Brain and Behavior Study of Autism from Infancy through School Age

项目摘要 此应用程序是一个自闭症卓越中心（ACE）网络补助金的竞争延续， “自闭症从婴儿到学龄的纵向大脑和行为研究”。此前的融资 支持一项前瞻性纵向研究，该研究收集了高质量的大脑成像和行为 评估自闭症谱系障碍（ASD）的高和低家族风险（HR，LR）儿童，2-4岁 时间点（包括3、6、9、12、15和24个月）和36个月的自闭症诊断再评估。这 该项目已成功地产生了50份已出版/正在印刷（#35）或正在审查（#15）的手稿; 并创造了21个外部供资机会，利用这一网络并扩大了这项工作的范围。 ACE网络竞争延续的总体目标是继续跟踪300名独特的队列 HR和100名LR儿童进入学龄期（7-10岁），进行详细的大脑和行为评估。学龄 是学术和社会功能对未来成功至关重要的时候，也是人力资源管理的时候。 儿童容易表现出共病精神障碍、同伴关系和学习困难。 这些问题可以比早期年龄更广泛和更详细地评估。从这个开始工作 一个网络揭示：（1）早期脑成像特征在6个月大时就可检测到，远早于ASD 在那些在24个月时继续诊断ASD的人中，诊断是可能的;（2）自闭症特异性大脑和 行为特征从6-24个月大的时候发生了很大的变化，随着自闭症的发展;（3）大脑特征， 第一年的生活与后来的ASD行为相关，并准确预测个体ASD诊断， 24个月拟议的工作扩展了这一坚实的基础。在这一建议中，我们的目标是：（1）描述学校- 年龄HR儿童的临床结果，并确定这些临床结果的早期预测因素， 我们已经确定了3-36个月的成像和行为特征;（2）表征大脑和大脑- 从婴儿期到学龄期HR-ASD的行为轨迹，并确定ASD相关大脑的时间 变化;以及（3）根据经验推导并验证HR组内的新亚组， 从婴儿期到学龄期的行为轨迹，结合分子遗传学的数据， 环境暴露。本研究的潜在影响包括：（1）早期识别（< 3年） 儿童谁更有可能发展学龄（7-10岁）的临床问题，增加了潜在的 早期干预;（2）通过识别年龄特异性脑靶点， 治疗效果和临床前跨物种研究的目标，以告知药物开发;以及（3） 基于大脑和行为轨迹，识别出具有生物学意义的衍生亚组 从婴儿期到学龄，这可以用来支持制定个性化的干预措施。

Project Summary This application is a competing continuation of an Autism Center of Excellence (ACE) Network grant now entitled, `A Longitudinal Brain and Behavior Study of Autism from Infancy through School Age`. Prior funding has supported a prospective, longitudinal study that has collected high quality brain imaging and behavior assessments in children at high- and low- familial risk (HR, LR) for an autism spectrum disorder (ASD), at 2-4 time points (including 3, 6, 9, 12, 15 and 24 months) with 36 month diagnostic re-assessment for autism. This project has been successful in producing 50 manuscripts either published/in press (#35) or under review (#15); and generated 21 external funding opportunities, leveraging this network and expanding the scope of this work. The overarching goal of this ACE Network competing continuation is to continue to follow a unique cohort of 300 HR and 100 LR children into school age (7-10 years) with detailed brain and behavior assessments. School age is a time when academic and social functioning are critically important for future success and a time when HR children are prone to manifest comorbid psychiatric disorders, difficulties with peer relationships, and learning problems which can be assessed more extensively and with greater detail than at earlier ages. Work from this network has revealed that: (1) early brain imaging features are detectable by 6 months of age, well before ASD diagnosis is possible, in those who go on to have an ASD diagnosis at 24 months; (2) autism-specific brain and behavior features change substantially from 6-24 months of age, as autism unfolds; and, (3) brain features in the first year of life are associated with later ASD behaviors and accurately predict individual ASD diagnosis at 24 months. The proposed work extends this solid foundation. In this proposal we aim to: (1) characterize school- age clinical outcomes of HR children and determine early predictors of those clinical outcomes from brain imaging and behavioral features we have already identified from 3-36 months; (2) characterize brain and brain- behavior trajectories in HR-ASD from infancy through school-age and identify the timing of ASD-related brain changes; and (3) empirically derive and validate novel subgroups within the HR group based on brain and behavior trajectories from infancy through school age, incorporating data from molecular genetics and environmental exposures. The potential impact of this study includes: (1) early identification (< 3 years) of children who are more likely to develop school-age (7-10 years) clinical problems, increasing the potential for early intervention; (2) informing intervention studies by identifying age-specific brain targets, biomarkers of treatment efficacy, and targets for pre-clinical, cross-species studies to inform drug development; and,(3) identifying empirically-derived and biologically-meaningful subgroups, based on brain and behavior trajectories from infancy to school age, that could be used to support development of individualized interventions.