SA51 - MONOAMINE OXIDASE A (MAOA) GENOTYPE AND METHYLATION MODERATES ASSOCIATIONS OF MALTREATMENT AND AGGRESSION IN WOMEN AND MEN

Abstract

Background Childhood maltreatment interacts with a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter region to modify the risk of aggressive behaviour. In females, the high-expressing variant (MAOA-L) interacts with maltreatment, whereas in males it is the low-expressing variant (MAOA-S) that interacts with maltreatment, highlighting a key sex-difference in the biology of aggression. It has been suggested that epigenetic processes, such as DNA methylation, may be one of the biological mechanisms underlying such gene-environment interactions. We investigated whether MAOA-uVNTR genotype, and methylation in a region spanning the MAOA first exon and part of the first intron, moderated associations between childhood physical and sexual abuse and aggressive behaviours in women and men. Methods A sample of 117 Swedish women and 77 men completed standardized diagnostic interviews, questionnaires to report maltreatment and aggressive behaviours, and provided saliva samples for DNA extraction. The MAOA-uVNTR polymorphism was genotyped, and methylation of a region of interest in MAOA (ChrX: 43,515,544 - 43,515,991) was analyzed. Results In women who experienced childhood maltreatment, MAOA-L and lower exonic methylation were associated with an increased number of aggressive behaviours. By contrast, among men who had experienced maltreatment, MAOA-S and higher exonic as well as lower intronic methylation were associated with an increased number of aggressive behaviors. Discussion Our study offers initial evidence that altered DNA methylation of MAOA may be one underlying biological mechanism accounting for gene-environment interactions of MAOA in aggressive behaviour. Further, our findings highlight the importance of considering sex-differences in the pathophysiology of aggression.