Longitudinal Outcomes and Neuroimaging of Fragile X Synd

脆性 X 综合征的纵向结果和神经影像学

• 批准号: 6606998
• 负责人: Allan L Reiss
• 金额: $ 70.91万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6606998
• 关键词: adolescence (12-20); age difference; anxiety; attention deficit disorder; autism; behavioral /social science research tag; bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain morphology; child (0-11); child behavior; child psychology; clinical research; cognition; cortisol; depression; family genetics; family structure /dynamics; fragile X syndromes; functional magnetic resonance imaging; gender difference; gene expression; handedness; human subject; hypothalamic pituitary adrenal axis; intelligence; longitudinal human study; outcomes research; pathologic process; siblings; socioeconomics

DESCRIPTION (provided by applicant): 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 o 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) 10 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 lQ-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.

描述（申请人提供）：脆弱的X综合征（FRAX）是最多的 遗传性心理障碍的常见原因超过100,000 在美国FMR1基因突变中受影响的个体引起了 临床表型包括增加异常认知风险， 行为和情感功能。这项5年研究的主要重点 在此应用中提出的是一个前瞻性的纵向延伸o 在当前赠款期间完成的工作，在此期间，关键认知， 行为，神经内分泌学，遗传和环境数据是 从美国和加拿大的120个家庭收集，每个家庭都有一个孩子 受Frax和典型发展的兄弟姐妹影响的概率。最好 我们的知识，这项研究将是对 较大的学龄儿童队列，在生物学和环境 预期评估了导致临床结果的因素。 我们还建议将调查扩展到这一点的神经生物学 使用高级脑成像技术的疾病。具体而言，纵向 成像研究将用于解释大脑的发育轨迹 与关键对照组相比，FRAX儿童的结构和功能。 具体目的：1）10使用纵向，前瞻性实验设计（带有 “时间1”和“时间2？评估），以阐明 与Frax相比的概率中的认知，行为和情感发展 对他们的性别兄弟姐妹； 2）指定的纵向轨迹 下丘脑 - 垂体 - 肾上腺（HPA）功能和FMR1基因的度量 在带有frax的概率中的表达； 3）利用神经传导技术 指定FRAX儿童的大脑结构和功能的轨迹 与特定的年龄，性别，手，SES和LQ匹配的对照相比 组。尽管对儿童的认知，行为和大脑的了解以及 在过去的20年中，有Frax的成年人已经成长了很大的成长，纵向 有这种情况的学龄儿童的数据有限。横截面 迄今为止的发现和有限的纵向数据支持了以下假设 标准化认知和适应性行为评分与年龄相关的下降 发生在学龄儿童中。但是，许多问题仍然存在 关于这种现象的未得到答复，特别是与程度有关的 时间和神经基础。这些未解决的问题提供了引人注目的 对大量学龄的纵向研究进行纵向研究的理由 按照本申请中提议的男孩和女孩。