Stork: Longitudinal Outcomes and Neuroimaging of Fragile X Syndrome

ALLAN L REISS (1993-07-01 to 2012-06-30) Longitudinal Outcomes and Neuroimaging of Fragile X Syndrome. Amount: $3607305



Fragile X syndrome (FraX) is the most common known cause of inherited mental impairment. FMR1 gene mutations, the cause of FraX, lead to reduced expression of FMR1 protein (FMRP) and increased risk for a particular profile of cognitive, behavioral and emotional dysfunction. Because of the similarity of these features to important (idiopathic) DSM-IV diagnoses, the study of individuals with FraX provides a window of understanding into disorders such as autism, social phobia, depression, and cognitive disability. The study of FraX also is a portal to the realization of innovative interdisciplinary research that spans multiple clinical and basic scientific domains. Such research provides new insights into understanding how genetic and environmental factors contribute to complex variations in typical and atypical human behavior. In this application, we describe plans to build on a unique study of individuals with FraX that has been in existence since 1992. In the first component of our research, we will continue a longitudinal study of 80 well-described individuals with FraX as they reach a critical phase of development - adolescence and young adulthood. Key cognitive, behavioral, neuroendocrinological, genetic and environmental data will be collected, and the relation of these data to functional outcome will be examined. This component of the study will represent the largest comprehensive, prospective investigation of a FraX cohort during adolescence and young adulthood. In the second component of our research, we will extend our investigation into the neurobiology of FraX using novel behavioral studies and advanced, multi-modal neuroimaging experiments to more fully elucidate brain structure, biochemistry, connectivity and function underlying aberrant cognition and behavior. Within the context of the second aim, we also will examine the efficacy of brief intervention trials focused on improving executive function and social behavior. These pilot trials will utilize innovative behavioral and real-time functional magnetic resonance imaging (rtfMRI) strategies and are designed to generate preliminary data to guide the development of new FraX specific treatments in the future. The Center for Interdisciplinary Brain Sciences Research (CIBSR), directed by the PI, Dr. Allan Reiss, represents one of only a handful of sites in the world that has made a long-term commitment to comprehensive, interdisciplinary research on FraX. The work performed in the CIBSR is particularly focused on applied investigation that will provide new knowledge, methods and tools to improve the lives of persons with FraX and their families.

脆性X综合征(FraX)是遗传性精神障碍最常见的已知病因。 FMR1基因突变是FraX的原因,导致FMR1蛋白(FMRP)的表达降低,并增加了认知,行为和情绪功能障碍特定特征的风险。由于这些特征与重要(特发性)DSM-IV诊断的相似性,FraX对个体的研究为自闭症,社交恐惧症,抑郁症和认知障碍等疾病提供了一个理解窗口。 FraX的研究也是跨越多个临床和基础科学领域实现创新跨学科研究的门户。这种研究提供了新的见解,了解遗传和环境因素如何有助于典型和非典型人类行为的复杂变化。在这个应用中,我们描述了自1992年以来一直存在的FraX个人独特研究的计划。在我们研究的第一个组成部分中,我们将继续对FraX达到的80位熟练人物进行纵向研究发展的关键阶段 - 青春期和青春期。将收集关键认知,行为,神经内分泌,遗传和环境数据,并对这些数据与功能结局的关系进行检验。这项研究的这一部分将代表青春期和年轻成年期间FraX队列的最大的综合性前瞻性调查。在我们研究的第二部分,我们将使用新的行为学研究和先进的多模态神经影像学实验来扩展我们对FraX的神经生物学的调查,以更充分地阐明大脑结构,生物化学,连通性和功能的异常认知和行为。在第二个目标的范围内,我们还将研究简要干预试验的功效,重点是改善执行机能和社会行为。这些试点试验将利用创新的行为和实时功能磁共振成像(rtfMRI)策略,旨在产生初步数据,以指导未来新型FraX特异性治疗的发展。由PI执行的跨学科脑科学研究中心(CIBSR),Allan Reiss博士代表了世界上少数几个对FraX进行全面,跨学科研究的承诺。 CIBSR的工作特别侧重于应用调查,将提供新的知识,方法和工具来改善FraX及其家属的生活。

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