Early life influences risk for psychiatric disorders

Philadelphia, PA – August 18, 2010 – For more than a century, clinical investigators have focused on early life as a source of adult psychopathology. Although the hypothesized mechanisms have evolved, a central notion remains: early life is a period of unique sensitivity during which experience confers enduring effects.

Neurodevelopmental disorders, which include mood disorders, schizophrenia, autism and eating disorders, have been associated with fetal antecedents such as maternal stress or infection and malnutrition. Sex is another factor that influences the risk for psychiatric disorders through poorly understood mechanisms.

We know little as to how the maternal environment alters offspring programming. Epigenetics, an area of research that is studying how environmental factors produce lasting changes in gene expression without altering DNA sequence, may provide new insights into this question.

A new review, published in Biological Psychiatry, has "incorporated the latest insight gained from clinical and epidemiological studies with potential epigenetic mechanisms from basic research," explained first author Dr. Tracy Bale. These key findings are from a conference on Early Life Programming and Neurodevelopmental Disorders held at the University of Pennsylvania.

For example, the authors discuss findings where maternal stress has been associated with an increased risk of schizophrenia in male offspring and may alter fetal brain growth. Data also indicate that maternal stress, infection, and/or exposure to famine contribute to an elevated risk for depression in offspring. Of critical importance, the brain continues to develop into adolescence, and so later influences, such as exposure to child abuse and/or neglect, must also be taken into account. Studies have consistently shown that adults who experience maltreatment as children are at a much greater risk of developing mood disorders.

Clearly, multiple factors are at play that influence an individual's disease risk. By applying the principals of personalized medication, one can view this science as "personalized prevention," as it aims to apply these principals earlier in the pathological process. Understanding and defining these disease mechanisms at the very earliest points in life could help identify novel targets in therapy and prevention.

The article is "Early Life Programming and Neurodevelopmental Disorders" by Tracy L. Bale, Tallie Z. Baram, Alan S. Brown, Jill M. Goldstein, Thomas R. Insel, Margaret M. McCarthy, Charles B. Nemeroff, Teresa M. Reyes, Richard B. Simerly, Ezra S. Susser, and Eric J. Nestler. Bale and Reyes are affiliated with the University of Pennsylvania, Philadelphia, Pennsylvania. Baram is with the University of California, Irvine, California. Brown and Susser are with the New York State Psychiatric Institute, New York, New York. Goldstein is with Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Insel is with the National Institute of Mental Health, Bethesda, Maryland. McCarthy is with the University of Maryland School of Medicine, Baltimore, Maryland. Nemeroff is from the University of Miami, Miller School of Medicine, Miami, Florida. Simerly is affiliated with University of Southern California, Los Angeles, California. Nestler is with the Mount Sinai School of Medicine, New York, New York. The article appears in Biological Psychiatry, Volume 68, Issue 4 (August 15, 2010), published by Elsevier.

The authors' disclosures of financial and conflicts of interests are available in the article.

Full text of the article mentioned above is available upon request. Contact Maureen Hunter at m.hunter@elsevier.com to obtain a copy or to schedule an interview.

This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

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