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

空气污染暴露和新出现的抑郁症风险：测试青春期外周炎症细胞因子的作用

• 批准号: 10526228
• 负责人: Erika M Manczak
• 金额: $ 23.57万
• 依托单位: UNIVERSITY OF DENVER (COLORADO SEMINARY)
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10526228
• 关键词: Address; Adolescence; Adolescent; Adverse effects; Affect; Air; Air Pollutants; Air Pollution; Area; Asthma; Automobile Driving; Biological; Biological Testing; Blood; Blood Banks; Blood specimen; Caliber; Cardiovascular Diseases; Censuses; Chronic Disease; Data; Development; Disease; Dose; Early identification; Environmental Exposure; Exposure to; Foundations; Future; Home; Immune; Immune signaling; Immunologic Markers; Immunologics; Impairment; Individual; Inflammation; Inflammation Mediators; Inflammatory; Inhalation; Intervention; Investigation; Knowledge; Lead; Link; Longitudinal prospective study; Major Depressive Disorder; Mediating; Mediation; Mediator of activation protein; Mental Depression; Mental Health; Methodology; Modeling; Observational Study; Ozone; Parents; Participant; Particulate Matter; Pathway interactions; Pattern; Peripheral; Pollution; Predisposition; Process; Production; Public Health; Recurrence; Research; Risk; Role; Schools; Signal Transduction; Specificity; Symptoms; Testing; Theoretical model; Therapeutic Intervention; Time; Uncertainty; Work; base; child depression; clinical biomarkers; cytokine; depressive symptoms; disability; disorder risk; fine particles; improved; inflammatory marker; insight; novel; physical conditioning; pre-clinical; prevent; psychologic; response; simulation; social; stem

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.

项目摘要 抑郁症是一种流行的、复发性的、经常慢性的疾病， 在其一生中，这些疾病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，本项目 试图测试外周细胞因子的改变作为空气和细胞因子之间联系的生物介质的作用。 污染暴露和青少年的抑郁症状。具体而言，本项目将利用 对120名青少年进行前瞻性纵向研究，以检查空气污染暴露与 抑郁症状和免疫标记的后续轨迹。通过直接评估 理论化的生物介质，重复评估的使用，以及复杂的空气污染暴露的创建 估计，我们将克服过去的障碍，取得进展，并严格测试假定的风险调解人。 利用储存的血液样本，作为正在进行的抑郁症社会贡献者父母研究的一部分 在青少年时期，这项工作将描述研究参与者在多个领域的空气污染暴露特征。 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 标记作为空气污染和抑郁症状之间的假定中介，测试竞争模型， 细胞因子（例如，促炎性细胞因子Th-1和Th-2），以确定与炎症相关的免疫标志物的特异性。 去冒险通过这种严格的方法，我们将准备进行强有力的测试， 空气污染暴露与抑郁症状之间的联系，并确定免疫参数 这可能会降低风险。在这样做的过程中，这个项目的见解将批判性地为未来的假设提供信息，以阐明 生物和心理级联反应，导致空气污染暴露对精神 确定新的干预目标，并最终减少相关的重大负担 抑郁症