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

基本信息

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
项目类别：
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

项目摘要

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.

尽管一系列产前暴露与不良神经发育结果有关，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，尤其是焦虑症和抑郁症，影响着全球超过 4 亿人这些疾病在儿童期和青春期过渡期间/之后急剧增加。识别早期风险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）按时间顺序发展；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，孕妇和儿童会接触复杂的化学混合物以及共同变化并相互作用的社会压力源。暴露差异在一定程度上促进健康不平等，因为有毒环境因素不是随机分布的，而是往往集中在隔离的有色人种社区。环境神经编程的复杂性尚未得到充分认识由于缺乏足够多的人口进行必要的纵向评估，生物采样和人口多样性，这将使我们能够共同考虑许多环境问题通过发展健康公平的视角来确定决定因素。在此，我们扩大了我们网站与国家的合作 ECHO 计划旨在阐明复杂混合物（环境空气污染物 (AP)、金属、压力和营养暴露）从子宫内开始，在对出现的内化问题进行编程时童年时期使用跨诊断框架。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，以及 (3) 唤醒/调节。我们的团队通过 3 次获得 ECHO 机会开发的方法为基础基础设施基金 (OIF) 拨款将使研究人员能够更充分地利用大量多样化的资金 ECHO 提供的样本、生命历程框架和暴露数据。我们将实施并传播通过协作 ECHO 科学取得的方法论进展包括：1) 卫星遥感 AP 重建过去暴露时间和剂量的模型； 2）新颖的高维混合统计； 3）统计方法来表征漏洞窗口并增强检测复杂交互的能力化学品、压力、营养和易感性因素（例如性别、种族/民族）； 4) 方法评估 ECHO 队列数据的组合性，以优化发现和复制。由于复杂本文考虑的暴露也在规划许多健康结果（例如，围产期、呼吸系统、肥胖、积极健康），我们的方法将广泛适用于国家 ECHO 计划。