS CAUSING THIS BRAIN SHRINKAGE?

In a word.Stress! Various potential causes of brain atrophy have been identified, including but not limited to: 1. Traumatic Brain Injury 2. Chronic emotional/mental stressors 3. Excessive Cortisol levels 4. Hyperactivity of the Sympathetic Nervous System; causing excessive adrenaline/noradrenaline 5. Reduced levels of Brain-derived Neurotrophic Factor (BDNF) 6. Deficiency of Lithium, vitamin B-12 and Acetylcholine. 7. Immobility and lack of exercise. The atrophy/shrinkage of the hippocampus and other regions of the brain seen in Posttraumatic Stress Disorder are most likely due to a combination of factors associated with chemical, emotional, genetic and physical stressors-coupled with essential nutrient deficiency, i.e. lithium, vitamin B-12, and acetylcholine. Chronically increased levels of stress hormones (adrenaline, noradrenaline, dopamine and cortisol), in response to stress, are associated with hippocampal atrophy. (30-33) The good news; Lithium lowers/normalizes all of these stress hormones.

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Genetic factors influencing hippocampal volume and neurogenesis (birth of new neurons) can play a major role particularly if there is a deficiency of a powerful Neurotrophin called Brainderived Neurotrophic Factor (BDNF). A deficiency in the genetic transcription (production of BDNF proteins) of BDNF has been discovered to be a direct cause of loss of brain cells in the hippocampus and maybe involved in numerous other areas of brain shrinkage. Chronic stress can alter genetic functions as well, thereby lowering the production of hippocampal BDNF which leads to the atrophy of brain cells in depressed patients as well as PTSD. (34-36) Lithium effect: Fortunately, Lithium increases abnormally low levels of BDNF to near normal levels in just 1-2 weeks. Lithium has been demonstrated to double the levels of BDNF in treatment resistant depression. See: Increase of plasma brain-derived neurotrophic factor levels in two psychotic depressed patients responding to lithium addition to paroxetine treatment. (Yoshimura et. al., 2007)(36)

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Chapter Twenty Seven

PTSD NEURO-CHEMICAL ALTERATIONS

Miscellaneous Neurotransmitters, Neurotrophins and Other Chemical Imbalances Associated with PTSD
There are four major neurotransmitters that have been identified as playing a possible role in PTSD: Serotonin Gamma-aminobutyric acid Glutamate Histamine Serotonin and Gamma-aminobutyric-acid (GABA) have been found to be reduced in PTSD. Lithium has been shown to increase Serotonin and GABA. Excessive levels of Glutamate and Histamine appear to play a role in PTSD and lithium reduces both of these neurotransmitters. Serotonin aka (5HT) Serotonin is a monoamine-neurotransmitter. SSRIs are the most common medication prescribed for anxiety disorders such as PTSD.(1) Serotonin neurotransmission is most influential in areas of the brain which are involved in mood, memory, regulation of behavior, learning and reducing obsessive disorder.(2) In a study examining serotonin platelet concentrations in suicidal veterans it was discovered that serotonin levels were significantly lower in suicidal veterans with PTSD compared to normal healthy controls. These results show that PTSD and suicidal behavior are related to disturbances in the central serotonergic system.(3) Lithium effect: Lithium increases the synthesis and release of serotonin and appears to stabilize serotonin neurotransmission.(4) Lithium increases serotonin levels in mood disorders, such as bipolar disorder (Fyr et. al., 1975)(5) and major depression, and probably does the very same for PTSD. Lithium increased serotonin synthesis in rat brain by approximately 80%.(6) Gamma-aminobutyric acid (GABA) GABA is an amino acid neurotransmitter that reduces and protects against anxiety and enhances memory. GABA levels are significantly reduced in PTSD patients and persist in those who suffer with PTSD over the long-term. GABA is believed to be a preventer of long term PTSD symptoms. High GABA levels appear to protect against chronic PTSD and may represent a marker of recovery from trauma.(Vaiva et. al., 2006) See: Relationship between posttrauma GABA plasma levels and PTSD at 1-year follow-up. (7)

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Reduced GABA levels were found in another anxiety disorder called Panic disorder. Patients with panic disorder had a 22% reduction in total occipital cortex GABA concentration compared with controls. Panic disorder is associated with reductions in total occipital cortex GABA levels. This abnormality might contribute to the pathophysiology of panic disorder. (Goddard et. al., 2001)(8) Lithium effect: Lithium significantly increases GABA levels in bipolar patients (9) and rats. (10)

Glutamate - Glutamate is an amino acid neurotransmitter that excites nerves and overstimulation can cause nerve cell death via excess neural excitotoxicity. It is believed that the glutamatergic systems play a role in the pathophysiology of PTSD.(11-13) Glutamate mediates corticotropin-releasing factor (CRF) release in various brain regions involved in the pathophysiology of PTSD; anti-glutamatergic agents could stabilize the CRF system and, thereby, improve the symptom complex of PTSD (re-experiencing, hyper-arousal, and avoidance).See: The role of the glutamatergic system in posttraumatic stress disorder. (Nair and Singh 2008)(11) Glutamate has been discovered to also play a pathological role in bipolar disorder. (Du et. al., 2004(14) Lithium effect: Lithium is an anti-glutamatergic agent. Lithium protects nerve cells from excessive glutamate stimulation of nerve cells. Lithium robustly and potently protects against glutamate-induced, N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in rat brain cells. (Chuang 2005) (15)

Histamine Histamine is an organic nitrogen compound and acts as a neurotransmitter that triggers the inflammatory response as part of the immune response to foreign objects within the system. Histamine is produced by white blood cells and increases the permeability of white cells to allow them to deal with the foreign pathogens affecting the tissues of the body. Excess histamine levels may be associated with PTSD.(16) Excess histamine turnover has been implicated in anxiety. Acute stress increases the histamine turnover in the brain. Antianxiety drugs decrease brain histamine turnover. See: The role of brain histamine in acute and chronic stresses. (Ito 2000) (16) Altered histamine receptors in the brain may be playing a role in numerous mental disorders such as PTSD, bipolar disorder, schizophrenia and major depression. Researchers are examining the connection between the histamine receptors within the prefrontal cortex and the potential of those receptors to influence cognitive function that is impaired in conditions with psychotic symptoms. (Jin et. al., 2009) (17) Lithium effect: Lithium decreases histamine turnover in rats.(18) Lithium also reduces histamine reactivity. (19) A study conducted on lithiums effect upon patients with asthma found that lithium reduced bronchial reactivity in airway smooth muscle. The authors concluded that this raises new therapeutic possibilities for the treatment of asthma.(19)

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Neuropeptides
Neuropeptides are small protein-like molecules used by nerve cells to communicate with each other. They are considered to be secondary neurotransmitters and modulators of neurons (brain cells). There are two neuropeptides that appear to be involved with PTSD, angiotensin II and neuropeptide S. Angiotensin II - Angiotensin II is a neuropeptide that has been implicated in the process of brain inflammation. Brain inflammation has been demonstrated to play a critical role in brain diseases such as, Alzheimer's, Parkinson's, Posttraumatic stress disorder, traumatic brain injury, Schizophrenia, and Major Depression. Drugs that block angiotensin II have been shown to have a broad and profound impact upon reducing inflammation of the brain in (20) rats. Lithium effect: Lithium reduces the effect of angiotensin II in normal individuals.(21) Neuropeptide S (NPS) - Increased NPS has been directly implicated in hypervigilance.(22) Hypervigilance is also referred to as hyperarousal, one of the most common symptoms of PTSD. Lithium effect: Lithium reduces behavioral and biochemical effects of neuropeptide S in mice. There is a body of evidence suggesting the involvement of NPS in wakefulness, anxiety, locomotor activity and oxidative stress damage. Behavioral studies revealed that the pretreatment with lithium prevented hyper-locomotion evoked by NPS. (Castro et. al., 2009)(23) Lithium reduces effects of NPS and this may be one of the ways that lithium reduces hypervigilant behavior associated with PTSD.

NEUROTROPHINS
Neurotrophins are a family of proteins that control the growth, function and survival of nerve cells. Neurotrophins are essential in the process of cell survival. (24) Neurotrophins are proteins secreted from brain cells that promote the survival of neurons and belong to a class of nerve growth factors. These growth factors are capable of signaling particular cells to survive, differentiate, or grow. Neurotrophic growth factors act by preventing the associated neuron from initiating programmed cell death thereby allowing the neurons to survive longer. Here I will mention two important neurotrophins for PTSD and traumatic brain injury. Brain derived neurotrophic factor (BDNF) Think of BDNF as Super-food for the brain. BDNF also can be thought of as a fertilizer for nerve growth and optimal function.

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A significant body of research suggests that dysregulation of neural brain-derived neurotrophic factor (BDNF) is found in conditions of PTSD and traumatic brain injury (TBI). Increased BDNF (a good thing) and activation of its intracellular receptors can produce neural network reconnection, nerve regeneration and improved sprouting of nerve dendrites and can improve nerve synaptic function. This action by BDNF may prove to be very useful in reversing cognitive deficits while improving emotional states in both PTSD and TBI. (25) I quote from an article published by the Department of Psychiatry, Yale University School of Medicine. There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic (brain) structures. (Duman et. al., 2006) (26) Lithium effect: Lithium also induces the expression of brain-derived neurotrophic factor (BDNF) and subsequent activation of TrkB, the receptor for BDNF, in cortical neurons. (Chuang 2004) The activation of BDNF is essential for the neuroprotective effects of Lithium. (27) Chronic stress decreases neurotrophin levels, thereby causing or making depression worse. Lithium increases neurotrophin levels i.e., brain-derived neurotrophic factor and (vascular endothelial growth factor), thereby significantly reducing structural and functional pathologies via promoting neurogenesis. (28,29) So we see here that BDNF is supporting neurogenesis (the birth of new brain cells). Finally, the stimulation of neurotrophic factors, such as brain-derived neurotrophic factor, which appears to enhance neurogenesis, may also prove to have anxiolytic (anxiety reducing) effects. (Gorman 2003) (30) Vascular endothelial growth factor (VEGF) - Neurotrophic vascular growth factors appear to be essential for the rebuilding of damaged brain tissue associated with traumatic brain injury. Recent findings have indicated that VEGF also has a direct effect on neural cells and may be involved in neuroprotection as well as angiogenesis, (growth of new blood vessels). (Wei et. al., 2005) (31) Lithium effect: Lithium increases VEGF. The expression of VEGF is reduced in the brain of stressed animals, but the effect of stress on VEGF levels was significantly reduced in animals receiving lithium. (31) Lithium prevents stress-induced reduction of vascular endothelium growth factor levels. (Silva et. al. 2007) (29) VEGF levels have not been measured in PTSD.

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Miscellaneous PTSD Neuro-Chemical Alterations

N-acetylaspartate (NAA) - N-acetylaspartate levels demonstrate overall brain health, specifically the health of brain cells. Reduced levels of NAA indicate neurological deficit and dysfunction. When brain cells are dying the amount of NAA is significantly reduced. Study titled: Abnormal N-acetylaspartate in hippocampus and anterior cingulate in posttraumatic stress disorder. (Schuff et. al., 2008) Center for Imaging of Neurodegenerative Diseases, DVA Medical Center, San Francisco, CA In this study it was shown that PTSD was associated with reduced N-acetylaspartate (NAA) in both the left and right hippocampus, furthermore, PTSD was associated with reduced NAA in the right anterior cingulate cortex. (Schuff et. al., 2008) (32) Correcting NAA deficiency may be a critical component in Alzheimers disease as the following study suggests. Study title: Reduced N-acetylaspartate content in the frontal part of the brain in patients with probable Alzheimer's disease. (Christiansen, Schlosser and Henriksen 1995) The concentration of NAA was significantly lower in the patients with probable Alzheimer's disease than in the healthy volunteers. No significant difference was found for any other metabolite concentration. (Christiansen et. al., 1995) (33) Lithium effect: Lithium effects in PTSD have not been studied. Lithium significantly increases NAA levels in bipolar patients. NAA concentrations may be a good marker for neuronal viability and/or functioning, it has been further suggested that some of the long term benefits of lithium may therefore be due to actions to improve these neuronal properties. (Silverstone et. al., 2003) (33A) Lithium increases N-acetyl-aspartate in the human brain. (Moore et. al., 2000) (34)

Cyclic adenosine monophosphate - aka Cyclic AMP (cAMP) - Recent research suggests that cAMP affects the function of higher-order thinking in the prefrontal cortex. Patients with Posttraumatic Stress Disorder showed significantly lower cAMP levels than those from 10 healthy control subjects. See: Cyclic AMP signal transduction in posttraumatic stress disorder. (Lerer et. al., 1987)(35) Lithium effect: Lithium has been found to increase cAMP levels in rats.(36) No data on humans is available at this time.

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Cytokines - Pro-inflammatory cytokines have been reported to be elevated in patients experiencing chronic stress. High levels of inflammatory cytokines are present in PTSD and have been linked to PTSD vulnerability in traumatized individuals. Study title: PTSD is associated with an excess of inflammatory immune activities. (Gill et.al., 2009) National Institutes of Health, Bethesda, MD Post-traumatic stress disorder (PTSD) is associated with inflammatory-related medical conditions. Current studies suggest an excess of inflammatory actions of the immune system in individuals with chronic PTSD. There is also evidence that excessive inflammation is in part due to insufficient regulation by cortisol. An excess of inflammatory immune activity may contribute to health declines in individuals with PTSD, and treating PTSD symptoms may reduce these risks. (Gill et. al., 2009)(37) In a study examining pro-inflammatory cytokines, 20 different cytokines was measured in PTSD patients and 18 of the 20 were significantly elevated compared to healthy controls. Six out of nine of the most common pro-inflammatory cytokines were present in PTSD and Panic disorder (PD) patients. 87% of the anxiety patients had six or more detectable levels of these pro-inflammatory cytokines of which IL-6 and IL-1beta were elevated commonly. These findings suggest that a generalized inflammatory state may be present in individuals with PD or PTSD. (Hoge et. al., 2009)(38) See: Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder.

Lithium effect: Like PTSD, Bipolar patients also have an imbalance of pro-inflammatory cytokines. Lithium restores the balance of IL-6 and IL-1beta in the monocytes (white blood cells) of bipolar patients. See: An imbalance in the production of IL-1beta and IL-6 by monocytes of bipolar patients: restoration by lithium treatment. ( Knijff 2007)(39) In a study to measure of the effects of lithium treatment upon pro-inflammatory cytokine IL-6, a total of 37 manic patients with bipolar disorder and 74 control subjects were recruited. After 6 weeks of lithium treatment, the levels of IL-6 were significantly decreased. The findings of this study suggest lithium has an anti-inflammatory effect and may significantly reduce systemic inflammation. The increased activity of pro-inflammatory (inflammation causing) cytokines may play a role in the pathophysiology of bipolar disorder.(40) Increased levels of IL-6 are associated with PTSD(41) particularly when PTSD is co-occurring with MDD(42) PTSD patients have increased cerebrospinal fluid (CSF) concentrations of IL-6.(43) IL-6 may cause brain inflammation and also (at least partially) the degeneration seen in Alzheimers and therefore medicines that reduce IL-6 may have significant promise.(44) Lithium significantly reduces IL-6. Lithium effect: Lithium treatment decreased IL-6 production in bipolar patients to normal levels after 6 weeks of successful treatment.(40) Lithium significantly reduces inflammatory cytokines in bipolar patients.(45-49) Lithium treatment normalized the IL-6 and IL-1beta ratios.(45) Lithium effects in PTSD have not been studied.

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NMDA Receptors Research indicates that NMDA receptors are likely influencing changes in the brain that have a long-term effect, increasing anxiety in response to severe stress(50) such as combat. Reduced NMDA receptor activity appears to reduce anxiety.(51) Lithium effect: Lithium reduces bipolar and anxiety-related, NMDA mediated neurotransmissions. (Rapoport et. al., 2009) (52)

Enzymes & Signaling Pathways

Cellular enzymes are involved in signaling (communication) pathways between nerve cells. Here we will examine the enzymes involved in the signaling pathways associated with PTSD. AKT - Increased levels of phosphorylated enzyme AKT, has been demonstrated to be involved in the (genetically engineered) mouse model of PTSD affecting the brain, hippocampus and amygdala.(53) Increased phosphorylated Akt levels were found in Alzheimers disease patients.
(54)

Lithium effect: Lithium reduces phosphorylated AKT levels associated with alcohol toxicity in rat brain. (Chakraborty et. al., 2008) (55)

WNT/beta-cantenin - Research upon WNT/beta-cantenin signaling strongly suggests that significant reductions of this Wnt signaling pathway are associated with degeneration of hippocampal neurons (condition seen in PTSD) and may be a cause of neurodegenerative diseases associated with an anxiety related response.(56) Anxiety disorders such as PTSD (stress-related illnesses) if not properly treated with nutritional remedies will likely be devastating over a lifetime as the brain has been shown to be degenerating in PTSD. Neurodegenerative illnesses such as Alzheimers may very well be triggered by chronic longterm stress responses. Researchers are examining the Wnt signaling connection with Alzheimers and it appears to be a very significant element of this devastating disease. Study titled: Wnt signaling in Alzheimer's disease: up or down, that is the question. (Boonen RA, van Tijn P, Zivkovic D 2009) Alzheimer's disease (AD) is a progressive neurodegenerative disorder, neuropathologically characterized by amyloid-beta (Abeta) plaques and hyperphosphorylated tau accumulation. The currently available evidence implies that disruption of tightly regulated Wnt signaling may constitute a key pathological event in AD. (Boonen et. al., 2009 (57) Lithium effect: While the downregulated (decreased) Wnt/beta-catenin pathway may be causal in the neurodegeneration of Alzheimers, this may be one of the critical ways that lithium is preventing Alzheimers disease. Lithium increases (up-regulates WNT signaling).(58)

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Lithium has been reported to be beneficial in animal models of brain injury, stroke, Alzheimer's, Huntington's, and Parkinson's diseases, Amyotrophic Lateral Sclerosis (ALS), spinal cord injury, and other conditions. Clinical trials assessing the effects of lithium are under way. A recent clinical trial suggests that lithium stops the progression of ALS. (Young 2009) See: Review of lithium effects on brain and blood. (59) GSK-3beta In a mouse model of PTSD it was discovered that GSK-3 beta (an enzyme implicated in bipolar disorder and neurodegenerative disease such as Alzheimers) levels were elevated in the brain areas of the amygdala and hippocampus. (60) Lithium effect: Lithium has been identified as a direct and selective inhibitor of GSK-3beta. At therapeutically relevant concentrations Lithium significantly reduces enzyme GSK-3beta activity (61,62) and thus may be therapeutic in the treatment of various degenerative diseases including Alzheimers, Parkinsons, PTSD, Diabetes, Cancer, Bipolar disorder, Stroke, Huntingtons and Chronic Inflammatory disease.(62,63)

Protein kinase C signaling (PKC) PKC is a family of enzymes that control the signaling between nerve cells (neurons) and is particularly influential in the prefrontal cortex an area of immense importance to working memory. Excessive amounts of PKC have been shown to lead to the destruction of the dendritic spines of neurons. Excessive protein kinase C (PKC) signaling, also leads to stress-induced structural changes of the prefrontal cortex. The findings of research suggest that PKC inhibitors may be neuroprotective in disorders with dysregulated PKC signaling such as post-traumatic stress disorder, bipolar disorder, schizophrenia, and lead poisoning.(64) Lithium effect: Lithium for treatment of bipolar disorder and schizophrenia inhibits protein kinase C signaling through intracellular actions.(65,66) These findings encourage the development of protein kinase C inhibitors for the treatment of mental illness. (Arnsten 2009)(65) Instead of taking drugs to control protein kinase C signaling I have a better idea! Lets take a natural organic solution, Lithium Orotate.

Lithium-Genetic Influence upon PTSD

As with all stress-related illnesses, genetics plays a critical role in the stress-response. Here we will review one of the many suspected genetic influences involved with PTSD and examine lithiums possible role in neutralizing the genetic weakness. The following example is only one of many genetic transcription factors that lithium influences, in stress-related illnesses like PTSD.

