Imaging genomics bares roots of rage

MRI illuminates links between a gene variant and impulsive, violent behavior, particularly in men with a history of child abuse, according to a study conducted at the National Institutes of Mental Health. The findings highlight the potential for imaging genomics to explain the mechanisms that underlie temperament.

The gene's influence seems small in relation to other genetic and psychosocial factors. But the accumulating data may help researchers understand how the gene biases the brain toward impulsive, aggressive behavior, said lead investigator Dr. Andreas Meyer-Lindenberg, an intramural researcher at the NIMH.

Meyer-Lindenberg and colleagues compared structural and functional MR brain scans of 97 male and female subjects, including carriers and noncarriers of one of two genes that control serotonin. The violence-related L-variant gene appears to enhance serotonin production in a way that affects male brain development.

Overall, L-carrying males and females exhibited structural and functional brain differences from noncarriers. But only males with the gene variant showed increased volume of the orbitofrontal cortex, which regulates motivation and impulses, and increased activity in the fear and memory (hippocampus) hubs during a task requiring subjects to remember emotionally negative information. Men with the L-variant gene also failed to activate the cingulated cortex, which inhibits impulsive behavior.

The findings validate previous NIMH studies that showed L-carrying men were more likely to react violently, but only if they had been abused as children. The heightened sensitivity of brain circuitry dealing with cognitive inhibition and memory in men with L-variant genes exposed to abuse during childhood may create a predisposition for impulsive-aggressive behavior, researchers concluded. The study was published in March in the Proceedings of the National Academy of Sciences.