Genotype and Phenotype of Response to Treatments of Autism

自闭症治疗反应的基因型和表型

• 批准号: 7065570
• 负责人: PATRICIA M RODIER
• 金额: $ 153.64万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-13 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7065570
• 关键词: autism; behavior therapy; behavioral /social science research tag; clinical research; cooperative study; diet therapy; genotype; human subject; nutrition related tag; phenotype

STAART CENTER: Individual differences in response to treatments of autism spectrum disorders (ASDs) present a serious problem in choice of treatment. If we could predict in advance which children would benefit from the available interventions and which would not, children could be matched to treatments. On the other hand, individual differences in response to treatment may represent an opportunity for studies of the etiology of autism. Responders and non-responders are likely to represent different subsets of the spectrum that may be genetic in origin. Along with other phenotypic characteristics of children with ASDs, response to treatment is a dimension that deserves investigation as a possible way to stratify the spectrum for genetic studies. We propose studies of children's response to two of the most commonly used treatments of ASDs: early intensive behavioral intervention (Project I) and the gluten-free, casein-free diet (Project II). Each treatment project is accompanied by a related neurobiological investigation. Project III is an examination of the neurobiology of facial expression and imitation, which are important in the behavioral interventions under study in Project I. Project IV is an investigation of the sense of taste in both humans and animals, based on preliminary evidence that children with ASDs have dysfunction in this modality. It addresses dietary issues broader than the specific diet under study in Project II. Each Project has a genetic component, to explore the relationship of six suspected candidate genes to treatment response and other phenotypic characteristics of children with ASDs. A Genetics Core will provide the molecular testing for these studies. Each Project will use an Assessment and Records Core for characterizing participants and/or identifying and recruiting appropriate participants. An Administrative core will oversee the program, providing budgetary oversight, internal and external review of progress, statistical services, interactions with the community, and regular interactions between investigators. This proposal takes advantage of an unusual environment. The availability of intensive early behavioral intervention at public expense facilitates treatment studies. A large population of children with ASDs and families anxious to participate in research facilitate recruitment. The presence of a biologically-oriented CPEA complements the Projects of the STAART Center.

STAART CENTER：对自闭症谱系障碍（ASD）治疗反应的个体差异在治疗选择上提出了严重的问题。如果我们能够提前预测哪些儿童会从现有的干预措施中受益，哪些不会，那么就可以为儿童匹配治疗方案。另一方面，对治疗反应的个体差异可能为研究自闭症病因学提供了机会。有反应者和无反应者可能代表谱系的不同子集，这些子集可能是遗传性的。与自闭症谱系障碍儿童的其他表型特征一样，对治疗的反应是一个值得研究的维度，作为对遗传研究谱进行分层的可能方法。我们建议研究儿童对两种最常用的自闭症谱系障碍治疗方法的反应：早期强化行为干预（项目 I）和无麸质、无酪蛋白饮食 （项目二）。每个治疗项目都伴随着相关的神经生物学研究。项目 III 是对面部表情和模仿的神经生物学的检查，这对于项目 I 所研究的行为干预非常重要。项目 IV 是对人类和动物味觉的调查，其基础是初步证据表明，自闭症谱系障碍 (ASD) 在这种模式下存在功能障碍。它解决的饮食问题比项目 II 中研究的特定饮食更广泛。每个项目都有一个遗传组成部分，旨在探索六个可疑候选基因与自闭症谱系障碍儿童的治疗反应和其他表型特征的关系。遗传学核心将为这些研究提供分子测试。每个项目将使用评估和记录核心来描述参与者和/或 确定并招募合适的参与者。行政核心将监督该计划，提供预算监督、内部和外部进展审查、统计服务、与社区的互动以及调查人员之间的定期互动。该提案利用了一个不寻常的环境。由公共费用提供的强化早期行为干预有助于治疗研究。大量患有自闭症谱系障碍的儿童和渴望参与研究的家庭促进了招募。以生物学为导向的 CPEA 的存在补充了 STAART 中心的项目。