Genetics and Physiology of Social Anxiety in Fragile X

脆性 X 症患者社交焦虑的遗传学和生理学

• 批准号: 7127711
• 负责人: DAVID R HESSL
• 金额: $ 15.14万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127711
• 关键词: adolescence (12-20); amygdala; anxiety disorders; autism; autonomic nervous system; avoidance behavior; behavior test; behavioral genetics; biomarker; child psychology; child with disability; clinical research; developmental disease /disorder; developmental neurobiology; fragile X syndromes; gender difference; gene expression; gene mutation; human subject; middle childhood (6-11); molecular genetics; patient oriented research; psychobiology; psychopathology; social behavior

DESCRIPTION (provided by applicant): The aim of this application is to develop the candidate's knowledge and skills in patient-oriented clinical research in the domain of neurodevelopmental disorders. Toward this aim, he will complete a program including formal coursework, mentored training, and a research project on the molecular genetics and psychophysiology of social anxiety in children with fragile X syndrome and the fragile X premutation. The research project includes measurement of biobehavioral markers of autonomic and amygdala function, fragile X mental retardation 1 (FMR1) mRNA and gene expression, and behavioral measures in children with fragile X and matched comparison samples of children with idiopathic developmental disability and typical development. The primary underlying hypothesis of the project is that the FMR1 mutation causes over-responsiveness of the amygdala to social stimuli, leading to symptoms of social anxiety and avoidance that are hallmark behavioral features of the fragile X behavioral phenotype. The study will also investigate whether this mechanism of increased anxiety contributes to autistic behaviors, particularly deficits in reciprocal social behavior, in children with fragile X. The candidate's ultimate goals are to become a clinical researcher able to compete for independent grant support, and to conduct high quality studies that will directly lead to improvement in the lives of individuals with fragile X, as well as to contribute to a better understanding of the genetic and physiological mechanisms underlying emotional and behavioral disturbance in children with neurodevelopmental disorders. By the end of the award period, the candidate will become a recognized clinical researcher in the area of neurodevelopmental disorders, and will receive funding to conduct research as an independent investigator.

描述（由申请人提供）：本申请的目的是培养候选人在神经发育障碍领域以患者为导向的临床研究方面的知识和技能。 为了实现这一目标，他将完成一个项目，包括正式课程、指导培训以及关于患有脆性 X 综合征和脆性 X 前突变的儿童社交焦虑的分子遗传学和心理生理学的研究项目。 该研究项目包括测量自主神经和杏仁核功能的生物行为标志物、脆性X智障1（FMR1）mRNA和基因表达，以及脆性X儿童的行为测量以及特发性发育障碍和典型发育儿童的匹配比较样本。 该项目的主要假设是，FMR1 突变导致杏仁核对社交刺激过度反应，导致社交焦虑和回避症状，这是脆弱 X 行为表型的标志性行为特征。 该研究还将调查这种焦虑增加的机制是否会导致患有 X 脆弱的儿童的自闭症行为，特别是互惠社会行为的缺陷。候选人的最终目标是成为一名能够竞争独立拨款支持的临床研究人员，并进行高质量的研究将直接改善脆性 X 染色体患者的生活，并有助于更好地了解神经发育障碍儿童情绪和行为障碍的遗传和生理机制。 奖励期结束时，候选人将成为神经发育障碍领域公认的临床研究员，并将获得资金作为独立研究者进行研究。