Is There a Role of Serotonin in the Disruptive Behavior Disorders? A Literature Review

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Abstract
The basic and clinical research literature is reviewed to assess the possible role of serotonin (5HT) in the modulation of brain functions that appear to be altered in the disruptive behavior disorders of childhood. Although the number of 5HT cell bodies are remarkably few, numbering in the thousands, they project extensively to almost all brain areas and appear involved in a large number of psychophysiologic functions. This supports a dimensional (symptom-related) rather than a categorical (diagnoses-related) view of central 5HT dysfunction in human behavior. There is substantial evidence implicating 5HT systems in the modulation of motor activity, impulsive aggression, and learning and memory. In both animals and humans, reductions in 5HT function appear to exacerbate hyperactivity and aggression, and agents that potentiate 5HT transmission reduce activity and aggression. Nonetheless, the clinical literature is insufficient to implicate 5HT systems in ADHD. Aggression in adults directed at the self and others may be associated with altered indices of central 5HT activity, regardless of psychiatric diagnoses. Initial findings on aggression in children and adolescent populations are consistent with adult data. When selective serotonergic agents are used clinically to treat hyperactivity or aggression, their clinical effects appear acutely, in contrast with the time course of their antidepressant and anxiolytic actions. This suggests that the therapeutic effect on activity and aggression may be related to the acute activation of serotonergic receptors rather than to the down-regulatory changes that appear after long-term treatments and that coincide with the onset of antidepressant effects. Learning disabilities have been frequently associated with disruptive behavior disorders in children. Serotonergic systems appear to play a role in memory and learning processes, but it is likely that different memory and performance functions may be differentially regulated by serotonergic neural networks. Controlled trials of specific 5HT reuptake blockers, selective 5HT agonists, and 5HT antagonists should be encouraged, both in acute and chronic administration, in order to examine their potential for treating childhood hyperactivity, conduct disorders, and perhaps also the learning deficits present in these children.