Developmental origins and early detection of ADHD and dysregulatory psychopathology

ADHD 和失调性精神病理学的发育起源和早期发现

• 批准号: 10320345
• 负责人: JOEL T NIGG
• 金额: $ 72.2万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10320345
• 关键词: 3 year old; 3-Dimensional; 5 year old; Affect; Affective; Age; Age-Months; Aggressive behavior; Algorithms; Anger; Area; Attention deficit hyperactivity disorder; Behavioral; Biological; Biological Markers; Birth; Blood Circulation; Brain; Breast Feeding; Child; Child Health; Clinical; Clinical Trials; Cognition; Data; Depressed mood; Development; Developmental Process; Diagnostic; Early Diagnosis; Early Intervention; Early identification; Electroencephalography; Emotional; Environmental Risk Factor; Fetal Development; Formulation; Fright; Frustration; Functional disorder; Future; Genetic; Goals; Hand; Healthcare; Impairment; Impulsivity; Individual; Infant; Inflammation; Inflammatory; Intercept; Intervention; Intervention Trial; Justice; Kynurenine; Learning; Life; Literature; Magnetic Resonance Imaging; Measurable; Measures; Mediating; Mental Health; Modeling; Nursery Schools; Outcome; Parents; Pathway interactions; Phenotype; Physiological; Pregnancy; Pregnancy Trimesters; Preschool Child; Program Development; Psychopathology; Regulation; Risk; Risk Factors; Risk Marker; Role; School-Age Population; Schools; Second Pregnancy Trimester; Serotonin; Shapes; Signal Transduction; Socialization; Symptoms; System; Testing; Third Pregnancy Trimester; Time; Toddler; Tryptophan; Up-Regulation; Weather; Woman; Work; base; behavioral outcome; caregiving; clinical application; clinical candidate; clinical risk; cohort; cost; early childhood; emotion dysregulation; emotion regulation; executive function; experimental study; family burden; fetal; follow-up; inattention; indexing; interest; negative affect; offspring; prenatal; prevent; prospective; relating to nervous system; sound; systemic inflammatory response; teacher

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.

项目概要： 该提案的目标是确定 ADHD 症状以及相关行为和行为的早期生命预测因子。 为此，我们对孩子从出生前到 4.5 岁——即将入学的年龄进行跟踪调查。 到了学龄前阶段，多动症和相关的行为和情绪失调问题通常不会出现。 到了学龄前，这一建议就很难被扭转了。 用于早期识别风险并发现早期生命机制，这些机制可以成为低风险但有效的目标 早期生命干预以防止这些问题的全面发生。 通过添加测量值、时间点和较年长的结果，我们将队列从幼儿期扩展到了婴儿期。 学龄前时期，精神病理学已经开始形成并能够相对可靠地表征。 要检查的机制是 (a) 生命早期的生物信号，重点是母体炎症和血清素能 怀孕期间的代谢物以及生命前三年这些信号的变化轨迹（b）大脑； 从出生到 3 岁的脑电图测量指标的发育（成本更低且更容易临床应用） (c) 早期护理中的行为动态，而关于多动症，人们对此知之甚少 炎症假说建立在 PI 发现的惊人初步数据的基础上。 在他们之前的工作中，脑电图指标也得到了初步证据的支持。 强有力的初步数据，并建立在多个理论家关于早期情绪调节在 基线（拦截）和变化（轨迹）的后续风险。 将检查措施以帮助评估在开发过程中特定领域或分析水平何时是最重要的 这些假设中的每一个都以独立的方式进行检验，然后与其他假设一起检验。 现有的研究结果将测试综合发展模型，如果成功，该研究将为人类开辟新的方向。 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 作为临床试验后续候选者的机制。