ACE: Translational Studies of Insistence on Sameness in Autism

UIC ACE将在未来5年内重点研究自闭症谱系障碍（ASD）中坚持一致性（IS）的遗传学、神经生物学、认知和情感过程以及药理学。评估中心将对大量自我报告患有自闭症谱系障碍的儿童进行筛查，并通过对父母进行ADI-R进一步筛查。符合自闭症的ADI-R标准的亵渎者将被招募进行进一步的研究，如果他们也被ADI-R IS项目分类为高IS （N=150）或低IS （N=100）。此外，高IS受试者需要在RBS-R的两个IS因素的总和上得到15分或以上，以避免药物遗传学试验的下限效应。这250名受试者将与225名先前研究的受试者及其父母一起被纳入项目1，自闭症中血清素的遗传学：神经化学和临床内表型，共计475名三人组。该项目将研究25个与自闭症和IS相关的血清素相关基因。强候选基因的重测序将在药理学项目（III）的所有受试者和项目II的低IS受试者中进行。此外，将收集250名受试者的血清素测量值，并与遗传和表型测量值进行分析。在项目二：自闭症中坚持一致性的认知、情感和神经化学过程的转化研究中，将对50名高IS受试者（也在项目三）、50名低IS受试者（也在项目一）和50名对照受试者进行IS的fMRI研究。此外，将使用平行行为和神经化学方法的大鼠研究。项目III: The Pharmacogenetics of Treatment for坚持同一性在自闭症中的治疗，旨在复制和扩展艾司西酞普兰治疗ASD中IS相关易怒的初步研究。项目四：自闭症相关血清素转运体（SERT）突变将提供先前发现的与自闭症患者高IS行为相关的突变特征。UIC ACE是一个令人兴奋的中心，汇集了不同学科的专家来全面研究is，这是Kanner在1943年描述的两个主要特征之一。

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.