Developmental origins and early detection of ADHD and dysregulatory psychopathology

项目摘要（与母公司奖无变化） 这项提案的目标是确定ADHD症状的早期预测因素以及相关的行为和 情绪问题为了做到这一点，儿童从出生前一直被跟踪到4.5岁--在学校的尖端 进入并顺利进入学前阶段。注意力缺陷多动障碍及相关的行为和情绪问题 调节异常通常在学龄前才被临床发现。到那时，它们很难逆转。这 该提案回应了文献中关于早期识别风险和发现早期生命机制的呼吁 这可以成为低风险但有效的早期生活干预的目标，以防止这些问题的全面发生。到 这样做，我们扩大了现有的母婴队列的研究，增加了措施，时间点，和一个老年人， 结果。我们将队列从蹒跚学步的年龄扩展到学龄前时期，此时精神病理学已经 开始成形，并能够相对可靠地表征。需要审查的主要机制有：（a） 生命早期的生物信号，主要关注妊娠期间的母体炎症和孕酮代谢物 以及这些信号在生命前三年的变化轨迹;（B）大脑发育，以指数表示 从出生到3岁的EEG测量（成本较低，在此阶段比MRI更容易临床应用）; 和（c）早期发育的行为动力学，关于前24个月的ADHD风险知之甚少 几个月的生活。炎症假说建立在PI在其先前研究中发现的惊人的初步数据基础上。 工作EEG指标同样得到了初步证据的支持。行为数据也有很强的 初步数据，并建立在多个理论家的建议，早期情绪调节的作用， 随后出现精神病理失调和多动症的风险。基线（截距）和变化（轨迹） 将检查一些措施，以帮助评估在开发过程中，某个特定领域或分析级别最 为后续结果提供信息。这些假设中的每一个都是以独立的方式进行检查的，然后 有了这些研究结果，将测试一个综合发展模型。如果成功，研究将开始 低风险但可能有效的早期干预的新方向，通过确定具体的，可衡量的， 可逆的风险因素或机制作为临床试验随访的候选者。

Project Summary (No change from Parent Award) The goal of this proposal is to identify early life predictors of symptoms of ADHD and associated behavioral and emotional problems. To do so children are followed from before birth to 4.5 years of age—on the cusp of school entry and well into the preschool period. ADHD and related problems with behavioral and emotional dysregulation are often not clinically identified until school age. By that point they are difficult to reverse. This proposal answers calls in the literature for earlier identification of risk and for discovery of early life mechanisms that can be targets for low-risk yet effective early life intervention to prevent the full onset of these problems. To do so we expand the study of an existing maternal-infant cohort by adding measures, time points, and an older outcome. We extend the cohort from the toddler years into the preschool period when psychopathology has begun to take shape and be able to be relatively reliably characterized. Key mechanisms to be examined are (a) biological signals in early life, focused on maternal inflammation and serotonergic metabolites during pregnancy and the trajectory of change in those signals in the first three years of life; (b) brain development as indexed by EEG measures from birth to age 3 years (lower cost and more readily clinically applicable than MRI at this stage); and (c) behavioral dynamics in early caregiving, about which little is known regarding ADHD risk in the first 24 months of life. The inflammation hypothesis builds on striking preliminary data uncovered by the PI's in their prior work. The EEG metrics likewise are supported by preliminary evidence. The behavioral data also have strong preliminary data and build on multiple theorists' proposals about the role of early emotional regulation in subsequent risk for dysregulatory psychopathology and ADHD. Both baseline (intercept) and change (trajectory) measures will be examined to help evaluate when in development a particular domain or level of analysis is most informative to subsequent outcome. Each of these hypotheses is examined in stand-alone fashion, and then with those findings in hand, an integrative developmental model will be tested. If successful the study will open new directions for low-risk yet potentially effective early intervention by identifying specific, measurable, and reversible risk factors or mechanisms as candidates for clinical trial follow up.