Genetic-imaging study of obsessive compulsive behavior in autism

项目总结(见说明)： 在这个项目中，我们将发展对与自闭症强迫症行为相关的临床症状和生物学因素(遗传学和脑形态测量)的范围的理解。自闭症是一种高度异质性的疾病。相当数量的患者在目前的治疗中并没有得到实质性的改善。我们将这一组患者称为难治性自闭症(DTT-自闭症)。我们的初步数据显示，这些患者表现出强迫行为(OCB)。我们将测试一个中心假设，即具有高OCB的自闭症参与者代表难治性自闭症(DTT-自闭症)的一个亚型，他们将具有额叶-纹状体回路和遗传易感性的异常成熟，类似于以前在强迫症谱(OCS)条件下研究的那些。利用OC谱(OCS)障碍的神经成像和遗传学的最新进展，该项目将检验这样一种假设，即患有OCB的自闭症将分享已在OCS障碍中证明的遗传和脑电路变化。我们将检验这一假设，即患有OCB的自闭症与额叶-纹状体回路的异常相关，就像强迫症和相关的OCS障碍一样。我们还将寻找OC相关基因的罕见和常见变异与自闭症OCB症状之间的联系。使用包括临床评估、神经成像和基因分型在内的多种方法，我们将确定患有OCB的自闭症的亚型。这项工作很重要，因为它研究了一组最需要治疗发展的自闭症患者。如果我们关于OC谱系障碍和自闭症与OCB之间的强烈生物学关系的假设是准确的，那么自闭症的新疗法可能会从正在进行的治疗难治性强迫症的干预研究中得出。

PROJECT SUMMARY (See instructions): In this project, we will develop an understanding of the range of clinical symptoms and biological factors (genetics and brain morphometry) that correlate with obsessive-compulsive behavior in autism. Autism is a highly heterogeneous disorder. A significant number of patients do not improve substantially with current treatments. We refer to this group of patients as difficult-to-treat autism (DTT-Autism). Our preliminary data suggest that these patients exhibit obsessive-compulsive behavior (OCB). We will test the central hypothesis that participants with autism with high OCB represent a subtype of difficult-to-treat autism (DTT-Autism) who will have abnormal maturation of frontal-striatal circuitry and genetic susceptibilities analogous to those previously studied in obsessive-compulsive spectrum (OCS) conditions. Capitalizing on recent progress in neuroimaging and genetics in OC spectrum (OCS) disorders, this project will test the hypothesis that autism with OCB will share genetic and brain circuitry changes that have been demonstrated in OCS disorders. We will test the hypothesis that autism with OCB will correlate with abnormalities in frontal-striatal circuitry as is true for OCD and related OCS disorders. We will also look for associations between rare and common variation in OC-related genes and OCB symptoms in autism. Using a combination of approaches including clinical assessment, neuroimaging and genotyping, we will characterize the subtype of autism with OCB. This work is important as it studies a group of autism patients who are in greatest need of treatment development. If our hypotheses about the strong biologic relationship between OC spectrum disorders and autism with OCB are accurate, novel treatments for autism may be drawn from ongoing research in interventions in treatment-refractory OCD.