Epigenetics 101

by William J. Walsh, Ph.D.
Walsh Research Institute
May 2013

Epigenetics is the system that determines gene regulation in humans. We have more than 20,000 genes and the only function of each gene is to make a specific protein. If the protein promotes a chemical reaction, it is called an enzyme. Every cell in the body contains an identical copy of DNA, but every tissue requires a unique combination of proteins and enzymes for optimal health. This selective production of proteins is achieved in early fetal development by a remarkable process called “bookmarking.”  For DNA, the marks involve the presence or absence of methyl groups at certain locations along the double helix. In general, methylation tends to inhibit or prevent gene expression, and the absence of a methyl mark tends to promote expression. Once established in the womb, the marks are firmly in place and usually persist throughout life. Environmental insults can produce deviant marks in the womb or later in life, and this is the cause of many physical and mental disorders.

In addition to direct methylation of DNA, gene expression of proteins may be controlled by chemicals that attach to histone proteins that provide the support structure for DNA. Histones are made up of eight linear proteins that are twisted together like a ball of yarn. DNA gently wraps around the histone balls due to electrostatic attraction: DNA is a weak acid and histones are slightly basic. In the case of histones, gene expression is often controlled by a competition between methyl and acetyl groups at histone “tails” that protrude from the ball configuration. If methyl wins the war, gene expression is inhibited. If acetyl dominates, expression of the protein is promoted.

Expression of a gene can occur only if certain large molecules can access the gene and its promoter region. Molecules called RNA polymerase are constantly swimming in the cell’s fluids looking for an exposed gene to express. Together with large molecules called transcription factors, RNA polymerase can produce a copy of the gene (called messenger RNA) that can escape through tiny pores in the cell’s nucleus and travel to the cell’s protein-production area (the reticulum). Methylation increases the basic charge of a histone whereas acetyl groups make histones less basic. By this mechanism, acetyl groups reduce the attraction between DNA and its histone, causing the DNA to uncoil from the histone and be available for expression. Methylation has the opposite effect causing the DNA and histone to compress and inhibit expression.

Most epigenetics research has been directed toward cancer and heart disease, but it’s becoming increasingly clear that many mental disorders are epigenetic in nature. The list includes autism, bipolar disorder, paranoid schizophrenia, schizoaffective disorder, post-traumatic stress, OCD, and antisocial-personality disorder. In most cases, an epigenetic disorder appears quite suddenly after a lifetime of relative wellness. Since these disorders involve deviant marks that survive cell divisions, the condition doesn’t “go away” and can persist for the remainder of life. Examples are regressive autism, Wilson’s Disease, and the sudden mental breakdowns often observed in bipolar and schizophrenia disorders.

It appears these conditions usually are caused by sudden or cumulative environmental insults in persons with a tendency for high oxidative stress. The environmental triggers may involve physical injury, illness, toxic metals, powerful medications, or emotional trauma. A gradually worsening environment may be responsible for recent epidemics of autism, breast cancer, and many other disorders.

The good news is that the gene regulation abnormalities from deviant marks appear to be reversible, suggesting a potential cure for epigenetic disorders. I can imagine a future in which newborns are scanned for deviant bookmarks, followed by treatment to normalize these chemical tags. This could eliminate the predispositions for cancer, heart disease and mental disorders that have plagued society for centuries. 

Although the technology for reversing deviant bookmarks is still unavailable, effective therapies for treatment of many epigenetic disorders are known today. For example, many paranoid schizophrenics exhibit excessive dopamine activity that can be normalized by Vitamin B-3 that uncoils DNA to increase gene expression of DAT proteins. In another example, methionine and SAMe act as serotonin reuptake inhibitors by compacting chromatin to reduce production of SERT transport proteins. We don’t yet know how to reverse deviant marks, but epigenetic science is guiding the development of therapies that uncoil or compact DNA to counter abnormal gene expression. It appears that nutrients and other natural substances are especially promising for dealing with epigenetic disorders. I believe the need for psychiatric medications will gradually fade away as science advances.

