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.

项目摘要（请参阅说明）： 在这个项目中，我们将对与自闭症中强迫性行为相关的临床症状和生物学因素（遗传学和脑形态计量学）的范围进行了解。自闭症是一种高度异质性疾病。当前治疗的大量患者无法大大改善。我们将这组患者称为难以治疗的自闭症（DTT-autism）。我们的初步数据表明这些患者表现出强迫症（OCB）。我们将测试一个中心假设，即具有高OCB的自闭症的参与者代表了难以治疗的自闭症（DTT-Sautism）的亚型，他们的额叶 - 纹状体回路异常成熟和与先前在强迫症（OCS）条件下研究的人相似。利用OC频谱（OCS）疾病的神经影像学和遗传学的最新进展，该项目将检验以下假设：OCB的自闭症将共享OCS疾病中已证明的遗传和脑电路变化。我们将检验以下假设：与OCD和相关的OCS疾病一样，OCB的自闭症将与额叶纹状体电路中的异常相关。我们还将寻找与自闭症相关基因的罕见和常见变异与自闭症中OCB症状之间的关联。使用包括临床评估，神经成像和基因分型在内的方法组合，我们将用OCB来表征自闭症的亚型。这项工作很重要，因为它研究了一群最需要治疗开发的自闭症患者。如果我们关于OC频谱障碍与自闭症与OCB之间牢固的生物学关系的假设是准确的，则可以从正在进行的治疗 - 难治性OCD的干预措施中提出新的自闭症治疗方法。