Catecholamines and aggression: the role of COMT and MAO polymorphisms

Abstract

Catecholaminergic systems are involved in the regulation of aggressive behavior; this regulation is implemented in interactions with other neurobiological mechanisms. Most of the available evidence indicates that norepinephrine and dopamine lower the threshold for an aggressive response to environmental stimuli. Two major enzymes are responsible for catecholamine catabolism in the brain: catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA). The transcriptional activity of the genes coding for these enzymes is governed by common functional polymorphisms. If aggressive behavior is enhanced by catecholaminergic activity, then the lower activity of COMT and MAOA (resulting in a slower inactivation of catecholamines) should indirectly enhance aggression. This prediction has been supported by most (but not all) observations in rodents and humans. Male mice that have either the COMT or the MAOA gene knocked out show elevated aggression. The allele that codes for the lower enzymatic activity of COMT has been associated with elevated aggressive behavior in several samples of psychiatric patients. Similarly, the alleles that code for the lower activity of MAOA were associated with the development of aggressive behavior in maltreated male children in a large birth cohort study. Collectively, these results suggest that COMT and MAOA polymorphisms represent a basic neurobiological mechanism that contributes to the regulation of aggressive behavior.