Neurobehavioral Research on Infants at Risk for Language Delay and ASD

 描述(由申请人提供)：寻找神经发育障碍早期风险的生物标志物和行为迹象已成为临床研究的重要方向，以努力提高诊断并开发最有效的治疗和预防干预措施。在我们目前的获奖期内，我们发现了几个显著的差异 在ASD的高家族风险婴儿(定义为有一个年长的兄弟姐妹患有该疾病)和低风险对照组婴儿之间，包括脑电波的改变，言语和面部的非典型偏侧化，以及皮质连接性降低，所有这些都可能作为早期风险标记。这些差异不仅在生命的第一年被识别出来，他们的发展轨迹也是不典型的；这一发现似乎是自闭症风险的标志。我们的发现提出了一些重要的问题，即这些风险标记物是否适用于后来被诊断为ASD的其他婴儿，特别是来自普通人群的婴儿，以及它们是否也可能作为其他相关疾病的风险标记物，特别是语言和社交沟通延迟。在下一个获奖期，我们通过增加一组在12个月时未能通过发育筛查(CSBS)的婴儿来解决这些问题。这一组将从普通儿科实践中提取，并将在12-14个月以及18、24和36个月时进行一系列电生理和行为测量，将其与高危婴儿兄弟姐妹和低风险对照进行比较，届时将评估诊断结果。该项目将解决两个具体目标。首先，神经和行为风险标记物(及其发育轨迹)区分ASD家族风险婴儿和低风险对照婴儿是否基于早期行为扩展到风险婴儿 在为期12个月的筛查仪器上检测到的差异？我们假设一些风险标记物将在两个高危人群中共享，尽管对于筛查组来说，这可能只适用于具有临床结果并显示不同发育轨迹的婴儿。其他风险标记物可能是有家族风险的婴儿所独有的。我们的第二个目标是解决这个问题：我们确定的神经和行为风险标记物的发育特征是否只预测到以后的ASD诊断，或者它们是否延伸到36个月后的其他非ASD神经发育结果，包括语言或社交沟通延迟？我们假设，我们的一些风险标记物将在这些非ASD相关(和重叠的)临床结果中共享，而其他风险标记物将是ASD结果所独有的。随着在婴儿中识别有神经发育障碍风险的行为和神经标记物的研究取得进展，我们的研究必须从家庭风险扩展到普通人群，并评估几种诊断结果的风险标记物。通过这种方式，我们的目标是促进对共同和独特机制的了解，这些机制最终可以成为更有针对性的干预措施的重点，而此时有最大的可塑性和防止不利后果的机会。

 DESCRIPTION (provided by applicant): Searching for biomarkers and behavioral signs of early risk for neurodevelopmental disorders has emerged as an important line of clinical research in an effort to improve diagnosis and develop the most effective treatments and preventive interventions. In our current award period we identified several significant differences between infants at high familial risk for ASD (defined as having an older sibling with the disorder) and low risk control infants, including alterations in EEG, atypical lateralization for speech and faces, and reduced cortical connectivity all of which might serve as early risk markers. These differences were not only identified during the first year of life, their developmental trajectories were also atypical; a finding that appears to be a hallmark of risk for ASD. Our findings open up important questions about whether these risk markers extend to other infants later diagnosed with ASD, particularly infants from the general population, and whether they might also serve as risk markers for other related disorders, particularly language and social communication delay. In the next award period we address these questions by adding a new group of infants who fail a developmental screener (the CSBS) at 12 months. This group will be drawn from general pediatric practices, and will be compared to high-risk infant siblings and low risk controls on a battery of electrophysiological and behavioral measures that will be administered at 12-14 months, and again at 18, 24 and 36 months, at which time diagnostic outcomes will be evaluated. The project will address two specific aims. First, Do neural and behavioral risk markers (and their developmental trajectories) that distinguish infants at familial risk for ASD from low risk controls extend to infants at risk based on early behavioral differences detected on a 12-month screening instrument? We hypothesize that some risk markers will be shared across both high-risk groups, though for the screened group this may only hold for infants with clinical outcomes and show different developmental trajectories. Other risk markers may be unique to infants at familial risk. Our second aim addresses the question: Do the developmental profiles of neural and behavioral risk markers we identify predict only to later diagnoses of ASD or do they extend to other non-ASD neurodevelopmental outcomes at 36 months, including language or social communication delay? We hypothesize that some of our risk markers will be shared across these non-ASD related (and overlapping) clinical outcomes, while others will be unique to ASD outcomes. As research progresses on identifying behavioral and neural markers in infants that are at risk for neurodevelopment disorders, it is critical that we extend our research beyond familial risk to the general population and to evaluate risk markers across several diagnostic outcomes. In this way our goal is to advance knowledge of the shared and unique mechanisms that can ultimately be the focus of more targeted interventions at a time when there is greatest plasticity and opportunity for preventing adverse outcomes.