Associations of the serotonin transporter promoter polymorphism with aggressivity, attention deficit, and conduct disorder in an adoptee population.

Prior studies of the Iowa Adoption cohorts have demonstrated that the degree of adoptee aggressiveness and conduct disorder has a significant genetic component. Other studies have implicated the neurotransmitter serotonin or polymorphisms in the serotonin transporter gene (5HTT) as an important source of variability in "externalizing" behaviors such as aggressivity, conduct disorder, and attention deficit-hyperactivity disorders (ADHD). Following this lead, we genotyped a subgroup of adoptees (n = 87) at high risk for these kinds of disorders with respect to the serotonin-transporter-linked promoter region (5HTTLPR) polymorphism, and used ordinal logistic regression to conduct an association study. Primary analysis failed to detect a main effect between 5HTTLPR status and subscales of aggressivity, conduct disorder, or attention deficit. However, when biologic parent status and sex of proband were considered, certain interactions between 5HTTLPR and other genetic risk factors were evident. One type of interaction with the LL variant of 5HTTLPR increased externalizing behavior in individuals with antisocial biologic parentage; a second interaction with one or more 5HTTLPR short variants (SS or SL) appeared to increase externalizing behaviors in conjunction with a genetic diathesis for alcoholism. Gender of adoptee also appeared to interact with 5HTTLPR. Male individuals with the short variant were more likely to have higher symptom counts for conduct disorder, aggressivity, and ADHD. In contrast, among females, the short variant (SS, SL) was associated with lower levels of such behavior. The results support the hypothesis that gene-biological family history interactions are involved in the externalizing behaviors studied and constitute interesting findings for future replication.