How schizophrenia develops: Major clues ...( Schizophrenia may occur in part beca...)

Schizophrenia may occur, in part, because of a problem in an intermittent on/off switch for a gene involved in making a key chemical messenger in the brain, scientists have found in a study of human brain tissue. The researchers found that the gene is turned on at increasingly high rates during normal development of the prefrontal cortex, the part of the brain involved in higher functions like thinking and decision-making but that this normal increase may not occur in people with schizophrenia.

The study was funded by the National Institutes of Healths National Institute of Mental Health (NIMH) and National Institute of Child Health and Human Development.

The gene, GAD1, makes an enzyme essential for production of the chemical messenger, called GABA. The more the gene is turned on, the more GABA synthesis can occur, under normal circumstances. GABA helps regulate the flow of electrical traffic that enables brain cells to communicate with each other. It is among the major neurotransmitters in the brain.

Abnormalities in brain development and in GABA synthesis are known to play a role in schizophrenia, but the underlying molecular mechanisms are unknown. In this study, scientists discovered that defects in specific epigenetic actions biochemical reactions that regulate gene activity, such as turning genes on and off so that they can make substances like the GAD1 enzyme are involved.

Results of the research were published in the October 17 issue of the Journal of Neuroscience, by Schahram Akbarian, MD, PhD, Hsien-Sung Huang, PhD student, and colleagues at the University of Massachusetts Medical School and Baylor College of Medicine.

This discovery opens a new area for exploration of schizophrenia, said NIMH Director Thomas R. Insel, MD. Studies have yielded very strong evidence that schizophrenia involves a decrease in the enzymes, like GAD1, that help make the neurotransmitter GABA. Now were starting to id
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