ACE: Translational Studies of Insistence on Sameness in Autism

描述(由申请人提供)：UIC ACE将在未来5年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(IS)的药理学。评估中心将对大量自闭症谱系障碍儿童进行筛查，以便通过向家长发放ADI-R进行进一步筛查。如果符合ADI-R自闭症障碍标准的亵渎者也被归类为高(N=150)或低IS(N=100)项目，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因素的总和上获得15分或更多分数，以避免药物遗传学试验的地板效应。这250名受试者将全部包括在项目I，自闭症中5-羟色胺的遗传学：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，总共475个三人组。这个项目将研究25个与5-羟色胺相关的基因，这些基因与自闭症有关，而且与IS更具特异性。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的重新测序。此外，将收集250名受试者的血清素测量数据，以进行遗传和表型测量分析。在项目II：自闭症坚持相同的认知、情感和神经化学过程的翻译研究中，将对项目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名对照受试者进行IS的功能磁共振研究。此外，将使用并行的行为和神经化学方法进行大鼠研究。项目III：自闭症坚持相同的治疗的药物遗传学设计是为了复制和推广艾司西普兰治疗自闭症相关刺激性的初步研究。项目四：自闭症相关5-羟色胺转运体(SERT)突变将提供以前发现的与自闭症受试者高IS行为相关的突变的特征。UIC ACE是一个令人兴奋的中心，它汇集了不同学科的专家，全面研究IS，这是坎纳在1943年描述的两个主要特征之一。

DESCRIPTION (provided by applicant): 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.