Genetic Transcription of c-Fos Protein - Acute stress triggers the induction and increase
(up-regulation) of genetic transcription factor c-Fos. (Perrotti et. al., 2004) (67)

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Increased c-Fos activation appears to be involved in PTSD. (Kaufer et. al., 1998) (68) Lithium effect: Lithium reduces the activation of transcription by the c-Fos gene and this may very well be one way that lithium reduces the severity of symptoms associated with PTSD. Investigations on the effect of chronic lithium on c-Fos mRNA expression in various rat brain regions have been examined. Chronic lithium produced significant reductions in basal c-Fos expression in the frontal cortex and hippocampus. The frontal cortex and hippocampus are directly related to symptoms of PTSD. Stress-induced c-Fos activation was significantly reduced by lithium in the frontal cortex, hippocampus, and pituitary. (69) The authors of this study suggest that suppression of c-Fos expression may be a factor in the long-term effects of lithium, inducing changes in expression of genes that regulate cFos and may very well be involved in the pathophysiology (chemical imbalance) of affective (mood) disorders, e.g. Posttraumatic stress disorder. (Miller and Math 1997) (69)

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Chapter Twenty Eight

Lithium for Miscellaneous Conditions

Attention Deficit Hyperactivity Disorder (ADHD) - In a randomized, double-blind, study comparing the drug-Ritalin and lithium in the treatment of ADHD it was found that lithium was equally effective in reducing the following ADHD symptoms:(1) aggression antisocial behavior anxiety depression hyperactivity impulsivity irritability learning disability The authors stated, the present study showed no differences in primary or secondary outcome measures between MPH and lithium. (Dorrego et. al., 2002)(1) Ritalin aka Methylphenidate (MPH)

AIDS/HIV Infection New research suggests that Lithium Orotate may be a breakthrough for the treatment of AIDS patients. The following study demonstrated that lithium reduced viral replication in assorted human blood cells by greater than 90%. The authors stated, These data demonstrate that lithium inhibits HIV replication by >90% at 0.5 to 0.75 mM, depending on the HIV isolate used, which is a dose that is within the recommended therapeutic plasma level of lithiumOur findings also identify lithium as having anti-HIV propertiesThe fact that lithium is inexpensive and is easily administered suggests that lithium treatment may be of benefit in developing countries (Kumar et. al., 2008)(2) Hey, what about our country? Lithium appears to have a profound effect upon the cognitive dysfunction associated with AIDS. The authors of this study state, The cognitive deficits in patients with HIV profoundly affect the quality of life of people living with this disease and have often been linked to the neuroinflammatory condition known as HIV encephalitis (HIVE). Lithium has been demonstrated in several pilot studies to protect against HIV encephalitis through the GSK3beta signaling pathway. (Crews et. al., 2009)(3) Lithium resulted in improved neuropsychological performance in antiretroviral-treated, impaired individuals in this small, open-label study. Based on published in vitro data, lithium may exert this effect by inhibiting neuronal glycogen synthase kinase-3beta. See: Lithium improves HIVassociated neurocognitive impairment. (Letendre et. al., 2006)(4) Study title: Lithium salts in AIDS and AIDS-related dementia. The authors state, lithium has been found to increase the synthesis of neuroprotective proteins and to exert possible neurotrophic effects in the human brain. These properties hold great promise in the

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treatment of AIDS-related neurological deficits such as dementia. (Harvey et. al., 2002)(5) See: (Neurotrophic effects)

Anxiety disorders - Double-blind, randomized controlled trials of lithium for anxiety disorders are non-existent. Only the anxiety associated with bipolar disorder and ADHD has been studied and with good results. The common thread between Generalized, Obsessive-compulsive, Panic, PTSD and Social anxiety disorders is a disruption of the primary stress hormones and or neurotransmitters and dysregulation of the HPA axis generating an irregular stress response in anxiety disorders. (Millar 2012) Additionally, Opioid neuropeptides, vasoactive intestinal peptide (VIP), neurokinines (substance P), somatostatin, neurotensin, neuropeptide Y, cholecystokinine, vasopressin or oxitocin have been related to the control of the stress response (Equiagaray et. al., 2004)(6) Amazingly, lithium has been demonstrated to elicit positive effects upon the majority of these chemical imbalances associated with the irregular stress response in anxiety disorders. Every client that I have consulted with has reported significant reduction of anxiety with Lithium Orotate supplementation.

Borderline personality disorder (BPD) - Mood stabilizers such as lithium are now commonly prescribed in the treatment of BPD with good results stabilizing mood.(7),(8)

Bruxism (grinding teeth) - Like so many other stress-related illnesses, bruxism may be due to excessive levels of adrenaline, noradrenaline and dopamine. In a study measuring the levels of adrenaline, noradrenaline and dopamine it was discovered that all of the patients had extremely high levels of these hormones/neurotransmitters.(9) Lithium may be a breakthrough for bruxism however it has not been studied yet. Lithium effect: See Chapter Seventeen for lithium effects upon noradrenaline and dopamine.

Drug abuse and withdrawal Low levels of lithium in the drinking water has demonstrated significant reduction in the incidences of arrests for possession of opium, cocaine, and their derivatives morphine, heroin, and codeine (Schrauzer and Shrestha 1990)(10) Lithium has been demonstrated to reduce the withdrawal symptoms in morphine-addicted rats. These findings support clinical reports that suggest that prophylactic treatment with Li+ attenuates the severity of the opiate withdrawal syndrome. (Reches et. al., 1982)(11) Lithium has been demonstrated to be beneficial in Marijuana withdrawal and long-term abstinence.(12) Lithium has been demonstrated to be beneficial in withdrawal of heroin and methamphetamine, stabilizing mood for these patients.(13)

Insomnia Lithium increases slow wave sleep, i.e., deep sleep. Study title: Lithium increases slow wave sleep: possible mediation by brain 5-HT2 receptors? (Friston et. al., 1989)(14)

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Lithium Orotate users find that they sleep much more deeply and wake up feeling much more rested. (Millar 2012)

Ischemic Heart disease Lithium has been demonstrated to provide profound protection against ischemic damage (loss of blood flow and oxygenation) to the heart and brain in humans and animals. Lithium has also been demonstrated to benefit cardiac arrhythmia.(15)

Multiple Sclerosis (MS) Evidence for the use of lithium in MS treatment is growing. Animal studies show promising results. See: (Lithium MS video)

Obsessive Compulsive Disorder (OCD) The majority of OCD patients are significantly helped by serotonin re-uptake inhibitors (SRIs). In open-label reports, the addition of lithium has yielded encouraging results. (Crespo-Facorro and Gomez-Hernandez 1997)(16) Other serotonergic medications such as lithium may be useful as adjuvant treatments in treatment-refractory OCD (Laird 1996)(17)

Osteoporosis It has been suggested that lithium has the ability to reduce fractures and increase bone density. our results suggest that maintenance therapy with lithium carbonate may preserve or enhance bone mass. (Zamani et. al., 2009)(18) In a population based analysis the authors state, Lithium seems to be protective against fractures. (Bolton et. al., 2008) (19) An analysis of lithium in mice revealed, lithium chloride increases bone formation and bone mass in mice. (Clment-Lacroix et al., 2005) (20) Lithium is associated with a decrease in the risk of fractures. (Vestegaard 2008) (21)

Panic disorder See anxiety disorders above.

Parkinsons disease Every study that I have examined holds out great promise for the future of lithium to make a profound difference in the treatment and or prevention of Parkinsons disease. The Buck Institute is presently conducting research on this topic. See: Lithium Profoundly Prevents Brain Damage Associated with Parkinson's Disease (22)

Pathological gambling (PG) - While no clinical trials exist for lithium, the evidence is strong that lithium may provide a profound relief for this debilitating condition. New research is revealing a strong case for lithium treatment in PG. Brain scans reveal an area of the brain (ventral caudate) that lithium is having a positive effect in the neurochemistry of PG patients. This led the authors of this study to the

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conclusion lithium treatment may reduce cognitive dysfunction and symptoms in PG patients. (Pallanti et. al., 2010)(23) A potential driver of the compulsion of gambling as in other addictions may very well be excessive noradrenaline. The PG patients were found to have significantly elevated noradrenaline levels in the urine and cerebrospinal fluid.(24) With regard to the levels of the primary stress hormones/neurotransmitters dopamine and noradrenaline, (sympatho-adrenergic system) pathological gamblers are found to have significantly elevated levels of dopamine and noradrenaline, as well as elevated heart rate when compared to non-pathological gamblers. The authors stated Casino gambling as a "real life" situation induces activation of the HPA-axis and the sympathoadrenergic system, with significantly more pronounced changes in problem gamblers. (Meyer et. al., 2004)(25) Like so many other stress-related illnesses PG is associated with hypothalamic-pituitary axis (HPA) dysfunction, imbalanced primary stress hormones and or neurotransmitters. In a study of pathological gambling the authors stated, Notably, both pathological gambling and drug addiction are characterized by aberrations in hypothalamic-pituitary-adrenal (HPA) axis responding. (Paris et. al., 2010)(26) See Chapter Seventeen for lithium effects upon noradrenaline, dopamine and page 97 for lithium effects upon the hypothalamic-pituitary-adrenal axis (HPAA).

Post-Partum Psychosis This devastating illness following child delivery can leave women desperately depressed and without hope. Lithium has been shown effective for some of the symptoms of post-partum psychoses (blues, depression and psychosis). The authors stated, electroconvulsive therapy and lithium have proved effective in the treatment of postpartum psychoses, depending on the symptoms. (Robinson and Stewart 1986)(27) Here again we see imbalances of noradrenaline.(28) We also find disturbances in dopamine and estrogen. Dr. Wiech et. al., stated, The onset of affective psychosis after childbirth was associated with increased sensitivity of dopamine receptors in the hypothalamus and possibly elsewhere in the brain. Such changes may be triggered by the sharp fall in circulating estrogen concentrations after delivery. (Wieck et. al., 1991)(29) Lithium effect: See Chapter Seventeen for lithium effects upon noradrenaline and dopamine. A possible reason lithium may help women in postpartum psychosis may be that lithium increases estrogen levels as it has been shown to do in animal studies.(30) New research suggests that postpartum blues may be related to changes in the hypothalamicpituitary-adrenal axis (HPAA). See: Study titled: Changes in the maternal hypothalamicpituitary-adrenal axis during the early puerperium may be related to the postpartum 'blues'. (Okeane et. al., 2011)(31) Lithium effect: See 97 for lithium effects upon the hypothalamic-pituitary-adrenal axis (HPAA).

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Schizophrenia/Schizoaffective disorder Lithium treatment of schizophrenia and schizoaffective disorder has been shown to give significant relief in about 50% of patients.(32),(33)

Self Mutilation (cutting) Lithium has been shown to be effective in the treatment of self mutilating behavior.(34) See also: Study title: Lithium for the control of aggressive and selfmutilating behaviour. (Wickham and Reed 1987)(35)

Tourettes syndrome Lithium has been shown to provide profound relief of tics and involuntary sounds. See: Comparison of lithium and haloperidol therapy in Gilles de la Tourette syndrome. (Erickson et. al., 1977)(36)

Transient Ischemic attack (TIA) There is a very fine line between a TIA and a full blown stroke. It pays to be prepared. While there is no research demonstrating that lithium prevents strokes it appears likely that lithium will dramatically reduce fatality rates and severe disablility following a stroke. Lithium effect: Lithium has been shown in animal studies to produce amazing protection against brain cell death due to stroke. The area of tissue death was reduced by 56% by lithium pretreatment.(37) Lithium also promotes remodeling (recovery) of damaged nerve tissue after stroke.(38) Perhaps the most exciting finding of lithium treatment comes after the stroke occurs. Lithium treatment given after (post-stroke) the stroke has occurred produces amazing recovery of the brain tissue, dramatically reducing brain cell death. Lithium reduces brain damage and produces neurological recovery.(39) Furthermore, lithium promotes the growth of new blood vessels around the stroke area enhancing swift recovery. Lastly, lithium enhanced the blood oxygenation levels as well.(40)

Violent behavior - Violent criminals have been shown to have significantly lower lithium levels within hair analysis than the general population. Hair analysis also reveals low lithium levels in learning disabled individuals and heart disease.(41) In municipal water supplies low in lithium, violent crimes homicide, suicide and rape rates are significantly higher (almost double) than those with higher lithium levels in the public water supply. A higher level of lithium in the drinking water has demonstrated significant reduction in the incidences of arrests for possession of opium, cocaine, and their derivatives morphine, heroin, and codeine (Schrauzer and Shrestha 1990)(10) Lithium effect: Study title: Lithium reduces pathological aggression and suicidality: a mini-review. (Mller-Oerlinghausen and Lewitzka 2010) The antisuicidal effects of lithium might possibly be related to its anti-aggressive effects which have been shown in various species, populations and settings, such as animals, inhabitants of nursing homes for the elderly, mentally handicapped subjects, children and adolescents with hyperactive, hostile and aggressive behavior, and particularly in hyperaggressive inmates of correction units and prisons. (Mller-Oerlinghausen and Lewitzka 2010)(42)

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Conclusion
Obviously there is an overwhelming connection between the chemical imbalances of MDD, PTSD, and suicide prevention in the therapeutic-breakthrough orthomolecular medicine, lithium. This is no doubt, the reason that lithium has been proven by Harvard Medical School to reduce the risk of suicide by as much as 90%. Lithium obviously works at the core chemical imbalances of these illnesses thereby strengthening the veteran in the most fundamental way. I invite you to tell a veteran family about this incredible breakthrough for MDD, PTSD and suicide. In so doing you will change many lives for the better. We have much more research to conduct on humans, as so many of these findings are identified only in animal research. Most of what we find to be true in animals is true in humans, but there are differences that must be identified. What should be very clear to you now, regardless of what is missing from the research is that lithium is

The Breakthrough Mineral for Mental, Neurological and Physical Illnesses, They Definitely Dont Want You To Know About!
To order the Lithium Orotate product that I trust and personally use, go to www.OpSetThemFree.com for details. I look forward to hearing from you regarding the results of your supplementation with Lithium Orotate. Furthermore your questions on this topic will be added to the questions and answers section on the website. You may email me at www.OpSetThemFree@Live.com Sincerely,

Dr. Mark Millar

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Bibliography Introduction
1. Robert Jesse, M.D., Ph.D. Statement before the House committee on Veterans Affairs Subcommittee on Oversight and Investigations July 14, 2010. http://www.va.gov/OCA/testimony/hvac/soi/100714RJ.asp 2. Valenstein M, McCarthy JF, Austin KL, Greden JF, Young EA, Blow FC. What happened to lithium? Antidepressant augmentation in clinical settings. Am J Psychiatry. 2006 Jul;163(7):1219-25. Erratum in: Am J Psychiatry. 2006 Sep;163(9):1648-9. PubMed PMID: 16816227. http://ajp.psychiatryonline.org/article.aspx?volume=163&page=1219 3. Khan A, Khan S, Kolts R, Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry. 2003 Apr;160(4):790-2. PubMed PMID: 12668373. 4 . Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr. 2002 Feb;21(1):14-21. Review. PubMed PMID: 11838882 5. VA Research Currents. Research News from the U.S. Department of Veterans Affairs. February 2008 http://www.research.va.gov/resources/pubs/docs/va_research_currents_feb_08.pdf 6. Jonathan Wright, M.D. The Importance of Lithium Supplementation. http://mysite.verizon.net/res003jh/lithium-orotate/id13.html 7. Mark Hyman M.D. http://store.ultrawellnesscenter.com/Store/Show/Brain-and-Mood-Support/743/Lithium-%28orotate%29,-5mg 8. Alice R. Laule, M.D. Lithium. http://www.futurevisionsfoundation.org/Lithium.htm 9. Lawrence Wilson, M.D. Lithium. http://www.drlwilson.com/ARTICLES/LITHIUM.htm 10. Kerry D. Friesen, M.D. Lithium Orotate http://www.lipids4life.com/nutritional-supplements/lithium-orotate/ 11. Schrauzer GN, Shrestha KP. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biol Trace Elem Res.1990 May;25(2):105-13. PubMed PMID: 1699579. 12. Ohgami H, Terao T, Shiotsuki I, Ishii N, Iwata N. Lithium levels in drinking water and risk of suicide. Br J Psychiatry. 2009 May;194(5):464-5; discussion 446. PubMed PMID: 19407280. 13. Kapusta ND, Mossaheb N, Etzersdorfer E, Hlavin G, Thau K, Willeit M, Praschak-Rieder N, Sonneck G, Leithner-Dziubas K. Lithium in drinking water and suicide mortality. Br J Psychiatry. 2011 May;198(5):346-50. PubMed PMID: 21525518. 14. Ward Dean M.D. Medical Questions and Answers about Lithium Orotate http://mysite.verizon.net/res003jh/lithiumorotate/id10.html 15. Zeana C. Magnesium orotate in myocardial and neuronal protection. Rom J Intern Med. 1999 Jan-Mar;37(1):91-7. Review. PubMed PMID: 15523949. 16. The EFSA Journal (2009) 1187, 1-25. European Food Safety Authority, 2009. Orotic acid salts as sources of orotic acid and various minerals added for nutritional purposes to food supplements 1 Scientific Opinion of the Panel on Food Additives and Nutrient Sources added to Food (ANS) http://www.efsa.europa.eu/en/scdocs/doc/ans_ej1187_Orotates_op_en.pdf?ssbinary=true 17. Golf SW, Bender S, Grttner J. On the significance of magnesium in extreme physical stress. Cardiovasc Drugs Ther. 1998 Sep;12 Suppl 2:197-202. PubMed PMID: 9794094. 18. Rodrigues, J. Orotic Acid: The Sexiest Sports Nutrition Nutrient in Existence. Body Building.com 2005 http://www.bodybuilding.com/fun/jrod10.htm#1 19. Diet and Fitness Today. Vitamin B13 Orotic Acid Copyright 2005-2012 Bodyventures. http://www.dietandfitnesstoday.com/vitaminB13.php 20. Rosenfeldt FL, Richards SM, Lin Z, Pepe S, Conyers RA. Mechanism of cardioprotective effect of orotic acid. Cardiovasc Drugs Ther. 1998 Sep;12 Suppl 2:159-70. PubMed PMID: 9794090. 21. Nikolova M, Nikolov R. [Antihypoxic action of orotic acid]. Eksp Med Morfol. 1981;20(3):171-6. Bulgarian. PubMed PMID: 7308124. 22. Jellinek H, Takcs E. Morphological aspects of the effects of orotic acid and magnesium orotate on hypercholesterolaemia in rabbits. Arzneimittelforschung. 1995 Aug;45(8):836-42. PubMed PMID: 7575742. 23. Yeh T Jr, Rebeyka IM, Jakoi ER, Johnson DE, Dignan RJ, Dyke CM, Wechsler AS. Orotic acid improves left ventricular recovery four days after heterotopic transplantation. Ann Thorac Surg. 1994 Aug;58(2):409-15. PubMed PMID: 8067840. 24. Mller G. [Metabolic effects of orotic acid]. Z Gesamte Inn Med. 1984 Jun 15;39(12):269-73. German. PubMed PMID: 6485418. 25. Ed Sharpe. http://teamcrown.net/newsiteb/2/How%20Orotates%20Work.pdf. How Orotates Work - The Biochemistry of Vitamin B13 26. Ward Dean M.D. The Safe, Unique Mineral with Multiple Uses http://mysite.verizon.net/res003jh/lithium-orotate/id11.html 27. Kabakov AY, Karkanias NB, Lenox RH, Papke RL. Synapse-specific accumulation of lithium in intracellular microdomains: a model for uncoupling coincidence detection in the brain. Synapse. 1998 Apr;28(4):271-9. PubMed PMID: 9517835. 28. Jonathan Wright, M.D. The Misunderstood Mineral. Part One. http://tahomaclinicblog.com/lithium-the-misunderstood-mineralpart-1/ 29. Jonathan Wright, M.D. The Misunderstood Mineral. Part Two. http://tahomaclinicblog.com/lithium-the-misunderstood-mineralpart-2/ 30. Young W. Review of lithium effects on brain and blood. Cell Transplant. 2009;18(9):951-75. Epub 2009 May 13. Review. PubMed PMID: 19523343. 31. Shaheen Lakhan, M.D. Nutritional Therapies for Mental Disorders http://www.nutritionj.com/content/7/1/2 32. Al Sears M.D. Brain Health December 25th, 2009 http://www.alsearsmd.com/merry-christmas/ 33. Sartori HE. Lithium orotate in the treatment of alcoholism and related conditions. Alcohol. 1986 Mar-Apr;3(2):97-100. PubMed PMID: 3718672. 34. Norman Shealy, M.D., Ph.D.The Shealy Protocols 2008 http://www.caycegoldengate.com/Flyers/Shealy%202%20Protocols.pdf 35. Ray Sahelian, M.D. Lithium supplement and medication http://www.raysahelian.com/lithium.html 36. Linda Fugate, PhD. Lithiums Potential Role in Preventing Alzheimers disease http://gordonresearch.com/Presentations/GRI_mar07/articles/lithium_potential_role.html

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37. Dietrich K. Klinghardt, M.D, PhD Lyme disease: A Look Beyond Antibiotics. http://www.samento.com.ec/sciencelib/4lyme/beyondantibiotics.html 38. Dr. R Stone, M.D. Trace Mineral Salt Lithium Orotate to Treat Many Diseases of the Brain http://tracemineralhealth.com/tracemineral-salt-lithium-orotate-to-treat-many-diseases-of-the-brain-brain-quantum-healing 39. Phuli Cohan, M.D. How I am Treating My Lyme. http://phulicohanmd.com/?cat=26 40. Garry F. Gordon, M.D., DO, MD(H) Dr. Gordons Personal Daily Protocol Lithium Orotate Beyond Lithium. http://gordonresearch.com/Protocols/Personal_Protocol.html 41. Jeffrey Dach, M.D. Beating Depression Naturally. http://www.drdach.com/wst_page8.html 42. James Howenstine, M.D. Lithium- How to Enlarge Your Brain and Improve Brain Performance. http://www.newswithviews.com/Howenstine/james11.htm 43. Emily Deans, M.D. Evolutionary Psychology: Could You Have a Lithium Deficiency? http://www.psychologytoday.com/blog/evolutionary-psychiatry/201201/could-you-have-lithium-deficiency 44. Malhi GS, Adams D, Berk M. Is lithium in a class of its own? A brief profile of its clinical use. Aust N Z J Psychiatry. 2009 Dec;43(12):1096-104. Review. PubMed PMID: 20001408.

