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

项目概要/摘要-项目1 抑郁症是全世界与心理健康有关的发病率的主要原因，影响约3亿人 人每年。抑郁症在女性中的流行率几乎是男性的两倍， 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有独特的风险 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率较低。 与生物有关的和环境空气污染物是已知的潜在可改变的环境暴露， 不成比例地影响健康差距人口，并越来越多地涉及 萧条怀孕是一个动态的生物和激素波动的时期，旨在支持胎儿 可能会增加对环境伤害的敏感性，并对以后的抑郁症产生影响。尽管 越来越多的证据表明产前空气污染对头几个月抑郁症状的影响 产后，没有研究表明在这个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学机制 环境暴露可能导致治疗方法的改进和相关发病率的降低。 抑郁症作为基因表达的主要调节因子，表观遗传机制，如microRNA（miRNA）， 可能是空气污染对抑郁症影响的重要介质。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 在产后头四年对500名妇女调查这些机制和以下具体目标， MADRES妊娠队列-一个持续的队列，主要是西班牙裔，社会经济- 洛杉矶市区的弱势妇女。我们将（1）调查产前暴露与 与交通有关的和区域性的空气污染与产后头四年的母亲抑郁症状 并检查这些关联是否因产前心理社会压力和文化适应因素而异;（2） 评估是否有持续的反应，在产后2年和4年之间的产前空气污染 暴露和神经内分泌（皮质醇、去甲肾上腺素和肾上腺素）以及促炎标志物（IL-6 和CRP）已知与抑郁症有关;（3）确定神经内分泌和 产前空气污染相关的炎症相关miRNA与母亲抑郁症的前四个相关性 并测试它们是否介导产前空气污染与产妇死亡之间的关联。 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 政策和治疗方法，以减少健康差距人群中的抑郁症负担。

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.