Neurobiological correlates of aggressive and disruptive behavior in clinically referred boys

Research has established an inverse relationship between central serotonin (5-HT) activity and aggressive behavior in animals human and adults. Low central 5-HT activity also plays a role in childhood aggression. Yet, the variable results of the few studies conducted in children indicate that there is no direct relationship between central 5-HT activity and childhood aggression. Attempts to reconcile the child studies of central 5-HT function suggest that the inconsistencies may be attributable to developmental, diagnostic, and/or familial factors. Other data suggest that seasonal variations in 5-HT activity may account for the inconsistency of central 5-HT findings in children.; This dissertation consists of a series of three studies designed to assess the impact that age, the presence of ADHD, familial aggression, and seasonally-related variance have on the relationship between central 5-HT activity and aggression in clinically-referred boys. Central 5-HT function was assessed in these studies by measuring the plasma prolactin response to an oral dose of the 5-HT releaser/reuptake inhibitor d,l-fenfluramine. It was hypothesized that the inverse relationship between central 5-HT and aggression in boys would be masked by seasonal fluctuations in 5-HT indices or by age, the presence of ADHD, or familial aggression.; These analyses reveled no evidence of seasonally-related variance nor do developmental and diagnostic factors seem to influence the impact that central 5-HT has on aggression in children. However, the association between central 5-HT and aggression did vary as a function of familial aggression. Specifically, familial aggression was associated with a subgroup of aggressive boys who had relatively lower central 5-HT activity. Since only about half of aggressive boys progress to adult violence, and familial aggression is a highly salient risk factor for persistence, these data provide compelling support for the hypothesis that low 5-HT function may be a marker or risk factor for such progression in aggressive prepubertal boys. These results also implicate low central 5-HT activity in the familial transmission of aggressive behavior. However, these hypotheses can only be adequately tested with a prospective study that follows aggressive children into adulthood.