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May 09, 2003

Wits and madness

Gene enhances prefrontal function at a price

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.

Posted by jason_s at 07:25 AM

Very interesting! The persistence of both the val and the met variant in the population (at least the European population - the only one mentioned in the article) would suggest that either the val/met heterozygote has the greatest reproductive fitness, or else the mutation is relatively recent. Actually I suppose a third possibility exists: the heterozygote is dead last in fitness while both homozygotes are fairly closely matched - but that seems unlikely. It's too bad they don't go into any details on how these gene variants affect intelligence - it certainly sounds like there's an effect, and I can't imagine that a short study would be that hard to conduct. But I suppose the topic is too sensitive, so they conduct researches focusing on links to pathologies of different kinds.

Posted by: bbartlog at May 9, 2003 02:35 PM

My guess is that the closer genetics gets to understanding heritability of mental and emotional traits, the trickier and more complicated the story will get. As I've said before, hemophilia is very well understood now, but the physiology of it is pretty complicated (there are a number of kinds of hereditary coagulation diseases. The discussions I've seen of the biology and heredity of behavioral traits and intelligence are far simpler than what I've seen about hemostasis/thrombosis, but it seems almost certain that the reality is far more complicated.

Posted by: zizka at May 9, 2003 06:38 PM