Some specific aims of this proposal are: (1) To determine whether there are abnormalities in markers of serotonergic activity in aggressive children. This will be accomplished by selecting aggressive children (primary diagnosis of aggressive conduct disorder) and by measuring peripheral markers of serotonergic activity: 3H-imipramine binding sites in platelets, 14C-5-HT uptake sites in platelets, 5-HT content in platelets, plasma tryptophan ratio tryptophan transport in red blood cells and serum prolactin levels after L-tryptophan challenge. (2) To analyze the biochemical data obtained form Specific Aim 1 for the influence of specific behavioral variables thought to be related to aggressivity. This will be accomplished by measuring impulsivity (rating sacales/experimental tasks), motor activity, neurological soft signs and neuropsychological test performance. Also, we propose (1) retrospective analysis of the biochemical data for the influence of coexisting diagnoses with conduct disorder (i.e., attention deficit disorder with hyperactivity and/or specific developmental disorders), (2) a cross-sectional study on maturational differences in serotonergic activity in children, (3) a correlational study between peripheral (platelet imipramine binding sites) and central (CSF 5-HIAA levels) serotonergic activity in living humans. The principle hypothesis tested is peripheral markers of serotonergic activity are related to aggressive behavior in children. We focus on the role of serotonin in impulsive aggressive behavior, characterized by impairment of response inhibition or """"""""impulsivity"""""""". We predict aggressive behavior is multidetermined and there are subtypes of aggression in children which differ primarily along the dimension of impulsivity. These studies will shed light on the role of serotonin as a contributing factor to some types of aggressive behavior which are probably influenced by genetic and psychosocial factors. Measurement of biochemical markers of serotonergic activity should permit cogent theorizing about specific aspects of 5-HT physiology involved in the aggression of children, thereby leading to the development of specific antiaggressive treatments. These studies may also provide a useful set of markers for a taxonomy of aggression and/or personality traits.
