STEREOTYPIES & MENTAL RETARDATION: NEUROBIOLOGICAL BASIS

描述：（改编自申请人的摘要）定型 行为（重复的，有节奏的，运动行为，如身体摇摆，头部 滚动或自击）在儿童和成人中都非常普遍 患有精神发育迟滞 关于功能或 这种行为的神经生物学基础，刻板印象通常是 难治的 大量的文学作品和 研究人员的初步数据表明， 多巴胺在表达刻板印象和自我伤害行为中的作用。 类似地，改变的肾上腺素能功能在 关于这些行为的神经化学药物的假设，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种体内估计值， 中枢多巴胺（例如，眨眼、反应时间、血浆HVA）和 中枢5-羟色胺（例如，血小板丙咪嗪结合）功能 精神发育迟滞的人， 刻板行为和匹配的对照组。 该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有效， 对刻板行为的处理。 虽然氯丙咪嗪及其 主要代谢产物氯丙咪嗪对血清素系统有明显作用 也具有多巴胺拮抗剂的特性。 因为事实证明 对强迫性仪式性行为的治疗非常有效 研究人员将检查它在治疗刻板印象和 在一个双盲安慰剂对照，交叉 study. 氯丙咪嗪的拟议试验既有充分的理由， 有希望的，鉴于刻板印象和自我伤害的相似性 强迫性的，仪式性的行为， 强迫症 从拟议的数据中获得的数据 研究应该提供重要的新信息， 病理生理学和治疗定型行为障碍。

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.