Chapter One Harvard Medical School Takes the Lead! The Suicide Breakthrough of Lithium
1. Baldessarini RJ, Tondo L, Davis P, Pompili M, Goodwin FK, Hennen J. Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Bipolar Disord. 2006 Oct;8(5 Pt 2):625-39. PubMed PMID: 17042835. Full study at http://onlinelibrary.wiley.com/doi/10.1111/j.1399-5618.2006.00344.x/pdf 2. Baldessarini RJ, Tondo L, Hennen J. Lithium treatment and suicide risk in major affective disorders: update and new findings. J Clin Psychiatry. 2003;64 Suppl 5:44-52. Review. PubMed PMID: 12720484. 3. Guzzetta F, Tondo L, Centorrino F, Baldessarini RJ. Lithium treatment reduces suicide risk in recurrent major depressive disorder. J Clin Psychiatry. 2007 Mar;68(3):380-3. PubMed PMID: 17388706. 4. Pompili M, Rihmer Z, Innamorati M, et al. Assessment and treatment of suicide risk in bipolar disorders. Expert Rev Neurother. 2009 Jan;9(1):109-36. Review. PubMed PMID: 19102673. 5. USA Today Civilian soldiers' suicide rate alarming. Nov 26, 2011 http://www.usatoday.com/news/military/2010-11-26-1Atroopsuicides26_ST_N.htm 6. American Psychiatric Association (APA) Practice Guideline for the Assessment and Treatment of Patients With Suicidal Behaviors (2003) http://www.psychiatryonline.com/content.aspx?aID=56792 7. American Psychiatric Association (APA) Practice Guideline for the Assessment and Treatment of Patients With Suicidal Behaviors (2003) 2010 Page 61-64 http://psychiatryonline.org/data/Books/prac/SuicidalBehavior_Inactivated_04-16-09.pdf 8. Dording CM. Antidepressant augmentation and combinations. Psychiatr Clin North Am. 2000 Dec;23(4):743-55. Review. PubMed PMID: 11147245. 9. Zivin K, Kim HM, McCarthy JF, Austin KL, Hoggatt KJ, Walters H, Valenstein M. Suicide mortality among individuals receiving treatment for depression in the Veterans Affairs health system: associations with patient and treatment setting characteristics. Am J Public Health. 2007 Dec;97(12):2193-8. PMID: 17971541; full report at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2089109/

Chapter Two Major Depression, PTSD & Suicide Statistics

1. Pfennig A, Kunzel HE, Kern N, et al. Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression. Biol Psychiatry. 2005 Feb 15;57(4):336-42. PubMed PMID: 1570534 2. Campbell DG, Felker BL, Liu CF, et. al. Prevalence of depression-PTSD comorbidity: implications for clinical practice guidelines and primary care-based interventions. J Gen Intern Med. 2007 Jun;22(6):711-8. PubMed PMID: 17503104; PubMed Central PMCID: PMC2219856. 3. Zivin K, Kim HM, McCarthy JF, Austin KL, Hoggatt KJ, Walters H, Valenstein M. Suicide mortality among individuals receiving treatment for depression in the Veterans Affairs health system: associations with patient and treatment setting characteristics. Am J Public Health. 2007 Dec;97(12):2193-8. PMID: 17971541; full report at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2089109/ 4. Pietrzak RH, Goldstein RB, Southwick SM, Grant BF. Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United tates: results from Wave 2 of the National Epidemiologic Survey on Alcohol andRelated Conditions. J Anxiety Disord. 2011 Apr;25(3):456-65. Epub 2010 Nov 26. PubMed PMID: 21168991; PubMed Central PMCID: PMC3051041. 5. Hendin H, Haas AP. Suicide and guilt as manifestations of PTSD in Vietnam combat veterans. Am J Psychiatry. 1991 May;148(5):586-91. PubMed PMID: 2018158. 6. Gregg Zoroya, USA TODAY 11/26/2010 http://www.usatoday.com/news/military/2010-11-26-1Atroopsuicides26_ST_N.htm 7. Bleich A, Koslowsky M, Dolev A, Lerer B. Post-traumatic stress disorder and depression. An analysis of comorbidity. Br J Psychiatry. 1997 May;170:479-82. PubMed PMID: 9307701. 8. CBS NEWS. Suicide Rate of Young Veterans Soars. January 11, 2010 www.cbsnews.com/stories/2010/01/11/national/main6083072.shtml 9. Veteran Journal Military News. Stemming the Tide: Suicide Rates for 2011 Continue to Climb. June 24th, 2011. http://www.veteranjournal.com/suicide-rates-for-2011/ 10. Armen Keteyian. CBS News. VA Hid Suicide Risk, Internal E-Mails Show. 4/21/2008 http://www.lb9.uscourts.gov/webcites/11documents/Veterans_CBS.pdf

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11. CBS News. CBS News Investigates Shocking Rate Of Veteran Suicides. November 14, 2007 http://crooksandliars.com/2007/11/15/cbs-news-investigates-shocking-rate-of-veteran-suicides 12. ROBERT JESSE, M.D., PH.D. HOUSE COMMITTEE ON VETERANS AFFAIRS SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS JULY 14, 2010. http://www.va.gov/OCA/testimony/hvac/soi/100714RJ.asp 13. Mental Health Advisory Team (MHAT) V. Operation Enduring Freedom 8 Afghanistan 14 February 2008 http://www.armymedicine.army.mil/reports/mhat/mhat_v/Redacted2-MHATV-OEF-4-FEB-2008Report.pdf 14. Gregg Zoroya, Civilian Soldiers' Suicide Rate Alarming!USA TODAY 11/26/2010 http://www.usatoday.com/news/military/201011-26-1Atroopsuicides26_ST _N.htm 15. Rob Hotakainen. Senators tell VA to reduce veteran suicides. McClatchy Newspapers, Washington Bureau, Wed, May. 25, 2011 Senators tell VA to reduce veteran suicideshttp://www.mcclatchydc.com/2011/05/25/v-print/114777/senators-tell-va-to-reduceveteran.html 16. Elisabeth Bumiller. Active-Duty Soldiers Take Their Own Lives at Record Rate. New York Times. January 19, 2012. http://www.nytimes.com/2012/01/20/us/active-duty-army-suicides-reach-record-high.html 17. Timothy Williams. Suicides Outpacing War Deaths for Troops. New York Times June 8, 2012 http://www.nytimes.com/2012/06/09/us/suicides-eclipse-war-deaths-for-us-troops.html 18. Kessler RC, Berglund P, Demler O, et. al. National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. PubMed PMID: 12813115. 19. Cougle JR, Resnick H, Kilpatrick DG. PTSD, depression, and their comorbidity in relation to suicidality: cross-sectional and prospective analyses of a national probability sample of women. Depress Anxiety. 2009;26(12):1151-7. PubMed PMID: 19842171.

Chapter Three Lack of Proper VA Care for Depressed Veterans Exposed.

1. Valenstein M, McCarthy JF, Austin KL, Greden JF, Young EA, Blow FC. What happened to lithium? Antidepressant augmentation in clinical settings. Am J Psychiatry. 2006 Jul;163(7):1219-25. Erratum in: Am J Psychiatry. 2006 Sep;163(9):1648-9. PubMed PMID: 16816227. 2. Valenstein M, McCarthy JF, Austin KL, Greden JF, Young EA, Blow FC. What happened to lithium? Antidepressant augmentation in clinical settings. Am J Psychiatry. 2006 Jul;163(7):1219-25. Erratum in: Am J Psychiatry. 2006 Sep;163(9):1648-9. PubMed PMID: 16816227. http://ajp.psychiatryonline.org/article.aspx?volume=163&page=1219 3. Amital D, Fostick L, Silberman A, Beckman M, Spivak B. Serious life events among resistant and non-resistant MDD patients. J Affect Disord. 2008 Oct;110(3):260-4. PubMed PMID: 18262654. 4.Pfennig A, Kunzel HE, Kern N, Ising M, Majer M, Fuchs B, Ernst G, Holsboer F, Binder EB. Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression. Biol Psychiatry. 2005 Feb 15;57(4):336-42. PubMed PMID: 15705348. 5. Chen YW, Dilsaver SC. Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders. Biol Psychiatry. 1996 May 15;39(10):896-9. PubMed PMID: 8860192. 6 .Hendin H, Haas AP. Suicide and guilt as manifestations of PTSD in Vietnam combat veterans. Am J Psychiatry. 1991 May;148(5): 586-91. PubMed PMID: 2018158. 7. American Psychiatric Association (APA) Practice Guideline for the Assessment and Treatment of Patients With Suicidal Behaviors (2003) http://www.psychiatryonline.com/content.aspx?aID=56792 8. American Psychiatric Association Practice Guidelines for the treatment of Psychiatric Disorders Compendium 2006. 9. Hearing before the Subcommittee on Oversight and Investigation of the Committee on Veterans Affairs, U.S. House of Representatives, One Hundred Eleventh Congress, Second Session, July 14, 2010 http://www.gpo.gov/fdsys/pkg/CHRG-111hhrg 58058/html/CHRG-111hhrg58058.htm 10. Zivin K, Kim HM, McCarthy JF, Austin KL, Hoggatt KJ, Walters H, Valenstein M. Suicide mortality among individuals receiving treatment for depression in the Veterans Affairs health system: associations with patient and treatment setting characteristics. Am J Public Health. 2007 Dec;97(12):2193-8. PMID: 17971541; full report at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2089109/ 11. U.S. Senator Patty Murray. http://www.murray.senate.gov/public/index.cfm/pattyinnews?ContentRecord_id=8fb548fa-fd19-47d7b2f0-67a829edb883 12. Pfennig A, Kunzel HE, Kern N, et al. Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression. Biol Psychiatry. 2005 Feb 15;57(4):336-42. PubMed PMID: 15705348. 13. Bleich A, Koslowsky M, Dolev A, Lerer B. Post-traumatic stress disorder and depression. An analysis of comorbidity. Br J Psychiatry. 1997 May;170:479-82. PubMed PMID: 9307701. 14. Hendin H, Haas AP. Suicide and guilt as manifestations of PTSD in Vietnam combat veterans. Am J Psychiatry. 1991 May;148(5):586-91. PubMed PMID: 2018158. 15. Oquendo M, Brent DA, Birmaher B, Greenhill L, Kolko D, Stanley B, Zelazny J, Burke AK, Firinciogullari S, Ellis SP, Mann JJ. Posttraumatic stress disorder comorbid with major depression: factors mediating the association with suicidal behavior. Am J Psychiatry. 2005 Mar;162(3):560-6. PubMed PMID: 15741474. 16. Fesler FA. Valproate in combat-related posttraumatic stress disorder. J Clin Psychiatry. 1991 Sep;52(9):361-4. PubMed PMID: 1894587. 17. Kornstein SG, Schneider RK. Clinical features of treatment-resistant depression. J Clin Psychiatry. 2001;62 Suppl 16:18-25. Review. PubMed PMID: 11480880. 17A

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Treatment-resistance: The primary cause of the Veteran Suicide Epidemic!

18. Crown WH, Finkelstein S, Berndt ER, Ling D, Poret AW, Rush AJ, Russell JM. The impact of treatment-resistant depression on health care utilization and costs. J Clin Psychiatry. 2002 Nov;63(11):963-71. PubMed PMID: 12444808. 19. Mental Health: A Report by the Surgeon General. http://www.surgeongeneral.gov/library/mentalhealth/chapter4/sec3.html 20. Blair-West GW, Cantor CH, Mellsop GW, Eyeson-Annan ML. Lifetime suicide risk in major depression: sex and age determinants. J Affect Disord. 1999 Oct;55(2-3):171-8. PubMed PMID: 10628886. 21. Thase ME. Treatment-resistant depression: prevalence, risk factors, andtreatment strategies. J Clin Psychiatry. 2011 May;72(5):e18. PubMed PMID: 21658343. 22. Hantouche E, Angst J, Azorin JM. Explained factors of suicide attempts in major depression. J Affect Disord. 2010 Dec;127(1-3):305-8. PubMed PMID: 20554011. 23. Lenze EJ, Sheffrin M, Driscoll HC, Mulsant BH, Pollock BG, Dew MA, Lotrich F, Devlin B, Bies R, Reynolds CF 3rd. Incomplete response in late-life depression: getting to remission. Dialogues Clin Neurosci. 2008;10(4):419-30. Review. PubMed PMID: 9170399; PubMed Central PMCID: PMC3181898.

Lithium Efficacy in Treatment-Resistant Depression (TRD) Lithium Response Rates in Treatment-Resistant MDD
24. Bauer M, Bschor T, Kunz D, Berghfer A, Strhle A, Mller-Oerlinghausen B.D ouble-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression. Am J Psychiatry. 2000 Sep;157(9):1429-35. PubMed PMID: 10964859. 25. .Nierenberg AA, Price LH, Charney DS, Heninger GR. After lithium augmentation: a retrospective follow-up of patients with antidepressant-refractory depression. J Affect Disord. 1990 Mar;18(3):167-75. PubMed PMID: 2139061. 26. Shergill SS, Robertson MM, Stein G, Bernadt M, Katona CL. Outcome in refractory depression. J Affect Disord. 1999 Aug;54(3):287-94. PubMed PMID: 10467973. 27. Lafferman J, Solomon K, Ruskin P. Lithium augmentation for treatment-resistant depression in the elderly. J Geriatr Psychiatry Neurol. 1988 Jan;1(1):49-52.PubMed PMID: 3150926. 28. Schreiber S, Shalev A. [Lithium augmentation for mianserin-resistant depression in the elderly]. Harefuah. 1992 Oct;123(7-8):250-1, 307. Hebrew. PubMed PMID: 1459497. 29. Bschor T, Lewitzka U, Pfennig A, Bauer M. [Twenty-five years of lithium augmentation]. Nervenarzt. 2007 Nov;78(11):1237-47. Review. German. PubMed PMID: 17458527. 30 Mendels J. Lithium in the treatment of depression. Am J Psychiatry. 1976 Apr;133(4):373-8. PubMed PMID: 1267033. 31. Inoue T, Nakagawa S, Kitaichi Y, Izumi T, Tanaka T, Masui T, Kusumi I, Denda K, Koyama T. Long-term outcome of antidepressant-refractory depression: the relevance of unrecognized bipolarity. J Affect Disord. 2006 Oct;95(1-3):61-7. PubMed PMID: 16797078 32. Katona CL. Lithium augmentation in refractory depression. Psychiatr Dev. 1988 Summer;6(2):153-71. Review. PubMed PMID: 3070547. 33.Bschor T, Bauer M. Efficacy and mechanisms of action of lithium augmentation in refractory major depression. Curr Pharm Des. 2006;12(23):2985-92. Review. PubMed PMID: 16918427. 34.Bauer M, Adli M, Bschor T, et al. Lithium's emerging role in the treatment of refractory major depressive episodes: augmentation of antidepressants. Neuropsychobiology. 2010;62(1):36-42. Epub 2010 May 7. Review. PubMed PMID: 20453533. 35. Bschor T, Lewitzka U, Pfennig A, Bauer M. [Twenty-five years of lithium augmentation]. Nervenarzt. 2007 Nov;78(11):1237-47. Review. German. PubMed PMID: 17458527. 36. Mendels J. Lithium in the treatment of depression. Am J Psychiatry. 1976 Apr;133(4):373-8. PubMed PMID: 1267033. 37. Inoue T, Nakagawa S, Kitaichi Y, et al. Long-term outcome of antidepressant-refractory depression: the relevance of unrecognized bipolarity. J Affect Disord. 2006 Oct;95(1-3):61-7. Epub 2006 Jun 22. PubMed PMID: 16797078. 38. Katona CL. Lithium augmentation in refractory depression. Psychiatr Dev. 1988 Summer;6(2):153-71. Review. PubMed PMID: 3070547. 39. Baumann P, Nil R, Souche A, et al. A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation. J Clin Psychopharmacol. 1996 Aug;16(4):307-14. PubMed PMID: 8835706. 40. Dinan TG. Lithium augmentation in sertraline-resistant depression: a preliminary dose-response study. Acta Psychiatr Scand. 1993 Oct;88(4):300-1. PubMed PMID: 8256650. 41. Thase ME, Kupfer DJ, Frank E, Jarrett DB. Treatment of imipramine-resistant recurrent depression: II. An open clinical trial of lithium augmentation. J Clin Psychiatry. 1989 Nov;50(11):413-7. PubMed PMID: 2509437. 42. Faravelli C, Marchetti G, Benvenuti P, Cabras PL. [Lithium in the prophylaxis of recurrent affective disorders. Effectiveness of low plasma levels and predictors to clinical response (author's transl)]. Riv Patol Nerv Ment. 1980 Nov-Dec;101(6):261-71. Italian. PubMed PMID: 6801749. 43. Dording CM. Antidepressant augmentation and combinations. Psychiatr Clin North Am. 2000 Dec;23(4):743-55. Review. PubMed PMID: 11147245. 44. Cipriani A, Smith K, Burgess S, Carney S, Goodwin G, Geddes J. Lithium versus antidepressants in the long-term treatment of unipolar affective disorder. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003492. Review. PubMed PMID: 17054174. 45. Hicks P, Hicks XP, Meyer H, Shisslak C. How best to manage treatment-resistant depression? J Fam Pract. 2010 Sep;59(9):490-7. Review. PubMed PMID: 20824225. http://stg.jfponline.com/Pages.asp?AID=8926&issue=July_2010&UID= 46. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. PubMed PMID: 17074942. 47. Cappiello A, McDougle CJ, Delgado PL, et al. Lithium and desipramine versus desipramine alone in the treatment of severe

