Monoamine Oxidase-A Genetic Variations Influence Brain Activity Associated with Inhibitory Control: New Insight into the Neural Correlates of Impulsivity

Background Previous evidence has shown that genetic variations in the serotonergic system contribute to individual differences in personality traits germane to impulse control. The monoamine oxidase-A (MAO-A) gene, coding for an enzyme primarily involved in serotonin and noradrenaline catabolism, presents a well-characterized functional polymorphism consisting of a variable number of tandem repeats in the promoter region, with high-activity and low-activity variants. High-activity allele carriers have higher enzyme expression, lower amine concentration, and present higher scores on behavioral measures of impulsivity than low-activity allele carriers. Methods We studied the relationship of this polymorphism to brain activity elicited by a response inhibition task (Go/NoGo task), using blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging in 24 healthy men. Results Direct comparison between groups revealed a greater BOLD response in the right ventrolateral prefrontal cortex (Brodmann’s area [BA] 45/47) in high-activity allele carriers, whereas a greater response in the right superior parietal cortex (BA 7) and bilateral extrastriate cortex (BA 18) was found in low-activity allele carriers. Conclusions These data suggest that a specific genetic variation involving serotonergic catabolism can modulate BOLD response associated with human impulsivity.