Developmental origins and early detection of ADHD and dysregulatory psychopathology

项目概要： 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-在入学的尖端， 进入学前阶段。多动症和相关的行为和情绪失调问题往往不是 在学龄前被临床确诊。到那时，它们很难逆转。这一建议回应了文献中的呼吁 早期识别风险和发现早期生命机制，这些机制可以成为低风险但有效的目标， 早期生活干预，以防止这些问题的全面发生。为此，我们扩大了对现有产妇的研究- 婴儿队列，通过增加措施，时间点和老年人的结果。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形成，并且能够相对可靠地表征。关键 要检查的机制是：（a）生命早期的生物信号，集中在母体炎症和炎性反应， （b）妊娠期间的代谢物和生命的前三年中那些信号的变化轨迹;（B）脑 从出生到3岁的EEG测量所指示的发育（更低的成本和更容易临床应用 比MRI在这个阶段）;和（c）行为动力学在早期发育，这是鲜为人知的关于多动症 生命的前24个月的风险。炎症假说建立在PI发现的惊人的初步数据之上 在他们之前的工作中。EEG指标同样得到了初步证据的支持。行为数据也有 强有力的初步数据，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，然后与这些假设一起进行检查。 研究结果在手，一个综合发展模式将进行测试。如果成功的话，这项研究将为 通过识别特定的、可测量的和可逆的风险因素进行低风险但可能有效的早期干预，或 机制作为临床试验随访的候选者。

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.