Developmental origins and early detection of ADHD and dysregulatory psychopathology

项目总结： 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，儿童从出生前一直跟踪到4.5岁--在入学和 一直到学龄前阶段。ADHD和与行为和情绪失调相关的问题通常不是 直到学龄前都经过临床鉴定。到那时，它们很难逆转。这项建议回应了文献中的呼声。 用于更早地识别风险并发现可作为低风险但有效目标的早期生命机制 早期生活干预，防止这些问题的全面发作。为此，我们扩大了对现有母体的研究- 通过增加措施、时间点和较老的结果来进行婴儿队列。我们将队列从蹒跚学步的年龄段扩展到 学龄前时期，这一时期的精神病理学已经初具规模，并能够相对可靠地表现出特征。钥匙 要研究的机制是：(A)早期生命中的生物信号，重点是母体炎症和5-羟色胺能 怀孕期间的代谢物和生命头三年这些信号的变化轨迹；(B)大脑 通过脑电波测量从出生到3岁的发育(成本更低，更容易在临床上应用 (C)早期照料的行为动力学，对ADHD知之甚少 在生命的前24个月中的风险。炎症假说建立在PI发现的惊人的初步数据上 在他们之前的工作中。脑电指标也同样得到了初步证据的支持。行为数据还包括 强大的初步数据，并建立在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，然后与那些 有了现有的发现，将测试一种综合发展模式。如果这项研究成功，将为 低风险但潜在有效的早期干预，通过确定特定、可测量和可逆的风险因素或 作为临床试验后续研究的候选机制。

PROJECT SUMMARY: 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.