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International Institute of Genetics and Biophysics and the Psychology Department at University
of Salerno in Italy (Cozzolino et al. 2013).
Results: The MHE Protocol Modulated Genes Expression in Human White Blood Cells
A summary of how the MHE protocol modulated activity-dependent genes expression in human
white blood cells is presented in figure three.
Figure 3. The MHE Protocol Regulates the SNCA Gene Expression (with permission by Cozzolino, et al.,
2013).
The most significant result in figure three was that the SNCA gene was highly and stably deregulated in the white blood cells (peripheral blood monocytes, PBMCs) of human subjects
within 1 and 24 hours after administration of the Mind-Body Healing Experience (MHE). Figure
three documents that only the SNCA gene transcript was down-regulated with highest significant
logFold change value of -2.5. The down-regulation observed in the other genes of the same
SNCA biological pathway had a logFold change values between -0.5 and -1.0, which suggests
that these were manifistations of normal cellular homeostasis.
Mind-Body Dysfunctions Associated with the SNCA Gene
Dysfunctions of the SNCA gene are known to be associated with autism, schizophrenia,
Parkinson disease, Alzheimer's disease, alcoholism, aging and a variety of stress related
dysfunctions. On the other hand the closely related form of the SNCA gene, the SNCB gene, is
implicated in healthy brain plasticity, memory, learning and behavior. The SNCA gene encodes
a small protein called alpha-synuclein. Alpha-synuclein is abundant in the brain, and smaller
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amounts are found in the heart, muscles, and other tissues, such as in peripheral blood including
mononuclear cells (Shin et al., 2000) and is secreted into blood plasma (El-Agnaf et al., 2003).
In the brain, alpha-synuclein is found mainly at the tips of neurons in specialized presynaptic
terminals. Although the function of alpha-synuclein is not entirely understood, studies suggest
that it plays an important role in maintaining a supply of synaptic vesicles in presynaptic
terminals which regulate the molecular dynamics of behavior, cognition,emotions, memory,
learning, and the qualia consciousness.
At least 18 mutations in the SNCA gene have been found associated with Parkinsons, a
neurodegenerative disease characterized by akinesia, rigidity, tremor, and postural instability a
condition characterized by progressive problems with movement and balance (Nuytemans et al.,
2010; Copped, 2012). It is unclear how alterations in SNCA gene expression are related to
Parkinson disease, but it is known that misfolded or excess alpha-synuclein proteins may cluster
together and impair the regulation of dopamine in specific regions of the brain. The excess alphasynuclein protein is related to increased expression of SNCA mRNA levels in dopaminergic
neurons (Maraganore et al., 2006; Grndemann et al., 2008). In Parkinsons disease the loss of
dopamine regulation weakens communication between the brain and muscles that is critical for
controlling the start and stop of voluntary and involuntary movements (Spillantini et al., 1997;
Braak et al., 2003).
Psychosocial Stress Modulates SNCA Gene Expression
Psychosocial Stress results in aberrant DNA methylation of the SNCA gene that is associated
with psychiatric conditions (Feinberg, 2007; Suzuki and Bird, 2008). DNA microarray analysis
of peripheral blood from patients with malignancies, infectious diseases, autoimmunity and
cardiovascular diseases are used to identify biomarkers of normal pathological and
pharmacological processes (Chaussabel et al., 2010; Staratschek-Jox et al., 2009). Studies of
patients with alcoholism (Bnsch et al., 2005; Foroud et al., 2007) and anorexia patients
(Frieling et al., 2007) documented hypermethylation of the SNCA promoter, suggesting how this
genes expression can be modulated epigenetically.
