Microcircuits for reward driven decision in Drosphila

果蝇奖励驱动决策的微电路

• 批准号: 9323532
• 负责人: Karla R. Kaun
• 金额: $ 29.66万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9323532
• 关键词: Affect; Anatomy; Animal Model; Autistic Disorder; Biological Factors; Biological Markers; Brain; Candidate Disease Gene; Centers of Research Excellence; Childhood; Clinical; Clinical assessments; Corpus striatum structure; Coupled; Data; Data Analyses; Diffusion Magnetic Resonance Imaging; Disease; Evaluation; Exhibits; Family; Foundations; Genes; Genetic; Genetic Heterogeneity; Genetic Predisposition to Disease; Genetic Variation; Genotype; Goals; Heterogeneity; Human; Individual; Instruction; Intervention; Lead; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Monitor; Mutation; Neuraxis; Neuropsychology; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Outcome; Participant; Patients; Population; Recruitment Activity; Refractory; Research; Rest; Severities; Societies; Source; Statistical Methods; Structure; Susceptibility Gene; Symptoms; Testing; Time; Variant; Work; autism spectrum disorder; brain circuitry; cohort; cost; developmental disease; epidemiology study; genetic association; high dimensionality; imaging genetics; imaging study; morphometry; neurodevelopment; neuroimaging; novel; novel therapeutics; therapy development; treatment response

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.

项目总结（见说明）： 在这个项目中，我们将了解与自闭症强迫行为相关的临床症状和生物因素（遗传学和脑形态测量学）的范围。自闭症是一种高度异质性的疾病。相当多的患者在目前的治疗下没有实质性改善。我们将这组患者称为难治性自闭症（DTT-自闭症）。我们的初步数据表明，这些患者表现出强迫行为（OCB）。我们将测试中心假设，即具有高OCB的自闭症参与者代表难以治疗的自闭症（DTT-自闭症）的亚型，其额叶-纹状体回路和遗传易感性异常成熟，类似于先前在强迫症谱系（OCS）条件下研究的那些。利用神经影像学和遗传学在OC谱系（OCS）障碍的最新进展，该项目将测试自闭症与OCB将共享已在OCS障碍中证明的遗传和脑回路变化的假设。我们将检验这一假设，即自闭症与OCB将与额-纹状体回路异常相关，这对强迫症和相关的OCS障碍也是如此。我们还将寻找罕见和常见的OC相关基因变异与自闭症OCB症状之间的关联。使用包括临床评估，神经影像学和基因分型的方法相结合，我们将与OCB的自闭症亚型的特点。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之间强烈的生物学关系的假设是准确的，那么自闭症的新治疗方法可能会从正在进行的难治性强迫症干预研究中得出。