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SLEEP

AND
BIOLOGICAL RHYTHMS
Marga. M. Maramis, dr., SpKJ(K)

Bag./SMF Psikiatri
FK UNAIR/RSU DR. SOETOMO
SURABAYA
2014

Keluhan Sulit Tidur


Primary sleep disorders
Secondary sleep disorders:
- gangguan psikiatri
- medikasi, drugs
- penyakit fisik
- gangguan irama sirkadian

Keluhan Sulit Tidur


Kuantitas
Kualitas
Early insomnia
Middle insomnia
Late insomnia
Dissomnia: amount, quality, or timing of a person's sleep
insomnia, hypersomnia, etc.
Parasomnia:
Primer
Sekunder: gangguan psikiatri, medikasi/drugs, penyakit
fisik, gangguan irama sirkadian

Sleep Disorders
Dyssomnia: Sleep disorders are a group of
conditions characterized by disturbance in the
amount, quality, or timing of a person's sleep
hypersomnia, insomnia, narcolepsy, breathingrelated sleep disorder, circadian rhythm sleep
disorder, RLS (Restless Leg Syndrome), PLMD
(Periodic Limb Movement Disorder)
Parasomnia: nightmare, sleep terror, sleep
walking, sleep talking, nocturnal enuresis

Dissomnia

Dissomnia
Gangguan tidur yang menyebabkan penderita
sulit untuk memulai tidur, mudah terbangun,
menyebabkan kantuk yang berlebihan
Terdiri atas: insomnia, hipersomnia, apnea tidur,
narkolepsi, sindroma kaki gelisah, gangguan gerak
anggota badan yang berkala, sindroma fase tidur
lanjut atau tertunda

Insomnia
Sleep deprivation is like food deprivation
Sleep disorders can have a significant
impact on our quality of life and also affect
the way we feel while we are awake
Affect 9-25% population
Short sleeper and long sleeper
Secondary insomnia: is a symptom not a
disease

Insomnia
One or more of the following despite adequate opportunity to
sleep:
- difficulty initiating sleep
- difficulty maintaining sleep
- waking up too early
- nonrestorative or poor quality of sleep
Plus one or more daytime impairment:
- fatigue, malaise, lack of energy, motivation or initiative
- daytime sleepiness
- attention, concentration, memory impairment
- prone to errors or accident at work or while driving
- mood disturbance, irritability, worries about sleep
- physical symptoms due to sleep loss (e.g. tension headache)
Stahl 2008

Prevalence of Insomnia Among Older


People Correlates with Health
67%

Percent with Any


Symptom of Insomnia

70
60
48%

50
40

42%
35%

30
20
10
0

None

One

Two or
three

Four or
more

Number of Diagnosed Medical Conditions


National Sleep Foundation. Sleep in America Poll 2003.; Kryger et al. Geriatrics 2004.

Other Correlates of Insomnia


Memory
Absenteeism
Accidents
Morbidity

Concentration
Attention
Problem
Solving/Coping
problems
Cant complete task
Reaction Time
Quality of Life

Benca RM. J Clin Psychiatry. 2001;62(suppl 10):33-38.


Weissman MM et al. Gen Hosp Psychiatry. 1997;19:245-250.

CIRCADIAN FACTORS
Jet lag
Shift work
Sleep scheduling
PSYCHIATRIC
FACTORS
Depression and other
disorder
Medication
MEDICATIONS,
DRUG, ALCOHOL
Acute effects
Tolerance
Withdrawal

Primary Insomnia
Restless Leg
Parasomnia
Periodic Limb Movement Disorder
Excessive Daytime Sleepiness

PSYCHOPHYSIOLOGIC/
CONDITIONING/FACTORS
Psychological factors
Physiologic tension,
arousal
Negative conditioning

Performance
Cognitive function
memory
Quality of life

TRIGGER
FACTOR OF
EXISTING
PSYCHIATRIC

INSOMNIA
OBESITAS

MEDICAL AND
CARDIO
NEUROLOGIC
VASCULAR
OTHER FACTOR
ILLNESS
Snoring
ABNORMALITY
Nonspecific factors
Sleep apnea
Specific factors
Medication
Modified from Carney PR, Berry RB, Geyer JD. Clinical Sleep disorders.
Lippincott William & Wilkins. 2005

The Reality
We spend at least 1/3 of our lives on sleep
Sleep less than 4 or greater than 10 hours per night are
statistically more likely to have a diminished life
expectancy
Sleep is a behavior
Because we remember very little about what happens
while we sleep, we tend to think of sleep more as a state
of consciousness than as behavior
The characterizes sleep is that the insistent urge of
sleepiness
Cant sleep 5 to 10 days: irrational, confused, paranoid,
halusination

The Elderly Spend More Time Awake


Elderly are prone to sleepiness earlier in the
circadian cycle and wake early in the morning
100%
90%
80%
70%
WAKE
60%
50% REM
40%
30%
20%
NREM
10%
0%
Birth 1 yr

Adolescent

Adult

Elderly

Martin J et al. Clin Psychol Rev 2000.; Ancoli-Israel S and Cooke


JR. J Am Geriatric Soc 2005.; Benca RM. Psychiatr Serv 2005.

