SCANS REVEAL HOW MAOA GENE VARIANT AFFECTS BRAIN STRUCTURE,
INCREASES RISK FOR AGGRESSION

A variant of a gene linked to aggression appears to affect behavior by weakening impulse control circuits in the brain, according to a new study.

The enzyme monoamine oxidase-A (MAOA) breaks down serotonin and several other neurotransmitters in the brain. Growing research links the low-activity (L) variant of the gene that codes for MAOA-a variant that results in higher levels of serotonin circulating in the brain-to aggressive behavior. While low levels of serotonin in adulthood are associated with depression and aggression, researchers suspect that high levels of serotonin during early development cause the brain to compensate, leading to alterations that make people more susceptible to violence and anxiety later in life.

Andreas Meyer-Lindenberg and colleagues used magnetic resonance imaging (MRI) to investigate how the L version of the MAOA gene translates into altered brain structure and function. Comparing people with the L variant to people with the high-activity H variant, the researchers found that:

• Individuals with the L variant had an 8% reduction in gray matter in the cingulate cortex and amygdala, both of which play a role in mood regulation. Conversely, males exhibited a 14% increase in volume in the orbital frontal cortex, a region key to motivation and impulse control. The researchers suspect that this increased volume reflects deficient pruning of neurons during development, resulting in impaired orbital frontal function.
• When asked to perform a task involving pictures of angry and fearful faces, individuals with the L variant showed higher activity in the amygdala (an area of the brain that responds to fear), while showing decreased activity in the orbital frontal cortex and other higher-brain regions that regulate fear responses.
• Men, but not women, with the L variant also showed increased reactivity in the amygdala and hippocampus when remembering emotionally negative information.
• Men with the L variant were impaired at a task requiring them to inhibit a simple motor response. They failed to activate the cingulate cortex, which typically helps to inhibit impulsive movements.

Overall, the findings indicate that individuals (and particularly men) with the L variant have smaller emotion- related brain structures, poor impulse control circuitry, and brain alterations that make them hypersensitive to threats. The gender difference appears to stem from the fact that the gene is on the X chromosome, and women have a second X chromosome that often carries the H variant.

"By itself," Meyer-Lindenberg says, "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 behavior."

The findings are consistent with earlier research (see related article, Crime Times, 2002, Vol. 8, No. 4, Page 1) showing that abused children are vastly more likely to develop antisocial behavior if they possess the L variant of the MAOA gene.

"Aggression-related gene weakens brain's impulse control circuits," news release, National Institute of Mental Health, March 20, 2006.

"Neural mechanisms of genetic risk for impulsivity and violence in humans," Andreas Meyer-Lindenberg et al., Proceedings of the National Academy of Sciences, March 29, 2006 (epub before print publication). Address: Andreas Meyer-Lindenberg, andreasml@nih.gov.