Functional Imaging of Flexibility in Autism: Informed by SLC6A4

自闭症灵活性的功能成像：由 SLC6A4 提供信息

• 批准号: 8091378
• 负责人: BENJAMIN YERYS
• 金额: $ 13.27万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-16 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8091378
• 关键词: Address; Age; Alleles; Anatomy; Architecture; Attention; Autistic Disorder; Behavior; Behavioral; Behavioral Genetics; Biological Markers; Blood specimen; Brain; Brain region; Centers for Disease Control and Prevention (U.S.); Child; Clinical; Cognitive; Collaborations; Control Groups; Corpus striatum structure; Data; Development; Development Plans; Diagnostic; Disease; Environment; Exhibits; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genes; Genetic; Genetic Techniques; Genome; Genomics; Genotype; Glutamate Carboxypeptidase II; Goals; Heterogeneity; Image; Individual; Intervention; Lead; Magnetic Resonance Imaging; Maps; Medical center; Mentors; Methods; Modeling; Motor; Nature; Neuroanatomy; Neurobiology; Neurocognitive; Neurologist; Neuropsychology; Neurosciences; Parietal; Parietal Lobe; Pediatric Hospitals; Performance; Philadelphia; Process; Reaction Time; Reading; Recruitment Activity; Relative (related person); Research; Research Personnel; Research Project Grants; Research Training; Rest; Sampling; Scientist; Serotonin; Societies; Stimulus; Stream; Structure; Symptoms; Techniques; Technology; Testing; Thinking; Training; Universities; Variant; Work; autism spectrum disorder; base; career development; disorder control; disorder risk; flexibility; genetic analysis; indexing; insight; interest; member; neglect; neuromechanism; neuropsychological; novel; prevent; programs; psychologic; public health relevance; relating to nervous system; research study; response; serotonin transporter

DESCRIPTION (provided by applicant): The immediate goals of this application include: training the candidate to become an independent clinical- researcher, and to addressing the brain (and genetic) basis of a cardinal, but neglected restricted, repetitive symptoms of autism spectrum disorders (ASD). Long term goals include: developing a model for integrative research, informing our understanding of the causes of ASD, and advancing our ability to test and target treatments for ASD. The research project uses well established neuroscience methods (functional MRI and genotyping) to investigate brain regions and genes involved in restricted, repetitive behavior and interest symptoms in ASD. Cognitive flexibility serves as a window into this symptom cluster, and the proposed studies address a limitation of past work by carefully parsing flexibility into its core components in children with ASD. Children with and without ASD will be genotyped for a serotonin transporter gene implicated in both ASD and cognitive flexibility and will participate in functional MRI and psychological batteries that assess cognitive flexibility and ASD symptoms. Children with ASD and the risk allele for the serotonin transporter gene are predicted to make more errors on flexibility tasks and show greater deviance in the structure and function of brain regions activated. The career development plan includes cross-disciplinary training in advanced MRI techniques, neuroanatomy, neurobiology, genetics, neuropsychology, and imaging genomics; training comes from formal didactics, directed readings and laboratoryexperiences with a distinguished panel of expert co-mentors with a neurologist as lead mentor. Research environment: The candidate's main training and research will occur in a burgeoning, collaborative autism research program at Children's National Medical Center and Georgetown University, and he will receive in-depth advanced training from established institutional and personal collaborations with scientists at the Children's Hospital of Philadelphia and Stanford University. PUBLIC HEALTH RELEVANCE: According to the Center for Disease Control, 1 in 150 children in the US has autism. Repetitive behaviors and rigid, inflexible thinking are cardinal symptoms of the disorder and prevent many otherwise high funcitoning people from being poductive members of main stream society. Yet our understanding of these symptoms remains limited at cognitive, brain, and genetic levels of analysis. The proposed work seeks to define neural and genetic contributors to this cluster of autism symptoms in order to help us pursue the causes of, and target interventions to treat, these core autism deficits.

描述（由申请人提供）：本申请的直接目标包括：培训候选人成为独立的临床研究人员，并解决基本主教但被忽视的自闭症谱系障碍的重复性症状（ASD）的大脑（和遗传）基础。长期目标包括：开发一个综合研究模型，了解我们对ASD原因的理解，并促进我们测试和针对ASD治疗的能力。该研究项目使用良好的神经科学方法（功能性MRI和基因分型）来研究与ASD中限制，重复行为和兴趣症状有关的大脑区域和基因。认知灵活性是进入此症状集群的窗口，拟议的研究通过将灵活性仔细地解析为ASD儿童的核心组成部分来解决过去工作的局限性。患有和没有ASD的儿童将针对与ASD和认知灵活性有关的5-羟色胺转运蛋白基因进行基因分型，并将参与评估认知灵活性和ASD症状的功能性MRI和心理电池。预计患有血清素转运蛋白基因的ASD儿童和风险等位基因在灵活性任务上会犯更多的错误，并在激活的大脑区域的结构和功能上显示出更大的偏差。职业发展计划包括高级MRI技术，神经解剖学，神经生物学，遗传学，神经心理学和成像基因组学的跨学科培训；培训来自正式的教学学，定向阅读和实验室经验，由杰出的专家联合委员会与神经科医生担任首席导师。研究环境：候选人的主要培训和研究将发生在儿童国家医学中心和乔治敦大学的蓬勃发展，合作自闭症研究计划中，他将接受与费城和斯坦福大学儿童医院的既定机构和个人合作的深入高级培训。 公共卫生相关性：根据疾病控制中心的说法，美国150名儿童中有1例患有自闭症。重复的行为和僵化，僵化的思维是这种疾病的基本症状，并阻止许多原本高的funcitton人成为主要流社会的表情成员。然而，我们对这些症状的理解在认知，大脑和遗传分析水平上仍然有限。拟议的工作旨在为这些自闭症症状定义神经和遗传因素，以帮助我们追求这些核心自闭症缺陷的原因和目标干预措施。