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Aggression-related gene weakens brain's impulse control circuits

n. These, in turn, influence how the brain gets wired during development. The variations may have more impact on males because they have only one copy of this X-chromosomal gene, while females have two copies, one of which will be of the H variant in most cases.

Several previous studies had linked increased serotonin during development with violence and the L version of MAO-A. For example, a 2002 study* by NIMH-funded researchers discovered that the gene's effects depend on interactions with environmental hard knocks: men with L were more prone to impulsive violence, but only if they were abused as children. Meyer-Lindenberg and colleagues set out to discover how this works at the level of brain circuitry.

Using structural MRI in 97 subjects, they found 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. Although 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.

While these changes were found in both men and women, two other experiments revealed gene-related changes in men only. In a task which required remembering emotionally negative information, men, but not women, with L
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Source:NIH/National Institute of Mental Health


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