Studies of a gene that affects how efficiently the brain's frontal lobes process information are revealing some untidy consequences of a tiny variation in its molecular structure and how it may increase susceptibility to schizophrenia. People with a common version of the gene associated with more efficient working memory and frontal lobe information processing may pay a penalty in adverse responses to amphetamine, in heightened anxiety and sensitivity to pain. Yet, another common version may slightly bias the brain toward a pattern of neurochemical activity associated with psychosis, report researchers at the National Institutes of Health (NIH).

Everyone inherits two copies of the catecho-O-methyltransferase (COMT) gene, one from each parent. It codes for the enzyme that metabolizes neurotransmitters like dopamine and norepinephrine and comes in two common versions. One version, met, contains the amino acid methionine at a point in its chemical sequence where the other version, val, contains a valine. Depending on the mix of variants inherited, a person's COMT genes can be typed met/met, val/val, or val/met.

"Since both versions of the COMT gene are common in the population they've been conserved as the human brain evolved -- it makes sense that each would confer some advantages and disadvantages," explained Daniel Weinberger, M.D., National Institute of Mental Health (NIMH), whose research team, headed by Venkata Mattay, M.D., reports on how the variants affect the brain's response to amphetamine in the May 13, 2003 Proceedings of the National Academy of Sciences, already published online.

"Genes don't directly encode for psychopathology, hallucinations, delusions and panic attacks. Rather, there is a very complicated path between a gene's influence on the regulation and function of a protein and such psychiatric phenomena," added Weinberger. "We're especially inter
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
7-May-2003

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