Publicly available data bases such as Gene Cards (http://www.GeneCards) document how
dysfunctions of SNCA gene expression is implicated in autism (Buxbaum et al., 2004),
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schizophrenia (Paunio et al., 2004), Parkinsons, Altzheimers, alcoholism (Reich et al., 1998)
and a variety of other stress related problems associated with post-traumatic stress disorder
(Neylan et al., 2011; Unternaehrer et al., 2012). Such stress promotes reactive oxygen species
(ROS) at the molecular-genomic level which leads to the formation of neurofibrillary tangles
associated with dysfunctions of consciousness, cognition and cell death (apoptosis) in
Alzheimers disease shown in figure four.
pathway of increased neuronal survival, brain plasticity and appropriate axon pruning, which
underpin positive adaptive behavior and consciousness. This healthy condition contrasts
strikingly with destructive reactive oxygen species (ROS) and amyloid plaque formation
associated with psychosocial stress and maladaptive consciousness in Alzheimers disease
illustrated on the right side of figure four.
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Figure 4. The Neural Connection in Mind-Body Communication and Healing The left side illustrates healthy
communication with increased neuronal survival, growth and brain plasticity. The right side illustrates
Amyloid Plaque and Neurofibrillary Tangle Formation in Alzheimers Disease (with permission by
www.Cell Signaling Technology).
It is interesting to note that the U.S. Patent office granted a patent on a molecular-genomic
agent (a drug) for inhibiting alpha-synuclein (SNCA) gene expression in the treatment of
neurodegenerative disorders (Bumcrot, 2009). This would be consistent with the
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therapeutic down regulation of dysfunctional mutations of the SNCA gene by the MHE
protocol. Further research by independent research groups is now required to confirm how the
molecular-genomic dynamics associated with administration of the MHE protocol could
facilitate translational medicine as well as the traditional cognitive-behavioral dynamics of
psychotherapy for ameliorating the ageing and stress related dysfunctions.
Further details of how the SNCA and SNCB genes are associated with the alternative pathways
of the health versus illness are illustrated in figure five. The computer algorithm that generated
figure five is based on an integration of millions of data points from publically available Gene
Wide Association Studies (GWAS) on the molecular-genomic scale (Jensen et al., 2009;
Szklarczyk et al., 2011).
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Figure 5. The SNCA and SNCB Genes in a Central Adaptive Complex Network (with permission by String 9.0,
http://String-db.org).
Remarkably clear, detailed, scientific images and information about any well known gene as
illustrated in five are freely available to the general public at String 9.0, http://String-db.org).
The implications of the MHE protocol for facilitating mind-body communication and healing
based on such images are documented in ENCODE The Encyclopedia of DNA Elements to
which we will now turn our attention.
ENCODE and A New Evidenced-Based General Theory of
Mind-Body Communication and Healing
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The MHE protocol could be used to formulate a more general theory of mind-body
communication and healing with the help of ENCODE. ENCODE The Encyclopedia of DNA
Elements has been published recently in 30 leading papers in major scientific journals such as
Nature, Science Genome Research and Genome Biology. We propose that ENCODE is the
major international research effort that is potentially capable of integrating the deep psychosocial
genomic basis of all scientific methods of facilitating mind-body communication and healing.
The ENCODE consortium introduced the biological significance of its research in this way
(ENCODE project consortium, 2012).
The human genome encodes the blueprint of life, but the function of the vast majority of its
nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project
has systematically mapped regions of transcription, transcription factor association, chromatin
structure and histone modification. These data enabled us to assign biochemical functions for
80% of the genome, in particular outside of the well-studied protein-coding regions. Many
discovered candidate regulatory elements are physically associated with one another and with
expressed genes, providing new insights into the mechanisms of gene regulation. The newly
identified elements also show a statistical correspondence to sequence variants linked to human
disease, and can thereby guide interpretation of this variation. Overall, the project provides new
insights into the organization and regulation of our genes and genome, and is an expansive
resource of functional annotations for biomedical research.
The human genome sequence provides the underlying code for human biology. Despite intensive
study, especially in identifying protein-coding genes, our understanding of the genome is far
from complete, particularly with regard to non-coding RNAs, alternatively spliced transcripts
and regulatory sequences. Systematic analyses of transcripts and regulatory information are
essential for the identification of genes and regulatory regions, and are an important resource for
the study of human biology and disease. Such analyses can also provide comprehensive views of
the organization and variability of genes and regulatory information across cellular contexts,
species and individuals.
