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将在接下来的5年中关注遗传学，神经生物学，认知和情感过程，以及在自闭症谱系障碍（ASD）中坚持相同（IS）的药理学（ASD）。评估核心将筛选大量患有自闭症谱系障碍的儿童样本，以通过将ADI-R给予父母进一步筛查。如果ADI-R为高（n = 150）或低为（n = 100），则将招募满足自闭症ADI-R标准的PROFANES，以进行进一步研究。此外，高IS受试者将需要根据RBS-R上的两个因素为15个或以上的受试者，以避免药物遗传试验的地板效应。这些250名受试者将全部包含在项目I，自闭症中的5-羟色胺遗传学：神经化学和临床内表型，以及225名先前研究的受试者及其父母，共有475个三重奏。该项目将研究25种与自闭症关联的5-羟色胺相关基因，并且更具体地是。强有力的候选基因将与药物遗传学项目（III）中的所有受试者一起进行，并且在项目II项目II中的较低受试者。此外，这250名受试者将采用遗传和表型测量的5-羟色胺度量来分析。在项目II中：认知，情感和神经化学过程的转化研究坚持自闭症的相同性，fMRI的IS研究也将对50个高级IS受试者进行，也将在项目III中，50个低为受试者（在项目I中）和50个控制受试者。此外，将使用平行行为和神经化学方法的大鼠研究。项目III：坚持自闭症相同的治疗方法的药物遗传学旨在复制和扩展依他普兰治疗ASD的依他普里治疗的初步研究。项目IV：自闭症相关的5-羟色胺转运蛋白转运蛋白（SERT）突变将提供先前发现与自闭症受试者的高度行为相关的突变的表征。 UIC ACE是一个令人兴奋的中心，将一组各种学科的专家汇集到全面研究中，是坎纳（Kanner）在1943年描述的两个基本特征之一。