About the author:  Dr. William J. Walsh is president or the nonprofit Walsh Research Institute in Illinois and directs physician-training programs in Australia, Ireland, Norway and other countries. Dr. Walsh has authored more than 200 scientific articles and reports and has five patents. He has presented his experimental research at the American Psychiatric Association, the U.S. Senate, the National Institute of Mental Health, and has been a speaker at more than 30 international conferences. He has developed biochemical treatments for patients with behavioral disorders, ADHD, autism, depression, anxiety disorders, schizophrenia, and Alzheimer’s disease that are used by doctors throughout the world.

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Autism | Bipolar Disorder | Schizophrenia

Reverse Social Entropy And The Autism Epidemic

by Bill Walsh, PhD

There are dozens of theories that attempt to explain the massive increases in autism throughout the world since 1950. These include increased vaccinations, greater exposure to mercury, industrial food processing, medication side effects, increased copper levels in the water supply, and changes in family dynamics. However, growing evidence that autism is an epigenetic disorder leads to an interesting new explanation for increased autism rates that I call “reverse social entropy”.

Convincing evidence that autism is an epigenetic gene-programming disorder is presented in Chapters 4 and 7 of my new book Nutrient Power. Autism features that are consistent with an epigenetic disorder include the following:

  • Abnormal methylation, the most common cause of deviant gene expression,
  • Vulnerability to environmental insults,
  • High oxidative stress,
  • Many cases of sudden and dramatic changes in mental/physical functioning (regressive autism),
  • Persistence of autism after onset, since deviant epigenetic bookmarks can persist throughout life,
  • A consistent syndrome of traits and symptoms resulting from deviant expression of several genes (food sensitivities, speech problems, socialization deficits, weak immune function, narrowed brain minicolumns, etc), and
  • Violation of the classical laws of Mendelian genetics.

After studying the biochemistry of more than 30,000 persons, it has become very clear that undermethylation is associated with perfectionism, competitiveness, a strong will and other positive features, but also with a high incidence of specific disorders including schizoaffective disorder, anorexia, obsessive-compulsive disorder, and autism. Undermethylated persons who escape the disorders tend to be high achievers compared to others. Most physicians, lawyers, great athletes, captains of industry, heads of state, and scientists exhibit undermethylation.

In past generations, many persons never travelled more than 50 miles from their birthplace. However, people are much more mobile today, and methylation enclaves have sprung up throughout society. A 2012 journal article1 by McGinnis et al reports that people in deprived areas exhibit higher global methylation than the general population. On the other hand, universities and affluent neighbourhoods are locations with a high percentage of undermethylated persons. The net result is that more undermethylated men and women are marrying each other, compared to past generations. These marriages are far more likely to result in autistic offspring since (a) an undermethylated in-utero environment is vulnerable to epigenetic disorders, and (b) nearly all autism-spectrum children are undermethylated.

I refer to this factor as “reverse social entropy”. Entropy is a thermodynamic concept that has mystified thousands of college students, but in simple terms it is a measure of randomness. In the physical world, entropy generally increases, reflecting a natural tendency for increased randomness and homogeneity. In this case, a more mobile society and other factors have caused the development of discrete populations with very different methylation characteristics. It seems likely that this has contributed significantly to the autism epidemic.

1. McGuinness, D., McGlynn, L.M., Johnson, P.C.D., et al. 2012. Socio-economic status is associated with epigenetic differences in the pSoBid cohort.  International Journal of Epidemiology 41(1): 151-160 

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Nutrient Power, Epigenetics And Mental Health

by William J. Walsh, PhD

I’m pleased to announce that my new book NUTRIENT POWER (Skyhorse Publishing, Inc.) has been completed. The book won’t be released to Amazon and bookstores until September, but early copies are now available here

The book presents a science-based nutrient therapy system that can help millions of patients throughout the world. The text is aimed at doctors, researchers, and families challenged by depression, anxiety, schizophrenia, ADHD, autism, and other brain disorders. This approach recognizes that nutrient imbalances can alter brain levels of key neurotransmitters, disrupt gene expression of proteins and enzymes, and cripple the body’s protection against environmental toxins. 