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A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry.2006;163:1519 1530. 52. Nierenberg AA, Papakostas GI, Petersen T, et al. Lithium augmentation of nortriptyline for subjects resistant to multiple antidepressants. J Clin Psychopharmacol. 2003;23:92-95. 53. Joffe RT, Sokolov ST, Levitt AJ. Lithium and triiodothyronine augmentation of antidepressants. Can J Psychiatry. 2006;51:791793. 54. Aronson R, Offman HJ, Joffe RT, et al. Triiodothyronine augmentation in the treatment of refractory depression. A metaanalysis. Arch Gen Psychiatry. 1996;53:842-848. 55. Berman RM, Fava M, Thase ME, et al. Aripiprazole augmentation in major depressive disorder: a double-blind, placebocontrolled study in patients with inadequate response to antidepressants. CNS Spectr. 2009;14:197-206. 56. Trivedi MH, Thase ME, Fava M, et al. Adjunctive aripiprazole in major depressive disorder: analysis of efficacy and safety in patients with anxious and atypical features. J Clin Psychiatry. 2008;69:1928-1936. 57. Simon JS, Nemeroff CB. Aripiprazole augmentation of antidepressants for the treatment of partially responding and nonresponding patients with major depressive disorder. J Clin Psychiatry. 2005;66:1216-1220. 58. Trivedi MH, Thase ME, Osuntokun O, et al. An integrated analysis of olanzapine/fluoxetine combination in clinical trials of treatment-resistant depression. J Clin Psychiatry. 2009;70: 387-396. 59. Alexopoulos GS, Canuso CM, Gharabawi GM, et al. Placebo-controlled study of relapse prevention with risperidone augmentation in older patients with resistant depression. Am J Geriatr Psychiatry. 2008;16:21-30 60. Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-refractory major depressive disorder: a randomized trial. Ann Intern Med. 2007;147:593-602 61. Keitner GI, Garlow SJ, Ryan CE, et al. A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression. J Psychiatr Res. 2009;43:205-214. 62. Garakani A, Martinez JM, Marcus S, et al. A randomized, double-blind, and placebo-controlled trial of quetiapine augmentation of fluoxetine in major depressive disorder. Int Clin Psychopharmacol. 2008;23:269-275. 63. Bauer M, Pretorius HW, Constant EL, et al. Extended-release quetiapine as adjunct to an antidepressant in patients with major depressive disorder: results of a randomized, placebo-controlled, double-blind study. J Clin Psychiatry. 2009;70:540-549. 64. Carpenter LL, Yasmin S, Price LH. Double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine. Biol Psychiatry. 2002;51:183-188. 65. Thase ME, Friedman ES, Biggs MM, et al. Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry. 2007;164:739-752. 66. Alpert JE, Mischoulon D, Rubenstein GE, et al. Folic acid (Leucovorin) as an adjunctive treatment for SSRI-refractory depression. Ann Clin Psychiatry. 2002;14:33-38. 67. Alpert JE, Papakostas G, Mischoulon D, et al. S-adenosyl-Lmethionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine. J Clin Psychopharmacol. 2004;24:661664. 68. The New York Times. A Victory for Veterans. May 18, 2011 Editorial Section 69. CBS NEWS. VA Hid Suicide Risk, Internal E-Mails Show. Armen Keteyian July 30, 2010 http://www.cbsnews.com/2100500690_162-4032921.html 70. Strategies for Suicide Prevention in Veterans January 2009 Department of Veterans Affairs Health Services Research & Development Service Evidence-based Synthesis Program.http://www.hsrd.research.va.gov/publications/esp/Suicide-Prevention2009.pdf. 71. American Psychiatric Association (APA) Practice Guideline for the Assessment and Treatment of Patients With Suicidal Behaviors (2003) http://www.psychiatryonline.com/content.aspx?aID=56792 72. IRA KATZ, M.D., PH.D. STATEMENT BEFORE: THE HOUSE COMMITTEE ON VETERANS AFFAIRS FULL COMMITTEE FEBRUARY 24, 2010 73. House Committee on Veterans Affairs Hearing on 05/06/2008: The Truth about Veterans Suicides http://veterans.house.gov/opening-statement/hon-bob-filner-chairman-and-a-representative-in-congress-from-the-state-of3 74. Guzzetta F, Tondo L, Centorrino F, Baldessarini RJ. Lithium treatment reduces suicide risk in recurrent major depressive disorder. J Clin Psychiatry. 2007 Mar;68(3):380-3. PubMed PMID: 17388706. 75. George J. Opfer. Inspector General VA Office of Inspector Genera l Healthcare Inspection Implementing VHAs Mental Health Strategic Plan Initiatives for Suicide Prevention May 10, 2007 Report No. 06-03706-126 76. Valenstein M, McCarthy JF, Austin KL, Greden JF, Young EA, Blow FC. What happened to lithium? Antidepressant augmentation in clinical settings. Am J Psychiatry. 2006 Jul;163(7):1219-25. Erratum in: Am J Psychiatry. 2006 Sep;163(9):1648-9. PubMed PMID: 16816227. http://ajp.psychiatryonline.org/article.aspx?volume=163&page=1219 77. Jerram T C & McDonald R (1978) In: Lithium in Medical Practice. Ed. F N Johnson and S Johnson. MTP Press,Lancaster; pp 407-413 Lancet (1979) ii, 619-620 78. Faravelli C, Marchetti G, Benvenuti P, Cabras PL. [Lithium in the prophylaxis of recurrent affective disorders. Effectiveness of low plasma levels and predictors to clinical response (authors transl)]. Riv Patol Nerv Ment. 1980 Nov-Dec;101(6):261-71. Italian. PubMed PMID: 6801749. 79. Dinan TG. Lithium augmentation in sertraline-resistant depression: a preliminary dose-response study. Acta Psychiatr Scand. 1993 Oct;88(4):300-1. PubMed PMID: 8256650.

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80. Alevizos B, Alevizos E, Leonardou A, Zervas I. Low dosage lithium augmentation in venlafaxine resistant depression: An openlabel study. Psychiatrike. 2012 Apr-Jun;23(2):143-8. PubMed PMID: 22796912. 81. Ahrens B, Mller-Oerlinghausen B. Does lithium exert an independent antisuicidal effect? Pharmacopsychiatry. 2001 Jul;34(4):132-6. PubMed PMID: 11518473. 82 Robert Jesse, M.D., Ph.D. Statement before the House committee on Veterans Affairs Subcommittee on Oversight and Investigations July 14, 2010. http://www.va.gov/OCA/testimony/hvac/soi/100714RJ.asp 83. Pompili M, Rihmer Z, Innamorati M, Lester D, Girardi P, Tatarelli R. Assessment and treatment of suicide risk in bipolar disorders. Expert Rev Neurother. 2009 Jan;9(1):109-36. Review. PubMed PMID: 19102673. 84. Ward Dean M.D. Medical Questions and Answers about Lithium Orotate http://mysite.verizon.net/res003jh/lithiumorotate/id10.html 85. Ward Dean M.D. The Safe, Unique Mineral with Multiple Uses http://mysite.verizon.net/res003jh/lithium-orotate/id11.html 86. Tondo L, Baldessarini RJ, Hennen J, Floris G, Silvetti F, Tohen M. Lithium treatment and risk of suicidal behavior in bipolar disorder patients. J Clin Psychiatry. 1998 Aug;59(8):405-14. PubMed PMID: 9721820.

Chapter Four The Calling

1. U.S. Department of Veterans Affairs. (2007). Fifth Annual Report of the Department of Veterans Affairs Undersecretary for Health Special Committee on Post-Traumatic Stress Disorder. 2. Epstein, Jack. (2005). US Wars and Post Traumatic Stress Disorder. San Francisco Chronicle, 6/22/05. 3. Kukla, Richard A., William E. et al.. (1990). Trauma and the Vietnam War Generation: Report of Findings from the National Vietnam Veterans Readjustment Study. New York: Brunner/Mazel. 4. Veterans for Common Sense 2009. http://www.youtube.com/watch?v=Y-YoueYBvCc 5. Bleich A, Koslowsky M, Dolev A, Lerer B. Post-traumatic stress disorder and depression. An analysis of comorbidity. Br J Psychiatry. 1997 May;170:479-82. PubMed PMID: 9307701. 6. Mann JJ, Apter A, Bertolote J, et al. Suicide prevention strategies: a systematic review. JAMA. 2005 Oct 26;294(16):2064-74. Review. PubMed PMID: 16249421. 7. Lnnqvist JK, Henriksson MM, Isomets ET, Marttunen MJ, Heikkinen ME, Aro HM, Kuoppasalmi KI. Mental disorders and suicide prevention. Psychiatry Clin Neurosci. 1995 May;49 Suppl 1:S111-6. Review. PubMed PMID: 9179954. 8. Ahearn EP, Chen P, Hertzberg M, et al.. Suicide attempts in veterans with bipolar disorder during treatment with lithium, divalproex, and atypical antipsychotics. J Affect Disord. 2012 Aug 4. [Epub ahead of print] PubMed PMID: 22871534.

Chapter Five Lithium Orotate Dosing

1. Smith DF, Schou M. Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate. J Pharm Pharmacol. 1979 Mar;31(3):161-3. PubMed PMID: 34690. 2. Sobanski T, Bagli M, Laux G, Rao ML. Serotonin syndrome after lithium add-on medication to paroxetine. Pharmacopsychiatry. 1997 May;30(3):106-7. PubMed PMID: 9211572.

Chapter Six Veterans What is causing these conditions?

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Lithium & the Hypothalamic-Pituitary-Adrenal Axis (HPA) & the Hypothalamic-Pituitary-Thyroid Axis (HPTA) in Major Depression, PTSD and Suicide
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The Shrinking Brain of MDD and PTSD

93. Cole J, Toga AW, Hojatkashani C, ET AL. Subregional hippocampal deformations in major depressive disorder. J Affect Disord. 2010 Oct;126(1-2):272-7. PubMed PMID: 20392498; PubMed Central PMCID: PMC3197834. 94. Koolschijn PC, van Haren NE, Lensvelt-Mulders GJ. Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp. 2009 Nov;30(11):3719-35.PubMed PMID: 19441021. 95. MacQueen G, Frodl T. The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? Mol Psychiatry. 2011 Mar;16(3):252-64. Epub 2010 Jul 27. Review. PubMed PMID: 20661246. 96. Apfel BA, Ross J, Hlavin J, et al. Hippocampal volume differences in Gulf War veterans with current versus lifetime posttraumatic stress disorder symptoms. Biol Psychiatry. 2011 Mar 15;69(6):541-8. Epub 2010 Nov 20. PubMed PMID: 21094937; PubMed Central PMCID: PMC3259803. 97. MacMaster FP, Kusumakar V. Hippocampal volume in early onset depression. BMC Med. 2004 Jan 29;2:2. PubMed PMID: 14969587; PubMed Central PMCID: PMC333436. 98. Monkul ES, Matsuo K, Nicoletti MA, et al. Prefrontal gray matter increasesin healthy individuals after lithium treatment: a voxelbased morphometry study. Neurosci Lett. 2007 Dec 11;429(1):7-11. PMCID: PMC2693231. 99. Lyoo IK, Dager SR, Kim JE, et al. Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: a longitudinal brain imaging study. Neuropsychopharmacology. 2010 Jul;35(8):1743-50. PubMed PMID:20357761; PubMed Central PMCID: PMC3055479. 100. Sassi RB, Nicoletti M, Brambilla P, et al. Increased gray matter volume in lithium-treated bipolar disorder patients. Neurosci Lett. 2002 Aug 30;329(2):243-5. PubMed PMID: 12165422. 101. Foland LC, Altshuler LL, Sugar CA, et al. Increased volume of the amygdala and hippocampus in bipolar patients treated with lithium. Neuroreport. 2008 Jan 22;19(2):221-4. PubMed PMID: 18185112. 102. Yucel K, McKinnon MC, Taylor VH, et al. Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Psychopharmacology (Berl). 2007 Dec;195(3):357-67. PubMed PMID: 17705060. 103. Bearden CE, Thompson PM, Dutton RA, et.al. Three-dimensional mapping of hippocampal anatomy in unmedicated and lithium-treated patients with bipolar disorder. Neuropsychopharmacology. 2008 May;33(6):1229-38. Epub 2007 Aug 8. PubMed PMID: 17687266. 104. Fornai F, Longone P, Cafaro L, et al. Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2052-7. PubMed PMID: 18250315; PubMed Central PMCID: PMC2538879. 105. Moore GJ, Cortese BM, Glitz DA, et al. A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients. J Clin Psychiatry. 2009 Apr 21;70(5):699-705. PubMed PMID: 19389332.

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Lithium Critically Essential in All Mood Disorders!

108. Manji HK, Moore GJ, Chen G. Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: a role for neurotrophic and neuroprotective effects in manic depressive illness. J Clin Psychiatry. 2000;61 Suppl 9:82-96. Review. PubMed PMID: 10826666.

Chapter Seven LITHIUM: The International Treatment of Choice for Depression and Suicide Prevention, a World-Wide Overview.
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Chapter Nine PTSD COMORBID ILLNESSES

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Fedorak RN, Field M. Antidiarrheal therapy. Prospects for new agents. Dig Dis Sci. 1987 Feb;32(2):195-205. Review. PubMed PMID: 3542447. 194. McFarlane AC. Stress-related musculoskeletal pain. Best Pract Res Clin Rheumatol. 2007 Jun;21(3):549-65. Review. PubMed PMID: 17602999. 195. Elfering A, Grebner S, Gerber H, Semmer NK. Workplace observation of work stressors, catecholamines and musculoskeletal pain among male employees. Scand J Work Environ Health. 2008 Oct;34(5):337-44. Epub 2008 Oct 14. PubMed PMID: 18853065. 196. Kranzler JD, Gendreau RM. Role and rationale for the use of milnacipran in the management of fibromyalgia. Neuropsychiatr Dis Treat. 2010 May 25;6:197-208. PubMed PMID: 20520784; PubMed Central PMCID: PMC2877602. 197. Yung CY. A review of clinical trials of lithium in neurology. Pharmacol Biochem Behav. 1984;21 Suppl 1:57-64. Review. PubMed PMID: 6240662.

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Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008 Mar 15;63(6):629-32. PubMed PMID: 17868655; PubMed Central PMCID: PMC2350188. 204. Fuller RW, Snoddy HD, Perry KW. Effect of prazosin on norepinephrine concentration and turnover in rat brain and heart. Arch Int Pharmacodyn Ther. 1978 Jan;231(1):30-41. PubMed PMID: 637622. 205. Daly CM, Doyle ME, Radkind M, et al. Clinical case series: the use of Prazosin for combat-related recurrent nightmares among Operation Iraqi Freedom combat veterans. Mil Med. 2005 Jun;170(6):513-5. PubMed PMID: 16001603. 206. Leskin GA, Woodward SH, Young HE, Sheikh JI. Effects of comorbid diagnoses on sleep disturbance in PTSD. J Psychiatr Res. 2002 Nov-Dec;36(6):449-52. PubMed PMID: 12393315. 207. Nesse RM, Cameron OG, Curtis GC, et al. Adrenergic function in patients with panic anxiety. Arch Gen Psychiatry. 1984 Aug;41(8):771-6. PubMed PMID: 6331337. 208. Charney DS, Heninger GR, Breier A. Noradrenergic function in panic anxiety. Effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1984 Aug;41(8):751-63. PubMed PMID: 6742977. 209. Garvey MJ, Tollefson GD, Orsulak PJ. Elevations of urinary MHPG in depressed patients with panic attacks. Psychiatry Res. 1987 Mar;20(3):183-7. PubMed PMID: 3588779. 210. Villacres EC, Hollifield M, Katon WJ, Wilkinson CW, Veith RC. Sympathetic nervous system activity in panic disorder. Psychiatry Res. 1987 Aug;21(4):313-21. PubMed PMID: 3628614. 211. Yaltho TC, Ondo WG. The use of gabapentin enacarbil in the treatment of restless legs syndrome. Ther Adv Neurol Disord. 2010 Sep;3(5):269-75. PubMed PMID: 21179617; PubMed Central PMCID: PMC3002665. 212. Manrquez JJ, Uribe P. Seborrhoeic dermatitis. Clin Evid (Online). 2007 Jul 1;2007. pii: 1713. PubMed PMID: 19454093; PubMed Central PMCID: PMC2943817. 213. Fredrikson M, Gunnarsson R. Psychobiology of stage fright: the effect of public performance on neuroendocrine, cardiovascular and subjective reactions. Biol Psychol. 1992 May;33(1):51-61. PubMed PMID: 1599999. 214. Stein MB, Tancer ME, Uhde TW. Heart rate and plasma norepinephrine responsivity to orthostatic challenge in anxiety disorders. Comparison of patients with panic disorder and social phobia and normal control subjects. Arch Gen Psychiatry. 1992 Apr;49(4):311-7. PubMed PMID: 1558465. 215. Gerra G, Zaimovic A, Zambelli U,et al. Neuroendocrine responses to psychological stress in adolescents with anxiety disorder. Neuropsychobiology. 2000;42(2):82-92. PubMed PMID: 10940763. 216. Aouizerate B, Martin-Guehl C, Tignol J. [Neurobiology and pharmacotherapy of social phobia]. Encephale. 2004 JulAug;30(4):301-13. Review. French. PubMed PMID: 15538306. 217. Westenberg HG. Recent advances in understanding and treating social anxiety disorder. CNS Spectr. 2009 Feb;14(2 Suppl 3):24-33. Review. PubMed PMID: 19238127. 218. Hill CE, Moon LD, Wood PM, Bunge MB. Labeled Schwann cell transplantation: cell loss, host Schwann cell replacement, and strategies to enhance survival. Glia. 2006 Feb;53(3):338-43. PubMed PMID: 16267833. 219. Vroemen M, Caioni M, Bogdahn U, Weidner N. Failure of Schwann cells as supporting cells for adult neural progenitor cell grafts in the acutely injured spinal cord. Cell Tissue Res. 2007 Jan;327(1):1-13. PubMed PMID: 16941122. 220. Santos-Benito FF, Ramn-Cueto A. Olfactory ensheathing glia transplantation: a therapy to promote repair in the mammalian central nervous system. Anat Rec B New Anat. 2003 Mar;271(1):77-85. Review. PubMed PMID: 12619089. 221. http://wiseyoung.wordpress.com/page/2/ 222. Brass LM, Page WF. Stroke in former prisoners of war. J Stroke Cerebrovasc Dis. 1996 Nov-Dec;6(2):72-8. PubMed PMID: 17894972. 223. Nonaka S, Chuang DM. Neuroprotective effects of chronic lithium on focal cerebral ischemia in rats. 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232. Brandsborg O, Christensen NJ, Lvgreen NA, et al. Increased sensitivity of gastrin release to adrenaline in duodenal ulcer. Gut. 1978 Mar;19(3):202-6. PubMed PMID: 631642; PubMed Central PMCID: PMC1411909. 233. Brandsborg O, Brandsborg M, Lvgreen NA, Christensen NJ. Increased plasma noradrenaline and serum gastrin in patients with duodenal ulcer. Eur J Clin Invest. 1978 Feb;8(1):11-4. PubMed PMID: 417926. 234. Christensen NJ, Jensen EW. Sympathoadrenal activity and psychosocial stress. The significance of aging, long-term smoking, and stress models. Ann N Y Acad Sci. 1995 Dec 29;771:640-7. PubMed PMID: 8597437. 235. Jrgensen LS, Christiansen P, Raundahl U, et al. Autonomic nervous system function in patients with functional abdominal pain. An experimental study. Scand J Gastroenterol. 1993 Jan;28(1):63-8. PubMed PMID: 8381557. 236. Graffner H, Farnebo LO, Holst J, Jrhult J. Pirenzepine depresses plasma noradrenaline in duodenal ulcer patients. Acta Chir Scand Suppl. 1984;520:41-4. PubMed PMID: 6150592. 237. Zheng ZT, Xing LP. Effect of furazolidone on gut catecholamine in cysteamine-induced duodenal ulcer in the rat. Scand J Gastroenterol. 1988 Oct;23(8):1020-4. PubMed PMID: 3201126. 238. Ivashkin VT, Minasian GA. [Randomized double-blind placebo-controlled study of drugs with anti-ulcer action and their use in associated pathology]. Ter Arkh. 1988;60(1):78-83. Russian. PubMed PMID: 3129806. 239. Wong RK, Boedecker B, Maydonovitch CL. Sex differences in gastric mucosal protection after 16, 16-dimethyl PGE2 and lithium chloride. Prostaglandins. 1986 Oct;32(4):555-61. PubMed PMID: 3025937.

Chapter Ten The Big Lie!

1. Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr. 2002 Feb;21(1):14-21. Review. PubMed PMID: 11838882. 2. http://www.nimh.nih.gov/health/publications/mental-health-medications/complete-index.shtml 3. Goodwin FK, Jamison KR. Manic-Depressive Illness (New York: Oxford University Press, 1990), p. 230. 4. Nieper HA. The clinical applications of lithium orotate. A two years study. Agressologie. 1973;14(6):407-11. PubMed PMID: 4607169. 5. Smith DF. Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats. Br J Pharmacol. 1976 Apr;56(4):399-402. PubMed PMID: 1260219; PubMed Central PMCID: PMC1666891. 6. Kling MA, Manowitz P, Pollack IW. Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate. J Pharm Pharmacol. 1978 Jun;30(6):368-70. PubMed PMID: 26768. 7. (2002) edition of The Bipolar Child: The Definitive and Reassuring Guide to Childhood's Most Misunderstood Disorder 8. Smith DF, Schou M. Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate. J Pharm Pharmacol. 1979 Mar;31(3):161-3. PubMed PMID: 34690. 9. Young W. Review of Lithium Effects on Brain and Blood. Cell Transplant. 2009 May 13. pii: Ct-2065. Young O. W. M. Keck Center for collaborative Neuroscience Rutgers, State University of New Jersey. PMID: 19523343 10. Straub DA. Calcium supplementation in clinical practice: a review of forms, doses, and indications. Nutr Clin Pract. 2007 Jun;22(3):286-96. Review. PubMed PMID: 17507729.

