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体征已成为临床研究的一条重要路线，旨在改善诊断并开发最有效的治疗和预防干预措施。在我们目前的奖励期间，我们确定了几个重大差异 在ASD的高家族风险婴儿（定义为有一个患有这种疾病的哥哥姐姐）和低风险对照婴儿之间，包括EEG的改变，语言和面部的非典型偏侧化，以及皮质连接减少，所有这些都可能作为早期风险标志。这些差异不仅在生命的第一年被发现，它们的发育轨迹也是非典型的;这一发现似乎是ASD风险的标志。我们的研究结果提出了一些重要的问题，即这些风险标志物是否延伸到后来诊断为ASD的其他婴儿，特别是普通人群中的婴儿，以及它们是否也可以作为其他相关疾病的风险标志物，特别是语言和社交延迟。在下一个奖励期，我们通过增加一组新的婴儿来解决这些问题，这些婴儿在12个月时没有通过发育筛查（CSBS）。该组将从一般儿科实践中抽取，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，与高风险婴儿兄弟姐妹和低风险对照进行比较，此时将评价诊断结果。该项目将针对两个具体目标。首先，区分ASD家族风险婴儿和低风险对照婴儿的神经和行为风险标志（及其发育轨迹）是否延伸到基于早期行为风险的婴儿？ 在12个月的筛查仪器上检测到的差异？我们假设两个高风险组的一些风险标志物是相同的，尽管对于筛查组来说，这可能只适用于具有临床结果的婴儿，并显示出不同的发育轨迹。其他风险标志物可能是唯一的婴儿在家族风险。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志物的发育特征是否仅预测ASD的后期诊断，或者它们是否扩展到36个月时的其他非ASD神经发育结果，包括语言或社交延迟？我们假设我们的一些风险标志物将在这些非ASD相关（和重叠）的临床结局中共享，而其他风险标志物将是ASD结局所独有的。随着研究在识别有神经发育障碍风险的婴儿中的行为和神经标志物方面的进展，我们将我们的研究从家族风险扩展到一般人群并评估几种诊断结果的风险标志物至关重要。通过这种方式，我们的目标是促进对共享和独特机制的了解，这些机制最终可以成为更有针对性的干预措施的重点，因为此时有最大的可塑性和预防不良后果的机会。

 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.