LONGITUDINAL OUTCOMES & NEUROIMAGING OF FRAGILE X SYND

纵向结果

• 批准号: 8363425
• 负责人: Allan L Reiss
• 金额: $ 0.51万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363425
• 关键词: Adrenal Glands; Adult; Affect; Age; Behavior; Behavioral; Biological Factors; Brain; Brain imaging; Canada; Child; Clinical; Cognition; Cognitive; Control Groups; Data; Development; Disease; Emotional; Environmental Risk Factor; Experimental Designs; FMR1 Gene; Family; Fragile X Syndrome; Funding; Gender; Gene Expression; Genetic; Grant; Handedness; Hypothalamic structure; Image; Imaging Techniques; Impairment; Individual; Inherited; Investigation; Knowledge; Longitudinal Studies; Measures; Modeling; Mutation; National Center for Research Resources; Neurobiology; Outcome; Pituitary Gland; Principal Investigator; Psyche structure; Research; Research Infrastructure; Resources; Risk; School-Age Population; Siblings; Source; Structure; Techniques; Time; To specify; United States National Institutes of Health; Work; age related; base; boys; clinical phenotype; cohort; computational anatomy; cost; girls; neuroimaging; proband; prospective; relating to nervous system

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Fragile X syndrome (fraX) is the most common known cause of inherited mental impairment with well over 100,000 individuals affected in the U.S. Mutations in the FMR1 gene give rise to a clinical phenotype that includes increased risk for aberrant cognitive, behavioral and emotional function. The major emphasis of the 5-year study proposed in this application is a prospective, longitudinal extension of the work completed during the current grant period, during which key cognitive, behavioral, neuroendocrinological, genetic and environmental data were collected from 120 families across the U.S. and Canada, each having a child proband affected with fraX and a typically developing sibling. To the best of our knowledge, this study would be the first longitudinal investigation of a large, school-age fraX cohort in which both biological and environmental factors contributing to clinical outcome were assessed on a prospective basis. We also propose to extend our investigation into the neurobiology of this disorder using advanced brain imaging techniques. Specifically, longitudinal imaging studies will be used to explicate the developmental trajectory of brain structure and function in children with fraX as compared to key control groups. Specific Aims: 1) To use a longitudinal, prospective experimental design (with "Time 1" and "Time 2" assessments) to elucidate the developmental trajectory of cognitive, behavioral and emotional development in probands with fraX compared to their like-gender siblings; 2)to specify the longitudinal trajectory of hypothalamic-pituitary-adrenal (HPA) function and measures of FMR1 gene expression in probands with fraX; and 3)to utilize neuromaging techniques to specify the trajectory of brain structure and function in children with fraX compared to specific age-, gender-, handedness-, SES- and IQ-matched control groups. Although knowledge of cognition, behavior and the brain in children and adults with fraX has grown considerably over the past 20 years, longitudinal data from school-age children with this condition are limited. Cross-sectional findings and limited longitudinal data to date support the hypothesis that an age-related decline in standardized cognitive and adaptive behavioral scores occurs among school-age children with fraX. However, many questions remain unanswered regarding this phenomenon, in particular as related to extent, timing and neural basis. These unanswered questions offer a compelling rationale for conducting a longitudinal study of a large group of school-age boys and girls with fraX as proposed in this application.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 脆性X综合征（fraX）是遗传性精神障碍最常见的已知原因，在美国有超过10万人受到影响。FMR 1基因突变引起临床表型，包括异常认知，行为和情感功能的风险增加。本申请中提出的5年研究的主要重点是对当前资助期内完成的工作进行前瞻性、纵向扩展，在此期间，从美国和加拿大的120个家庭收集了关键的认知、行为、神经内分泌、遗传和环境数据，每个家庭都有一个受fraX影响的儿童先证者和一个典型的发育中的兄弟姐妹。据我们所知，这项研究将是第一次纵向调查的一个大的，学龄fraX队列中的生物和环境因素有助于临床结果进行了评估的前瞻性基础上。我们还建议使用先进的大脑成像技术扩展对这种疾病的神经生物学的研究。具体而言，纵向成像研究将用于阐明与关键对照组相比，fraX儿童的大脑结构和功能的发育轨迹。具体目标：1）采用纵向、前瞻性实验设计（用“时间1”和“时间2”评估）阐明fraX先证者与其同性同胞相比的认知、行为和情感发展的发展轨迹; 2）详细说明fraX先证者下丘脑-垂体-肾上腺（HPA）功能的纵向轨迹和FMR 1基因表达的测量; 3）利用神经成像技术来确定fraX儿童与特定年龄、性别、利手、SES和智商匹配的对照组相比的脑结构和功能的轨迹。尽管在过去的20年里，对患有fraX的儿童和成人的认知、行为和大脑的了解有了相当大的增长，但来自患有这种疾病的学龄儿童的纵向数据是有限的。迄今为止，横断面研究结果和有限的纵向数据支持这一假设，即在fraX学龄儿童中，标准化认知和适应行为评分出现与年龄相关的下降。然而，关于这种现象，特别是与程度，时间和神经基础有关的许多问题仍然没有答案。这些未回答的问题提供了一个令人信服的理由进行纵向研究的一大群学龄男孩和女孩与fraX在本申请中提出的。