This continuation project is designed primarily to explore the relationship between central serotonergic (5-HT) function and aggressive behavior in children with and without attention-deficit hyperactivity disorder (ADHD). Central 5-HT will be assessed by measuring the prolactin response to a challenge dose of the 5-HT releaser/reuptake inhibitor fenfluramine, as compared to a placebo challenge. The primary goal is to extend the previous assessment of central 5-HT function to aggressive non- ADHD children and normal controls, in addition to new groups of aggressive and non-aggressive ADHD children. Secondarily, the symptom dimensions of impulsivity and hyperactivity will be assessed to determine their differential relationships with central 5-HT junction and aggression, and the relationship between academic achievement and the norepinephrine metabolite MHPG will be examined in ADHD and non-ADHD children. Children participating in this study will be divided into four groups of seven to eleven year-old boys: ADHD non-aggressive (N = 20), ADHD aggressive (N = 20), aggressive non-ADHD (N = 20) and normal controls (N= 20). The primary questions that will be addressed in this study are: 1. Is the difference in prolactin (PRL) response to fenfluramine (FEN) between aggressive and non-aggressive ADHD children due to an enhanced response relative to normals in aggressive ADHD children, a diminished response in non-aggressive ADHD children relative to normals, or is the PRL response to FEN in both aggressive and non-aggressive ADHD children different from that of normal children? 2. Is the enhanced PRL response to FEN challenge in aggressive, relative to non-aggressive, ADHD children related to an interaction between ADHD and aggression or is it characteristic of aggressive behavior in children irrespective of ADHD? Secondary aims of this project are a) to determine whether-the relationship between the PRL response to FEN and measures of impulsivity and activity level are similar or different in ADHD and non-ADHD patient groups; and b) to replicate the previous finding of an inverse relationship between plasma MHPG and measures of academic achievement in ADHD children, and to determine whether this relationship is limited to children with ADHD.
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