Understanding genetic risk for aggression: Clues from the brain's response to social exclusion

Background: Although research indicates a relationship between the monoamine oxidase-A (MAOA) gene and aggression, the interven-ing neural and psychological mechanisms are unknown. Individuals with the low expression allele (MAOA-L) of a functional polymorphism in the MAOA gene might be prone to aggression because they are socially or emotionally hyposensitive and thus care less about harming others or because they are socially or emotionally hypersensitive and thus respond to negative social experiences with defensively aggressive behavior. Methods: We investigated the relationships between the MAOA polymorphism, trait aggression, trait interpersonal hypersensitivity, and neural responses to social exclusion in 32 healthy men and women. Results: The MAOA-L individuals (men and women) reported higher trait aggression than individuals with the high expression allele (MAOA-H). The MAOA-L individuals reported higher trait interpersonal hypersensitivity and showed greater dorsal anterior cingulate cortex (dACC) activity (associated with rejection-related distress) to social exclusion compared with MAOA-H individuals, consistent with a social hypersensitivity hypothesis. Moreover, the MAOA-aggression relationship was mediated by greater dACC reactivity to social exclusion, suggesting that MAOA might relate to aggression through socioemotional hypersensitivity. Conclusions: These data suggest that the relationship between MAOA and aggression might be due to a heightened rather than a reduced sensitivity to negative socioemotional experiences like social rejection.