Chapter Eleven Dr. Hans Nieper The Creator of Lithium Orotate!

1. Nieper HA. Recalcification of bone metastases by calcium diorotate. Agressologie. 1970;11(6):495-502. 2. Zhang A, Huang X, Luo P, Jiang X. [Study on inhibition and prevention of tumor and antioxidative effects of lithium carbonate in tumor bearing mice]. Wei Sheng Yan Jiu. 1998 Mar;27(2):77-80. Chinese. PubMed PMID: 10682609. 3. Ronchi A, Salaroli R, Rivetti S, Della Bella E, Di Tomaso T, Voltattorni M,Cammelli S, Ceccarelli C, Giangaspero F, Barbieri E, Cenacchi G. Lithium induces mortality in medulloblastoma cell lines. Int J Oncol. 2010 Sep;37(3):745-52. PubMed PMID: 20664944. 4. Sjholm A. Intracellular signal transduction pathways that control pancreatic beta-cell proliferation. FEBS Lett. 1992 Oct 19;311(2):85-90. Review. PubMed PMID: 1327880. 5. Wu YY. [Modulation effect of lithium on IL-2 and IFNr production by human peripheral blood mononuclear cells]. Zhonghua Zhong Liu Za Zhi. 1992 Sep;14(5):337-9. Chinese. PubMed PMID: 1337888. 6. Nieper HA. Mineral transporters. New Dynamics of Preventive Medicine; 1974: 43-54. 7. Nieper HA. The clinical applications of lithium orotate. A two year study. Agressologie. 1973;14(6):407-11. 3 8. Nieper HA. Revolution In Technology, Medicine and Society. Oldenburg, Germany: MIT Verlag; 1985 9. Kabakov AY, Karkanias NB, Lenox RH, Papke RL. Synapse-specific accumulation of lithium in intracellular microdomains: a model for uncoupling coincidence detection in the brain. Synapse. 1998 Apr;28(4):271-9. PubMed PMID: 9517835. 10. Sartori HE. Lithium orotate in the treatment of alcoholoism and related conditions Alcohol. 1986;3(2):97-100 11. Huang X, Lei Z, El-Mallakh RS. Lithium normalizes elevated intracellular sodium. Bipolar Disord. 2007 May;9(3):298-300. PubMed PMID: 17430305. 12. Rosenfeldt FL. Metabolic Supplementation with orotic acid and magnesium orotate. Cardiovascular Drugs and Therapy. 1998;12(Supplemental 2):147-52.

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Chapter Twelve Modern Medical Technology Measuring Intracellular Lithium Concentrations

1. Kato T, Takahashi S, Inubushi T. Brain lithium concentration by 7Li- and 1H-magnetic resonance spectroscopy in bipolar disorder. Psychiatry Res. 1992 May;45(1):53-63. PubMed PMID: 1410078. 2. Mary Elvira Weeks, Discovery of the Elements. (2003) p125 Kessinger Publishing. 3. Lam HR, Christensen S. Regional and subcellular localization of Li+ and other cations in the rat brain following long-term lithium administration. J Neurochem. 1992 Oct;59(4):1372-80. PubMed PMID: 1402889. 4. Soares JC, Krishnan KR, Keshavan MS. Nuclear magnetic resonance spectroscopy: new insights into the pathophysiology of mood disorders. Depression. 1996;4(1):14-30. Review. PubMed PMID: 9160650. 5. Gyulai L, Wicklund SW, Greenstein R, et. al. Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder. Biol Psychiatry. 1991 Jun 15;29(12):1161-70. PubMed PMID: 1888798. 6. Kushnir T, Itzchak Y, Valevski A, Lask M, Modai I, Navon G. Relaxation times and concentrations of 7Li in the brain of patients receiving lithium therapy. NMR Biomed. 1993 Jan-Feb;6(1):39-42. PubMed PMID: 8457425 7. Komoroski RA, Pearce JM. Estimating intracellular lithium in brain in vivo by localized 7Li magnetic resonance spectroscopy. Magn Reson Med. 2008 Jul;60(1):21-6. PubMed PMID: 18581407.

Chapter Thirteen Veteran Health Administration Treatment of Major Depressive Disorder

1. Valenstein M, McCarthy JF, Austin KL, et al. What happened to lithium? Antidepressant augmentation in clinical settings. Am J Psychiatry. 2006 Jul;163(7):1219-25. PubMed PMID: 16816227. 2. Khan A, Khan S, Kolts R, Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry. 2003 Apr;160(4):790-2. PubMed PMID: 12668373. 3. www.accessdata.fda.gov/drugsatfda_docs/label/2009/014399s065lbl.pdf 4. Cipriani A, Smith K, Burgess S, Carney S, Goodwin G, Geddes J. Lithium versus antidepressants in the long-term treatment of unipolar affective disorder. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003492. Review. PubMed PMID: 17054174. .

Antipsychotics are Controversial for the Treatment of MDD

5. Papakostas GI, et al. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry. 2007 Jun;68(6):826-31. PubMed PMID:17592905. 6. Schreiber S, Shalev A. [Lithium augmentation for mianserin-resistant depression in the elderly]. Harefuah. 1992 Oct;123(7-8):250-1, 307. Hebrew.PubMed PMID: 1459497. 7. Bauer M, Adli M, Baethge C, Berghfer A, Sasse J, Heinz A, Bschor T. Lithium augmentation therapy in refractory depression: clinical evidence and neurobiological mechanisms. Can J Psychiatry. 2003 Aug;48(7):440-8. Review.PubMed PMID: 12971013. 8. Mendels J. Lithium in the treatment of depression. Am J Psychiatry. 1976 Apr;133(4):373-8. PubMed PMID: 1267033. 9. Inoue T, Nakagawa S, et al.. Long-term outcome of antidepressant-refractory depression: the relevance of unrecognized bipolarity. J Affect Disord. 2006 Oct;95(1-3):61-7. Epub 2006 Jun 22. PubMed PMID: 16797078. 10. Katona CL. Lithium augmentation in refractory depression. Psychiatr Dev. 1988 Summer;6(2):153-71. Review. PubMed PMID: 3070547. 11. Baumann P, Nil R, Souche A, et al.. A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistantdepressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation. J Clin Psychopharmacol. 1996 Aug;16(4):307-14. PubMed PMID:8835706. 12. Dinan TG. Lithium augmentation in sertraline-resistant depression: a preliminary dose-response study. Acta Psychiatr Scand. 1993 Oct;88(4):300-1.PubMed PMID: 8256650. 13. Thase ME, Kupfer DJ, Frank E, Jarrett DB. Treatment of imipramine-resistantrecurrent depression: II. An open clinical trial of lithium augmentation. J Clin Psychiatry. 1989 Nov;50(11):413-7. PubMed PMID: 2509437. 14. Faravelli C, Marchetti G, Benvenuti P, Cabras PL. [Lithium in the prophylaxis of recurrent affective disorders. Effectiveness of low plasma levels and predictors to clinical response (author's transl)]. Riv Patol Nerv Ment. 1980 Nov-Dec;101(6):261-71. Italian. PubMed PMID: 6801749. 15. Healy D, Harris M, Tranter R. et al. Lifetime suicide rates in treated schizophrenia: 1875-1924 ad 1994-1998 cohorts compared. Br J Psychiatry. 2006 Mar;188:223-8. PubMed PMID: 16507962. 16. Yerevanian BI, Koek RJ, Mintz J. Bipolar pharmacotherapy and suicidal behavior Part 3: impact of antipsychotics. J Affect Disord. 2007 Nov;103(1-3):23-8. Epub 2007 Jun 29. PubMed PMID: 17604119.

The Antidepressant/Antipsychotic Fiasco

17. Irving Kirsch, Alan Scoboria, Sarah S. Nicholls, Thomas J. Moore. The Emperor's New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration. Prevention & Treatment, 2002Volume 5, Article 23. http://alphachoices.com/repository/assets/pdf/EmperorsNewDrugs.pdf 18. Kirsch I. Antidepressants and the placebo response. Epidemiol Psichiatr Soc.2009 Oct-Dec;18(4):318-22. PubMed PMID: 20170046. 19. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008 Jan 17;358(3):252-60. PubMed PMID: 18199864.

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20. Feifel D. More depressing news on antidepressants: should we panic? Psychiatry (Edgmont). 2008 Apr;5(4):35-6. PubMed PMID: 19727307; PubMed Central PMCID: PMC2719549.27a. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719549/ 21. Sharon Begley. The Depressing News About Antidepressants. Newsweek. Jan 28, 2010. http://www.thedailybeast.com/newsweek/2010/01/28/the-depressing-news-about-antidepressants.html 22. Fournier JC, DeRubeis RJ, Hollon SD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010 Jan 6;303(1):47-53. Review. PubMed PMID: 20051569. (29) 23. Salynn Boyles. Antidepressants No Better Than Placebo? WebMD Health News. Feb. 27, 2008. www.webmd.com/mentalhealth/news/20080227/antidepressants-no-better-than-placebo 24. www.guardian.co.uk/society/2008/feb/26/mentalhealth.medicalresearch 25. Marilyn Elias, Study: Antidepressant barely better than placebo. USA TODAY. Health and Science. 07/07/2002 www.usatoday.com/news/health/drugs/2002-07-08-antidepressants.htm 26. www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM173233.pdf 27. www.cbsnews.com/stories/2010/01/11/national/main6083072.shtml 28. http://www.albany.edu/sourcebook/pdf/t31372007.pdf 29. Goodwin FK, Fireman B, Simon GE, Hunkeler EM, Lee J, Revicki D. Suicide risk in bipolar disorder during treatment with lithium and divalproex. JAMA. 2003 Sep 17;290(11):1467-73. PubMed PMID: 13129986. 30. Baldessarini RJ, Tondo L, Hennen J, Viguera AC. Is lithium still worth using? an update of selected recent research. Harv Rev Psychiatry. 2002;10:59-75. PMID: 11897747 31. Sajatovic M, Valenstein M, Blow F, Ganoczy D, Ignacio R. Treatment adherence with lithium and anticonvulsant medications among patients with bipolar disorder. Psychiatr Serv. 2007 Jun;58(6):855-63. PubMed PMID: 17535948. 32. Yerevanian BI, Koek RJ, Mintz J. Bipolar pharmacotherapy and suicidal behavior Part 3: impact of antipsychotics. J Affect Disord. 2007 Nov;103(1-3):23-8. Epub 2007 Jun 29. PubMed PMID: 17604119. 33. Leslie DL, Mohamed S, Rosenheck RA. Off-label use of antipsychotic medications in the department of Veterans Affairs health care system. Psychiatr Serv. 2009 Sep;60(9):1175-81. PubMed PMID: 19723731. 34. www.ahrq.gov/news/press/pr2007/antipsypr.htm 35. Shekelle P, Maglione M, Bagley S, et al. Efficacy and Comparative Effectiveness of Off-Label Use of Atypical Antipsychotics [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2007 Jan. Available from http://www.ncbi.nlm.nih.gov/books/NBK43235/ PubMed PMID: 20704049. www.effectivehealthcare.ahrq.gov/ehc/products/5/64/Atypical_Executive_Summary.pdf 36. Mohamed S, Leslie DL, Rosenheck RA. Use of antipsychotics in the treatment of major depressive disorder in the U.S. Department of Veterans Affairs. J Clin Psychiatry. 2009 Jun;70(6):906-12. Epub 2009 May 5. PubMed PMID: 19422760 37 Van Praag HM. A stubborn behaviour: the failure of antidepressants to reduce suicide rates. World J Biol Psychiatry. 2003 Oct;4(4):184-91. Review. PubMed PMID: 14608590.

Chapter Fourteen Why Has Lithium Not Been Prescribed to Veterans?

1. Faravelli C, Marchetti G, Benvenuti P, Cabras PL. [Lithium in the prophylaxis of recurrent affective disorders. Effectiveness of low plasma levels and predictors to clinical response (author's transl)]. Riv Patol Nerv Ment. 1980 Nov-Dec;101(6):261-71. Italian. PubMed PMID: 6801749. 2. Dinan TG. Lithium augmentation in sertraline-resistant depression: a preliminary dose-response study. Acta Psychiatr Scand. 1993 Oct;88(4):300-1. PubMed PMID: 8256650. 3. www.psychatlanta.com/documents/lithium.pdf 4. Anton RF, Paladino JA, Morton A, Thomas RW. Effect of acute alcohol consumption on lithium kinetics. Clin Pharmacol Ther. 1985 Jul;38(1):52-5. PubMed PMID: 4006376. 5. Kling MA, Manowitz P, Pollack IW. Rat brain and serum lithium concentrationsmafter acute injections of lithium carbonate and orotate. J Pharm Pharmacol. 1978 Jun;30(6):368-70. PubMed PMID: PMID: 26768

Chapter Fifteen Depression Overview

1. www.nimh.nih.gov/health/publications/depression/complete-index.shtml 2. Shalev AY, Freedman S, Peri T, Brandes D, Sahar T, Orr SP, Pitman RK. Prospective study of posttraumatic stress disorder and depression following trauma. Am J Psychiatry. 1998 May;155(5):630-7. PubMed PMID: 9585714. 3. World Health Organization. Global Burden of Disease 2004 Update; Health Statistics and Information Department, WHO: Geneva, Switzerland. 2008; http://www.who.int/healthinfo/-global_burden_disease/GBD_report_2004update_full.pdf/, Pharmaceuticals 2010, 3, 3522-3542; doi:10.3390/ph3123522 4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington (DC): The Association; 1994. 5. Fava M, Hwang I, Rush AJ, Sampson N, Walters EE, Kessler RC. The importance of irritability as a symptom of major depressive disorder: results from the National Comorbidity Survey Replication. Mol Psychiatry. 2010 Aug;15(8):856-67. Epub 2009 Mar 10. PubMed PMID: 19274052; PubMed Central PMCID: PMC3012558. 6. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. PubMed PMID: 12813115. 7. Chen YW, Dilsaver SC. Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders. Biol Psychiatry. 1996 May 15;39(10):896-9. PubMed PMID: 8860192.

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8. National Alliance of Mental Health: Veteran Depression Statistics http://www.nami.org/Template.cfm?Section=Depression&Template=/ContentManagement/Contentdisplay.cfm&ContentID=88939 9. Mental Health Advisory Team (MHAT) V, Report: Operation Iraqi Freedom 06-08, Operation Enduring Freedom 8, February 14, 2008: http://www.armymedicine.army.mil/reports/mhat/mhat_v/Redacted1-MHATV-4-FEB-2008-Overview.pdf. 10. Department of Veterans Affairs, Fifth Annual Report of the Department of Veterans Affairs Undersecretary for Healths Special Committee on Post-Traumatic Stress Disorder, 2005, p.12. ` 11. The Presidents Commission on Care for Americas Returning Wounded Warriors, Final Report, July 30, 2007, p. 15: http://www.pccww.gov/docs/Kit/Main_Book_CC%5BJULY26%5D.pdf. 12. Bleich A, Koslowsky M, Dolev A, Lerer B. Post-traumatic stress disorder and depression. An analysis of comorbidity. Br J Psychiatry. 1997 May;170:479-82. PubMed PMID: 9307701. 13. PTSD Research Quarterly-National Center for PTSD. Volume 20/No. 1 ISSN: 1050-1835 Winter 2009. 14. Gregg Zoroya. Rise in PTSD cases from two wars strains resources.USA TODAY November 30, 2011. http://www.usatoday.com/news/military/story/2011-11-29/PTSD-cases-rise/51476604/1 15. Epstein, Jack. (2005). US Wars and Post Traumatic Stress Disorder. San FranciscoChronicle, 6/22/05. 16. Kukla, Richard A., William E. Schlenger, John A. Fairbank, Richard et al.. (1990). Trauma and the Vietnam War Generation: Report of Findings from the National Vietnam Veterans Readjustment Study. New York: Brunner/Mazel. 17. U.S. Department of Veterans Affairs. (2007). Fifth Annual Report of the Department of Veterans Affairs Undersecretary for Health Special Committee on Post-Traumatic Stress Disorder. 18. Baldessarini RJ, Tohen M. Is there a long-term protective effect of mood-altering agents in unipolar depressive disorder? Psychopharmacol Ser.1988;5:130-9. Review. PubMed PMID: 3045797.

Chapter Sixteen How Does Lithium Work in the Brain? The hypothalamic-pituitary axis (HPA) axis PART TWO
1. Maurizi CP. A mechanism of mania and the chemistry of dreams: a hypothesis.South Med J. 1984 Dec;77(12):1491-3. Review. PubMed PMID: 6390694.

Hypothalamic Hormones Involved in MDD Dysregulated Hypothalamic Hormones

2. de Kloet CS, Vermetten E, Geuze E, Wiegant VM, Westenberg HG. Elevated plasma arginine vasopressin levels in veterans with posttraumatic stress disorder. J Psychiatr Res. 2008 Feb;42(3):192-8. Epub 2007 Jan 11. PubMed PMID: 17222428. 3. Goekoop J, de Winter R, Wolterbeek R, et al. Support for two increased vasopressinergic activities in depression at large and the differential effect of antidepressant treatment. J Psychopharmacol. 2011 Oct;25(10):1304-12. Jul 12. PubMed PMID: 20624797. 4. Scantamburlo G, Ansseau M, Legros JJ. [Role of the neurohypophysis in psychological stress]. Encephale. 2001 MayJun;27(3):245-59. Review. French.PubMed PMID: 11488255. 5. van Londen L, Goekoop JG, van Kempen GM, et al. Plasma levels of arginine vasopressin elevated in patients with major depression. Neuropsychopharmacology. 1997 Oct;17(4):284-92. PubMed PMID: 9326754. 6. Splendiani G, Cond S. [Diuretic therapy in heart failure]. G Ital Nefrol. 2006 Jan-Feb;23 Suppl 34:S74-6. Italian. PubMed PMID: 16634001. 7, Penney MD, Hampton D. The effect of lithium therapy on arginine vasopressin secretion and thirst in man. Clin Biochem. 1990 Jun;23(3):233-6. PubMed PMID: 2372937. 8. Austin MC, Janosky JE, Murphy HA. Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men. Mol Psychiatry. 2003 Mar;8(3):324-32. PubMed PMID: 12660805. 9. Kasckow JW, Baker D, Geracioti TD Jr. Corticotropin-releasing hormone in depression and post-traumatic stress disorder. Peptides. 2001 May;22(5):845-51.Review. PubMed PMID: 11337099. 10. Bremner JD, Licinio J, Darnell A, Krystal JH, Owens MJ, Southwick SM, Nemeroff CB, Charney DS. Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder. Am J Psychiatry. 1997 May;154(5):624-9. PubMed PMID: 9137116; PubMed Central PMCID: PMC3233756.. 11. Golier JA, Schmeidler J, Yehuda R. Pituitary response to metyrapone in Gulf War veterans: relationship to deployment, PTSD and unexplained health symptoms.Psychoneuroendocrinology. 2009 Oct;34(9):1338-45. PubMed PMID: 19446401. 12. Johnson JE, Cerbone A, Malaspina D. Corticotropin-releasing factor in posttraumatic stress disorder (PTSD) with secondary psychotic symptoms, nonpsychotic PTSD, and healthy control subjects. Biol Psychiatry. 2003 Dec 15;54(12):1382-8. PubMed PMID: 14675802. 13 Raadsheer FC, Hoogendijk WJ, Stam FC, Tilders FJ, Swaab DF. Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology. 1994 Oct;60(4):436-44. PubMed PMID: 7824085. 14. Schmider J, Lammers CH, Gotthardt U, Dettling M, Holsboer F, Heuser IJ. Combined dexamethasone/corticotropin-releasing hormone test in acute and remitted manic patients, in acute depression, and in normal controls: I. Biol Psychiatry. 1995 Dec 15;38(12):797-802. PubMed PMID: 8750037. 15. Nemeroff CB. New vistas in neuropeptide research in neuropsychiatry: focus on corticotropin-releasing factor. Neuropsychopharmacology. 1992 Feb;6(2):69-75. Review. PubMed PMID: 1610487. 16. Gilmor ML, Skelton KH, Nemeroff CB, Owens MJ. The effects of chronic treatment with the mood stabilizers valproic acid and lithium on corticotropin-releasing factor neuronal systems. J Pharmacol Exp Ther. 2003 May;305(2):434-9. Epub 2003

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Jan 24. PubMed PMID: 12606697. 17. Husum H, Math AA. Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes. Neuropsychopharmacology. 2002 Nov;27(5):756-64. PubMed PMID: 12431850. 18. Kasckow JW, Baker D, Geracioti TD Jr. Corticotropin-releasing hormone in depression and post-traumatic stress disorder. Peptides. 2001 May;22(5):845-51.Review. PubMed PMID: 11337099. 19. Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev. 2005 May;4(2):141-94. Review.PubMed PMID: 15996533. 20. Pierrehumbert B, Torrisi R, Laufer D, Halfon O, Ansermet F, Beck Popovic M. Oxytocin response to an experimental psychosocial challenge in adults exposed to traumatic experiences during childhood or adolescence. Neuroscience. 2010 Mar 10;166(1):168-77. Epub 2009 Dec 16. PubMed PMID: 20018229. 21. Cohen H, Kaplan Z, Kozlovsky N, Gidron Y, Matar MA, Zohar J. Hippocampal microinfusion of oxytocin attenuates the behavioural response to stress by means of dynamic interplay with the glucocorticoid-catecholamine responses. J Neuroendocrinol. 2010 Aug;22(8):889-904. Epub 2010 Apr 6. PubMed PMID: 20403087. 22. Cui SS, Bowen RC, Gu GB, Hannesson DK, Yu PH, Zhang X. Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation. J Neurosci. 2001 Dec 15;21(24):9867-76. PubMed PMID: 11739594. 23. Sattin A. The role of TRH and related peptides in the mechanism of action of ECT. J ECT. 1999 Mar;15(1):76-92. Review. PubMed PMID: 10189620. 24. A. J. Prange, JR , P. P. Lara, I. C. Wilson et al. Effects of Thyrotropin-Releasing Hormone in Depression. The Lancet volume 300, Issue 7785, 11 Nov. 1972 pg. 999-1002 doi:10.1016/S0140-6736(72)92407-5 25. Morley JE, Brammer GL, Sharp B, Yamada T, Yuwiler A, Hershman JM. Neurotransmitter control of hypothalamic-pituitarythyroid function in rats. Eur J Pharmacol. 1981 Mar 26;70(3):263-71. PubMed PMID: 6112152.

