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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD030615-05
Application #
2609100
Study Section
Human Development and Aging Subcommittee 3 (HUD)
Project Start
1992-09-23
Project End
2000-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Florida
Department
Psychiatry
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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Bodfish, J W; Newell, K M; Sprague, R L et al. (1997) Akathisia in adults with mental retardation: development of the Akathisia Ratings of Movement Scale (ARMS). Am J Ment Retard 101:413-23
Lewis, M H; Bodfish, J W; Powell, S B et al. (1996) Plasma HVA in adults with mental retardation and stereotyped behavior: biochemical evidence for a dopamine deficiency model. Am J Ment Retard 100:413-8
Bodfish, J W; Newell, K M; Sprague, R L et al. (1996) Dyskinetic movement disorder among adults with mental retardation: phenomenology and co-occurrence with stereotypy. Am J Ment Retard 101:118-29
Lewis, M H; Bodfish, J W; Powell, S B et al. (1996) Clomipramine treatment for self-injurious behavior of individuals with mental retardation: a double-blind comparison with placebo. Am J Ment Retard 100:654-65
Powell, S B; Bodfish, J W; Parker, D et al. (1996) Self-restraint and self-injury: occurrence and motivational significance. Am J Ment Retard 101:41-8

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