Project 1: Maternal Prenatal Exposure to Environmental and Psychosocial Stressors and Long-term Risk of Depression

项目 1：母亲产前暴露于环境和社会心理压力因素与长期抑郁风险

• 批准号: 10058750
• 负责人: Theresa M Bastain
• 金额: $ 34.31万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10058750
• 关键词: Acculturation; Adolescence; Affect; Air Pollutants; Air Pollution; Animals; Awareness; Biological; Brain; Cell physiology; Chronic stress; Communities; Country; Development; Disadvantaged; Disease; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Epinephrine; Event; Exposure to; Fetal Development; Functional disorder; Gene Expression; Gene Targeting; Genetic Predisposition to Disease; Hispanics; Hormonal; Hormones; Human; Hydrocortisone; Individual; Inflammatory; Interleukin-6; Language; Lead; Life; Los Angeles; Major Depressive Disorder; Mediating; Mediator of activation protein; Mental Depression; Mental Health; Mental disorders; MicroRNAs; Morbidity - disease rate; Neurosecretory Systems; Norepinephrine; Not Hispanic or Latino; Pathway interactions; Policies; Population; Postpartum Depression; Postpartum Period; Predisposition; Pregnancy; Recording of previous events; Recurrence; Regulator Genes; Reproductive Periods; Risk; Risk Factors; Role; Social status; Stress; Subgroup; Symptoms; Testing; Victimization; Woman; ambient air pollution; cohort; coping; critical period; cytokine; depressive symptoms; design; environmental stressor; health care service; health disparity; improved; inflammatory marker; maternal depression; maternal risk; men; middle age; modifiable risk; neuroinflammation; perceived stress; preference; prenatal; prenatal exposure; psychosocial; public health priorities; response; social; social disadvantage; social stressor; socioeconomic disadvantage; stressor

PROJECT SUMMARY/ABSTRACT--PROJECT 1 Depression is the leading cause of mental health-related morbidity worldwide, affecting approximately 300 million people annually. Depression is nearly twice as prevalent among women than men and multiple individual and psychosocial risk factors are associated with risk of depression. Hispanic women in the US have unique risk factors for depression and other mental health disorders relative to non-Hispanic women including overcoming stress associated with acculturation as well as lower awareness and utilization of mental health care services. Traffic-related and ambient air pollutants are potentially modifiable environmental exposures that are known to disproportionately impact health disparity populations and have increasingly been implicated in risk of depression. Pregnancy is a period of dynamic biological and hormonal fluctuations designed to support fetal development that may increase susceptibility to environmental insults and effects on later depression. Despite growing evidence of the impact of prenatal air pollution on depressive symptoms in the first few months postpartum, there have been no studies on whether exposures during this critical period may increase long-term risk of maternal depression. Understanding biological mechanisms that mediate downstream effects of environmental exposures may lead to improved treatment approaches and reductions in morbidity associated with depression. As primary regulators of gene expression, epigenetic mechanisms, such as microRNA (miRNA), may be important mediators of air pollution effects on depression. MiRNA regulate numerous cellular processes, including neuroendocrine and inflammatory pathways important in depression pathophysiology. We will investigate these mechanisms and the following specific aims in 500 women in the first four postpartum years in the MADRES pregnancy cohort—an ongoing cohort of predominantly Hispanic, socioeconomically- disadvantaged women in urban Los Angeles. We will (1) investigate the association of prenatal exposures to traffic-related and regional air pollution with symptoms of maternal depression in the first four years postpartum and examine whether these associations vary by prenatal psychosocial stressors and acculturation factors; (2) evaluate whether there is a sustained response at 2 and 4 years postpartum between prenatal air pollution exposures and neuroendocrine (cortisol, norepinephrine and epinephrine) and pro-inflammatory markers (IL-6 and CRP) known to be associated with depression; and (3) determine the role of neuroendocrine and inflammatory-related miRNA in prenatal air pollution-related associations in maternal depression in the first four years postpartum and test whether they mediate associations between prenatal air pollution and maternal depression as well as examine the functional relevance of these miRNA. Results from this study may improve policy and treatment approaches to reduce the burden of depression among health disparity populations.

项目概要/摘要——项目 1 抑郁症是全球心理健康相关发病率的主要原因，影响约 3 亿人 人每年。女性抑郁症患病率几乎是男性的两倍，而且多个个体和群体 心理社会风险因素与抑郁症风险相关。美国的西班牙裔女性面临独特的风险 与非西班牙裔女性相关的抑郁症和其他精神健康障碍的因素，包括克服 与文化适应相关的压力以及对精神卫生保健服务的认识和利用较低。 与交通相关的污染物和环境空气污染物是潜在可改变的环境暴露，已知 对健康差异人口的影响不成比例，并且越来越多地涉及以下风险： 沮丧。怀孕是一个生物和荷尔蒙动态波动的时期，旨在支持胎儿 可能会增加对环境损害的敏感性以及对以后抑郁症的影响的发展。尽管 越来越多的证据表明产前空气污染对头几个月的抑郁症状有影响 产后，尚无研究表明这一关键时期的暴露是否会长期增加 产妇抑郁症的风险。了解介导下游效应的生物机制 环境暴露可能会导致治疗方法的改进和相关发病率的降低 患有抑郁症。作为基因表达的主要调节因子，表观遗传机制，例如 microRNA (miRNA)， 可能是空气污染对抑郁症影响的重要调节因素。 miRNA 调节许多细胞过程， 包括在抑郁症病理生理学中重要的神经内分泌和炎症途径。我们将 对 500 名妇女在产后头四年内调查这些机制和以下具体目标 MADRES 怀孕队列——一个持续的队列，主要由西班牙裔、社会经济地位高的人组成 洛杉矶市区的弱势妇女。我们将 (1) 调查产前暴露与 与交通相关和区域性的空气污染，在产后头四年内出现孕产妇抑郁症状 并检查这些关联是否因产前社会心理压力源和文化适应因素而变化； (2) 评估产前空气污染在产后 2 年和 4 年是否存在持续反应 暴露和神经内分泌（皮质醇、去甲肾上腺素和肾上腺素）和促炎标记物（IL-6） 和 CRP）已知与抑郁症有关； (3) 确定神经内分泌和 产前空气污染相关 miRNA 与孕产妇抑郁症的关联 前四期 产后数年并测试它们是否介导产前空气污染与孕产妇之间的联系 抑郁症以及检查这些 miRNA 的功能相关性。这项研究的结果可能会有所改善 减轻健康差异人群抑郁症负担的政策和治疗方法。