The book demonstrates that depression, schizophrenia, and ADHD are umbrella terms that encompass disorders with widely differing brain chemistries and symptoms. Nutrient therapies tailored for five depression biotypes, three schizophrenia biotypes, and various ADHD conditions are presented along with several case histories. 

Other book highlights include the Walsh Theory of Schizophrenia, an epigenetic model of autism, a promising new Alzheimer’s treatment, and recommendations for reducing crime and violence. Individualized nutrient therapy treatments that have produced thousands of reports of recovery are presented along with several case histories. This modality is more scientific than trial-and-error use of psychiatric drugs, and is aimed at true normalization of the brain. More than 90 Australian physicians have been trained in this modality.

Epigenetics is a word unfamiliar to most Australians, but will soon be known to everyone. This emerging science is steadily revealing the causes of many of the world’s most challenging medical disorders, such as cancer and heart disease, and is providing a roadmap for development of vastly improved therapies. In an exciting development, new research indicates that many mental disorders also appear to be epigenetic in nature, and that improved treatments may be in the offing for schizophrenia, clinical depression, autism, ADHD, and criminal behaviour. Moreover, there is a good chance that these new therapies will be based on natural substances rather than drug medications. 

Epigenetics is a somewhat complicated subject and my book provides a detailed description of the processes involved and their impacts on brain function. There are more than a trillion cells in the human body, and each cell contains an identical copy of a person’s DNA. However, gene expression rates in brain, kidney, skin, heart and other tissues must be different for survival, and gene programming is established during the first few months of fetal development to accomplish this objective. In order to obtain the correct mix of enzymes and proteins in different organs, some genes are selectively “turned off” and others “turned on”. This process is called epigenetics, which means “above genetics”.

We are now learning that many diseases thought to be genetic are instead epigenetic in nature. The culprit is usually an environmental insult that alters gene expression “bookmarks” either in utero or later in life. Since deviant bookmarks can survive many cell divisions, the disorder doesn’t go away. There is considerable evidence that epigenetic errors are responsible for mental breakdowns experienced in schizophrenia, bipolar disorder, the sudden emergence of OCD, and the striking symptoms associated with regressive autism. It appears that deviant epigenetic bookmarks may be reversed by future therapies. In some cases, this could result in a permanent cure requiring no additional treatment. I hope epigenetics research aimed at mental disorders will become a major priority throughout the world.

My book asserts that today’s emphasis on prescription medications will not stand the test of time, and that the field of psychiatry needs a new direction. Psychiatric drugs suffer from a fundamental limitation – Introduction of foreign molecules that result in an abnormal condition rather than producing normalcy. Recent advances in epigenetics and the molecular biology of the brain have provided a roadmap for the development of effective, natural, drug-free therapies that do not produce serious side effects. An intensive research effort is needed to develop advanced epigenetic therapies that use chemicals natural to the body to normalize brain function, and thus avoid the nagging problem of drug side effects. Psychiatric medications have served society well over the past 50 years, but the need for drug therapies will gradually fade away as brain science advances. I believe we may be approaching a grand new era in the field of mental health. 

About the author:  Dr. William J. Walsh is president of the non-profit Walsh Research Institute in Illinois and directs physician-training programs in Australia, Norway, and other countries. Dr. Walsh has authored more than 200 scientific articles and reports and has five patents. He has presented his experimental research at the American Psychiatric Association, the U.S. Senate, the National Institutes of Mental Health, and has been a speaker at 28 international conferences. He has developed biochemical treatments for patients with behavioural disorders, ADHD, autism, depression, anxiety disorders, schizophrenia, and Alzheimer’s disease that are used by doctors throughout the world.

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ADD & ADHD | Autism | Depression | Schizophrenia