Developmental origins and early detection of ADHD and dysregulatory psychopathology

项目总结(与家长奖不变) 这项建议的目标是确定ADHD症状的早期生活预测因子以及相关的行为和 情绪问题。为了做到这一点，对儿童从出生前到4.5岁--在上学的尖端--进行跟踪 进入并顺利进入学龄前阶段。ADHD及相关的行为和情绪问题 通常直到学龄期才能在临床上发现调节失调。到那时，它们很难逆转。这 该建议回应了文献中关于及早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爆发。至 为此，我们通过增加措施、时间点和较年长的母婴队列来扩大对现有母婴队列的研究 结果。我们将队列从蹒跚学步的年龄段扩展到学龄前阶段，那时精神病理学 初具规模，并能够相对可靠地表征。需要审查的主要机制有：(A) 早期生命中的生物信号，重点是孕期母体炎症和5-羟色胺能代谢产物 以及这些信号在生命的头三年中的变化轨迹；(B)大脑发育，由 EEG测量从出生到3岁(成本更低，在这个阶段比MRI更容易临床应用)； 和(C)早期照料的行为动力学，关于前24个月的ADHD风险知之甚少 几个月的生命。炎症假说建立在PI之前发现的惊人的初步数据上 工作。脑电指标也同样得到了初步证据的支持。行为数据也有很强的 初步数据和基于多个理论家关于早期情绪调节在 随之而来的风险是调节障碍、精神病和多动症。基线(拦截)和改变(轨迹) 将检查措施，以帮助评估开发中的特定领域或分析级别最多的时间 对随后的结果提供信息。这些假设中的每一个都是以独立的方式进行检查的，然后 有了这些发现，一种综合发展模式将得到测试。如果成功，这项研究将开始 低风险但潜在有效的早期干预的新方向，通过确定具体、可衡量和 可逆的危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.