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A gene related to aggression weakens the brain

National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) researchers have found out that gene previously linked to impulsive violence appears// to weaken brain circuits that regulate impulses, emotional memory and thinking in humans.

It was studied through brain scans that revealed that people with this version of gene – especially males – tended to have relatively smaller emotion-related brain structures, a hyperactive alarm center and under-active impulse control circuitry.

This was reported by NIMH intramural researchers Andreas Meyer-Lindenberg, M.D., Daniel Weinberger, M.D., Ph.D., and colleagues in the Proceedings of the National Academy of Sciences during the week of March 20, 2006.

According to NIH Director Elias A. Zerhouni, M.D., who conducted MRI studies earlier in his career said, "These new findings illustrate the breathtaking power of 'imaging genomics' to study the brain's workings in a way that helps us to understand the circuitry underlying diversity in human temperament. By itself, this gene is likely to contribute only a small amount of risk in interaction with other genetic and psychosocial influences; it won't make people violent. But by studying its effects in a large sample of normal people, we were able to see how this gene variant biases the brain toward impulsive, aggressive behaviour."

The gene is one of two common versions that code for the enzyme monoamine oxydase-A (MAO-A), which breaks down key mood-regulating chemical messengers, most notably serotonin.

Structural MRI in 97 subjects was taken for the study and the results were that those with L showed reductions in gray matter (neurons and their connections) of about 8 percent in brain structures of a mood-regulating circuit (cingulate cortex, amygdala) among other areas. Volume of an area important for motivation and impulse regulation (orbital frontal cortex) was increased by 14 percent in men only. Altho ugh the reasons are unknown, this could reflect deficient pruning – the withering of unused neuronal connections as the brain matures and becomes more efficient, speculates Meyer-Lindenberg.

The researchers then looked at effects on brain activity using functional MRI (fMRI) scans. While performing a task matching emotionally evocative pictures – angry and fearful faces – subjects with L showed higher activity in the fear hub (amygdala). At the same time, decreased activity was observed in higher brain areas that regulate the fear hub (cingulate, orbital frontal, and insular cortices) – essentially the same circuit that was changed in volume.

Daniel Weinberger, M.D., Ph.D. said, "Heightened sensitivity in brain circuits important to cognitive inhibition and memory for negative emotional information may contribute to increased vulnerability of men with L exposed to abuse during childhood. Since only men showed gene effects in several of these circuits, this could lead to a situation where multiple brain control mechanisms are impaired and contribute to manifestly violent behavior, a kind of genetic double jeopardy."

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