Pituitary Functions
26. Schrauzer GN Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr. 2002 Feb;21(1):14-21. PMID: 11838882 .

Pituitary Hormones Involved in MDD Dysregulated Pituitary Hormones

27. Yerevanian BI, Woolf PD, Iker HP. Plasma ACTH levels in depression before and after recovery: relationship to the dexamethasone suppression test. Psychiatry Res. 1983 Nov;10(3):175-81. PubMed PMID: 6320245. 28. Stetler C, Miller GE. Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosom Med. 2011 Feb-Mar;73(2):114-26. Epub 2011 Jan 21. PubMed PMID: 21257974. 29 Francis J Dunne Depression and pain: is there a common pathway? BJMP 2011;4(1):a411 March 2011, Volume 4, Number 1 www.bjmp.org/files/2011-4-1/bjmp-2011-4-1-a411.pdf 30. Anisman H, Ravindran AV, Griffiths J, Merali Z. Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Mol Psychiatry. 1999 Mar;4(2):182-8. PubMed PMID: 10208451. 31. Young EA, Carlson NE, Brown MB. Twenty-four-hour ACTH and cortisol pulsatility in depressed women. Neuropsychopharmacology. 2001 Aug;25(2):267-76. PubMed PMID: 11425510 32. Gerra G, Leonardi C, Cortese E, et al.. Adrenocorticotropic hormone and cortisol plasma levels directly correlate with childhood neglect and depression measures in addicted patients. Addict Biol. 2008 Mar;13(1):95-104.Epub 2008 Jan 14. PubMed PMID: 18201294. 33. Falk WE, Mahnke MW, Poskanzer DC. Lithium prophylaxis of corticotropin-induced psychosis. JAMA. 1979 Mar 9;241(10):1011-2. PubMed PMID: 216818. 34. Yoshida-Hiroi M, Tsuchida Y, Yoshino G, Hiroi N. Intranasal administration of ACTH(1-24) stimulates catecholamine secretion. Horm Metab Res. 2005 Aug;37(8):489-93. PubMed PMID: 16138261. 35. Bschor T, Baethge C, Adli M, et al. Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression. Depress Anxiety. 2003;17(1):43-8. PubMed PMID: 12577277. 36. Haden ST, Brown EM, Stoll AL, Scott J, Fuleihan GE. The effect of lithium on calcium-induced changes in adrenocorticotrophin levels. J Clin Endocrinol Metab. 1999 Jan;84(1):198-200. PubMed PMID: 9920083. 37. Bschor T, Lewitzka U, Sasse J, Adli M, Kberle U, Bauer M. Lithium augmentation in treatment-resistant depression: clinical evidence, serotonergic and endocrine mechanisms. Pharmacopsychiatry. 2003 Nov;36 Suppl 3:S230-4. Review. PubMed PMID: 14677084. 38. Young EA, Midgley AR, Carlson NE, Brown MB. Alteration in the hypothalamic-pituitary-ovarian axis in depressed women. Arch Gen Psychiatry. 2000 Dec;57(12):1157-62. PubMed PMID: 11115329. 39. Hunter R, Christie JE, Whalley LJ, Bennie J, Carroll S, Dick H, Goodwin GM, Wilson H, Fink G. Luteinizing hormone responses to luteinizing hormone releasing hormone (LHRH) in acute mania and the effects of lithium on LHRH and thyrotrophin releasing hormone tests in volunteers. Psychol Med. 1989 Feb;19(1):69-77. PubMed PMID: 2498919. 40. Allagui MS, Hfaiedh N, Vincent C, Guermazi F, Murat JC, Croute F, El Feki A. Changes in growth rate and thyroid- and sexhormones blood levels in rats under sub-chronic lithium treatment. Hum Exp Toxicol. 2006 May;25(5):243-50. PubMed PMID: 16758766. 41. M Kusalic and F Engelsmann. Effect of lithium maintenance treatment on hypothalamic pituitary gonadal axis in bipolar men. J Psychiatry Neurosci. 1996 May; 21(3): 181186. PMCID: PMC1188765 42 Heilig M, Zachrisson O, Thorsell A, et al. Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. J Psychiatr Res. 2004 Mar-Apr;38(2):113-21. PubMed PMID: 14757324.

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43. Widerlv E, Lindstrm LH, Wahlestedt C, Ekman R. Neuropeptide Y and peptide YY as possible cerebrospinal fluid markers for major depression and schizophrenia, respectively. J Psychiatr Res. 1988;22(1):69-79. PubMed PMID: 3397912. 44 Math AA, Husum H, El Khoury A, et al. Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities. Do neuropeptides play a role? Physiol Behav. 2007 Sep 10;92(1-2):226-31 PMID: 17572454 45. Zachrisson O, Math AA, Stenfors C, Lindefors N. Region-specific effects of chronic lithium administration on neuropeptide Y and somatostatin mRNA expression in the rat brain. Neurosci Lett. 1995 Jul 14;194(1-2):89-92. PubMed PMID: 7478221.

Chapter Seventeen The Hypothalamic-Pituitary-Adrenal axis (HPAA) & Primary Stress Hormone Imbalances of Major Depressive Disorder (MDD)

1. Schatzberg AF, Orsulak PJ, Rosenbaum AH, Kruger ER, Schildkraut JJ, Cole JO. Catecholamine measures for diagnosis and treatment of patients with depressive disorders. J Clin Psychiatry. 1980 Dec;41(12 Pt 2):35-9. PubMed PMID: 7440524. 2. Gjerris A. Do concentrations of neurotransmitters in lumbar CSF reflect cerebral dysfunction in depression? Acta Psychiatr Scand Suppl. 1988;345:21-4.PubMed PMID: 2906516. 3. Beckmann H, ST-Laurent J, Goodwin FK. The effect of lithium on urinary MHPG in unipolar and bipolar depressed patients. Psychopharmacologia. 1975 Jun 19;42(3):277-82. PMID: 1161986 4. Davis JM, Koslow SH, Gibbons RD, et al. Cerebrospinal fluid and urinary biogenic amines in depressed patients and healthy controls. Arch Gen Psychiatry. 1988 Aug;45(8):705-17. PubMed PMID: 2456047. 5. Linnoila M, Karoum F, Rosenthal N, Potter WZ. Electroconvulsive treatment and lithium carbonate. Their effects on norepinephrine metabolism in patients with primary, major depressions. Arch Gen Psychiatry. 1983 Jun;40(6):677-80. PubMedPMID: 6221709. 6 Seminars in General Adult Psychiatry By George Stein, Greg Wilkinson Pg. 34 the toxic effects of adrenaline]. Biull Eksp Biol Med. 1981 Jun;91(6):694-6. Russian. PubMed PMID: 6268223. 7. Sobieva ZI, Karpova MN, Kryzhanovskaia EG. [Effect of lithium preparations on the toxic effects of adrenaline]. Biull Eksp Biol Med. 1981 Jun;91(6):694-6. Russian. PubMed PMID: 6268223. 8. Garvey MJ, Tuason VB. Do low levels of MHPG in depressive spectrum patients normalize after successful treatment? Neuropsychobiology. 1996;34(4):188-91.PubMed PMID: 9121619. 9. Muscettola G, Potter WZ, Pickar D, Goodwin FK. Urinary 3-methoxy-4-hydroxyphenylglycol and major affective disorders. A replication and new findings. Arch Gen Psychiatry. 1984 Apr;41(4):337-42. PubMed PMID: 6703853. 10. Karege, Ph. Bovier, J.-M. Gaillard, R. Tissot. Plasma MHPG and AMDP depression relations, evolution and drug effect in a follow-up study of depressed patients. Human Psychopharmacology: Clinical and Experimental. Volume 6, Issue 1, pages 1117, March 1991 DOI: 10.1002/hup.470060103 11. Lambert G, Johansson M, Agren H, Friberg P. Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders. Arch Gen Psychiatry. 2000 Aug;57(8):787-93. PubMed PMID: 10920468. 12. Manji HK, Hsiao JK, Risby ED, Oliver J, Rudorfer MV, Potter WZ. The mechanisms of action of lithium. I. Effects on serotoninergic and noradrenergic systems in normal subjects. Arch Gen Psychiatry. 1991 Jun;48(6):505-12. PubMed PMID: 1645513. 13. Gjerris A, Werdelin L, Rafaelsen OJ, Alling C, Christensen NJ. CSF dopamine increased in depression: CSF dopamine, noradrenaline and their metabolites in depressed patients and in controls. J Affect Disord. 1987 Nov-Dec;13(3):279-86. PubMed PMID: 2960721. 14. Gjerris A. Do concentrations of neurotransmitters in lumbar CSF reflect cerebral dysfunction in depression? Acta Psychiatr Scand Suppl. 1988;345:21-4. PubMed PMID: 2906516. 15. Hamner MB, Diamond BI. Plasma dopamine and norepinephrine correlations with psychomotor retardation, anxiety, and depression in non-psychotic depressed patients: a pilot study. Psychiatry Res. 1996 Oct 16;64(3):209-11. PubMed PMID: 8944399. 16. Schmidt K, Nolte-Zenker B, Patzer J, et al. Psychopathological correlates of reduced dopamine receptor sensitivity in depression, schizophrenia, and opiate and alcohol dependence. Pharmacopsychiatry. 2001 Mar;34(2):66-72. PubMed PMID: 11302566. 17. Fyr B, Petterson U, Sedvall G. The effect of lithium treatment on manic symptoms and levels of monoamine metabolites in cerebrospinal fluid of manic depressive patients. Psychopharmacologia. 1975 Oct 14;44(1):99-103. PubMed PMID: 1105629. 18. Linnoila M, Karoum F, Potter WZ. Effects of antidepressant treatments on dopamine turnover in depressed patients. Arch Gen Psychiatry. 1983 Sep;40(9):1015-7. PubMed PMID: 6225405. 19. Eroglu L, Atamer-Simsek S. Effect of lithium on stress-induced changes in the brain levels of monoamines in rats. Arzneimittelforschung. 1980;30(12):2115-7. PubMed PMID: 6111324 20. Nozu T, Furukawa T. [Effects of lithium chloride on norepinephrine and dopamine metabolism in the rat brain]. Nihon Yakurigaku Zasshi. 1976 Jul;72(5):619-25. Japanese. PubMed PMID: 1033111. 21. Rastoge RB, Singhal RL. Lithium: modification of behavioral activity and brain biogenic amines in developing hyperthyroid rats. J Pharmacol Exp Ther. 1977 Apr;201(1):92-102. PubMed PMID: 850149. 22. Elphick M. Effects of carbamazepine on dopamine function in rodents. Psychopharmacology (Berl). 1989;99(4):532-6. PubMed PMID: 2574483.

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23 Gottberg E, Grondin L, Reader TA. Acute effects of lithium on catecholamines, serotonin, and their major metabolites in discrete brain regions. J Neurosci Res. 1989 Mar;22(3):338-45. PubMed PMID: 2709448. 24. Young AH. Cortisol in mood disorders. Stress. 2004 Dec;7(4):205-8. Review. PubMed PMID: 16019585. 25. Ehlert U, Nater UM, Bhmelt A. High and low unstimulated salivary cortisol levels correspond to different symptoms of functional gastrointestinal disorders. J Psychosom Res. 2005 Jul;59(1):7-10. PubMed PMID: 16126090. 26. Erolu L, Atamer-Simsek S, Yazici O, Keyer-Uysal M, Yksel S. A study of the relationship between serum lithium and plasma cortisol levels in manic depressive patients. Br J Clin Pharmacol. 1979 Jul;8(1):89-90. PubMed PMID: 552303; PubMed Central PMCID: PMC1429719. 27. Smigan L, Perris C. Cortisol changes in long-term lithium therapy. Neuropsychobiology. 1984;11(4):219-23. PubMed PMID: 6436729.

Chapter Eighteen Hypothalamic-Pituitary-Thyroid axis

1. Sender Palacios MJ, Vernet Vernet M, Prez Lpez S, Faro Coloms M, Rojas Blanc M, Pallisa Gabriel L. [Functional thyroid pathology in the elderly]. Aten Primaria. 2004 Sep 15;34(4):192-7. Spanish. PubMed PMID: 15388067. 2. Kathol RG, Delahunt JW. The relationship of anxiety and depression to symptoms of hyperthyroidism using operational criteria. Gen Hosp Psychiatry. 1986 Jan;8(1):23-8. PubMed PMID: 3943712. 3. Demet MM, Ozmen B, Deveci A, Boyvada S, Adigzel H, Aydemir O. Depression and anxiety in hyperthyroidism. Arch Med Res. 2002 Nov-Dec;33(6):552-6. PubMed PMID: 12505101. 4. Kathol RG, Turner R, Delahunt J. Depression and anxiety associated with hyperthyroidism: response to antithyroid therapy. Psychosomatics. 1986 Jul;27(7):501-5. PubMed PMID: 3737839. 5. Gulseren S, Gulseren L, Hekimsoy Z, Cetinay P, Ozen C, Tokatlioglu B. Depression, anxiety, health-related quality of life, and disability in patients with overt and subclinical thyroid dysfunction. Arch Med Res. 2006 Jan;37(1):133-9. PubMed PMID: 16314199. 6. Eigenmann F, Brgi H. [Lithium acetate, a useful and well tolerated thyrostatic for selected cases of hyperthyroidism]. Schweiz Med Wochenschr. 1978 Nov 25;108(47):1850-3. German. PubMed PMID: 581407. 7 Pimenov LT. [Use of lithium carbonate in the therapy of diffuse toxic goiter]. Probl Endokrinol (Mosk). 1982 Jan-Feb;28(1):26-32. Russian. PubMed PMID: 6801641. 8. Petrov NM. [Experience using lithium carbonate in the complex treatment of diffuse toxic goiter]. Ter Arkh. 1985;57(12):32-6. Russian. PubMed PMID: 3937256. 9. Petrov NM, Petrova NS. [Dynamics of the hormone profile and cardiovascular changes in toxic goiter as affected by lithium carbonate]. Probl Endokrinol (Mosk). 1983 Nov-Dec;29(6):23-7. Russian. PubMed PMID: 6318217. 10. Bistriceanu M, Roca TR, Mocanu I, Bistriceanu I, Voinea F. Effect of short-term lithium carbonate administration in hyperthyroidism, with or without associated ophthalmopathy. Endocrinologie. 1986 Apr-Jun;24(2):109-13. PMID: 3090679 11. Jonderko G, Marcisz C. [Short-term use of lithium carbonate in the treatmentof thyrotoxicosis]. Z Gesamte Inn Med. 1979 Aug 1;34(15):408-11. German. PubMed PMID: 93353. 12. Akin F, Yaylali GF, Bastemir M. The use of lithium carbonate in the preparation for definitive therapy in hyperthyroid patients. Med Princ Pract. 2008;17(2):167-70. Epub 2008 Feb 19. PubMed PMID: 18287805. 13. Burman KD, Dimond RC, Earll JM, Wright FD, Wartofsky L. Sensitivity to lithium in treated Graves' disease: effects on serum T4, T3 and reverse T3. J Clin Endocrinol Metab. 1976 Sep;43(3):606-13. PubMed PMID: 989049. 14. Baumgartner A, von Stuckrad M, Mller-Oerlinghausen B, Grf KJ, Krten I. The hypothalamic-pituitary-thyroid axis in patients maintained on lithium prophylaxis for years: high triiodothyronine serum concentrations are correlated to the prophylactic efficacy. J Affect Disord. 1995 Jun 8;34(3):211-8. PubMed PMID:7560549. 15. Takahashi S, Kondo H, Yoshimura M, Ochi Y. Thyroid function levels and thyrotropin responses to TRH administration in manic patients receiving lithium carbonate. Folia Psychiatr Neurol Jpn. 1975;29(3):231-7. PubMed PMID: 814073. 16. Lazarus JH. The effects of lithium therapy on thyroid and thyrotropin-releasing hormone. Thyroid. 1998 Oct;8(10):909-13. Review. PubMed PMID: 9827658.

