Predicting risk and resilience in ASD through social visual engagement

本申请建立在我们实验室的最新研究基础上，我们在实验室中收集了数据，从2005年开始， 出生后头两个月，来自自闭症谱系障碍（ASD）高危婴儿。以下 在36个月时确诊，对ASD阳性婴儿的分析显示， 接近照顾者，从至少2个月大，ASD婴儿遵循显着不同的 从典型的同龄人的发展轨迹，与其他人的眼睛固定下降，并增加固定 身体和物体区域。他们对照顾者的视觉注视测量的纵向变化非常高， 与24个月时临床结局的严重程度相关。此外，仅根据 出生后的前6个月，测量他们在看别人的眼睛和身体时的发展变化率。 预测诊断分类具有高灵敏度和特异性。据我们所知， 现存文献中最早已知的自闭症谱系障碍指标，标志着推进我们的研究迈出了关键的第一步 了解ASD的发育发病机制。它们还推动我们的努力， 尽早诊断出ASD是促进最佳长期结果的关键因素。 本申请将基于这些发现来研究社交视觉的发展概况。 参与作为风险指数（目标1）;作为积极结局的特征（目标2）;以及作为治疗的预测因素 早期干预的反应（目标3）。该项目将招募330名婴儿，包括 患有自闭症的儿童的婴儿兄弟姐妹处于发展ASD的高风险（HR-ASD，N=230）; 无ASD家族史的发育迟缓高风险婴儿（HR-DD，N=50）; 发育迟缓风险低，预期为典型发育（LR-TDx，N=50）。数据将 从出生后第一个月开始纵向前瞻性收集，并进行确证性诊断。 36个月的评估。这个项目直接解决了自闭症的几个理想目标 由NIH机构间自闭症协调委员会提出，重点是早期风险的识别; 发育发病机制的测量;以及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.