Collaborative effort has schizophrenia in its sights

The complexity of schizophrenia has long been a barrier to understanding the disorder, with no definitive understanding of triggers, underlying biology or its unrelenting persistence after onset. Institute of Health and Biomedical Innovation (IHBI) researcher Dr Joanne Voisey is collaborating with US peers to gain a better understanding.

Extensive international study into schizophrenia has so far led to plausible explanations but not necessarily in-depth understanding. Researchers around the world agree that schizophrenia involves a combination of genetic and environmental factors. They believe the emerging research field of epigenetics is best placed to provide explanations of the disorder.

Epigenetics refers to changes in gene expression, or the distinction between active and inactive genes, that does not involve changes to the underlying DNA. 

An example of a mechanism that causes these changes is DNA methylation. Dr Voisey says methylation profiling enables the measurement of the activity of thousands of genes at once. “The methylation profiles allow us to determine differences seen between schizophrenia patients with particular symptom severity and their response to medication,” she says. 

Dr Voisey is leading IHBI’s collaboration with the Walsh Research Institute in Illinois in the US, using a prestigious Hilton Family Foundation Inc grant of $165 838. An aim of the research is to provide evidence that schizophrenia is a gene-regulation disorder. Such a disorder is characterised by an abnormality or impairment in regulatory mechanisms that govern metabolism, immune response or organ function.

“Our objective is to identify specific genes that are dysregulated, so we can target them with improved treatments,” Dr Voisey says. “We also aim to use epigenetics to eventually enable identification of people at risk of developing schizophrenia and provide strategies for effective prevention.”

Beyond investigating epigenetic avenues, the collaboration will study environmental factors that can cause altered gene expression.

“Researchers are developing effective methods for identifying cancer-prevention genes that have been ‘turned off’ by environmental factors. Our study aims to determine if a similar approach will work in schizophrenia.”

It is probable that some people are born with a predisposition to developing schizophrenia and that certain factors, including stress or use of drugs such as marijuana, LSD or speed, can trigger their first episode. 

Dr Voisey says a key element missing in most research is recognition that schizophrenia may be an ‘umbrella’ term used to describe several different disorders. The Walsh Research Institute has identified three major schizophrenia biotypes based on their database of 3600 diagnosed patients.

“Our study is expected to provide sharper, more definitive evidence that schizophrenia is epigenetic in nature, validate the classification of schizophrenia into biotypes and identify specific gene-regulation abnormalities for each biotype,” she says.

The ultimate aim is to understand triggers; develop tools for identifying at-risk people and providing early diagnosis; and introduce effective prevention and treatment strategies based on the specific schizophrenia biotypes.

“I am excited to be working with the Walsh Research Institute as we have a common goal of discovering better diagnoses and treatment options for patients,” Dr Voisey says. 

“It is such a debilitating disorder and antipsychotic treatments don’t target individual symptoms. Side effects can be just as negative as some of the schizophrenia symptoms. By identifying DNA methylation patterns we are targeting both environmental and genetic risk factors which may uncover more of the schizophrenia puzzle.”

SCHIZOPHRENIA

A medical condition affecting the normal functioning of the brain, interfering with a person’s ability to think, feel and act. People with schizophrenia have one personality. It is a myth that those affected have a split personality.

SYMPTOMS

Outside of treatment, people with schizophrenia experience persistent symptoms of what is called psychosis. These include:

  • Confused thinking: The everyday thoughts that let us live our daily lives become confused and don’t join up properly.
  • Delusions: Holding a belief that is not held by others of the same cultural background.
  • Hallucinations: Seeing, hearing, feeling, smelling or tasting something that is not actually there. Often disembodied voices that no one else can hear.
  • Associated symptoms: Low motivation and changed feelings.

TREATMENT

  • Can reduce and even eliminate the symptoms, generally including a combination of medication and community support. Both are usually essential for the best outcome.
  • Medication: Can assist the brain to restore its usual chemical balance.
  • Community support: Should include information, accommodation, help with finding suitable work, training and education, psychosocial rehabilitation and mutual support groups. Understanding and acceptance is very important.

This article was published in the Queensland University of Technology (QUT) Institute of Health and Biomedical Innovation (IHBI) newsletter June 2016, edition 26.

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Schizophrenia

The Walsh Theory Of Schizophrenia

A Novel Theory Of Schizophrenia

A flaw in existing theories has been the failure to recognize that schizophrenia is an umbrella term that includes at least three very different disorders, each presenting a distinctive set of symptoms and traits. It seems most unlikely that these disparate mental illnesses arise from the same underlying cause. I believe a proper theory of schizophrenia must include the following elements:

  • Separate causation for the major phenotypes,
  • Explanation for the “mental-breakdown” event that usually occurs in late adolescence or young adulthood,
  • Explanation for the life-long persistence of schizophrenia after the mental breakdown, and
  • Explanation why this familial (heritable) disorder violates classical laws of Mendelian genetics.