The two main reasons for


sleeping are
Restoration rejuvenates, refreshes; allows
brain to perform certain tasks (e.g.,
memory), allows certain physiological
processes to take place (e.g., replenishment
of biochemicals)
Functioning amount and quality of sleep
directly impacts how functional a person is
during the day
Carney PR, Berry RB, Geyer JD. Clinical Sleep disorders.
Lippincott William & Wilkins. 2005

Sleep helps you to restore and


rejuvenate many body functions
Memory and learning Sleep seems to organize memories, as well as
help you to recover memories. After you learn something new, sleep
may solidify the learning in your brain.
Mood enhancement and social behaviors - The parts of the brain that
control emotions, decision-making, and social interactions slow down
dramatically during sleep, allowing optimal performance when awake.
REM sleep seems especially important for a good mood during the day.
Tired people are often cranky and easily frustrated.
Nervous system Some sleep experts suggest that neurons used during
the day repair themselves during sleep. When we experience sleep
deprivation, neurons are unable to perform effectively, and the nervous
system is impaired.
Immune system Without adequate sleep, the immune system
becomes weak, and the body becomes more vulnerable to infection and
disease.
Growth and development Growth hormones are released during
sleep, and sleep is vital to proper physical and mental development.

Functions of REM Sleep


REM sleep deprivation: make subject had to be
awakened from REM sleep more frequently; after several
days, subjects show a rebound phenomenon (spent much
greater than normal percentage of the recovery night in
REM sleep) when permitted to sleep normally
There is a need for a certain amount of REM sleep
Highest proportion of REM sleep is seen during the most
active phase of brain development REM sleep could be
setting the stage for brain growth to occur
Animal study: REM sleep perform function that facilitate
learning (2 evidence: after deprive from REM sleep
animal cant learn; after training animal increase in REM
sleep)

Sleep function and memory


The process of binding memories together
evolves over time. As we sleep or focus on
other tasks, our brain forges connections in
the background, fitting newly learned
information into a bigger picture and
connecting the dot takes time.

Wakefulness and Sleep (1)


Wakefulness:
- Alpha waves: 8-12 Hz
- Beta waves: 13-30 Hz
Sleep: Non-REM and REM sleep
Non-REM sleep:
- Stage 1: Theta waves: 3,5 7,5 Hz 10 minutes later:
- Stage 2: Theta waves, sleep spindles (short bursts of waves of
12-14 Hz occur between 2-5 times a minute during stage 1-4 of
sleep), K complexes (sudden, sharp waveforms, found only
during stage 2, one per minute, often can be trigger by noises,
especially unexpected noises 15 minutes later:
- Stage 3: Delta waves < 3,5 Hz, 20-50% delta activity
around 20 minutes
- Stage 4: the distinction between stage 3 and 4 (called slowwave sleep) is not clear-cut, > 50% delta activity, the deepest of
sleep, loud noise can awakened and the person acts groggy and
confused 45 minutes later:

Wakefulness and Sleep (2)


REM sleep: EEG become desynchronized with a
sprinkling of theta waves, eyes are rapidly daring back and
forth, EMG becomes silent, paralyzed; might not react to
noises, but easily aroused by meaningful stimuli such as
sound of her name, awakened from REM sleep, a person
appears alert and attentive
Associated with increased heart rate, increased blood
pressure, decrease tone in the bodys skeletal muscles
(exception: eye muscles), hyperventilation (excessively
deep and rapid breathing), clitoral and penile erection and
vivid, recallable dreams
REM sleep useful in fasilitating memory (resgitrationretention-organization-reorganization) and learning process
Total REM sleep 1,5 to 2 hours per night (the first REM
sleep only about 9 minutes)
REM sleep never starts normal sleep (except narcoleptic
patient

E.E.G. (Hans Berger, 1929)


Abnormal brain activity on the EEG tracing by:
Sleep-induction
Sleep deprivation
Hyperventilation
Photic stimulation

