Air pollution exposure and emerging depression risk: Testing the role of peripheral inflammatory cytokines during adolescence

项目摘要 抑郁症是一种普遍的、反复发作的慢性疾病，大约21%的人会受到影响 在他们的一生中，并与严重的损害和相当大的公共卫生负担有关。 为了阐明导致抑郁症状发生和发展的因素，目前的项目 旨在测试外周细胞因子的变化作为空气与空气之间联系的生物中介的作用 青少年的污染暴露和抑郁症状。具体而言，当前项目将利用 120名青少年的前瞻性纵向研究，以检查空气污染暴露与 随后的抑郁症状和免疫标志物的轨迹。通过直接评估 理论化的生物介体，重复评估的使用，以及复杂的空气污染暴露 据估计，我们将克服过去的障碍取得进展，并严格测试一个假定的风险调解人。 利用储存的血液样本作为正在进行的关于抑郁症社会贡献者的父母研究的一部分 在青春期，这项工作将表征研究参与者在多个领域的空气污染暴露 时间尺度(目标1)，然后将用于确定空气污染之间的剂量-反应关系 以及6个月期间抑郁症状的轨迹(目标2)。最后，它将探测外周免疫 作为空气污染和抑郁症状之间假定中介的标志物，测试了相互竞争的模型 细胞因子(如促炎因子、Th-1和Th-2)来确定免疫标记物的特异性 去冒险。通过这种在方法上严格的方法，我们将准备好进行强有力的方向性测试 空气污染暴露与抑郁症状的关系及免疫学参数的确定 这可能会调解风险。在这样做的时候，这个项目的洞察力将为未来的假设提供关键的信息，以阐明 导致空气污染暴露对精神健康产生不良影响的生物和心理连锁效应 确定干预工作的新目标，并最终减轻相关的重大负担 患有抑郁症。

Project Summary Depression is a prevalent, recurrent, and frequently chronic disorder that affects approximately 21% of individuals in their lifetime and is associated with significant impairment and considerable public health burden. To elucidate factors that contribute to the onset and development of depressive symptoms, the current project seeks to test the role of alterations in peripheral cytokines as a biological mediator of associations between air pollution exposure and depressive symptoms in adolescents. Specifically, the current project will utilize a prospective longitudinal study of 120 adolescents to examine associations between air pollution exposure and subsequent trajectories of depressive symptoms and immune markers. Through the direct assessment of theorized biological mediators, use of repeated assessments, and creation of sophisticated air pollution exposure estimates, we will overcome past roadblocks to progress and rigorously test a putative mediator of risk. Leveraging stored blood samples collected as part of an ongoing parent study of social contributors to depression during adolescence, this work will characterize air pollution exposure for study participants across multiple timescales (Aim 1), which will then be utilized to determine dose-response associations between air pollution and trajectories of depressive symptoms across a 6-month period (Aim 2). Lastly, it will probe peripheral immune markers as putative mediations between air pollution and depressive symptoms, testing competing models of cytokines (e.g., proinflammatory, Th-1, and Th-2) to determine the specificity of the immune markers in relation to risk. Through this methodologically rigorous approach, we will be poised to conduct strong tests of directional associations between air pollution exposure and depressive symptoms and to identify immunological parameters that may mediate risk. In doing so, insights from this project will critically inform future hypotheses to elucidate biological and psychological cascades that contribute to the adverse effects of air pollution exposure on mental health to identify novel targets for intervention efforts and ultimately reduce the significant burdens associated with depression.