The ENCODE project aims to delineate all functional elements encoded in the human genome.
Operationally, we define a functional element as a discrete genome segment that encodes a
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evolution from RNA world (Atkins et al., 2011; Darnell, 2011; Yarus, 2010) to our modern
epigenomic world of bioinformatic transitions from cognition and consciousness to eRNA, DNA
and mRNA is consistent with a general theory of mind-body communication and healing. From
our current perspective the key to resolving the Cartesian mind-body dualism and the Chalmers
hard problem of consciousness is to conceptualize both mind and body as information
transduction (Holland, 2012; Tegmark, 2013). This is focused on the bioinformatic eRNA-DNAmRNA loop between mind and gene in a new epigenomic theory of mind-body communication
and healing that has important implications for integrating our inner and outer nature briefly
summarized as The RNA-DNA Mind-Body Theory of Psychotherapeutic communication and
Healing in Box 1.
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ENCODE research implies the need for a new bioinformatic conception genes and their
relationships to the environment as complex adaptive systems (Holland, 2012). Figure six is our
proposal for a very broad functional definition of the gene as a complex adaptive system that
embraces the entire daily and hourly Basic Rest-Activity Cycle (BRAC) of life processes on all
levels from the mind to gene (Lloyd & Rossi, 1992, 2008). We propose that research on these
four major levels of The Psychosocial Genome: Mind, Mirror Neurons, Genes and the
Brain/Body illustrated in figure six can be generalized into a new evidence-based theory of mindbody communication and healing summarized here.
1.
Mind Research in the top circle embraces the classical experimental research of historical
psychology (Boring, 1950) updated with the more recent bioinformatic and consciousness
studies of art, beauty, creativity, music, truth, dreams, meditation, and yoga (Rossi,
1972/1985/2000, 2002, 2004, 2007, 2012, Rossi, Mortimer & Rossi, 2014xcvxcv). Key research
at this top level of consciousness, dreaming, and imagination explores the Novelty-NuminosumNeurogenesis-Effect as an adaptive complex motivational system, which integrates gene
expression with brain plasticity and mind-body healing illustrated in this chapter and related
papers (Cole et al., 2007-2011; Creswell et al., 2012; Dusek et al., 2008; Lichtenberg et al.,
2000, 2004; Rossi, Iannotti, Cozzolino et al., 2008).
2.
Mirror Neuron Research initiated by Rizzolatti, Gallese (Rizzolatti & Sinigaglia, 2008)
and others at the University of Parma in Italy has been greatly expanded from its original neural
level focus in the specific F5 area of the brain to include all epigenomic processes engaging
behavior and consciousness. Bird song research, for example, documents how micro eRNAs
respond to thought by modulating the genomic transcription/translation process via qualiadependent gene expression. Clayton, a specialist in songbird neurogenomics, made the salient
comment, this is the first time a microRNA has been shown to respond to a particular thought
process (Saey, 2010; Warren, Clayton et al., 2010; Clayton, 2013; Drnevich et al., 2012;
Gunaratne et al., 2011).
2007, 2008) from mind to gene. Figure five updates the Watson/Crick central dogma of
molecular biology, DNA codes for RNA, which codes for protein, to include consciousness.
Conscious thoughts dialogue with our genes via the bioinformatic epigenomic loop mediating
between nature and nurture we illustrated previously in Figure three. Cognitions are converted
into eRNAs (enhancer RNAs) to enhance DNA (gene expression), which codes for mRNAs
(messenger
RNAs),
which
are
messengers
that
generate
the
proteins
(hormones,
neurotransmitters, cytokines, etc.) throughout the complex adaptive mirror neuron system to
facilitate mind-body communication and healing (Rossi, 2002, 20004, 2007, 2012).
3.
Genomics Research via the ENCODE project that includes activity and experience-
dependent gene expression is currently manifesting a profound breakout on the epigenetic level.