Delta and theta: foci of brain pathology, diffusely in


delirium
Alpha: during relaxation, diminished attentiveness and the
eyes closed
Beta: during attentiveness with eyes open, effect of certain
medications
Spiking, spike and domes: sharp waves seizure activity,
exception: 6 and 14 per second positive spiking can be
normal or seen in minimum brain dysfunction/ADHD; 3
per second spikes and domes are seen in petit mal epilepsy
and digitalis treated patients
Evoked potentials: are electrical responses of the brain to
stimuli such as sounds (auditory evoked potentials) or
visual images (visual evoked potentials)

Adenosine and NREM


As a mediator of the sleepiness following
prolonged wakefulness
Coffee and tea contain adenosine receptor
antagonist
Accumulate selectively in the basal
forebrain during prolong wakefulness
Promote transition to SWS by inhibiting
cholinergic wakefulness-promoting basal
forebrain neuron.

Yawning
Normal and physiological behavior
3 month after conception
Some animal (crocodile, fish, bird, snake) also
yawning
It happens 6 seconds
Psychotic patiens seldom yawning
Can become a sign of brain damage (epilepsi,
etc.), brain tumor, bleeding, motion sickness,
withdrawal of drugs, brain infection

Sleep Apnea
Fall asleep and cease to breathe
Especially people who snore
During sleep apnea, the level of carbon dioxide in the
blood stimulates chemoreceptors and the person wake up,
gasping for air; The oxygen level of the blood returns to
normal and the person fall asleep
Most cases caused by an obstruction of the airway that can
be corrected surgically or relieved by a device that attached
to the sleepers face and provides pressurized air that keeps
the airway open

Narcolepsy

Narcolepsy (narke = numbness; lepsis = seizure), neurological disorder,


sleep or some of its components at inappropriate times
Primary symptom is the sleep attack, an overwhelming urge to sleep that
can happen at any time but occurs most often under monotonous, boring
conditions
Sleep generally lasts 2-5 minutes, the person wakes up and feeling
refreshed
Brain abnormality that disrupts the neural mechanisms that control
various aspects of sleep and arousal; aspects of REM sleep intrude into
the waking state; generally skip the slow-wave sleep that normally begins
a nights sleep and go directly into REM sleep from waking; the sleep
often disrupted by periods of wakefulness
Is a genetic disorder that is influenced by unknown environmental factors
Hypocretin or orexin (hypothalamus contains the cell bodies of all of the
neurons that secrete this peptide; orexin, peptide plays in the control of
eating and metabolism)
Can be treated with stimulants: methylphenidate and catecholamine
agonist, juga modafinil (acts on hypocretinergic neurons)

Sleep paralysis
A symptom of narcolepsy
REM sleep paralysis
Inability to move just before the onset of sleep or upon
waking in the morning when a person is already lying
down
The mental components of REM sleep intrude into sleep
paralysis: the person dream while lying awake, paralyzed:
hypnagogic hallucinations: when falling asleep
Hypnopompic hallucinations: when waking up
REM sleep phenomena: cataplexy, sleep paralysis,
hypnagogic hallucinations can be alleviated by
antidepressant drugs which facilitate serotonin and
noradrenergic activity

Cataplexy
Cataplexy (jata = down, plexis = stroke), a person will
suddenly wilt and fall like a sack of flour, the person will lie
with fully conscious for a few seconds to several minutes
Phenomena of REM sleep, muscular paralysis occurs at an
appropriate time; this loss of tonus is caused by massive
inhibition of motor neurons in the spinal cord
Cataplexy is usually precipitated by strong emotion or by
sudden physical effort, especially if the patient is caught
unawares;
Laughter, anger, an effort to catch a suddenly thrown object
can trigger a cataplectic attack
People who do not have cataplexy, sometimes lose muscle
strength after a bout of intense laughter

Rem Sleep Behavior Disorder


REM sleep is accompanied by paralysis, although the
motor cortex and subcortical motor systems are extremely
active, people are unable to move at this time
The behavior of people who exhibit REM sleep behavior
disorder corresponds with the contents of their dreams
It seems to be a neurodegenerative disorder with at least
some genetic component
Associated with Parkinsons disease and multiple
system atrophy
Fail to exhibiting paralysis during REM sleep
Drugs that are used to treat the symptoms of cataplexy will
aggravate the symptoms of REM sleep behavior disorder
Treated by benzodiazepine, clonazepam

Parasomnia

Parasomnia
Tidak berkaitan dengan proses tidur sendiri
Gangguannya meliputi:
- gangguan tingkah laku tidur REM
- teror tidur
- somnambulism
- ngompol saat tidur
- bruxism
- sindroma kematian bayi mendadak (Sudden Infant Death
Syndrome = SIDS):1-2 dari 1000 kelahiran hidup, bayi
umur 10-12 minggu, Eskimo dan kulit hitam risiko lebih
besar, etiologi tak diketahui

