Understanding mental illness through gene-environment interactions

Biological Psychiatry, published by Elsevier, is very pleased to present a special section of its February 1st issue devoted to fundamental new insights into epigenetics, a field of research devoted to understanding how the environment can produce long-lasting or even heritable changes in gene function without altering the DNA sequence.

The study of epigenetics in psychiatry promises several key advances, as noted by Eric J. Nestler, M.D., Ph.D., a Deputy Editor for Biological Psychiatry and an expert in this field. First, it enables, for the first time, direct study of mechanisms controlling transcription, the process of expressing the genetic information coded within DNA, in the brains of behaving animals as well as in brain tissue from humans studied at autopsy. Second, some epigenetic changes in the brain are likely to be extremely long-lived, and thereby represent potential mechanisms by which life events, or psychotropic drugs or even psychotherapy, can produce stable, long-lasting changes in behavior. Third, epigenetics can be viewed as a third general type of mechanism, in addition to genetic and environmental factors, that contributes to an individual's unique vulnerability or resistance to a psychiatric disturbance. Dr. Nestler adds that, "for example, epigenetic changes, including those that occur randomly during the highly complex process of brain development, could help explain the high discordance rates between monozygotic twins seen for many psychiatric syndromes, the chronic relapsing nature of these syndromes, and the striking differences in prevalence for several psychiatric illnesses observed between men vs. women."

One of the Review articles in this issue, by J. David Sweatt, Ph.D., addresses the role of epigenetic mechanisms in controlling behavioral function and dysfunction. Specifically, he discusses recent findings that demonstrate that individuals' life experiences drive changes in the central nervous system, particularly in relation to learning and memory. Dr. Sweatt is also a talented artist and his painting adorns the cover of this issue of Biological Psychiatry. In another Review, Akbarian and Huang discuss mutations of genes that are involved in the regulation of histone lysine methylation, a type of epigenetic modification, that are associated with neurodevelopmental diseases, including mental retardation, autism and schizophrenia. They include novel approaches on examining how these mechanisms operate in a healthy or diseased brain. In the final epigenetics article of this issue, Monteggia and Kavalali examine the epigenetics of Rett syndrome, a neurodevelopmental disorder that causes mental retardation and autistic-like behavior, as it arises from mutations in a gene that is believed to alter synaptic transmission.

In all, these epigenetics papers provide fundamental new insights into the complex issues of gene-environment interactions and will aid future work that attempts to advance our understanding of mental illness.

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