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: 10376831
• 负责人: Theresa M Bastain
• 金额: $ 26.38万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10376831
• 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; Exposure to; Fetal Development; Functional disorder; Gene Expression; Gene Targeting; Genetic Predisposition to Disease; Hispanic; Hormonal; Hormones; Human; Hydrocortisone; Individual; Inflammatory; Interleukin-6; Language; Lead; Los Angeles; Major Depressive Disorder; Mediating; Mediator of activation protein; Mental Depression; Mental Health; Mental Health Services; Mental disorders; MicroRNAs; Morbidity - disease rate; Neurosecretory Systems; Norepinephrine; Not Hispanic or Latino; Pathway interactions; Persons; Policies; Population; Postpartum Depression; Postpartum Period; Predisposition; Pregnancy; Recording of previous events; Recurrence; Regulator Genes; Reproductive Periods; Risk; Risk Factors; Role; Social status; Stress; Stressful Event; Subgroup; Symptoms; Testing; Victimization; Woman; ambient air pollution; cohort; coping; critical period; cytokine; depressive symptoms; design; disadvantaged women; environmental stressor; fine particles; health care service; health disparity populations; improved; inflammatory marker; maternal depression; maternal risk; men; middle age; modifiable risk; neuroinflammation; perceived stress; preference; prenatal; prenatal exposure; psychosocial; psychosocial stressors; public health priorities; response; social; social disadvantage; social stressor; socioeconomic disadvantage

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.

项目摘要/摘要 - 项目1 抑郁症是全球与心理健康相关的发病率的主要原因，影响了约3亿 每年的人。抑郁症在女性中几乎是男性和多个人的两倍，而 社会心理风险因素与抑郁症的风险有关。美国的西班牙裔妇女有独特的风险 相对于非西班牙裔妇女的抑郁症和其他心理健康障碍的因素包括克服 与文化化以及心理保健服务的认识和利用相关的压力。 与交通相关的环境空气污染物可能是可修改的环境暴露，已知 不成比例地影响健康差异人群，并增加了与 沮丧。怀孕是旨在支持胎儿的动态生物学和骑马波动的时期 发展可能会增加对环境侮辱的敏感性以及对以后抑郁症的影响。尽管 越来越多的证据表明产前空气污染对最初几个月的抑郁症状的影响 产后，没有关于在这个关键时期是否会增加长期暴露的研究 造物抑郁症的风险。了解介导下游影响的生物学机制 环境暴露可能会导致治疗方法改善和相关发病率的降低 抑郁。作为基因表达的主要调节剂，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介体。 miRNA调节许多细胞过程， 包括神经内分泌和炎症途径在抑郁病理生理中很重要。我们将 研究这些机制和以下特定目的在前四年的500名女性中 马德雷斯怀孕队列 - 持续的主要是西班牙裔，社会经济 - 洛杉矶城市的弱势妇女。我们将（1）调查产前暴露与 产后最初四年，与交通相关的区域空气污染与母体抑郁症的症状 并检查这些关联是否因产前心理压力源和培养因素而变化； （2） 评估产后2和4年之间在产前空气污染之间有持续的反应 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（IL-6 和CRP）已知与抑郁有关； （3）确定神经内分泌和 在前四个的产妇抑郁症中，与炎症相关的miRNA在产前污染相关的关联中 产后多年，并测试它们是否介导产前空气污染与孕产妇之间的关联 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改善 减少健康差异人群中抑郁症的政策和治疗方法。