Brain and Behavior Study of Autism from Infancy through School Age

项目摘要 这项申请是自闭症卓越中心(ACE)网络赠款的竞争性延续，现名为， “自闭症从婴儿期到学龄期的纵向大脑和行为研究。”之前的资金已经 支持一项前瞻性的纵向研究，该研究收集了高质量的大脑成像和行为 2-4岁自闭症谱系障碍(ASD)的高、低家族风险(HR，LR)儿童的评估 3个月、6个月、9个月、12个月、15个月和24个月的时间点，36个月的自闭症诊断再评估。这 该项目成功地制作了50份已出版/出版(第35号)或正在审查(第15号)的手稿； 并创造了21个外部筹资机会，利用这一网络，扩大了这项工作的范围。 此次ACE网络竞争延续的首要目标是继续跟踪300人的独特队列 HR和100名LR儿童进入学龄(7-10岁)，进行详细的大脑和行为评估。学龄 是一个学术和社交功能对未来成功至关重要的时代，也是一个人力资源 儿童容易表现出精神障碍、同伴关系困难和学习困难。 可以比早期更广泛和更详细地评估的问题。从这里开始工作 网络显示：(1)早期的大脑成像特征在6个月大的时候就可以检测到，远远早于ASD 在那些24个月后被诊断为ASD的人中，诊断是可能的；(2)自闭症特有的大脑和 随着自闭症的发展，6-24个月大的婴儿的行为特征会发生很大的变化；以及，(3) 出生第一年与较晚的ASD行为相关，并准确预测ASD的个体诊断 24个月。拟议的工作扩展了这一坚实的基础。在这项建议中，我们的目标是：(1)描述学校- HR儿童的年龄和临床结局的脑功能早期预测因素 我们已经确定的3-36个月的成像和行为特征；(2)表征大脑和大脑- HR-ASD从婴儿期到学龄期的行为轨迹和ASD相关脑的时间 变化；以及(3)基于大脑和大脑的经验推导和验证HR组内的新的子组 从婴儿期到学龄期的行为轨迹，结合了来自分子遗传学和 暴露在环境中。这项研究的潜在影响包括：(1)早期发现(&lt；3年) 更有可能出现学龄期(7-10岁)临床问题的儿童，增加了患 早期干预；(2)通过确定特定年龄的脑靶点、生物标记物 治疗效果，以及为药物开发提供信息的临床前、跨物种研究的目标；以及，(3) 根据大脑和行为轨迹识别经验性派生的和具有生物意义的亚群 从婴儿期到学龄期，这可以用来支持个性化干预的发展。

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.