Exogenous testosterone and the monoamine-oxidase A polymorphism influence anger, aggression and neural responses to provocation in males

Abstract Testosterone and the monoamine oxidase-A (MAOA) polymorphism are potential neuromodulators for aggression. By acting on similar brain circuits, they might interactively influence human behavior. The current study investigates the causal role of testosterone on aggression-related brain activity and the potential interaction with the MAOA polymorphism. In a double-blind process, 93 healthy males received a testosterone or placebo gel. In an fMRI session, participants performed a Taylor aggression paradigm in which they received provoking feedback and could afterwards decide how aggressively they would react. Testosterone and cortisol levels as well as subjective anger were assessed prior and after the task. Circulating testosterone levels were higher in carriers of the long compared to the short MAOA allele. An interaction of the MAOA polymorphism and testosterone administration was identified in the cuneus, where short allele carriers in the placebo group showed diminished activity in the decision period. Task-related anger was significantly higher in this group. Overall, a mesocorticolimbic network was implicated in processing of high versus low provoking feedback, and core hubs of the default mode network were implicated in the subsequent decision after high versus low provocation. Testosterone administration increased activation in this network. The data provides evidence for an interaction of the MAOA polymorphism and exogenous testosterone on anger and suggests that interactive effects on the brain signal could underlie differential emotional reactivity. The increased default mode activation in the testosterone group suggests an enhanced engagement of social cognition related regions possibly supporting responsivity towards social provocation.