Problem Associated
with Slow-wave Sleep
Some maladaptive behaviors occur during slow-wave
sleep, especially during the deepest phase stage 4
Nocturnal enuresis, somnambulism, pavor nocturnus =
night terrors (anguished screams, trembling, a rapid pulse,
usually no memory of what caused the terror)
No related to REM sleep
No associated with mental disorders or personality
variables
The best treatment for somnambulism and pavor nocturnus
is no treatment at all

Effects of Sleep Deprivation


Sleep is needed to keep the body functioning normally,
provides the opportunity for the brain to rest
Some report affected in cognitive ability, perceptual
distortions or hallucinations, trouble concentrating on mental
tasks
Cerebral metabolic rate and cerebral blood flow decline about
75 % of the waking level during stage 4 sleep
During slow-wave sleep, regions that have the highest levels
of activity during waking show the highest levels of delta
waves
If awakened during slow-wave sleep: act groggy, confused
Fatal familial insomnia, inherited neurological disorder:
damage to portions of the thalamus; deficits in attention and
memory, endocrine system, progressive insomnia, reduction
in sleep spindles and K complexes, only brief episodes of
REM sleep

Bruxism (Teeth grinding)


Reduce stress
Starting an exercise program, seeing a physical therapist
Prescription for muscle relaxants are among some of the options
that may be offered
Other tips to help you stop teeth grinding include:
Avoid or cut back on foods and drinks that contain caffeine,
such as colas, chocolate, and coffee
Avoid alcohol. Grinding tends to intensify after alcohol
consumption
Do not chew on pencils or pens or anything that is not food
Avoid chewing gum as it allows your jaw muscles to get more
used to clenching and makes you more likely to grind your teeth
Train yourself not to clench or grind your teeth. If you notice
that you clench or grind during the day, position the tip of your
tongue between your teeth. This practice trains your jaw
muscles to relax
Relax your jaw muscles at night by holding a warm washcloth
against your cheek in front of your earlobe

Circadian Rhythm

BIOLOGICAL CLOCKS:

Much of our behavior follows regular rhythms (around 90 minutes cycle of


REM and slow-wave sleep; 24-hour cycle; seasonal breeding)
Circadian rhythms (circa = about; dies = day): daily rhythms in behavior
and physiological processes are found throughout the plant and animal world
Some of these rhythms are passive responses to changes in illumination
(rat will sleep all day if the lights turn on for 24 hours)
Other rhythms are controlled by mechanism within the organism, by
internal clocks (tends to run a little slow, most mammals tends to be
approximately 25 hours)
In the natural environment, day and night are defined by the rising and
setting of the sun, the internal clock is reset each day and the cycles take 24
haours; Light serves as a zeitgeber (= time giver), it synchronizes the
endogenous rhythm
A brief period of bright light will reset their internal clock, advancing or
retarding it, depending upon when the light flash occur
If animal is exposed to bright light soon after dusk (= petang), the
biological clock is set back to an earlier time, as if dusk had not yet
arrived
If the light occurs late at night, the biological clock is set ahead to a later
time, as if dawn had already come

THE SUPRACHIASMATIC
NUCLEUS
Primary biological clock located in the
suprachiasmatic nucleus (SCN) of the
hypothalamus
Control over the timing of sleep cycles
Lesions in SCN disrupt circadian pattern but dont
affect the total amount of sleep
Photochemical named melanopsin in the retina
responsible for synchronization of diurnal rhythms

SCN and Pineal Gland (Epiphysis)


Lights go through optic nerve, retinohypothalamic
tract (RHT) and stimulate Supra Chiasmatic
Nucleus (SCN) in the anterior hypothalamus and
finally to the pineal gland inhibited synthesis of
melatonin
Melatonin synthesis and release by the pineal
gland from serotonin
Pineal gland is rich in serotonin, electromagnetic
sensitive and photosensitive

SCN in Hypothalamus
Pineal body

Grow
horm th
one

Body
temperature

Pla
sm
a co
rtis
ol

Melatonin

CONTROL OF SEASONAL RHYTHMS:


THE PINEAL GLAND AND MELATONIN:
Control of seasonal rhythms involves the pineal gland,
on top of the midbrain, just in front of the cerebellum
Pineal gland secretes a hormone called melatonin (ability
to turn the skin temporarily dark in fish, reptiles and
amphibians) during the night
Dark color is produced by a chemical called melanin
Melatonin acts back on various structures in the brain,
including the SCN (contain melatonin receptors) and
control hormones, physiological processes and behaviors
that show seasonal variations

