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

项目 3：具有自闭症遗传风险的婴儿的发育轨迹

基本信息

批准号：
10698091
负责人：
DIMA AMSO
金额：
$ 106.19万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-06 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10698091
关键词：
Age Months Anxiety Attention Auditory Auditory area Autism Diagnosis Autonomic nervous system Behavior Therapy Behavioral Symptoms Brain Brain Stem Cities Classification Cognitive Communication Complex Computer Analysis Data Development Diagnosis Diagnostic Doctor of Philosophy Early Diagnosis Early Intervention Electroencephalography Ethnic Origin Evaluation Facial Expression Family Foundations Frequencies Future Genetic Genetic Risk Genetic Screening Gestational Age Goals Hypersensitivity Infant Intervention Knowledge Language Language Development Lead Life Locomotion Measures Motor Movement Musculoskeletal Equilibrium Neurophysiology - biologic function Newborn Infant Nonverbal Communication Outcome Parents Pathway interactions Pattern Perception Phenotype Play Process Race Relative Risks Risk Role Sample Size Sampling Science Self Efficacy Sensory Shapes Social Development Statistical Data Interpretation Statistical Models Stimulus System Techniques Temperament Vision Visual Visual Cortex Visual attention autism spectrum disorder cohort contextual factors design experience fetal gaze gene environment interaction grasp heart rate variability high risk individuals with autism spectrum disorder infant outcome information gathering innovation joint attention knowledge integration multidisciplinary multisensory neural neurobehavioral neurodevelopment operation outreach postnatal prospective resilience response risk variant service intervention sex sleep quality social social communication sound sustained attention

项目摘要

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.

项目概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异。这提前为发育轨迹表明的婴儿提供了症状前干预的机会早期偏离典型模式。据我们所知，之前没有研究检验过这种组合是否基因筛查和早期神经发育途径的精确轨迹可能有助于更早地对已确定患有自闭症遗传风险的婴儿进行诊断。基于这一重大知识差距，项目 3 建议当婴儿 3 至 15 个月大时，每 3 个月纵向评估一次神经发育。 PROGRESS 队列将包括 N = 300 名婴儿的最终样本：已识别遗传风险中 N = 200 (IGR) 组和 N = 100 胎龄、性别、种族/民族、语言和邮政编码匹配的对照婴儿没有确定的遗传风险（非 IGR）。我们将检查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、多感官、运动）、社会发展和语言/交流（目标 3），以确定是否以及何时这些轨迹因遗传风险群体而异。位于 PROGRESS 中心使我们能够结合多个分析层面的措施（目标 4），包括遗传风险（项目 1）、亲代经验和自我效能（项目 2）、神经发育轨迹（项目 3）和诊断结果（评估核心）。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）阐明发育机制并实现早期诊断已确定患有自闭症遗传风险的婴儿。我们将与传播和外展核心合作，分享新兴知识，并为家长提供适当的支持以及与早期干预服务的联系。总之，项目 3 利用了多元化大城市中的代表性抽样策略、大样本量结合密集的纵向评估和多学科团队科学方法，来表征已确定患有自闭症遗传风险的婴儿的神经行为轨迹。