Chapter Nineteen Lithium Normalizes Secondary Chemical Imbalances Associated with MDD
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Prog Neuropsychopharmacol Biol Psychiatry. 1985;9(1):83-90. PubMed PMID: 2859636. 14. Regnll G, Widerlv E, Ekman R. Delta sleep-inducing peptide in CSF of patients with affective illness is elevated by lithium treatment. Biol Psychiatry. 1988 May;24(1):112-6. PMID: 337027215. 15. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002 Dec;21(6):495-505. Review. PubMed PMID: 12480795. 16. Basselin M, Kim HW, Chen M, et al. Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation. J Lipid Res. 2010 May;51(5):1049-56. PubMed PMID: 20040630; PubMed Central PMCID: PMC2853431 . 17. Fraser T, Tayler H, Love S. Fatty acid composition of frontal, temporal and parietal neocortex in the normal human brain and in Alzheimer's disease. Neurochem Res. 2010 Mar;35(3):503-13. Epub 2009 Nov 11. PubMed PMID: 19904605. 18. Allagui MS, Hfaiedh N, Vincent C, et al. Changes in growth rate and thyroid- and sex-hormones blood levels in rats under subchronic lithium treatment. Hum Exp Toxicol. 2006 May;25(5):243-50. PubMed PMID: 16758766 19. Galea LA, Wide JK, Barr AM. Estradiol alleviates depressive-like symptoms in a novel animal model of post-partum depression. Behav Brain Res. 2001 Jul;122(1):1-9. PubMed PMID: 11287071. 20. Banay-Schwartz M, Wajda IJ, Manigault I, DeGuzman T, Lajtha A. Lithium: effect on [3H]spiperone binding, ionic content, and amino acid levels in the brain of rats. Neurochem Res. 1982 Feb;7(2):179-89. PubMed PMID: 7121707. 21. Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC. Reduced prefrontal glutamate/glutamine and gammaaminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry.2007 Feb;64(2):193-200. PubMed PMID: 17283286. 22. Wang JF, Shao L, Sun X, Young LT. 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Rezin GT, Cardoso MR, Gonalves CL, Scaini G, Fraga DB, Riegel RE, Comim CM, Quevedo J, Streck EL. Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression. Neurochem Int. 2008 Dec;53(6-8):395-400. Epub 2008 Sep 27. PubMed PMID: 18940214. 27. McIntyre RS, Soczynska JK, Konarski JZ, Woldeyohannes HO, Law CW, Miranda A, Fulgosi D, Kennedy SH. Should Depressive Syndromes Be Reclassified as "Metabolic Syndrome Type II"? Ann Clin Psychiatry. 2007 Oct-Dec;19(4):257-64. Review. PubMed PMID: 18058283. 28. Gardner A, Boles RG. Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):730-43. Epub 2010 Aug 5. Review. PubMed PMID: 20691744. 29. Bachmann RF, Wang Y, Yuan P, Zhou R, Li X, Alesci S, Du J, Manji HK. Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage. Int J Neuropsychopharmacol. 2009 Jul;12(6):805-22. Epub 2009 Jan 19. PubMed PMID: 19149911; PubMed Central PMCID: PMC2779114 . 30. Kusalic M, Engelsmann F. Effect of lithium maintenance treatment on hypothalamic pituitary gonadal axis in bipolar men. J Psychiatry Neurosci. 1996 May;21(3):181-6. PubMed PMID: 8935330; PubMed Central PMCID: PMC1188765. 31 Lackner JE, Rcklinger E, Schatzl G, Lunglmayr G, Kratzik CW. Are there symptom-specific testosterone thresholds in aging men? BJU Int. 2011 Oct;108(8):1310-5. doi: 10.1111/j.1464-410X.2010.09986.x. Epub 2011 Jan 13. PubMed PMID: 21231990. 32. Irwin M, Caldwell C, Smith TL, Brown S, Schuckit MA, Gillin JC. Major depressive disorder, alcoholism, and reduced natural killer cell cytotoxicity. Role of severity of depressive symptoms and alcohol consumption. Arch Gen Psychiatry. 1990 Aug;47(8):713-9. 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34. Zorrilla EP, Luborsky L, McKay JR, Rosenthal R, Houldin A, Tax A, McCorkle R, Seligman DA, Schmidt K. The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun. 2001 Sep;15(3):199-226. PubMed PMID: 11566046. 35. Zorrilla EP, Luborsky L, McKay JR, Rosenthal R, Houldin A, Tax A, McCorkle R, Seligman DA, Schmidt K. The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun. 2001 Sep;15(3):199-226. PubMed PMID: 11566046. 36. Valencia J, Hernndez-Lpez C, Martnez VG, Hidalgo L, Zapata AG, Vicente A,Varas A, Sacedn R. Transient beta-catenin stabilization modifies lineage output from human thymic CD34+CD1a- progenitors. J Leukoc Biol. 2010 Mar;87(3):405-14. Epub 2009 Dec 1. PubMed PMID: 19952356. 37. Kubera M, Bubak-Satora M, Holan V, Krol W, Basta-Kaim A, Roman A, Skowron-Cendrzak A, Shani J. Modulation of cellmediated immunity by lithium chloride. Z Naturforsch C. 1994 Sep-Oct;49(9-10):679-83. PubMed PMID: 7945679. 38. Wu Y, Cai D. Study of the effect of lithium on lymphokine-activated killer cell activity and its antitumor growth. Proc Soc Exp Biol Med. 1992 Dec;201(3):284-8. PubMed PMID: 1332071 39. Moore GJ, Bebchuk JM, Hasanat K, Chen G, Seraji-Bozorgzad N, Wilds IB, Faulk MW, Koch S, Glitz DA, Jolkovsky L, Manji HK. Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2's neurotrophic effects? Biol Psychiatry. 2000 Jul 1;48(1):1-8. PubMed PMID: 10913502. 40. Olvera RL, Caetano SC, Stanley JA., et al. Reduced medial prefrontal N-acetyl-aspartate levels in pediatric major depressive disorder: a multi-voxel in vivo(1)H spectroscopy study. Psychiatry Res. 2010 Nov 30;184(2):71-6. PubMed PMID: 20864319; PubMed Central PMCID: PMC2963721. 41. J. John Mann, M.D. The Medical Management of Depression N Engl J Med 2005; 353:1819-1834 October 27, 2005 www.nejm.org/doi/full/10.1056/NEJMra050730 42. Michael S. Ritsner, Abraham Weizman. Neuroactive steroids in brain functions, behavior, and disorders: Novel Strategies for Research and Development pg 373 Springer, 2008 43. Marx CE, Yuan P, Kilts JD, et al. Neuroactive steroids, mood stabilizers, and neuroplasticity: alterations following lithium and changes in Bcl-2 knockout mice. Int J Neuropsychopharmacol. 2008 Jun;11(4):547-52. PubMed PMID: 18257969. 44. Pae CU, Marks DM, Han C, Patkar AA, Steffens D. Does neurotropin-3 have a therapeutic implication in major depression? Int J Neurosci. 2008 Nov;118(11):1515-22. Review. PubMed PMID: 18853330. 45. Otsuki K, Uchida S, Watanuki T, et al. Altered expression of neurotrophic factors in patients with major depression. J Psychiatr Res. 2008 Oct;42(14):1145-53. PubMed PMID: 18313696. .

Lithium reduces the following secondary chemicals found to be excessively elevated in MDD.
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Chapter Twenty Toxic Heavy Metal Causes of MDD

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Chapter Twenty One Posttraumatic Stress Disorder

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Pharmaceutical Treatment of PTSD

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Chapter Twenty Two PTSD CHEMICAL IMBALANCES PART TWO Lithium, PTSD and their relationship to the hypothalamic-pituitary axis (HPA)
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Circadian Rhythm Altered by a Dysregulated Hypothalamus

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PTSD Dysregulated Pituitary Hormone

89. Yoshida-Hiroi M, Tsuchida Y, Yoshino G, Hiroi N. Intranasal administration of ACTH(1-24) stimulates catecholamine secretion. Horm Metab Res. 2005 Aug;37(8):489-93. PubMed PMID: 16138261. 90 Gerra G, Zaimovic A, Zambelli U, Timpano M, Reali N, Bernasconi S, Brambilla F. Neuroendocrine responses to psychological stress in adolescents with anxiety disorder. Neuropsychobiology. 2000;42(2):82-92. PubMed PMID: 10940763. 91. Smith MA, Davidson J, Ritchie JC, etal. The corticotropin-releasing hormone test in patients with posttraumatic stress disorder. Biol Psychiatry. 1989 Aug;26(4):349-55. PubMed PMID: 2548631. 92. Falk WE, Mahnke MW, Poskanzer DC. Lithium prophylaxis of corticotropin-induced psychosis. JAMA. 1979 Mar 9;241(10):1011-2. PubMed PMID: 216818. 93. Daban C, Vieta E, Mackin P, Young AH. Hypothalamic-pituitary-adrenal axis and bipolar disorder. Psychiatr Clin North Am. 2005 Jun;28(2):469-80. Review. PubMed PMID: 15826743.

PTSD Dysregulated Pituitary Neuropeptide

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Chapter Twenty Three Primary Stress Hormone Imbalances of PTSD - Lithium Normalizes the Primary Hormonal Imbalances of Posttraumatic Stress Disorder
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Chapter Twenty Four PTSD & Bipolar disorder, Chemical Imbalance Similarities
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Chapter Twenty Five Comparison of Brain Scans PET, SPECT, and fMRI Brain Scan Studies Similarities between Bipolar disorder & PTSD
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Chapter Twenty Six Lithium Promotes Neurogenesis

1. Hanson ND, Nemeroff CB, Owens MJ. Lithium, but not fluoxetine or the corticotropin-releasing factor receptor 1 receptor antagonist R121919, increases cell proliferation in the adult dentate gyrus. J Pharmacol Exp Ther. 2011 Apr;337(1):180-6. Epub 2011 Jan 10. PubMed PMID: 21220416; 2. Kim JS, Chang MY, Yu IT, Kim JH, Lee SH, Lee YS, Son H. Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo. J Neurochem. 2004 Apr;89(2):324-36. PubMed PMID: 15056276. 3. Boku S, Nakagawa S, Masuda T, Nishikawa H, Kato A, Toda H, Song N, Kitaichi Y, Inoue T, Koyama T. Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jan 15;35(1):111-7. Epub 2010 Oct 1. PubMed PMID: 20888882. 4. Bora E, Fornito A, Ycel M, Pantelis C. Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biol Psychiatry. 2010 Jun 1;67(11):1097-105. PMID: 20303066 5. Monkul ES, Matsuo K, Nicoletti MA. et al. Prefrontal gray matter increases in healthy individuals after lithium treatment: a voxelbased morphometry study. Neurosci Lett. 2007 Dec 11;429(1):7-11. PubMed PMID: 17996370; PMCID: MC2693231. 6. Bearden CE, Thompson PM, Dalwani M, et al. Greater cortical gray matter density in lithium-treated patients with bipolar disorder. Biol Psychiatry. 2007 Jul 1;62(1):7-16. Epub 2007 Jan 19. PubMed PMID: 17240360.

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The Incredible Shrinking Brain of Post-traumatic Stress Disorder

9. Carrion VG, Weems CF, Reiss AL. Stress predicts brain changes in children: a pilot longitudinal study on youth stress, post traumatic stress disorder, and the hippocampus. Pediatrics. 2007 Mar;119(3):509-16. PubMed PMID: 17332204. 10 . Chen S, Li L, Xu B, Liu J. Insular cortex involvement in declarative memory deficits in patients with post-traumatic stress disorder. BMC Psychiatry. 2009 Jun 18;9:39. PubMed PMID: 19538748; PubMed Central PMCID: PMC2704184. 11. Werner NS, Meindl T, Engel RR, et al. Hippocampal function during associative learning in patients with posttraumatic stress disorder. J Psychiatr Res. 2009 Jan;43(3):309-18. PubMed PMID: 18490028 12 . Yucel K, McKinnon MC, Taylor VH, et al. Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Psychopharmacology (Berl). 2007 Dec;195(3):357-67. PubMed PMID: 17705060. 13. Geuze E, Vermetten E, Bremner JD. MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol Psychiatry. 2005 Feb;10(2):160-84. Review. PubMed PMID: 15356639. 14 . Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, Delaney RC, McCarthy G, Charney DS, Innis RB. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995 Jul;152(7):973-81. PMID: 7793467 15. Gurvits TV, Shenton ME, Hokama H, et al. Magnetic resonance imaging study of hippocampal volume in chronic, combatrelated posttraumatic stress disorder. Biol Psychiatry. 1996 Dec 1;40(11):1091-9. PubMed PMID: 8931911 16. Pavi L, Gregurek R, Rados M, et al. Smaller right hippocampus in war veterans with posttraumatic stress disorder. Psychiatry Res. 2007 Feb 28;154(2):191-8 PubMed PMID: 17258898. 17. Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK. Enhancement of hippocampal neurogenesis by lithium. J Neurochem. 2000 Oct;75(4):1729-34. 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Three-dimensional mapping of hippocampal anatomy in unmedicated and lithium-treated patients with bipolar disorder. Neuropsychopharmacology. 2008 May;33(6):1229-38. Epub 2007 Aug 8. PubMed PMID: 17687266. 23. Monkul ES, Yildiz A, C Soares J. [Magnetic resonance spectroscopy (MRS) applications in bipolar disorder]. Turk Psikiyatri Derg. 2004 Summer;15(2):138-47. Review. Turkish. PubMed PMID: 15208769. 24. Yildiz-Yesiloglu A, Ankerst DP. Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Aug 30;30(6):969-95. PMID: 16677749 25. Schuff N, Neylan TC, Fox-Bosetti S, et al. Abnormal N-acetylaspartate in hippocampus and anterior cingulate in posttraumatic stress disorder. Psychiatry Res. 2008 Feb28;162(2):147-57. PubMed PMID: 18201876; PubMed Central PMCID: PMC2443727. 26 . Yildiz-Yesiloglu A, Ankerst DP. Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Aug 30;30(6):969-95. PMID: 16677749 . 27. Moore GJ, Bebchuk JM, Hasanat K, et al. Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2's neurotrophic effects? Biol Psychiatry. 2000 Jul 1;48(1):1-8. PubMed PMID: 10913502. 28. Silverstone PH, Wu RH, O'Donnell T, Ulrich M, Asghar SJ, Hanstock CC. Chronic treatment with lithium, but not sodium valproate, increases cortical N-acetyl-aspartate concentrations in euthymic bipolar patients. Int Clin Psychopharmacol. 2003 Mar;18(2):73-9. PubMed PMID: 12598817 . 29. Forester BP, Finn CT, Berlow YA, Wardrop M, Renshaw PF, Moore CM. Brain lithium, N-acetyl aspartate and myo-inositol levels in older adults with bipolar disorder treated with lithium: a lithium-7 and proton magnetic resonance spectroscopy study. Bipolar Disord. 2008 Sep;10(6):691-700. PubMed PMID: 18837863. 30. Colla M, Schubert F, Bubner M, et al. Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol. Mol Psychiatry. 2009 Jul;14(7):696-704, 647 PMID: 18347601 31. Bremner JD. Traumatic stress: effects on the brain. Dialogues Clin Neurosci. 2006;8(4):445-61. Review. PubMed PMID: 17290802; PubMed Central PMCID: PMC3181836. 32. Sanacora G. New understanding of mechanisms of action of bipolar medications. J Clin Psychiatry. 2008;69 Suppl 5:22-7. Review. PubMed PMID: 19265637. 33. Bremner JD, Elzinga B, Schmahl C, Vermetten E. 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Chapter Twenty Seven PTSD NEURO-CHEMICAL ALTERATIONS

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Miscellaneous PTSD Chemistry References

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Enzymes & Signaling Pathway References

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Lithium-Genetic Influence upon PTSD

67. Perrotti LI, Hadeishi Y, Ulery PG, et al. Induction of deltaFosB in reward-related brain structures after chronic stress. J Neurosci. 2004 Nov 24;24(47):10594-602. PubMed PMID: 15564575 68. Kaufer D, Friedman A, Seidman S, Soreq H. Acute stress facilitates long-lasting changes in cholinergic gene expression. Nature. 1998 May 28;393(6683):373-7. PubMed PMID: 9620801. 69. Miller JC, Math AA. Basal and stimulated C-fos mRNA expression in the rat brain: effect of chronic dietary lithium. Neuropsychopharmacology. 1997 Jun;16(6):408-18. PubMed PMID: 9165496.

Chapter Twenty Eight Lithium for Miscellaneous Conditions

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285

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Crespo Facorro B, Gomez-Hernndez R. [The treatment of the resistant obsessive-compulsive disorder: an update]. Actas Luso Esp Neurol Psiquiatr Cienc Afines. 1997 Jan-Feb;25(1):61-9. Review. Spanish. PubMed PMID: 9133159. 17. Laird LK. Issues in the monopharmacotherapy and polypharmacotherapy of obsessive-compulsive disorder. Psychopharmacol Bull. 1996;32(4):569-78. Review. PubMed PMID: 8993077. 18. Zamani A, Omrani GR, Nasab MM. Lithium's effect on bone mineral density. Bone.2009 Feb;44(2):331-4. Epub 2008 Oct 18. PubMed PMID: 18992857. 19. Bolton JM, Metge C, Lix L, et al. Fracture risk from psychotropic medications: a population-based analysis. J Clin Psychopharmacol. 2008 Aug;28(4):384-91. PubMed PMID: 18626264. 20. Clment-Lacroix P, Ai M, Morvan F, et al. Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17406-11. PMID: 16293698; PubMed Central PMCID: PMC1297659. 21. Vestergaard P. Skeletal effects of central nervous system active drugs: anxiolytics, sedatives, antidepressants, lithium and neuroleptics. Curr Drug Saf. 2008 Sep;3(3):185-9. Review. PubMed PMID: 18690999. 22. The Buck Institute for Research On Aging. Lithium Profoundly Prevents Brain Damage Associated with Parkinson's Disease. http://www.buckinstitute.org/buck-news/lithium-profoundly-prevents-brain-damage-associated-parkinsons-disease 23. Pallanti S, Haznedar MM, Hollander E, et al. Basal Ganglia activity in pathological gambling: afluorodeoxyglucose-positron emission tomography study. Neuropsychobiology.2010;62(2):132-8. PubMed PMID: 20588072. 24. Roy A, Adinoff B, Roehrich L, et al. Pathological gambling. A psychobiological study.Arch Gen Psychiatry. 1988 Apr;45(4):369-73. PubMed PMID: 2451490. 25. Meyer G, Schwertfeger J, Exton MS, et al. Neuroendocrine response to casino gambling in problem gamblers. Psychoneuroendocrinology. 2004 Nov;29(10):1272-80. PubMed PMID:15288706. 26. Paris JJ, Franco C, Sodano R, et al. Gambling pathology is associated with dampened cortisol response among men and women. Physiol Behav. 2010 Feb 9;99(2):230-3. PubMed PMID: 19361537; PubMed Central PMCID: PMC2813972. 27. Robinson GE, Stewart DE. Postpartum psychiatric disorders. CMAJ. 1986 Jan 1;134(1):31-7. Review. PubMed PMID: 3510069; PubMed Central PMCID: PMC1490588. 28. Doornbos B, Fekkes D, Tanke MA, de Jonge P, Korf J. Sequential serotonin and noradrenalin associated processes involved in postpartum blues. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jul 1;32(5):1320-5. PubMed PMID: 18502014. 29. Wieck A, Kumar R, Hirst AD, et al. Increased sensitivity of dopamine receptors and recurrence of affective psychosis afterchildbirth. BMJ. 1991 Sep 14;303(6803):613-6. PubMed PMID: 1805821; PubMed Central PMCID: PMC1671107. 30. Allagui MS, Hfaiedh N, Vincent C, et al. Changes in growth rate and thyroid- and sex-hormones blood levels in rats under subchronic lithium treatment. Hum Exp Toxicol. 2006 May;25(5):243-50. PubMedPMID: 16758766. 31. O'Keane V, Lightman S, Patrick K, et al.. Changes in the maternal hypothalamic-pituitary-adrenal axis during the early puerperium may be related to the postpartum 'blues'. J Neuroendocrinol. 2011 Nov;23(11):1149-55. doi: 10.1111/j.1365-2826.2011.02139.x. PubMed PMID: 22004568. 32. Small JG, Kellams JJ, Milstein V, Moore J. A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients. Am J Psychiatry. 1975 Dec;132(12):1315-7. PubMed PMID: 1106217. 33. Carman JS, Bigelow LB, Wyatt RJ. Lithium combined with neuroleptics in chronic schizophrenic and schizoaffective patients. J Clin Psychiatry. 1981 Mar;42(3):124-8. PubMed PMID: 6110654. 34. Sovner R, Hurley A. The management of chronic behavior disorders in mentallyretarded adults with lithium carbonate. J Nerv Ment Dis. 1981 Mar;169(3):191-5. PubMed PMID: 6782191. 35. Wickham EA, Reed JV. Lithium for the control of aggressive and self-mutilating behaviour. Int Clin Psychopharmacol. 1987 Jul;2(3):181-90. Review. PubMed PMID: 3320183. 36. Erickson HM Jr, Goggin JE, Messiha FS. Comparison of lithium and haloperidol therapy in Gilles de la Tourette syndrome. Adv Exp Med Biol. 1977;90:197-205. PubMed PMID: 270894. 37. Nonaka S, Chuang DM. Neuroprotective effects of chronic lithium on focal cerebral ischemia in rats. Neuroreport. 1998 Jun 22;9(9):2081-4. PubMed PMID: 9674597. 38. Guo S, Arai K, Stins MF, et al. Lithium upregulates vascular endothelial growth factor in brain endothelial cells and astrocytes. Stroke. 2009 Feb;40(2):652-5. Epub 2008 Oct 30. PubMed PMID: 18974377. 39. Ren M, Senatorov VV, Chen RW, Chuang DM. Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6210-5. PubMed PMID: 12732732; PubMed Central PMCID: PMC156351 40. Kim YR, van Meer MP, Tejima E, et al. Functional MRI of delayed chronic lithium treatment in rat focal cerebral ischemia. Stroke. 2008 Feb;39(2):439-47. PubMed PMID: 18187690. 41. Schrauzer GN, Shrestha KP, Flores-Arce MF. Lithium in scalp hair of adults, students, and violent criminals. Effects of supplementation and evidence for interactions of lithium with vitamin B12 and with other trace elements. Biol Trace Elem Res. 1992 Aug;34(2):161-76. PubMed PMID: 1381936. 42. Mller-Oerlinghausen B, Lewitzka U. Lithium reduces pathological aggression and suicidality: a mini-review. Neuropsychobiology. 2010;62(1):43-9. Epub 2010 May 7. Review. PubMed PMID: 20453534.

