Mount Sinai ECHO site for Perinatal Environment and Development Studies

西奈山 ECHO 围产期环境和发展研究网站

• 批准号: 10745103
• 负责人: KECIA Nicole CARROLL
• 金额: $ 496.09万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10745103
• 关键词: 20 year old; Adolescence; Affect; Age; Air Pollutants; Anxiety; Anxiety Disorders; Arousal; Attention; Award; Biogenesis; Central Nervous System; Chemicals; Child; Childhood; Color; Communities; Complex; Complex Mixtures; Conceptions; Data; Depressive disorder; Development; Diagnostic; Dimensions; Disease; Dose; Early identification; Enrollment; Environment; Environmental Risk Factor; Ethnic Origin; Etiology; Exposure to; Funding; Future; Genes; Geography; Grant; Health; Infrastructure; Intervention; Joints; Life; Life Cycle Stages; Link; Measures; Mediator; Mental Depression; Metals; Methodology; Methods; Micronutrients; Modeling; Mood Disorders; Mothers; Negative Valence; Nitrogen Dioxide; Nutrition Surveys; Nutritional; Obesity; Outcome; Ozone; Participant; Pathway interactions; Pattern; Perinatal; Persons; Pilot Projects; Policies; Population; Population Characteristics; Population Heterogeneity; Predisposition; Pregnancy; Pregnant Women; Problem behavior; Process; Psychopathology; Psychosocial Factor; Quality of life; Race; Regulation; Research; Research Domain Criteria; Research Personnel; Risk; Risk Factors; Risk Reduction; Role; Sample Size; Sampling; Science; Site; Statistical Methods; Stress; Symptoms; System; Toxin; Woman; Work; Youth; cognitive control; cognitive system; cohort; comorbidity; design; effective intervention; emotion regulation; environmental chemical; fine particles; health equity; health inequalities; high dimensionality; in utero; infancy; insight; lens; longitudinal design; maternal stress; neurobehavioral; novel; nutrition; perinatal environment; physical conditioning; prenatal; prenatal exposure; prenatal stress; prevent; programs; psychological stressor; recruit; remote sensing; resilience factor; respiratory; segregation; sex; social stressor; statistics; theories

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.

尽管产前暴露与不良的神经发育结果有关， 与终生精神病理学风险相关的早期神经行为因素的关联研究较少。 内化问题，最明显的是焦虑和抑郁症，影响着全球超过4亿人， 这些疾病在儿童期和向青春期过渡期间/之后急剧增加。识别早期风险 和弹性因素的内化障碍是至关重要的设计和实施有效的干预措施 以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 适应不良的发展从子宫内开始，中枢神经系统（CNS）依次发育， 不同功能域的特定过程和网络组件（例如，注意力、情绪调节） 因此，毒素的影响取决于接触时间和剂量。性别特异性效应 也存在。此外，孕妇和儿童接触复杂的化学品混合物， 共同变化并相互作用的社会压力源。暴露的差异部分驱动健康 不公平，因为有毒环境因素不是随机分布的，而是往往集中在 种族隔离的社区环境神经编程的复杂性还没有完全被 由于缺乏足够大的人群进行必要的纵向评估， 生物取样和种群多样性，以便能够共同考虑一些环境问题， 通过发展健康公平的透镜。在此，我们扩大我们的网站的工作与国家 ECHO计划阐明复杂混合物（环境空气污染物（AP），金属，应力和 营养暴露）开始在子宫内，在编程的内在问题，出现在 使用transdiagnosis框架。我们将评估跨诊断（TD）的维度特征， 选择研究领域标准（RDoC）：（1）负价系统，（2）认知系统，和（3） 唤醒/调节。我们建立在我们的团队通过3个获得ECHO机会开发的方法之上， 基础设施资助（OIF）赠款，这将使研究人员能够更充分地利用大型多样化 ECHO提供的样本、生命过程框架和暴露数据。我们将实施和传播 通过ECHO科学合作取得的方法学进展，包括：1）卫星遥感 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，以确定脆弱性窗口的特征，并增强检测复杂相互作用的能力 在化学品、压力、营养和易感性因素（例如，性别、种族/民族）;以及4） 评估ECHO队列数据的可组合性，以优化发现和复制。存在着复杂的 这里考虑的暴露也在规划许多健康结果中起作用（例如，围产期， 呼吸，肥胖，积极健康），我们的方法将广泛适用于国家ECHO计划。