Common features of the different types of schizophrenia include (a) relative normalcy prior to the mental breakdown, (b) psychosis, (c) cognitive deficits, (d) loss of social skills, (e) high anxiety, (f) enlarged brain ventricles and smaller volumes in cortex and other brain areas, and (g) benefits often achieved using atypical antipsychotic medications. There is a common thread in these disorders, despite their very great differences in biochemistry. Eventually I realized that the three major schizophrenia phenotypes shared the following important features: (1) vulnerability to epigenetic errors that can alter gene expression, and (2) weakened protection against oxidative stress. These insights led to my theory of schizophrenia which is presented below:

Walsh Theory Of Schizophrenia

Thesis 1:  Schizophrenia is Epigenetic in Nature:  A psychotic “breakdown” is usually followed by a lifetime of mental illness and misery. This often permanent change in functioning results from altered chromatin bookmarks that regulate gene expression. Since the deviant marks are maintained during future cell divisions, the condition doesn’t “go away”.

Thesis 2: Weak Antioxidant Protection is a Distinctive Feature of Schizophrenia:  Most schizophrenics exhibit a genetic or acquired weakness in antioxidant protection. Evidence from my extensive chemistry database includes generally low levels of glutathione, cysteine, selenium, zinc, polyunsaturated fats, together with high levels of non-ceruloplasmin copper. 

Thesis 3:  Oxidative Overload Produces Deviant Epigenetic Marks in Schizophrenia: Cancer researchers have identified cumulative oxidative stress as a trigger that can transform healthy cells into cancer cells by altering epigenetic marks that permanently change gene expression. Examples include (a) skin cancer developing after years of excessive sun exposure, and (b) lung cancer following years of cigarette smoking. It’s not a coincidence that nearly all schizophrenia patients exhibit excess oxidative stress. The onset of schizophrenia occurs when oxidative stresses exceed the threshold level needed to alter chromatin marks that regulate gene expression.

Thesis 4:  Methylation Imbalances Promote Epigenetic Vulnerability to Oxidative Stress:  Abnormal methylation of chromatin is a leading cause of epigenetic errors in gene expression. The combination of oxidative overload and a methyl imbalance can produce gene expression changes that result in a chronic schizophrenia condition. The two most prevalent forms of schizophrenia develop in persons who exhibit either (a) methyl overload or (b) methyl deficiency. The two resulting psychotic disorders exhibit very different brain chemistry and symptoms.

A. Overmethylation – About 46% of persons diagnosed with schizophrenia exhibit excessive methylation of chromatin along with weak antioxidant protection. Mental breakdowns generally occur during severe physical or emotional traumatic events that produce overwhelming oxidative stress and deviant gene marks. This schizophrenia biotype is a sensory disorder that generally involves auditory, tactile, or visual hallucinations. This condition is associated with elevated activity of dopamine and norepinephrine, and reduced glutamate activity at NMDA receptors.  The most common DSM-4 diagnosis is paranoid schizophrenia.

B. Undermethylation – About 28% of persons diagnosed with schizophrenia exhibit low methylation of chromatin together with weak antioxidant protection. Mental breakdowns generally occur during severe physical or emotional traumatic events that produce a separate set of altered gene marks. This schizophrenia biotype essentially is a thought disorder with delusions and catatonic tendencies the primary symptoms. This condition is associated with low activity at serotonin, dopamine, and NMDA receptors. The most common DSM-4 diagnoses are Schizoaffective Disorder or Delusional Disorder.

Thesis 5: Extraordinary Weakness in Antioxidant Protection Can Produce Schizophrenia in the Absence of Methyl Imbalances:  The third major schizophrenia phenotype develops in persons with an inborn severe deficit in antioxidant protection. This condition is arbitrarily termed “Pyrrole Disorder” due to the presence of excessive pyrrole levels in blood and urine. Mental breakdowns occur for these persons during periods of extreme physical or mental stress in which deviant epigenetic marks are established. This condition is characterized by extraordinary anxiety, rapid mood swings, and often involves both auditory hallucinations and delusional beliefs. Brain chemistry abnormalities include (a) depressed glutamate activity at NMDA receptors, and (b) very depressed GABA activity.

Thesis 6:  Failure to Follow Classical Laws of Genetic Inheritance Results From the Epigenetic Nature of Schizophrenia:  Schizophrenia is strongly heritable (runs in families) but fails to obey Mendel’s classic laws of genetic inheritance. There are countless examples of identical twins where one sibling develops the disorder and the other does not. In addition, intensive research efforts to identify the schizophrenia gene (or genes) have met with little success. Epigenetics provides two explanations for the non-Mendelian nature of schizophrenia: (a) Environmental insults are required to produce deviant epigenetic marks and environmental conditions are highly variable for different individuals, and (b) Transgenerational epigenetic inheritance (TEI) contributes to schizophrenia heritability by transmitting deviant epigenetic marks to one’s children and grandchildren.

