Stereotypies & Mental Retardation: Neurobiological Basis

描述(申请人提供)：异常重复行为(刻板印象、自我伤害、强迫)是精神发育迟滞个体表现出的各种异常行为中最重要的。尽管如此，人们对它们的病理生物学知之甚少，有效的躯体治疗在很大程度上还没有得到对照试验的证实。例如，很少有对照研究检验药物治疗精神发育迟滞患者异常重复行为的疗效。然而，有证据可以推测5-羟色胺摄取抑制剂和非典型抗精神病药物的疗效。目前，几乎没有信息来指导临床医生决定哪一类药物对哪些类别的异常重复行为和哪些个体更有效。此外，几乎没有工作试图确定可能预测差异治疗反应的变量。因此，这项建议的重点是评估选择性5-羟色胺再摄取抑制剂(SSRI)和非典型抗精神病药物对多种异常重复行为的相对疗效。此外，我们将在以前工作的基础上建立一套措施，这些措施(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衡量标准。具体目标将包括：1)确定重复性和非重复性行为障碍的时间结构和环境依赖性；2)确定区分不同类别异常重复行为受试者的生理(运动、自主)变量；3)评估非典型抗精神病药物和选择性5-羟色胺再摄取抑制剂(SSRI)在治疗精神发育迟滞患者异常重复行为方面的不同疗效；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有效性。

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.