A version of a gene previously linked to impulsive violence appears to weaken brain circuits that regulate impulses, emotional memory and thinking in humans, researchers at the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) have found.
Brain scans revealed that people with this version - especially males - tended to have relatively smaller emotion-related brain structures, a hyperactive alarm center and under-active impulse control circuitry. The study identifies neural mechanisms by which this gene likely contributes to risk for violent and impulsive behavior through effects on the developing brain.
NIMH intramural researchers Andreas Meyer-Lindenberg, M.D., Daniel Weinberger, M.D., Ph.D., and colleagues report on their magnetic resonance imaging (MRI) study online in the Proceedings of the National Academy of Sciences during the week of March 20, 2006.
"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," said NIH Director Elias A. Zerhouni, M.D., who conducted MRI studies earlier in his career.
"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," explained Meyer-Lindenberg. "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 behavior."
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. The previously identified violence-related, or L, version, contains a different number of repeating sequences in its genetic code than the other version (H), likely resulting in lower enzyme activity and hence higher levels of serotonin. 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.