STEREOTYPIES & MENTAL RETARDATION: NEUROBIOLOGICAL BASIS

描述：(改编自申请者的摘要)刻板印象 行为(重复的、有节奏的、运动动作，如身体摇摆、头部 打滚或自打)在儿童和成人中都很普遍 精神发育迟滞。人们对功能性的或 这种行为的神经生物学基础，而刻板印象通常是 难治性的。一大堆文学作品和 调查人员的初步数据表明，中央银行在 多巴胺在刻板印象和自我伤害行为中的表达。 同样，5-羟色胺能功能改变在 关于这些行为的神经化学药物的假说，以及 来自临床和动物研究的大量证据支持 中枢多巴胺和5-羟色胺系统之间的强大相互作用。 因此，拟议的研究将比较几个活体估计的 中枢多巴胺(例如，眨眼、反应时间、血浆HVA)和 中枢5-羟色胺(如血小板丙咪嗪结合)在脑内的作用 精神发育迟滞的人 刻板印象的行为和相匹配的对照组受试者。 被提议的项目的第二个主要目标是检验假设 三环类抗抑郁药氯丙咪嗪将被证明在 对刻板印象行为的治疗。虽然氯丙咪嗪及其 主要代谢物对5-羟色胺系统有明显作用，氯丙咪嗪 也具有多巴胺拮抗剂的特性。因为它已经被证明是 在治疗强迫症和仪式性行为方面非常有效， 研究人员将检查其在治疗刻板印象和 双盲、安慰剂对照、交叉试验中的自我伤害行为 学习。拟议的氯丙咪嗪试验既有充分的理由，也有 有希望，考虑到刻板印象和自我伤害的相似之处 行为以强迫性、仪式性的行为为特征 强迫症。从建议中获得的数据 研究应该提供重要的、关于 刻板行为障碍的病理生理学和治疗。

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.