Stereotypies & Mental Retardation: Neurobiological Basis

描述（由申请人提供）：异常重复行为（刻板印象、自残、强迫行为）是智力迟钝个体表现出的各种异常行为中最重要的。尽管如此，对其病理生物学知之甚少，有效的体细胞治疗在很大程度上未经对照试验证实。例如，很少有对照研究检验了药物治疗智力迟钝患者异常重复行为的疗效。然而，有证据表明，假设5-羟色胺摄取抑制剂和非典型抗精神病药物都有效。目前，很少有信息来指导临床医生决定哪种药物类别可能对哪种类型的异常重复行为和哪种个体更有效。此外，很少有工作试图确定可能预测不同治疗反应的变量。因此，本研究的重点是评估选择性血清素再摄取抑制剂（SSRI）和非典型抗精神病药在多种异常重复行为中的相对疗效。此外，我们将在之前工作的基础上建立一套测量方法，(a)将提供关于重复行为障碍的新信息，(b)将预测药物反应，(c)将作为药物疗效的结果测量。具体目标将包括：1)识别重复性和非重复性行为障碍的时间结构和环境依赖性；2)识别生理（运动、自主）变量，以区分有或没有不同类别的异常重复行为的受试者；3)评价非典型抗精神病药与选择性5 -羟色胺再摄取抑制剂（SSRI）治疗智力低下患者异常重复行为的差异疗效；4)评估时间、环境和生理变量作为药物反应和药物治疗结果预测因子的效用。

DESCRIPTION (provided by applicant): Abnormal repetitive behaviors (stereotypies, self-injury, compulsions) are foremost among the varieties of aberrant behavior exhibited by individuals with mental retardation. Despite this, little is known about their pathobiology and efficacious somatic treatments are largely unconfirmed by controlled trials. For example, few controlled studies have examined the efficacy of pharmacological treatment of abnormal repetitive behavior in individuals with mental retardation. There is evidence, however, to hypothesize the efficacy of both 5-HT uptake inhibitors and atypical antipsychotics. Currently, there is little information to guide the clinician in deciding which drug class may be more effective for which categories of abnormal repetitive behaviors and for which individuals. Moreover, little work has attempted to identify variables that may predict differential treatment response. Thus, the focus of this proposal is to assess the relative efficacy of a selective serotonin reuptake inhibitor (SSRI) and an atypical antipsychotic across multiple categories of abnormal repetitive behaviors. In addition, we will build upon our previous work to establish sets of measures that (a) will provide novel information about repetitive behavior disorders, (b) will predict drug response, and (c) that will serve as outcome measures of drug efficacy. The specific aims will include: 1) identifying the temporal structure and environmental dependence of repetitive and non-repetitive behavior disorders; 2) identifying physiological (motor, autonomic) variables that discriminate subjects with and without discrete categories of abnormal repetitive behaviors; 3) evaluating the differential efficacy of an atypical antipsychotic and a selective serotonin reuptake inhibitor (SSRI) in treating abnormal repetitive behaviors in individuals with mental retardation; 4) evaluating the utility of temporal, environmental and physiological variables as both predictors of drug response and outcomes of pharmacotherapy.