Predicting risk and resilience in ASD through social visual engagement

本应用程序建立在我们实验室最近的研究基础上，我们在实验室中收集了数据，从 生命的头两个月，来自自闭症谱系障碍(ASD)的高危婴儿。跟随 36个月时的确证诊断，对ASD阳性婴儿的分析显示，当观察 接近照顾者，从至少2个月大开始，患有自闭症的婴儿遵循显著不同的 典型同龄人的发展轨迹，对他人眼睛的注视减少，对他人的注视增加 身体区域和对象区域。他们对照顾者的视觉注视测量的纵向变化很高 与24个月后临床结局的严重程度相关。此外，仅根据在 生命的前6个月，测量他们看着别人的眼睛和身体的发育变化速度 预测性诊断分型具有较高的敏感性和特异性。据我们所知，这些是 现存文献中已知的最早的ASD指标，并标志着在推进我们的 对ASD发病机制的认识。它们还推动了我们的努力，使 ASD的早期诊断--这是促进最佳长期预后的关键因素。 本应用将在这些发现的基础上研究社会视觉的发展概况 参与度作为风险指数(目标1)；作为积极结果的概况(目标2)；以及作为治疗的预测因素 早期干预反应(目标3)。330名婴儿将参加这一项目，包括 自闭症儿童的婴儿兄弟姐妹是发展成ASD的高危人群(HR-ASD，N=230)； 无自闭症家族史的发育迟缓高危婴儿(HR-DD，N=50)；儿童 发育延迟的风险较低，预计为典型发育(LR-TDX，N=50)。数据将是 纵向和前瞻性收集，从出生第一个月开始，并进行确认性诊断 在36个月时进行评估。这个项目直接解决了自闭症患者的几个理想目标 第四，由NIH机构间自闭症协调委员会提出，重点是识别早期风险； 发育发病机制的措施；治疗和结果的预后指标。

The present application builds on recent research in our laboratory in which we collected data, beginning in the first 2 months of life, from infants at high-risk for autism spectrum disorder (ASD). Following confirmatory diagnosis at 36 months, analyses of ASD-positive infants revealed that when looking at an approaching caregiver, from at least 2 months of age, infants with ASD follow a significantly different developmental trajectory from typical peers, with decline in fixation on others' eyes and increased fixation on body and object areas. Longitudinal change in measures of their visual fixation to caregivers was highly correlated with severity of clinical outcome at 24 months. In addition, based only on data collected in the first 6 months of life, measures of their developmental rate of change in looking at others' eyes and bodies predicted diagnostic classification with high sensitivity and specificity. To our knowledge, these are the eariiest known indicators of ASD in the extant literature and mark crucial first steps in advancing our understanding of the developmental pathogenesis of ASD. They also advance our efforts to enable the eariiest possible diagnostic identification of ASD-a critical factor in promoting optimal long-term outcome. The present application will build on these findings to study developmental profiles of social visual engagement as risk indices (Aim 1); as profiles for positive outcome (Aim 2); and as predictors of treatment response in eariy intervention (Aim 3). A cohort of 330 infants will be enrolled in this project, consisting of infant siblings of children with autism who are at High Risk for developing an ASD (HR-ASD, N=230); infants at High Risk for Developmental Delays without familial history of ASD (HR-DD, N=50); and children at Low Risk of developmental delays, with Typical Development expected (LR-TDx, N=50). Data will be collected longitudinally and prospectively, beginning in the first month of life, with confirmatory diagnostic assessment at 36 months. This project directly addresses several of the aspirational goals for autism set forth by the NIH Interagency Autism Coordinating Committee, with emphasis on identification of eariy risk; measures of developmental pathogenesis; and prognostic indicators for treatment and outcome.