Mount Sinai ECHO site for Perinatal Environment and Development Studies

尽管一系列产前暴露与不利的神经发育结果有关， 与早期神经行为因素相关的终生精神病理风险的相关性研究较少。 内在化问题，尤其是焦虑和抑郁障碍，影响着全球4亿人 这些障碍在儿童时期和过渡到青春期期间/之后急剧上升。识别早期风险 而内化障碍的弹性因素对于设计和实施有效的干预措施至关重要 减轻他们的健康负担。环境、基因、性别和生命阶段之间的相互作用影响正常和 不适应的发展。从子宫开始，中枢神经系统(CNS)按顺序发育， 不同功能域的特定过程和网络组件(例如，注意力、情绪调节) 按时间顺序发展；因此，毒素的影响取决于暴露时间和剂量。特定性别的影响 也是存在的。此外，孕妇和儿童暴露在复杂的化学品混合物中以及 共同变化并相互影响的社会压力源。暴露的差异在一定程度上推动了健康 不平等是因为有毒环境因素不是随机分布的，而往往集中在 隔离的有色人种社区。环境神经编程的复杂性还没有完全 由于缺乏足够大的人口和必要的纵向评估， 生物抽样和种群多样性，使联合审议若干环境问题成为可能 通过发展健康公平的视角确定决定因素。在此，我们扩大了我们网站的工作与国家 ECHO程序，以阐明复杂混合物(环境空气污染物(AP)、金属、压力和 营养暴露)，从子宫开始，到内化出现的问题的编程 儿童时期使用一个跨诊断框架。我们将评估跨诊断(TD)维度特征 选择研究领域标准(RDoC)：(1)负价系统，(2)认知系统，(3) 觉醒/调节。我们以我们的团队通过3个获奖的Echo机会开发的方法为基础 基础设施资助(OIF)赠款，使研究人员能够更充分地利用 Echo提供的样本、生命历程框架和暴露数据。我们将实施和传播 通过协作回波科学取得的方法学进展，包括：1)卫星遥感AP 重建过去暴露时间和剂量的模型；2)新的高维混合统计；3) 统计方法，用于表征漏洞窗口并增强检测复杂交互作用的能力 在化学品中，压力、营养和易感因素(例如，性别、种族/族裔)；以及4)方法 评估回声队列数据的可组合性，以优化发现和复制。作为一个复杂的 在此考虑的暴露也在规划若干健康结果(例如，围产期， 呼吸、肥胖、阳性健康)，我们的方法将广泛适用于国家ECHO计划。

Although a range of prenatal exposures have been linked to adverse neurodevelopmental outcomes, associations with early neurobehavioral factors related to lifetime psychopathology risk are less well studied. Internalizing problems, most notably anxiety and depressive disorders, affect >400 million people globally with a sharp rise in these disorders in childhood and during/after the transition to adolescence. Identifying early risk and resiliency factors for internalizing disorders is critical to designing and implementing effective interventions to lessen their health burden. Interactions among environment, genes, sex, and life stage influence normal and maladaptive development. Starting in utero, the central nervous system (CNS) develops sequentially, with specific processes and network components of distinct functional domains (e.g., attention, emotion regulation) developing in a timed order; thus, effects of toxins depend on exposure timing as well as dose. Sex-specific effects also exist. Moreover, pregnant women and children are exposed to complex mixtures of chemicals as well as social stressors that co-vary and interact with each other. Differences in exposures in part drive health inequities because toxic environmental factors are not randomly distributed, but are often concentrated in segregated communities of color. The complexity in environmental neuroprogramming has not been fully assessed due to a lack of sufficiently large populations with the requisite longitudinal assessments, biosampling, and population diversity that would enable joint consideration of a number of environmental determinants through a developmental health equity lens. Herein, we expand our site's work with the national ECHO program to elucidate the role of complex mixtures (ambient air pollutants (APs), metals, stress, and nutritional exposures) starting in utero, in the programming of internalizing problems that emerge over childhood using a transdiagnostic framework. We will assess transdiagnostic (TD) dimensional features across select Research Domain Criteria (RDoC): (1) negative valence systems, (2) cognitive systems, and (3) arousal/regulation. We build upon methods our team developed via 3 awarded ECHO Opportunity for Infrastructure Funding (OIF) grants that will allow researchers to more fully capitalize on the large diverse sample, life course framework, and exposure data that ECHO provides. We will implement and disseminate methodological advances through collaborative ECHO science including: 1) satellite remote sensing AP models that reconstructpast exposure timing and dose; 2) novel high dimensional mixture statistics; 3) statistical methods to characterize windows of vulnerability and enhance power to detect complex interactions among chemicals, stress, nutrition and susceptibility factors (e.g., sex, race/ethnicity); and 4) methods to evaluate the combinability of ECHO cohort data to optimize discovery and replication. As the complex exposures considered herein also play a role in programming a number of health outcomes (e.g., perinatal, respiratory, obesity, positive health), our methods will be broadly applicable to the national ECHO program.