286

Index
Abraham, Aju, 100 Adrenaline, 85-88 lithium balancing, 90 Afari, Niloofar, 124 Affective illness, 26 Agren, Hans, 88 AIDS, 240, Aihara, Masako, 99 Allagui, Mohamed S., 243 Alcohol, 116 abuse, 116 lithium, 116,117 Alcoholism, 20, 21, 97, 99, 101,116, 117, 137,147, 161, 226 ALS, 36, 62, 105, 133, 222, 225, 237 Alzheimers disease, 19, 21, 52, 73, 100-101, 124, 178, 204, 223, 225-226, 233, 235-238 dosing, 135 American Psychiatric Association, 5, 29, 39 Amital, Howard, 38,42 Amsterdam, Jay D., 126 Amyotrophic Lateral Sclerosis, (ALS) 36, 62, 105, 133, 222, 225, 237 Antidepressants, 5 Anton, Raymond F., 160 Anxiety, Apfel, Bridgitte A., 102 Applehoff, Bente C., 100 arachidonic acid,118 Arnsten, Amy F. T., 238 Arteriosclerosis, 118 arachidonic acid, 118 lithium, 118 Arthritis, 117 lithium, 117 Ashbeel, Roy, 86 Asthma, 117 lithium, 118 Atypical psychosis, 118 lithium, 118 Austin, Mark C., 192 ADHD, 121, 240, 241 Avdibegovi, Esmina, 213 Ayers Luke W,. 194

Bipolar disorder, 119 brain atrophy reduced, 123- 124 lithium, 119 stress hormones, 119-120 Birgit, Ahrens, 54 Blair-West, George W., 43 Bleich, Andre, 33 Bloom, Floyd E., 196 Bolton, James M., 242 Bonnavion , Patricia, 196 Boonen, Rick A. C. M., 237 Bougerol, T. 109 Boyle, Maureen P., 99 Boyles, Salynn, 155 Bremner, Douglas J., 192, 226 Bschor, Tom, 44, 45, 97,108, 191 Bumiller, Elisabeth, 35 Brgi, H.,175, 217 Bushman, Chad, 183

back pain, 119 lithium, 119 stress hormones, 119 Baethge, Christopher, 98, 191 Bagchi, N. 98, 190 Baker, Dewleen G., 192 Baldessarini, Ross J., 4, 27, 48, 164 Basselin, Mireille, 118, 178 Bauer, Michael, 45, 191 Bauer, Martina, 98,109 Baumann, Petra, 45 Baumgartner, Andreas, 175 Bearden, Carrie E., 223, 228 Beckham, Jean C., 119 Beckman, Heike, 91, 172 Begley, Sharon, 155 Bertschy, Gilles, 110 Beyer, John, L., 228

Cade, John, 131,136 Campbell, Duncan, 32 Carrion Victor G, 225 Carvalho, A.F., 108 Castro, Antonio A. M., 233 CBS video, 33 Centorrino, Franca, 27 Chakraborty, Goutam, 237 Chen, Guang, 102, 227 Chen, Shulin, 226 Chen, Yuan-Who, 38,163 Christiansen, Per, 235 Chrousos George P., 192, 211 Chuang De-Maw., 232, 234 Cipriani, Andrea, 45, 152 Clment-Lacroix, Philippe, 242 Cohan, Phuli, 21 Cohen, Haim Y., 193 Cole, James, 100 Colitis, 121 cytokines,121 lithium, 121 stress hormones, 121 Consultation with Dr. Millar, 24 Cortisol, 88 lithium balancing, 92 Cowdry, Rex, 99 Chronic fatigue syndrome, 120 lithium,120 chronic pain disorder,120 Cougle, Jesse, 36 Crespo-Facorro, Benedicto, 242 Crews, Leslie, 240 Crown, William, 43 Cui, Shu-Sen., 194,

Dach, Jeffrey, 21 Dallal, A, 108 Daly, Christopher M., 90, 207 Davis, John M., 172 Davis, Paula, 27 Dean, Ward, 11, 17, 20, 55-56, 134

287

Deans, Emily, 8 de Hooge, JK, 108 de Kloet, Carien S., 166, 192, 193 Delahanty, Douglas L., 199 de Lecea, Luis, 196 de Montigny, Claude, 108 Denys Menchon D., 194 Depression, 5, 37, 38, 41-46, 103, 162 Depressed Immune system,120 Diabetes, 121 lithium, 121 Diarrhea, 121 cytokines, 121 lithium, 121 stress hormones, 121 Dinan, Timothy, G., 45, 159 Dopamine, 85-88 lithium balancing, 91 Doornbos, Bennard, 243 Dording, Christina M., 31 Dorrego Mara F., 240 Du, Jing, 232 Duman, Ronald S., 234 Duval, Fabrice, 97 Eczema, 121 lithium, 121 Edison, Thomas, 66 Eguiagaray, Josefina G., 241 Eigenmann, Franz, 175, 217 Elhert, Ulrike, 174 Elias, Marilyn, 155 Elphick, Maurice R., 92 Epilepsy, 137, 161, Epstein, Jack, 164 Erickson, HM Jr, 244 Eroglu, L, 91, 210 European Food Safety Authority, 16 Explosive disorder, 121 lithium, 121 stress hormones, 121

Friston, Karl J., 241 Frodl, Thomas, 101 Fugate, Linda, 21 Fuller, Richard W., 207 Fyro, Bengt, 91, 231

Galfalvy, Hanga, 87 Garvey, MJ, 172 Gastro-esophageal reflux disorder,123 lithium, 123 stress hormones, 123 Generalized anxiety disorder, 124 brain atrophy, 124 Geracioti, Thomas D., 86, 115, 202 Geuze, Elbert, 226 Gill, Jessica M., 236 Gilmor Michelle L., 193 Gjerris, A. C., 172-73 Goddard, Andrew W., 232 Goekoop, Jaap, 166 Golier, Julia A., 192 Goodwin, Frederick K., 27 Gordon, Garry F., 21 Gorman, Jack M., 234 Gottberg, Estela, 92 Grafova, VN, 120 Grof, E, 194 Grof, Paul, 194 Guo, Shuzhen, 244 Gurvits, Tamara V., 227 Guzzetta, Francesca, 27

Falk, William E., 169, 197 Faravelli, Carlo, 45, 159 Fatigue, 122 HPA, 122 lithium, 122 stress hormones, 122 Fava, Maurizio, 162 Feifel, David, 155 Ferrucci, Michela, 223 Fesler, FA, 41 Fibromyalgia, 122 lithium, 122 stress hormones, 122 Flashbacks, 123 lithium, 123 noradrenaline, 123 Foland, Lara C., 227 forgetfulness, 123 lithium, 123 Fornai, Francesco, 222 Fournier, Jay C., 155 Fox News, cable, 181 video, 9-10 Freeman, Marlene P., 218 Freeman, Scott A., 218 Friesen, Kerry D., 8

Hamner, Mark B., 173 Handwerger, Kathryn, 189 Hantouche, Elie, 43, Harpaz-Rotem, Ilan, 208 Harvard, Suicide studies, 26-28 Harvey, Brian H., 240 Heilig, Markus, 170 Heim, Christine, 99, 190 Henden, Herbert, 32 Hennen, John, 27 Henriksen, Ole, 235 Herpes, 126 Hicks, Paul, 46 Hippocampus, 101 atrophy, 101, 102 Hippocrates of Cos, 66 HIV infection, 240 Hoge, Elizabeth A., 236 Hotakainen, Rob, 34 Howenstine, James, 21 Huang, Xuhui, 149 Hubbert, King M., 40 Huntingtons disease, 133, 223, 226, 238, Husum, Henriette, 193 Hyman, Mark, 8 Hypothalamus, 94 dysregulation, 96 function, 95, 165 malfunction, 94

288

Hypothalamic-Pituitary Axis, 94 adrenal axis, 94, 97,114,116 functions, 95 thyroid axis, 94, 97

Immune system, 120 depressed, 120 Inflammatory bowel disease, 126 Inoue, Takashi, 45 Irle, Eva, 124 Irritable bowel syndrome, 127 Ischemic heart disease, 125, 242 Ito, Chiharu, 232

Jesse, Robert, 4, 24, 36, 54 Jin, Chang Yun., 232 Joelving, Frederik, 209 Jokinen, Jussi, 97, 189 Jovanovic, Tanja, 190, 201

Leslie, Douglas L., 157 Lester, David, 89 Letendre, Scott L., 240 Lewitzka, Ute, 244 Linnoila, Markku, 91, 172 Lithium, augmentation, 106-110 drinking water, 9 efficacy, 44-46 essentiality, 7, 8 mood disorders, 104 neurogenesis, 102 normalizes dysregulated HPA, 94 normalizes stress hormones, 90-3 suicide statistics, 26-28 thesis, 94 therapeutic effects, 97-100, 102, 116-130 Lithium Orotate, 11 dosing, 17, 18, 23, 46, 63, 71-82 intracellular absorption, 16 mineral transport diagram, 12 precautions while supplementing, 83 response rates, 18 retail store, 17 veteran study, 64 vs. Pharma-lithium, 16

Kabakov, Anatoli, 147 Kanter, Evan D., 212 Kapusta, Nestor D., 9 Karege, Bovier, 173 Karlovic, Dalibor, 215 Kasckow, John W., 192, 193 Kato, Takeo, 150 Katona, Cornelius L E., 45 Katz, Ira, 50, 51 Kaufer, Daniela, 238 Kauffman, CD., 194 Kessler Ronald C., 36 Khan, Muhammad A., 152 Kim, Young R., 244 Kirsch, Irving, 153, 154 Kjellman, Bengt, 99 Klaassens, Ellen R., 190 Kling, Mitchel A., 138 Knijff, Esther M., 236 Komoroski, Richard A., 151 Koolschijn, P. Cdric M.P., 100 Kornstein, Susan, 43 Kosten, Thomas R., 85, 115, 200 Kovacic, Zrnka, 93 Krieger, Gary R., 88 Kukla, Richard A., 164 Kumar, Anvita, 240 Kung, Jen-Chuang, 195 Kushnir, Talma, 151

Lafferman, Jeffrey, 107 Laird, Kyle K., 242 Lakhan, Shaheen, 18 Lam, Henrik R., 150 Lambert, Gavin, 173 Langeland, William E., 194 Laule, Alice R., 8 Lavandera, Ed, 133 Lazarus, John H., 98, 190, 216 Lepkifker, Elie, 107 Lenze, Eric J., 43 Lerer, Bernard, 235

MacQueen, Donald G., 101 Major affective disorders, 27 Major depression, 26 stress hormones, 96 Malhi, Gin S., 22, 108 Manji, Husseini K., 91, 104,173,177, 204, Martinez-Lavin, Manuel, 122 Marx, Christine E., 179 Mason, John, 213, 214, 215 Mathe, Aleksander A., 197, 239 Maurizi, Charles P., 165 McFarlane, Alexander C., 99, 190, 212 McIntyre, Roger S., 110, 178 Meador-Woodruff, James, 99 Mellman, Thomas A., 89, 206 Mendels, Joe, 45 Meta-analysis, 26, 106 Meyer,Gerhard, 243 Meyer, Jeffery H., 179 Migraine, 20, 21, 94, 124, 125, 137, 147, 205, 209 Mihaljevic, Sanea, 88 Miller, Jacob C., 239 Miller, Lisa J., 195 Missig, Galen, 194 Mission statement, 66 Monkul, Serap E., 102, 224 Moore, Gregory J., 229, 235 Morgan, Charles A., III. 197 Morley, John E., 98, 190 Muller, Anton, 17 Mller-Oerlinghausen, Bruno, 244 Multiple Sclerosis, 242 Murray, Patty, 34, 40 Muscettola, Giovanni, 173 musculoskeletal complaints, 127

Nair, Jyotsna, 232 Nieper, Hans, 11, 137-138,145-147, 149, 160-161 Nemeroff, Charles B., 167, 193

289

Nierenberg, Andrew A., 106 Nightmares, 127 mineral transport diagram, 12 Nixon, Richard, 30 Nonaka, Satoru, 244 Noradrenaline, 85-88 lithium balancing, 91 nightmares, 89 sleep disorders, 89-90 Nordstrom, Peter, 97, 189 Nozu, Tsukasa, 92

Post-partum psychosis, 243 Posttraumatic stress disorder, 181 adrenaline, 114-116 co-occurring diseases, 114-130 chemical imbalances, 6, 111-113 cortisol, 96 dopamine, 114 noradrenaline, 114 serotonin, 114 stress hormones, 96 Prange, AJ, 190, 216 Prazosin, 90

OBrien, John T., 100 Obsessive Compulsive, 62, 104, 242 Ohgami, Hirochika, 9 OKeane, Veronica, 243 Olff, Miranda, 189, 194 Olsztyn, Stanley, 18 Opfer, George, 52 Oquendo, Maria, 41 Orthomolecular medicine, 66-67, 133, 239 Orotic Acid, 16 Osteoarthritis, 128 Osteoporosis, 62, 242 Ostroff, Robert B., 87 Otsuki, Koji, 179 Ott, True A., 22 Otto, Michael W., 218 Ozawa, Hitoshi, 98, 190

Pace, Thaddeus, 99, 190 Pain syndrome, 119, 120, Pallanti, Stefano M., 242 Panic disorder, 128 Panic disorder, 62, 104, 116, 128, 196, 197, 207, 232, 236, 241, 242, Papakostas, George I., 153 Paralysis, 62, 129 Paris, Jean-Marc, 243 Parkinsons disease, 133, 135, 204, 223, 225-226, 233, 237, 238 Pathological gambling, 242, 243 Pauling, Linus, 66 Pavic, Ladislav, 227 Pekary, Eugene A., 194 Perez-Cruet, Jorge, 93 Pereira, Maria, 177 peripheral nerve pain, 128 Perris, C, 92, 211 Perrotti, Linda I., 238 Pervanidou, Panagiota, 99, 190, 192, 211 Pfennig, Andrea, 32, 97 Pharmaceutical lithium, dosing, 9, 17, 23, 30, 46, 53-55 origin, 8 toxicity, 7 Phelps, Jim, 103 Pierrehumbert Blaise, 194 Pietrzak, Robert H., 32 Pimenov, LT, 217 Pituitary, 94 dysregulation, 96 function, 95 Piwowarska, Jadwiga, 99 Poesener, Joel A., 99 Pomara, Nunzio, 100 Pompili, Maurizio, 27, 28

Raadsheer F C., 192 Rand corporation, 184 Rapoport, Stanley I., 237 Raskind, Murray A., 208 Rasmusson, Ann M., 196 Rastoge, RB, 92 Reches, Amit, 241 Recurrent Major Depression, 26 Reed, JV, 244 Regnell, G., 178, 198 Ren, Ming, 244 Restless legs syndrome, 128, 195 Rheumatoid arthritis, 117, Rieckhoff, Paul, 34, 40 Robinson, Gene E., 243 Roca, Robert P., 215 Rohleder, Nicolas, 99, 190 Rosen, Jeffery, B., 194 Rosenfeldt, Franklin L., 149 Rosenheck, Robert A., 208 Rothschild, Anthony J., 100 Rybakowski, Janusz K., 98, 99, 191

Sahelian, Ray, 21 Sajatovic, Martha, 156 Sartori, H. E., 20 Sattin, Albert, 194 Sautter Frederick J., 192 Savas, Lara S., 127 Savitz, Jonathan, 228 Scantamburlo, Gabrielle, 166 Schatzberg, Alan F., 172 Schelling, Gustav, 212 Schizoaffective, 4, 19, 26, 27, 30, 50, 81, 243, Schizophrenia, 19, 21, 39, 52, 243 Schlosser, Andreas, 235 Schmidt, Klaus N., 173 Schou, Mogens, 72, 139, 141-142 Schrauzer, Gerard N., 7, 8, 11, 118, 131, 168-169, 241,244 Schreiber, Stefan, 107 Schuff, Norbert, 228, 235 Schulkin, Jay, 194 Schulz, Pierre, 195 Schulze, Thomas, G., 106 Sears, Al, 20 Seborrhoeic dermatitis,128 Self Mutilation, 244 Semba, Jun'ichi , 98, 191 Senanayake Shayani S., 194 Seraidarian, Paula, 241 Serotonin, 89 lithium balancing, 93 Sharpe Ed, 17

290

Shealy, Norman, 18 Shekelle, Paul, 157 Sher, Leo, 97 Shergill, Sukhwinder S., 107 Shin, Lisa M., 189 Shingles, 62, 116, 128, 129 Shinseki, Eric, 58 Silva, Rui, 234 Silverstone, Peter H., 235 Sinai, Cave, 98, 189 Singh, Sarbjot, Ajit, 232 Small, J. G. Chris,. 118 Smigan, Ludovit, 92 Smith, Mark A., 197 Soares, Jair C., 150 Sobieva, S I., 91 Social anxiety, 241 Sovieva, Z. I., 172 Social Anxiety Disorder,128 Southwick, Steven M., 121 Spencer, Corrine M., 97, 191 Spinal cord injury, 120, 128, 129, 222, 224, 225, 237 Steimer, Thierry, 195 Stone, R, 21 Strawn, Jeffrey R., 86, 196, 202 Stroke, 129, 237, 238, 244 substance abuse, 130 Suicide, chemical imbalances, 87 prevention, 9 rates & statistics, 4, 5 ,9, 27, 32-36, 58 sleep disorder, 89 triggers, 105 Summation, 70 Surgeon General, 43 Swaab, Dick F., 100 Swann, Alan C., 91, 200, 202 Sympathetic nervous system, 114,116

van Heeringen , Kees,88 van London, Liesbeth, 166 Van Praag, Herman M., 158 van Tijn, Paula, 237 Varghese, Femina P., 97 Vermetten Eric, 226, Vestergaard, Peter, 242 Veteran videos, 58 Veterans Administration, Fifth Annual Report, 2007, 57 Research Currents, 8 Resistance to lithium treatment, 52 Suicide Hearings, 50 Suicide strategies, 48, 49 Violence, 88, 89, 132, 244, Viral, Virus, 62, 120, 126, 240 Vitamin Shoppe store, 17 Voors, Antonie, 118

Wang, Sheila, 213, 215 Weeks, Mary E., 150 Wei, Ling, 234 Werner, Natalie, S., 226 Widerlov, E., 170 Wieck, Andreas D., 243 Wickham, E.A., 244 Williams, Timothy, 35 Wilson, Lawrence, 8 Winstock, Adam R., 241 Witteveen Anke B., 194 Wright, Jonathan, 8, 18, 19, 21, 51, 55, 71, 134 The Misunderstood Mineral, 19

Takahashi, Satoko, 217 Taylor, Fletcher B., 90, 207 Thase, Michael. E., 43, 45 Thyroid, 95 stress response, 95 Tollefson, Gary, 100 Tondo, Leonardo, 27 Torticollis, 127 Tourettes syndrome, 244 Transient ischemic attack, 244 Traskman-Bendz, Lil, 88 Traumatic brain injury, 101, 129, 130, 181,206, 220, 233, 234, 244 Treatment-resistant depression, 5, 37, 38, 41-46, 103 Treiser, SL, 93 Trudeau, Kevin, 6 Tuason, VB., 173 Tucker, Phebe, 190, 210 Turner, Erick H., 154

Yehuda, Rachel, 85-86, 115, 116, 190, 200, 209, 212 Yerevanian, Boghos, 156 Yoshimura, Reiji, 230 You, Zhen Dong,. 194 Young, Allan H., 100 Young, Wise, 19, 23, 100, 119, 120, 129, 140, 169, 174, 224, 225, 238 Yucel, Kaan, 226, 228

Zamani, Ali, 242 Zeana, Cosmina, 16 Zivin, Kara, 32 Zivkovic, Danica, 237 Zoroya, Gregg, 32, 34, 40, 164

Ulcer, 121, 126, 127, 130 USA TODAY, 29, 32

Valenstein, Marcia, 37, 40 Van Den Eede, Filip, 120

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