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Epigenetic Changes Linked to Schizophrenia, Bipolar Disorder
> 3/12/2008 12:19:01 PM

In a study published this week in the American Journal of Human Genetics, researchers from the Krembil Family Epigenetic Laboratory at the Centre for Addiction and Mental Health (CAMH), have reported a particular pattern of epigenetic changes in individuals with schizophrenia and bipolar disorder. Epigenetic changes refer to chemical alterations in a gene that do not involve mutations in the DNA sequence, and their presence in individuals suffering from these psychiatric disorders may suggest new ways of understanding the molecular origins of these disorders.

Epigenetic modifications regulate cell development and gene functioning, and the presence of these modifications differ from person to person, even among pairs of identical twins. Although the genetic makeup of identical twins is extremely similar, the mechanisms that control the activation or deactivation of genes, and thus the amount of protein certain genes produce, can be different. These subtle variations can influence the individual's phenotype, including their likelihood of developing certain diseases and conditions. In this current study, the researchers, led by Dr. Arturas Petronis, studied one particular epigenetic process called methylation, which involves the addition of a chemicals to sequences of DNA in a way that deactivates or reduces the activity of genes.

With postmortem brain tissue samples from over 100 people (35 had schizophrenia, 35 had bipolar disorder, and 35 were matched controls), the researchers examined DNA from the frontal cortex. They studied over 12,000 locations on the human genome and observed differences in the methylation of genes between healthy and mentally ill brains. While some of these differences were unique to brains affected by schizophrenia or bipolar disorder, others were associated with both disorders. Overall, about one in every 200 genes from individuals with schizophrenia or bipolar disorder showed these epigenetic differences. Tellingly, many of these changes were connected with biological processes already linked with mental illness, such as neurotransmission (especially of glutamate and GABA) and neurodevelopment in the brain.

The various factors affecting mental illness are complicated and their effects are often interconnected. In a press release, Dr. Petronis explained how epigenetics may be an important contributing influence in the development of mental illness: "The DNA sequence of genes for someone with an illness like schizophrenia and a for someone without a mental illness often look the same; there are no visible changes that explain the cause of a disease. But we now have tools that show us changes in the second code, the epigenetic code, which may give us some very important clues for uncovering the mysteries of major psychosis and other complex non-Mendelian illnesses."

Epigenetics may be a key area of investigation for future studies, especially as some research has indicated that epigenetic changes could represent a connection between genetic and environmental influences. Studies have shown that epigenetic changes can accumulate over time and may be fueled by environmental triggers. In light of this, the patterns identified in the brains of individuals with schizophrenia and bipolar disorder in this study may have been produced by the presence of mental illness and not the other way around. Further study is needed to clarify how these modifications occur and what role they play in complex origins of psychiatric disorders.

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