Project 3: Developmental trajectories in infants at genetic risk for autism

项目摘要 基因筛查现在可以在自闭症行为症状出现之前识别风险变体。这 进步为婴儿的症状前干预提供了机会， 早期偏离典型模式。据我们所知，没有先前的研究已经检查了是否组合 基因筛选和早期神经发育途径的精确轨迹可能使早期神经发育成为可能。 对已确定患有自闭症遗传风险的婴儿进行诊断。基于这一巨大的知识差距，项目3 建议在婴儿3至15个月大时，每3个月对神经发育进行一次纵向评估。 PROGRESS队列将包括N = 300名婴儿的最终样本：已确定遗传风险中N = 200名 (IGR)组和N = 100例胎龄、性别、种族/民族、语言和邮政编码匹配的对照婴儿 无已确定遗传风险（非IGR）。我们将研究自主神经的发育轨迹， 系统和神经功能（目标1），信息收集感知和行动系统（目标2：视觉，听觉， 多感觉，运动），社会发展和语言/沟通（目标3），以确定是否和何时 这些轨迹在遗传风险群体中有所不同。位于进步中心，使我们能够 联合收割机在多个层次的分析措施（目标4），包括遗传风险（项目1），父母 经验和自我效能（项目2），神经发育轨迹（项目3）和诊断结果 （核心评价）。我们将这种创新设计与复杂的统计建模技术（统计 和计算分析核心），以阐明发展机制，并使早期诊断， 有自闭症遗传风险的婴儿我们将与传播和外联核心合作， 新的知识，并为父母提供适当的支持和早期干预服务的联系。 总之，项目3在多样化的大城市中利用了具有代表性的抽样策略，大样本量 结合密集的纵向评估和多学科团队科学方法， 具有已确定的自闭症遗传风险的婴儿的神经行为轨迹。

PROJECT SUMMARY Genetic screening can now identify risk variants before the emergence of behavioral symptoms of autism. This advance affords opportunity for presymptomatic intervention in infants whose developmental trajectories indicate early deviation from typical patterns. To our knowledge, no prior study has examined whether the combination of genetic screening and precise trajectories of early neurodevelopmental pathways might enable earlier diagnosis in infants with identified genetic risk for autism. Based on this significant knowledge gap, Project 3 proposes to longitudinally assess neurodevelopment every 3 months when infants are 3 to 15 months of age. The PROGRESS cohort will include a final sample of N = 300 infants: N = 200 in the Identified Genetic Risk (IGR) group and N = 100 gestational age, sex, race/ethnicity, language, and zip code-matched control infants without Identified Genetic Risk (non-IGR). We will examine developmental trajectories of autonomic nervous system and neural function (Aim 1), information-gathering perception and action systems (Aim 2: visual, auditory, multisensory, motor), and social development and language/communication (Aim 3) to determine if and when these trajectories deviate across genetic risk groups. Being situated in the PROGRESS Center allows us to combine measures across multiple levels of analysis (Aim 4) including genetic risk (Project 1), parental experience and self-efficacy (Project 2), trajectories of neurodevelopment (Project 3), and diagnostic outcomes (Assessment Core). We pair this innovative design with sophisticated statistical modeling techniques (Statistical and Computational Analysis Core) to elucidate developmental mechanisms and to enable earlier diagnosis in infants at identified genetic risk for autism. We will partner with the Dissemination and Outreach Core to share emerging knowledge and to provide parents with appropriate support and linkage to early intervention services. In summary, Project 3 leverages a representative sampling strategy in a diverse large city, a large sample size paired with dense longitudinal assessments, and a multidisciplinary team science approach, to characterize neurobehavioral trajectories in infants at identified genetic risk of autism.