Mechanisms of Social Engagement in Autism Spectrum Disorders

自闭症卓越中心的申请要求对自闭症谱系障碍（ASD）的行为，大脑和分子方面的跨学科研究计划提供五年的支持。它建立在长期的计划研究，重点是社会化的早期机制及其在ASD中的破坏，对大脑结构和功能的神经发育影响，以及与社会障碍相关的遗传和细胞遗传学病因。该应用程序由5个项目和3个核心组成。项目I、II和III关注同一组12至24个月大的ASD婴儿及其在36至48个月大时的结果。他们的目标包括量化的视觉扫描行为的背景下，自然的社会情况下，凝视处理，听觉偏好与语言和交际技能的收购。这些研究的一个副产品是在第二年的生活中开发基于性能的ASD筛选器。项目4使用MRI来研究一组10岁儿童的结构和功能连接指数，这些儿童从24个月大起就通过我们的CPEA和STAART赠款进行纵向随访。项目5的重点是鉴定导致ASD的罕见遗传变异，作为发现这些疾病所涉及的分子途径的一种手段。它利用了在项目I至III下招募的非常好表征的婴儿队列，建立在我们小组最近的发现基础上，这些发现涉及发育障碍中Contactin和Contactin相关分子家族的细胞遗传学异常和序列突变，并利用了加州大学洛杉矶分校合作者的独立结果，这些结果表明ASD的风险增加是由这些分子中的一种常见单倍型引起的。这5个项目通过行政核心提供的经过验证的治理和沟通进行整合和支持。评估核心将确保在我们的临床卓越和方法严谨的传统，以及特点鲜明的科目.数据分析和方法核心将提供研究设计和数据分析方面的持续咨询，并在全中心范围的数据挖掘和方法创新方面进行合作。耶鲁ACE解决了NIH机构间自闭症协调委员会的几个关键行动项目，包括婴儿的神经发育标记物和筛查，功能特异性神经回路和遗传原因。

This application for an Autism Center of Excellence requests five years of support for an interdisciplinary program of research on behavioral, brain and molecular aspects of the autism spectrum disorders (ASD). It builds on longstanding programmatic research focused on early mechanisms of socialization and their disruption in ASD, on their neurodevelopmental implications for brain structure and function, and on genetic and cytogenetic etiologies associated with social disorders. This application consists of 5 projects and 3 cores. Projects I, II, and III focus on the same cohort of 12- to 24-month-old infants with ASD and their outcome at 36- to 48-months of age. Their objectives include quantification of visual scanning behavior in the context of naturalistic social situations, gaze processing, and auditory preferences associated with the acquisition of language and communicative skills. A byproduct of these studies is the development of performance-based screeners for ASD in the second year of life. Project 4 uses MRI to study indices of structural and functional connectivity in a cohort of 10-year-olds who have been followed-up longitudinally since the age of 24 months through our CPEA and STAART grants. Project 5 focuses on the identification of rare genetic variants contributing to ASDs as a means of discovering molecular pathways involved in these disorders. It leverages the exceedingly well characterized cohort of infants recruited under projects I to III, builds upon our groups' recent findings implicating both cytogenetic abnormalities and sequence mutations in Contactin and Contactin associated family of molecules in developmental disorders, and capitalizes on independent results by collaborators at UCLA suggesting increased risk for ASD resulting from a common haplotype in one of these molecules. The 5 projects are integrated and supported through proven governance and communication provided by an Administrative Core. An Assessment Core will ensure well- characterized subjects in our tradition of clinical excellence and methodological rigor. A Data Analytic and Methodology Core will provide ongoing consultation on study design and data analysis, and collaborate on Center-wide data mining and methodological innovations. The Yale ACE addresses several key action items of the NIH Interagency Autism Coordinating Committee, including neuro-developmental markers and screening in infants, function-specific neural circuitry, and genetic causes.