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: 10673057
• 负责人: Erika M Manczak
• 金额: $ 18.92万
• 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/10673057
• 关键词: Address; Adolescence; Adolescent; Adverse effects; Affect; Air; Air Pollutants; Air Pollution; Area; Asthma; Automobile Driving; Biological; Biological Markers; Biological Testing; Blood; Blood Banks; Blood specimen; Cardiovascular Diseases; Censuses; Chronic Disease; Data; Development; Diameter; Disease; Dose; Early identification; Environmental Exposure; Exposure to; Future; Home; Immune; Immune signaling; Immunologic Markers; Immunologics; Impairment; Individual; Inflammation; Inflammation Mediators; Inflammatory; Inhalation; Intervention; Investigation; Knowledge; Link; Major Depressive Disorder; Mediating; Mediation; Mediator; 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; Vulnerable Populations; Work; child depression; cytokine; depressive symptoms; disability; disorder risk; fine particles; improved; inflammatory marker; insight; longitudinal, prospective study; novel; physical conditioning; pre-clinical; prevent; psychologic; response; simulation; social; stem; theories

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.

项目概要 抑郁症是一种普遍存在、反复发作且常常是慢性的疾病，影响约 21% 的人 个人一生中都会受到影响，并与严重的损害和相当大的公共健康负担有关。 为了阐明导致抑郁症状发生和发展的因素，当前的项目 旨在测试外周细胞因子的变化作为空气之间关联的生物介质的作用 青少年的污染暴露和抑郁症状。具体来说，当前项目将利用 对 120 名青少年进行的前瞻性纵向研究，探讨空气污染暴露与 抑郁症状和免疫标志物的后续轨迹。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 据估计，我们将克服过去的进展障碍，并严格测试假定的风险中介。 利用作为正在进行的抑郁症社会因素家长研究的一部分收集的储存的血液样本 在青春期，这项工作将描述多个研究参与者的空气污染暴露情况 时间尺度（目标 1），然后用于确定空气污染之间的剂量反应关联 以及 6 个月内抑郁症状的轨迹（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，测试相互竞争的模型 细胞因子（例如促炎性细胞因子、Th-1 和 Th-2）以确定相关免疫标记物的特异性 去冒险。通过这种方法论上严格的方法，我们将准备对方向进行强有力的测试 空气污染暴露与抑郁症状之间的关联并确定免疫学参数 这可能会调解风险。在此过程中，该项目的见解将为未来的假设提供重要信息，以阐明 生物和心理连锁反应导致空气污染暴露对精神产生不利影响 确定干预措施的新目标并最终减轻相关的重大负担 患有抑郁症。