Gene defect, aggression tied in some males


WASHINGTON -- Scientists have identified a tiny genetic defect that appears to predispose some men toward aggression, impulsiveness and violence, a discovery that is likely to rekindle the harsh debate over the causes of criminal and abnormal behavior.

Researchers emphasized, however, that the finding was thus far limited to a single large family, and that the inherited illness was likely to be quite rare in the general population.

Nevertheless, scientists said the discovery counts as a persuasive advance for human behavioral genetics, a field that lately has been in disarray as previous announcements of genes for manic-depression, schiH1 and alcoholism either have been disproved or come under withering criticism.

In the new work, researchers from the Netherlands and the United States studied a large Dutch family with a history of erratic and often hostile behavior among some, but not all, males in the group. Those afflicted often react to the most mildly stressful occasions with aggressive outbursts, shouting at, cursing or assaulting the person they deem a threat.

At other times, the men have committed arson, attempted rape and exposed themselves in public. In addition, their intelligence is on the low end of normal, with an average IQ of around 85 to 90.

The researchers have linked the abnormal behaviors to mutations in the gene responsible for the body's production of monoamine oxidase-a, an enzyme critical for breaking down chemicals that allow brain cells to communicate.

The scientists do not yet know the exact mechanism of the disorder, but they propose that lacking the metabolic enzyme, the brains of afflicted men end up with excess deposits of potent signaling molecules like serotonin, dopamine and noradrenaline. Those surplus neurotransmitters in turn stimulate erratic, often hostile conduct.

"A human behavior like aggression is very complex," said Dr. Han G. Brunner, a geneticist at University Hospital in Nijmegen, the Netherlands. "But our study shows that in certain instances a biological factor clearly influences the behavior." Dr. Brunner is the lead author of the new report, which is appearing today in the journal Science.

Comparing the monamine oxidase-a genes in five afflicted and 12 nonafflicted males of the family, the scientists found a difference in only a single biochemical building block among the thousands that make up the gene, a type of defect called a point mutation. In each case, those who showed a predisposition to aggressive, impulsive behavior had the mutation, and those who did not show such symptoms lacked it.

Biochemical analysis of the men's skin cells also showed a severe deficiency in the essential enzyme.

The researchers do not yet know how many people worldwide may suffer from the enzyme deficiency.

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