Relationship between central serotonergic function and aggression in prepubertal boys: effect of age and attention-deficit/hyperactivity disorder.

Data indicate that diminished central serotonergic (5-HT) function is related to aggression in adults, but discrepant findings in children suggest that age or the presence of attention-deficit/hyperactivity disorder (ADHD) may influence this relationship. This study examined whether age or ADHD affects the association between 5-HT and aggression in 7-11-year old clinically-referred boys. Forty-six boys were divided into non-aggressive ADHD, aggressive ADHD, and aggressive non-ADHD groups based on responses to interviews and ratings of behavior. Central 5-HT function was assessed by measuring the prolactin response to a 1-mg/kg oral dose of D,L-fenfluramine. There was no significant difference in the prolactin response across the three groups of boys. Furthermore, when examined dimensionally, prolactin response was largely unrelated to ratings of aggression, even after controlling for ADHD. Finally, age was not associated with prolactin response, and had no effect on the relationship between prolactin response and aggression. This study provides further evidence that there is no clear relationship between central 5-HT function and aggression in disruptive boys. Moreover, these data do not confirm the hypothesis that age or the presence of ADHD influence the relationship between 5-HT and childhood aggression.

ADHD and reading disabilities: a cluster analytic approach for distinguishing subgroups.

Data suggest that children with reading disability (RD) and non-RD children with attention-deficit/hyperactivity disorder (ADHD) may comprise distinct subgroups. Research has been hampered by variance in definitional criteria, which results in the study of different subgroups of children. Using cluster analysis, this study empirically divided children with ADHD (N = 54), based on their Full Scale IQ (FSIQ) and reading ability. Four distinct subgroups emerged in which cognitive, behavioral, and neurochemical function was compared. Cluster 1 was of average FSIQ and reading scores; Cluster 2 was of average FSIQ but showed impairment in reading; Cluster 3 had high FSIQ and reading scores; and Cluster 4 had low scores in both domains. The groups had different patterns of cognitive, behavioral, and neurochemical function, as determined by discrepancies in Verbal-Performance IQ, academic achievement scores, parent aggression ratings, and a measure of noradrenergic function. These distinctions are discussed with regard to etiology, treatment, and long-term outcome.

Noradrenergic mechanisms in ADHD children with and without reading disabilities: a replication and extension.

OBJECTIVE: To examine noradrenergic (NA) function in children with attention-deficit hyperactivity disorder (ADHD) by replicating and expanding upon a previous finding that ADHD children with and without reading disabilities (RD) differ in plasma levels of the NA metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG). METHOD: Plasma levels of MHPG were compared in ADHD children who were subdivided on the basis of the presence or absence of RD. Subsequently, this replication sample was combined with a previously studied sample to further explore the relationship between plasma MHPG levels and measures of cognitive function in children with ADHD. RESULTS: Plasma levels of MHPG were significantly lower in ADHD children without RD, compared with those with RD, replicating a published finding. Analyses in the combined sample indicated that, among children with ADHD, plasma MHPG levels were inversely associated with measures of academic achievement and verbal processing, but not parent or teacher ratings of behavior or continuous performance test measures of attention and impulsivity. CONCLUSIONS: These data indicate that children with ADHD are not homogeneous with regard to NA function and that neurochemical variation is closely associated with differences in clinical characteristics of the children.

Changes in plasma prolactin and catecholamine metabolite levels following acute needle stick in children.

Changes in plasma levels of prolactin (PRL), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) following insertion of an indwelling catheter into a forearm vein were assessed in 11 boys with attention-deficit hyperactivity disorder. Results indicated decreases in plasma PRL and HVA, but not MHPG, from the time of needle stick until 105 min post-insertion. These data indicate a significant increase in plasma PRL and HVA in children following needle stick which gradually decreases over a 1.5-2-h period. These stress-induced changes indicate that values obtained immediately after needle insertion cannot be assumed to accurately reflect baseline levels.

Age-related changes in the association between serotonergic function and aggression in boys with ADHD.

The results of several studies have indicated an inverse relationship between central serotonergic (5-HT) mechanisms and aggression in animals and adults, but studies in children have yielded conflicting results. This study assessed 5-HT function, using a fenfluramine (FEN) challenge procedure, in an attempt to replicate a previously reported enhancement of the prolactin (PRL) response to FEN in aggressive relative to nonaggressive ADHD boys. The study failed to replicate the previous finding. Samples from both studies were then examined to reconcile the discrepant findings. The samples differed significantly in age. The entire group (n = 50) was then divided into older and younger subgroups and reanalyzed using a two-way (age-group x aggression) analysis of covariance (ANCOVA) controlling for plasma medication level. The ANCOVA generated a significant age-group x aggression interaction. Young aggressive boys had a significantly greater PRL response to FEN than young nonaggressive boys, but no such difference existed in the older age-group. These findings raise the possibility of different developmental trajectories in 5-HT function between aggressive and nonaggressive boys.