Key research is now exploring complex adaptive systems of information transduction in the
transcription process arising from ~2 million eRNAs carrying signals from the physical
environment and psychosocial milieus to genes bearing ~3 million docking sites recently
summarized by the ENCODE Consortium (2012). This is well documented in human
psychobiology, for example, by dynamic changes in DNA methylation of stress-associated genes
such as oxytocin receptor (OXTR) and brain-derived neurotropic factor (BNDF) in sickness
versus healthy adaptation and healing (Unternaehrer et al., 2012). Free public data bases are
being updated daily by the National Institute of General Medical Sciences, which offers
information on The New Genetics (http://publications.nigms.nih.gov/thenewgenetics/)
4.
Brain and Body Research has a new psychobiological foundation in the translational
process of coding for mRNAs, proteins at the molecular-genomic level. Key research explores
how these proteins, often called mother molecules, are cleaved into the neurotransmitters,
hormones, and cytokines of the complex adaptive system of psychoneuroimmunology (Irwin &
Vedhara, 2005), which integrate cells of the mind, brain and body that ultimately facilitate the
dynamics of memory, learning, behavior, and the qualia of consciousness itself via
synaptogenesis and neuroplasticity, etc. (Rossi & Rossi, 2013). Gene Cards is another Free
Public data base that integrates new research information daily (http://www.GeneCards.com).
The epigenomic cycle of figure six is associated with the 4-stage 90-120 minute basic-rest
activity creative cycle that takes place naturally on all levels from mind to gene as documented
previously (Bar-Joseph et al., 2012; Lloyd & Rossi, 1992, 2008; Rossi, 2002, 2004, 2007, 2012;
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Rossi & Rossi, 2011, 2013). Notice how we give precise bioinformatic meaning to the
commonly used but vague psychological terms of the 4-stage creative cycle such as
Crisis/Opportunity (stage 1), Intuition (stage 2), Adaption/Healing (stage 3) and
Insight/Applications (stage 4). The implications of this new epigenomic evidence-based
general theory of mind-body communication and healing range from the practical, such as the
development of more effective psychiatric drugs and psychotherapy, to the profoundly
philosophical issues of integrating mind and matter.
We may ask, for example: Why have many controversial psychiatric drugs been failing for more
than 30 years (Fibiger, 2012; Hyman, 2012; Insel, 2012; Sanders, 2013)? Our perspective
suggests that such drugs were originally developed and assessed to operate at the bottoms-up
body-mind transitions of molecular biology (between stages 3 and 4) rather than focusing on the
top down mind-body transitions of psychosocial genomics (between stages 1, 2 and 3). This
implies that current and future research to create more efficacious psychiatric drugs needs to
conceptualize the evolutionarily complex and subtle bioinformatic dialogues between the qualia
of consciousness and the microRNA-DNA transitions in stages 1, 2 and 3 of human experience
in figure five (Rossi, 2012; Rossi & Rossi, 2011; 2013; Smith-Vikos, 2013).
Summary and Conclusions
This theoretical review and pilot study explores a new protocol, The Mind-Body Healing
Experience (MHE) that integrates mind and matter in an evidence-based theory of psychosocial
genomics. We document how the SNCA gene could be down-regulated in the peripheral blood
monocytes of the immune system of human subjects within 1 and 24 hours after administration
of The Mind-Body Healing Experience (The MHE Protocol), a structured psychosocial genomic
approach to the top down therapeutic applications of consciousness in therapeutic hypnosis,
psychotherapy and translational medicine. Dysfunctions of the SNCA gene are known to be
associated with autism, schizophrenia, Parkinson disease, Alzheimer's disease, alcoholism, aging
and stress related dysfunctions of consciousness. On the other hand the closely related isoform of
the SNCA gene, the SNCB gene, is implicated in healthy brain plasticity, memory, learning,
behavior and consciousness itself. Further research with appropriate clinical groups and controls
is now required to confirm how psychosocial epigenomic processes associated with behavior and
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consciousness could modulate the complex adaptive systems of gene expression, brain plasticity,
memory, learning, behavior and the qualia of human consciousness.
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