STEREOTYPIES & MENTAL RETARDATION: NEUROBIOLOGICAL BASIS

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DESCRIPTION: (Adapted From The Applicant's Abstract) Stereotyped behavior (repetitive, rhythmical, motor acts such as body rocking, head rolling or self-hitting) is highly prevalent in both children and adults with mental retardation. Little is known about the functional or neurobiological basis of such behavior, and stereotypies are typically refractory to treatment. A large body of literature and the investigators' preliminary data point to an important role of central dopamine in the expression of stereotyped and self-injurious behavior. Similarly, altered serotonergic function figures prominently in hypotheses about the neurochemical medication of these behaviors, and considerable evidence from both clinical and animal studies supports a robust interaction between central dopamine and serotonin systems. Thus, the proposed studies will compare several in vivo estimates of central dopamine (e.g., eye blink, reaction time, plasma HVA) and central serotonin (e.g., platelet imipramine binding) function in individuals with mental retardation who engage in high rates of stereotyped behavior and in matched control subjects. A second major goal of the proposed project is to test the hypothesis that the tricyclic antidepressant clomipramine will prove efficacious in the treatment of stereotyped behavior. Although clomipramine and its major metabolite clearly have actions on serotonin systems, clomipramine also has dopamine antagonist properties. Because it has proven to be highly effective in the treatment of compulsive, ritualistic behavior, the investigators will examine its efficacy in treating stereotyped and self-injurious behavior in a double-blind placebo-controlled, cross-over study. The proposed trial of clomipramine is both well justified and promising, given the similarity of stereotyped and self-injurious behavior to the compulsive, ritualistic behavior characteristic of obsessive-compulsive disorder. The data obtained from the proposed studies should provide important, new information about the pathophysiology and treatment of stereotyped behavior disorders.