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 抑郁是一种普遍，经常性且经常慢性疾病，大约影响的21％ 个人一生，与重大损害和巨大的公共卫生负担有关。 为了阐明导致抑郁症状发作和发展的因素，当前项目 试图测试改变外周细胞因子的作用，作为空气之间关联的生物介体 青少年的污染暴露和抑郁症状。具体来说，当前项目将使用 对120名青少年的前瞻性纵向研究，以检查空气污染与 随后的抑郁症状和免疫标记的轨迹。通过直接评估 理论化的生物介体，使用重复评估以及创造复杂的空气污染暴露 估计，我们将克服过去的障碍，以进步并严格测试假定的风险中介。 利用储存的血液样本作为对抑郁症的社会贡献者的持续父母研究的一部分 在青春期，这项工作将表征多个研究参与者的空气污染暴露 时间尺度（AIM 1），然后将其用于确定空气污染之间的剂量反应关联 在一个6个月的时间里（目标2），抑郁症状的轨迹和抑郁症状的轨迹。最后，它将探测外周免疫 标记是空气污染和抑郁症状之间的推定介导，测试竞争模型 细胞因子（例如促炎，TH-1和TH-2）确定免疫标记的特异性 冒险。通过这种方法上严格的方法，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 这可能会介导风险。这样，这个项目的见解将严重告知未来的假设以阐明 生物学和心理级联反应会导致空气污染暴露对心理的不利影响 健康以确定干预工作的新颖目标，并最终减轻相关的巨大负担 抑郁。