Melatonin
Secreted by the
pineal gland

Neural efferents from the SCN to the pineal gland


regulate the output of melatonin

CHANGES IN CIRCADIAN RHYTHMS:


SHIFT WORK AND JET LAG
The internal circadian rhythms become desynchronized with the
external environment in shift work and jet lag
Try to provide strong zeitgebers at the appropriate time help
to ease the transition
If a person is exposed to bright light before the low point in the
daily rhythm of body temperature (occurs an 1-2 hour before
awakens) the persons circadian rhythms is delayed
If the exposure after the low point the circadian rhythm is
advanced
Melatonin acting on receptors in the SCN affect the sensitivity
of SCN neurons to zeitgebers and alter the circadian rhythms
Bedtime melatonin helped to synchronize circadian rhythms
and improve the sleep of blind people for whom light cannot
serve as a zeitgeber

Drugs for Insomnia


1. Benzodiazepine hypnotics
2. GABA-A positive allosteric modulators (PAMs)
as hypnotics: zaleplon, zolpidem, zopiclone
3. Melatonergic hypnotics: melatonin, ramelteon
4. Serotonergic hypnotics: trazodone
5. Histamine H1 antagonists as hypnotics:
antihistamine but antagonist of muscarinic
receptors; TCA doxepin; mirtazapine; quetiapine

Ramelteon: Melatonin Agonist

MT1 and MT2 receptor agonist


Approximately 10 times more potent than melatonin
Longer-lasting effect than melatonin
Approved for insomnia due to sleeping in a novel
environment
Reduced sleep onset
May increase total sleep time
Minimal memory impairment
No evidence of tolerance or withdrawal symptoms
Some patients experience sluggishness

Miyamoto. Sleep, 2003; Roth. Sleep, 2005; Rozerem (ramelteon) data sheet, 2005.

Behavioral Therapy
Sleep hygiene
Use bedroom only for sleep
Wake up at same time every day
Avoid caffeine, alcohol, and exercise before bed
Avoid naps
Stimulus control therapy
Reassociate bed with sleep
Leave bedroom if unable to sleep within 20 minutes
Return only when very sleepy
Others:
Relaxation therapy, hypnotherapy
Paradoxical intention therapy
Sleep restriction therapy
Morin and Espie. Insomnia: A Clinicians Guide to Assessment and Treatment.
2003; Bootzin and Perlis. J Clin Psychiatry. 1992; Spielman et al. Sleep 1987.

20 KIAT TIDUR YANG BAIK


SLEEP HYGIENE:
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Kurangi stres sebanyak mungkin


Olahraga untuk tampil bugar
Buatlah pikiran selalu tertantang sepanjang hari
Makan makanan yang tepat
Berhenti merokok
Mengurangi kafein
Jauhi alkohol menjelang tidur
Mandi dengan air hangat sebelum tidur
Pertahankan suasana nyaman dalam kamar tidur
Ciptakan ritual sebelum tidur
Lakukan aktivitas seksual yang menyenangkan
Pertimbangkan kebersamaan
Hindari lingkungan penuh dengan hewan
Kosongkan pikiran pada waktu akan tidur
Coba beberapa tehnik relaksasi pada waktu akan tidur
Hindari usaha terlalu keras untuk dapat tidur
Batasi waktu tidur
Belajar menghargai tidur
Gunakan jurnal tidur kinerja puncak saat setiap makan pagi
Konsultasi pada dokter

REFERENCES:
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Fadem B: Behavioral Science in Medicine, Lippincott Williams & Wilkins, 2004. ISBN 0-7817-3669-2
McConnell JV, Philipchalk RP: Understanding Human Behavior 7th ed., Harcourt Brace Jovanovich
College Publishers, USA, 1992. ISBN 0-03-055747-X.
Mesulam MM: Some Anatomic Principles Related to Behavioral Neurology and Neuropsychology, in
Feinberg TE, Farah MJ (eds.): Behavioral Neurology and Neuropsychology 2nd ed, Mc Graw Hill,
London, 2003, pp 45-56. ISBN 0-07-137432-9.
Sierles, F.S, MD: Behavioral Science for the boreds 2nd ed., MacGraw-Hill International Editions. 1989.
ISBN 0-07-113672-X
Sinton CM, McCarley RW: Neurophysiology and neuropsychiatry of Sleep and Sleep Disorders in
Neuropsychiatry 2nd ed. Schiffer RB, Rao SM, Fogel BS (eds.), Lippincott Williams & Wilkins, 2003.
ISBN 0-7817-2655-7.