Gene-environment link confirmed in conduct disorder
July 19, 2004

The hypothesis that the risk of antisocial behavior is predicted by a genotype-environment interaction is supported by a twin study published this week in the Archives of General Psychiatry.

The authors, from Virginia Institute for Psychiatric and Behavioral Genetics, say that their findings replicate those of Caspi et al, who recently showed that a functional polymorphism in the promoter of the monoamine oxidase A (MAO-A) gene and childhood maltreatment were associated with a significantly increased risk of antisocial behavior.

In the present study, Deborah Foley and team studied 514 male twins aged 8-17 years from the community-based Virginia Twin Study for Adolescent Behavioral Development. A control group was formed by 823 male twins who were too old to participate in the study.

Recent history of conduct disorder was assessed in all subjects, as was childhood adversity, maternal symptoms of antisocial personality, and MAO-A genotype.

Results showed that adversity but not MAO-A had a major impact on the risk of conduct disorder. However, low MAO-A activity increased the risk of conduct disorder only in the presence of an adverse childhood environment.

"This is an important finding because it suggests that specific genotypes may be associated with increasing or decreasing risks for psychiatric disorder contingent on environmental exposures," write Foley et al.

"Moreover, relevant genetic factors may not be detected at all unless the target sample is stratified by salient environmental factors."

Neither a passive nor an evocative genotype-environment correlation accounted for the interaction, as indicated by computer modeling.

The authors contend that, while there has traditionally been a strong emphasis on the independent effects of genes and environments in complex diseases, the findings of Caspi et al, which are replicated here, suggest that analysis of the joint effects of measured genes and environments "may indicate an important way forward for psychiatric genetics".


Arch Gen Psychiatry 2004; 61: 738-744