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

项目摘要/摘要--项目1 抑郁症是全球心理健康相关疾病的主要原因，影响了大约3亿人。 每年都有人。抑郁症在女性中的流行程度几乎是男性的两倍，而且有多个个体和 心理社会风险因素与抑郁风险相关。美国的西班牙裔女性有独特的风险 与非西班牙裔妇女相关的抑郁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程度较低。 与交通相关的和环境空气污染物是潜在的可改变的环境暴露，已知 对健康差距人群造成不成比例的影响，并越来越多地被卷入 抑郁症。怀孕是一段动态的生物和荷尔蒙波动的时期，旨在支持胎儿 可能会增加对环境侮辱的敏感性，并对后来的抑郁症产生影响的发展。尽管 越来越多的证据表明，出生前几个月空气污染对抑郁症状的影响 产后，还没有关于在这一关键时期暴露是否会增加长期风险的研究 母亲抑郁的风险。了解调节蛋白下游效应的生物学机制 环境暴露可能会改善治疗方法并减少相关的发病率 患有抑郁症。作为基因表达的主要调节因素，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中介因素。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通路。我们会 年对500名产后4年的500名妇女进行了这些机制和以下具体目标的调查 Madres怀孕队列--这是一个持续的队列，主要是西语裔，具有社会经济意义-- 洛杉矶市区的弱势女性。我们将(1)调查产前暴露与 与交通相关的区域性空气污染与产后前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应激源和文化适应因素而异；(2) 评估产前空气污染对产后2年和4年是否有持续反应 暴露与神经内分泌(皮质醇、去甲肾上腺素和肾上腺素)和促炎标志物(IL-6)的关系 和C反应蛋白)已知与抑郁有关；和(3)确定神经内分泌和 前四组孕妇抑郁与产前空气污染相关的炎性miRNA相关性 并测试它们是否在产前空气污染和产妇之间的关系中起中介作用。 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 减少健康差距人群中抑郁负担的政策和治疗方法。

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.