Purchase Nutrient Power by William J Walsh from The Walsh Research Institute

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Books | Schizophrenia

Potential Financial Savings By Using Targeted Nutritional Treatment Of Mental Health

Dr Richard Stuckey

One Schizophrenia patient who was in a floridly psychotic phase at the time of consultation. For 3 years prior to his appointment he had spent an average of 30 days per year in hospital.

Over the next decade he has lived independently. He exercises, shops, catches public transport, is in regular contact with his psychiatrist, takes both pharmaceutical and nutritional medicine, is not employed and has not been in hospital.

If his prior hospital admission rate had persisted he would have had 300 hospital days over 10 years and al-lowing $1500 a day this would have amounted to $450,000. A considerable saving to Medicare for only one patient.

In 2010 I published a 12 month follow up on 567 consec-utive patients who consulted me . Of the 157 patients with a diagnosis of depression, Bipolar, Addictive Disorder and Schizophrenia they had accumulated approx 300 hospital admission days.

157 treated patients , 300 hospital days - 2 hospital days per patient.

We were able to contact 26 patients who did not start this program - between them they had accumulated 650 hospital days in one year.

26 untreated patients, 650 hospital days, 25 hospital days per patient.

If the treated group had not attended and had the same hospital rate as the non treated group there would have been 3635 extra hospital days and allowing $1500 per day there was an estimated saving to Medicare of $5,435,500 by 1 doctor in 1 year.

These comments were made at the 2013 Anniversary Dinner.

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Schizophrenia

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

Review of Nutrient Power

“Nutrient Power” 

By Dr. William J Walsh

Published by Skyhorse Publishing Inc. 

Available through Walsh Research Institute website http://www.walshinstitute.org/

Just released, ‘Nutrient Power’ is a terrific read if you want to understand what makes a person tick – why they do the oddest things. He focuses on behaviour disorders - and their relationship to body chemistry. He looks at the mind-body connection – particularly with regard to mental disorders.

He carefully takes you through each mental disorder - depression, ADHD, Schizophrenia, autism, anxiety, behavioural disorders and others - dedicating an entire chapter to each one. For example did you know there are five different types of depression? Each type has its own chemistry and therefore needs its own specific nutrient supplementation. The good news is that his nutrient therapy can be administered at the same time as the anti-depressants – often with these medications being lowered and in many cases stopped altogether.

Dr Walsh then discusses his research on Alzheimer ‘s disease – and the chemistry behind it – and how there could be an answer for those people afflicted by it. Plus he looks at the field of epigenetics – how our genes are turned on and off – and how this can affect our vital organs like our brain, heart, skin etc. He postulates that the environment – either in utero or later in life - can over-ride our genetic imprint and how this can lead to the various mental disorders and many other diseases. Epigenetics is gaining popularity in medical research fields – but Dr. Walsh’s book gives an in depth discussion, understandable by the ordinary educated person, on this latest hot topic in science.

Although he has written the book for ‘doctors, medical researchers, and families afflicted by these diseases’ – and as such is scientifically based – it is a fascinating look at the science behind the mind- body connection. The basic premise is that if a person’s body chemistry is imbalanced, this can have a pronounced impact on what neurotransmitters their brain makes. These neurotransmitters dictate our behavioural patterns. Dr Walsh shows how such simple things as a copper imbalance can cause post-natal depression – for example. Altering these levels can cure such an affliction – even over-ride the genetic code or environmental toxins that causes the condition. Similarly there are three different biotypes for Schizophrenia, and numerous ADHD conditions. These are presented with case histories and the individualized nutrient therapies that have helped literally thousands of patients recover. In fact, Dr Walsh has treated over 1000 patients and trained over 90 doctors in Australia alone. 

Initally Dr. Carl Pfeiffer devised the program – called the Pfeiffer treatment - when he was researching Schizophrenia.  Since Dr. Pfeiffer’s demise, Dr. Walsh has taken over the research and broadened the field to include children with autism and varying disorders.   Dr Walsh’s initial research was based on violent behaviour of prisoners in the US.

Dr. Walsh clearly demonstrates how and why Psychiatry could gain a whole new direction – as individualized nutrients take over from psychiatric medications. These medications, he argues, “have nagging side effects” and “do not produce normalcy” of the brain.

 

Dr. Walsh is President of the Walsh Research Institute in USA and directs training programs for doctors and physicians in Australia, Norway and other countries. He has written 200 scientific papers and presented his research to the American Psychiatric Association, the US Senate, the National Institute of Mental Health, and has been a keynote speaker at 28 conferences. 

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Alzheimers | Autism | Behavioural disorders | Depression | Schizophrenia

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