The Evolutionary Basis of the Developmental Course and Etiologies of Anxiety and Disruptive Behaviors during Early Adolescence

摘要/摘要：包括我们自己在内的越来越多的证据表明，在子宫内暴露于心理社会 压力与焦虑升高(ANX)和破坏性行为(DB)症状的风险有关。在这 应用程序，我们将在我们现有的暴露于和未暴露于超级风暴桑迪(SS)的儿童出生队列的基础上继续发展。 在子宫里。SS随机地给我们队列中的孕妇和她们的后代分配压力条件，给予 美国有一个独特的机会来进行准宫内应激实验.使用我们深层次的表型队列，我们 建议研究子宫内SS暴露是否调节出生后应激环境的影响， 放大(双击式加速模型)或屏蔽(应力接种模型)出生后的影响 强调ANX和DB的症状。我们将继续测量不同类型的产后压力(标准， 父母教养不良和COVID相关)，以检查产后应激源的大小、性质、时间和持续时间 影响这种症状的方向和影响。除了基于DSM的诊断结果，我们还 将利用NIMH RDoC并专注于负价和认知控制系统(NVS/CCS)，这将 能够以跨诊断的视角观察出生前和出生后应激相关的行为和大脑变化。 在我们之前的工作之后，我们还将检查行为表型的性别特定表现(更多 女孩的内化问题和男孩的更多外化问题)，并探索SES在 与行为上的个体差异相交。因为大脑是大脑的中枢调节器官 压力/适应和调节，我们将使用神经成像来评估大脑结构、功能和 在青春期前和青春期后的早期，使用我们队列中的一个子样本，研究边缘-额叶回路的连接性。我们的 队列从子宫内开始跟踪，并进行完整的后续评估(神经行为、临床和生物学 当他们进入青春期前/青春期(9-13岁)时，这种情况将继续下去，这是此类问题的风险高峰期， 性-二形性。具体地说，我们将：1)考察SS相关压力和出生后心理社会的影响 环境对临床和适应性神经行为轨迹的影响；2)研究产前SS应激和 出生后应激对NVS/CCS脑结局(结构和功能)的影响并评估NVS/CCS的程度 结构变化在产前SS暴露与儿童焦虑和DB症状之间起中介作用；3)发展 基于生物学和行为测量的青春期早期NVS/CCS结局预测模型 在子宫和/或儿童生命的第一个十年中获得。因为青春期前是发育的重要时期 ANX和DB的过渡和高风险，我们将在我们独特的临床和存储存储库的基础上构建 头发样本，并继续通过以下方式绘制儿童神经行为发育和精神病理风险图表 年龄在9-13岁之间。与神经成像一起研究神经机制，以 NVS/CCS和使用ABCD研究中的任务，我们的研究具有独特的地位来阐明 NVS/SSV中的胎儿程序和威胁敏感性调节焦虑和反应性攻击的风险。

Summary/Abstract: Accumulating evidence, including our own, indicates that in utero exposure to psychosocial stress is associated with risks for elevated anxiety (ANX) and disruptive behavior (DB) symptomatology. In this application, we will build on our existing birth cohort of children exposed and unexposed to Superstorm Sandy (SS) in utero. SS randomly “assigned” stressful conditions to pregnant women and their offspring in our cohort, giving us a unique opportunity to conduct a quasi-experiment of in utero stress. Using our deeply phenotyped cohort, we propose to investigate whether in utero SS exposure modulates the impact of the postnatal stressful environment, either amplifying (double-hit acceleration model) or shielding (stress inoculation model) the effects of postnatal stress on ANX and DB symptomatology. We will continue to measure different types of postnatal stress (normative, poor parenting, and COVID-related) to examine if magnitude, nature, timing and duration of the postnatal stressors influences the direction and impact on such symptomatology. As well as the DSM-based diagnostic outcomes, we will utilize the NIMH RDoC and focus on Negative Valence and Cognitive Control Systems (NVS/CCS), which will enable a transdiagnostic perspective of pre- and postnatal stress-related changes in behavior and the brain. Following our prior work, we will also examine sex-specific manifestations of the behavioral phenotypes (more internalizing problems in girls and more externalizing in boys) and explore the moderating role of SES when intersecting with individual differences in behaviors. As the brain is the central modulatory organ of stress/adaptation and regulation, we will use neuroimaging to assess changes in brain structure, function, and connectivity in limbic-frontal circuitry during early pre- and post-puberty, using a subsample of our cohort. Our cohort was followed from in utero, with completed follow-up assessments (neurobehavioral, clinical, and biological specimens), which will continue as they enter pre/puberty (ages 9-13), a time of peak risks for such problems and sex-dimorphism. Specifically, we will: 1) examine the effects of SS-related stress and the postnatal psychosocial environment on trajectories of clinical and adaptive neurobehaviors; 2) study the impact of prenatal SS stress and postnatal stress on NVS/CCS brain outcomes (structure and function) and evaluate the extent to which NVS/CCS structural changes mediate between prenatal SS-exposure and child anxiety and DB symptoms; and 3) develop predictive models for NVS/CCS outcomes in early adolescence based on biological and behavioral measures obtained in utero and/or the first decade of the child’s life. As pre/puberty is an important period of developmental transition and heightened risk for ANX and DB, we will build on our unique repository of both clinical and stored hair samples and continue to chart children’s neurobehavioral development and risk for psychopathology through ages 9-13. Together with the inclusion of neuroimaging to investigate neural mechanisms centered on the NVS/CCS and using tasks from the ABCD study, our study is uniquely positioned to elucidate the mechanisms of fetal programing and threat sensitivity in the NVS/SSV that modulate the risks for anxiety and reactive aggression.