Abstract
Previous research has reported that a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter can moderate the association between early life adversity and increased risk for violence and antisocial behavior. In this study of a combined population of psychiatric outpatients and healthy volunteers (N = 235), we tested the hypothesis that MAOA genotype moderates the association between early traumatic life events (ETLE) experienced during the first 15 years of life and the display of physical aggression during adulthood, as assessed by the Aggression Questionnaire. An ANOVA model including gender, exposure to early trauma, and MAOA genotype as between-subjects factors showed significant MAOA×ETLE (F1,227 = 8.20, P = 0.005) and gender×MAOA×ETLE (F1,227 = 7.04, P = 0.009) interaction effects. Physical aggression scores were higher in men who had experienced early traumatic life events and who carried the low MAOA activity allele (MAOA-L). We repeated the analysis in the subgroup of healthy volunteers (N = 145) to exclude that the observed G×E interactions were due to the inclusion of psychiatric patients in our sample and were not generalizable to the population at large. The results for the subgroup of healthy volunteers were identical to those for the entire sample. The cumulative variance in the physical aggression score explained by the ANOVA effects involving the MAOA polymorphism was 6.6% in the entire sample and 12.1% in the sub-sample of healthy volunteers. Our results support the hypothesis that, when combined with exposure to early traumatic life events, low MAOA activity is a significant risk factor for aggressive behavior during adulthood and suggest that the use of dimensional measures focusing on behavioral aspects of aggression may increase the likelihood of detecting significant gene-by-environment interactions in studies of MAOA-related aggression.
Highlights
Expressions of violent behavior such as aggression are influenced by a complex and dynamic interplay of biological, psychological and social variables
We studied a mixed population of psychiatric outpatients and healthy volunteers to test the hypothesis that the monoamine oxidase A (MAOA) variable number tandem repeat (VNTR) polymorphism moderates the association between early traumatic life events experienced during the first fifteen years of life and the display of physical aggression during adulthood
A functional discrimination analysis showed that in our sample the three female genotypes were indistinguishable by physical aggression scores of the Aggression Questionnaire (Wilk’s l = 0.99; F2,170 = 0.74, P = 0.47; AQPA, see Materials and Methods [22]) and for the purposes of our analysis, we grouped heterozygous female participants together with low-low homozygous females following the convention of a previous study [23]
Summary
Expressions of violent behavior such as aggression are influenced by a complex and dynamic interplay of biological, psychological and social variables. Individual differences in aggressive behavior are at least partly heritable and presumably result from the interaction between genetic and environmental factors [1]. In the development of adult antisocial and violent behavior, the environmental factors considered influential include in utero exposure to pathogens and birth complications [3], childhood abuse or neglect [4,5], and family relationships, home environment, and other social variables [6]. Since MAOA is an X-linked gene [11], hemizygous males from this family effectively represent functional gene knockouts. This mutation is extremely rare and has not been found in any other pedigree. The 3.5-and 4-repeat forms show high MAOA mRNA expression and high enzyme activity, while the 2-, 3-and 5-repeat forms show low MAOA mRNA expression and low enzyme activity [12,13]
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