ACE: Translational Studies of Insistence on Sameness in Autism

ACE：自闭症坚持同一性的转化研究

• 批准号: 7904995
• 负责人: Edwin H Cook
• 金额: $ 191.27万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-06 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904995
• 关键词: ACE; Translational; Studies; Insistence; Sameness

The UIC ACE will focus over the next 5 years on the genetics, neurobiology, cognitive and affective processes, and pharmacology of insistence on sameness (IS) in autism spectrum disorders (ASD). A large sample of children with self-reported autism spectrum disorder will be screened by the Assessment Core for further screening by administration of the ADI-R to the parents. Profanes meeting ADI-R criteria for autistic disorder will be recruited for further study if they are also classified by the ADI-R IS items as high (N=150) or low IS (N=100). In addition, high IS subjects will need to score 15 or more on the sum of two IS factors on the RBS-R to avoid floor effects for the pharmacogenetic trial. These 250 subjects will all be included in project I, Genetics of Serotonin in Autism: Neurochemical and Clinical Endophenotypes, along with 225 previously studied subjects and their parents for a total of 475 trios. This project will study 25 serotonin- related genes for association with autism and with IS more specifically. Resequencing of strong candidate genes will be conducted with all of the subjects in the pharmacogenetic project (III) and with the low IS subjects in project II. In addition, the 250 subjects will have serotonin measures collected for analysis with genetic and phenotype measures. In Project II: Translational Studies of Cognitive, Affective and Neurochemical Processes Underlying Insistence on Sameness in Autism, fMRI studies of IS will be conducted on 50 high IS subjects also in Project III, 50 low IS subjects (also in Project I) and 50 control subjects. In addition, rat studies in which parallel behavioral and neurochemical approaches will be used. Project III: The Pharmacogenetics of Treatment for Insistence on Sameness in Autism has been designed to replicate and extend a preliminary study of escitalopram treatment of IS related irritability in ASD. Project IV: Autism-Associated Serotonin Transporter (SERT) Mutations will provide characterization of mutations previously found to be associated with high IS behaviors in subjects with autism. The UIC ACE is an exciting center that brings together experts in a diverse set of disciplines to comprehensively study IS, one of the two cardinal features described by Kanner in 1943.

UIC ACE将在未来5年内专注于自闭症谱系障碍（ASD）的遗传学，神经生物学，认知和情感过程以及坚持相同性（IS）的药理学。一个大样本的儿童与自我报告的自闭症谱系障碍将筛选评估核心进一步筛选管理的ADI-R的父母。如果符合ADI-R自闭症标准的非专业人士也被ADI-R IS项目分为高IS（N=150）或低IS（N=100），则将招募他们进行进一步研究。此外，高IS受试者将需要在RBS-R上的两个IS因子之和上得分15分或以上，以避免药物遗传学试验的下限效应。这250名受试者将全部纳入项目I，自闭症血清素的遗传学：神经化学和临床内表型，沿着225名先前研究的受试者及其父母，共475个三人组。该项目将研究25个与孤独症和IS更具体的关联的血清素相关基因。将对药物遗传学项目（III）中的所有受试者和项目II中的低IS受试者进行强候选基因重测序。此外，将收集250名受试者的血清素测量值，用于遗传和表型测量的分析。在项目II中：在自闭症中坚持相同性的认知，情感和神经化学过程的转化研究，IS的fMRI研究将在项目III中的50名高IS受试者，50名低IS受试者（也在项目I中）和50名对照受试者中进行。此外，将使用平行的行为和神经化学方法进行大鼠研究。项目三：孤独症坚持相同性治疗的药物遗传学研究旨在复制和扩展艾司西酞普兰治疗ASD IS相关易激惹的初步研究。项目四：自闭症相关5-羟色胺转运蛋白（SERT）突变将提供先前发现的与自闭症受试者的高IS行为相关的突变的表征。UIC ACE是一个令人兴奋的中心，汇集了不同学科的专家，全面研究IS，这是Kanner在1943年描述的两个主要特征之一。