LONGITUDINAL OUTCOMES & NEUROIMAGING OF FRAGILE X SYND

纵向结果

基本信息

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
项目类别：
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

项目摘要

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.

该子项目是利用资源的众多研究子项目之一由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持并且子项目的主要研究者可能是由其他来源提供的，包括其他 NIH 来源。子项目可能列出的总成本代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。脆性 X 综合征 (fraX) 是遗传性精神障碍最常见的原因，在美国有超过 100,000 人受到影响。FMR1 基因突变会导致临床表型，包括认知、行为和情绪功能异常的风险增加。本申请中提出的为期 5 年的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 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。和加拿大，各有一名患有 fraX 的儿童先证者和一名正常发育的兄弟姐妹。据我们所知，这项研究将是对大型学龄 fraX 队列的首次纵向调查，其中对影响临床结果的生物和环境因素进行了前瞻性评估。我们还建议使用先进的脑成像技术来扩展对这种疾病的神经生物学的研究。具体来说，纵向成像研究将用于阐明 fraX 儿童与关键对照组相比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（“时间 1”和“时间 2”评估）来阐明 fraX 先证者与同性兄弟姐妹相比的认知、行为和情感发展轨迹； 2）用fraX确定先证者下丘脑-垂体-肾上腺（HPA）功能的纵向轨迹和FMR1基因表达的测量； 3）利用神经影像学技术来确定 fraX 儿童与特定年龄、性别、用手习惯、SES 和 IQ 匹配的对照组相比的大脑结构和功能轨迹。尽管在过去 20 年里，有关 fraX 儿童和成人的认知、行为和大脑的知识有了显着增长，但来自患有这种疾病的学龄儿童的纵向数据仍然有限。迄今为止的横断面研究结果和有限的纵向数据支持这样的假设：患有 fraX 的学龄儿童标准化认知和适应性行为分数与年龄相关下降。然而，关于这一现象的许多问题仍未得到解答，特别是与程度、时间和神经基础有关的问题。这些悬而未决的问题为对本申请中提出的一大群患有 fraX 的学龄男孩和女孩进行纵向研究提供了令人信服的理由。