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We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children's sensitivity to environmental insults.
Childhood maltreatment is a universal risk factor for antisocial behavior. Boys who experience abuse-and, more generally, those exposed to erratic, coercive, and punitive parenting-are at risk of developing conduct disorder, antisocial personality symptoms, and of becoming violent offenders (1, 2). The earlier children experience maltreatment, the more likely they are to develop these problems (3). But there are large differences between children in their response to maltreatment. Although maltreatment increases the risk of later criminality by about 50%, most maltreated children do not become delinquents or adult criminals (4). The reason for this variability in response is largely unknown, but it may be that vulnerability to adversities is conditional, depending on genetic susceptibility factors (5, 6). In this study, individual differences at a functional polymorphism in the promoter of the monoamine oxidase A (MAOA) gene were used to characterize genetic susceptibility to maltreatment and to test whether the MAOA gene modifies the influence of maltreatment on children's development of antisocial behavior.
The MAOA gene is located on the X chromosome (Xpl 11.23-11.4) (7). It encodes the MAOA enzyme, which metabolizes neurotransmitters such as norepinephrine (NE), serotonin (5-HT), and dopamine (DA), rendering them inactive (8). Genetic deficiencies in MAOA activity have been linked with aggression in mice and humans (9). Increased aggression and increased levels of brain NE, 5-HT, and DA were observed in a transgenic mouse line in which the gene encoding MAOA was deleted (10), and aggression was normalized by restoring MAOA expression (11). In humans, a null allele at the MAOA locus was linked with male antisocial behavior in a Dutch kindred (12). Because MAOA is an X-linked gene, affected males with...