Epigenetics, air pollution, and childhood mental health

表观遗传学、空气污染和儿童心理健康

• 批准号: 10613987
• 负责人: Kelly J Brunst
• 金额: $ 60.39万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10613987
• 关键词: 12 year old; 5 year old; Accounting; Acute; Adolescence; Adolescent; Adult; Affect; Affective; Age; Air Pollutants; Air Pollution; Anxiety; Area; Behavior; Behavioral; Biological; Birth; Blood; Boston; Brain; Carbon Black; Central Nervous System; Characteristics; Child; Childhood; Chronic; Cognitive; Complex; Consent; CpG Islands; Cross-Sectional Studies; DNA Methylation; DNA Sequence; Data; Development; Diameter; Disease; Early Diagnosis; Elderly; Elements; Environment; Environmental Exposure; Epigenetic Process; Etiology; Exposure to; Follow-Up Studies; Functional disorder; Future; Gene Expression; Genes; Genetic Transcription; Goals; HIV/AIDS; Health; Hypersensitivity; Inflammation; Inflammatory; Inhalation; Intervention; Life Cycle Stages; Link; Measures; Mental Depression; Mental Health; Mental disorders; Methylation; Molecular; Monitor; Nature; Obsessive-Compulsive Disorder; Olfactory Nerve; Outcome; Oxidative Stress; Oxidative Stress Pathway; Particulate Matter; Pathway interactions; Phenotype; Pollution; Prevalence; Prevention; Research; Research Design; Risk; Risk Factors; Role; Sampling; Separation Anxiety; Site; Social Phobia; Stimulus; Stream; Substance abuse problem; Suicide; Symptoms; Teenagers; Testing; Visit; Youth; ambient air pollution; anxiety symptoms; biomarker identification; child depression; childhood anxiety; cohort; depressive symptoms; disorder risk; early onset; epidemiology study; epigenome; epigenomics; fine particles; follow-up; health assessment; health data; individual variation; methylation biomarker; methylomics; myelination; neurodevelopment; neurotoxicity; novel marker; oxidative damage; peripheral blood; prenatal; prenatal exposure; promoter; psychiatric symptom; sociodemographics; suicidal; traffic-related air pollution; ultrafine particle

Project Summary Anxiety and depression are among the most debilitating disorders worldwide and increase the risk for later-life adverse health outcomes including chronic anxiety and depression, substance abuse and suicide. Anxiety and depression are also the most common psychiatric disorders among adolescents with symptoms presenting as early as 4-5 years of age. Yet, we still have a poor understanding of the etiology of anxiety and depression in youth and the mechanisms involved. Air pollutants are widely recognized for their ability to affect the central nervous system and adversely impact neurodevelopment during childhood. The epigenome is particularly sensitive to environmental stimuli and studies targeting inflammatory and oxidative stress pathways have identified DNA methylation changes resulting with exposure to air pollutants. Oxidative stress and inflammation, however, are not the only pathways involved in air pollution neurotoxicity or the pathophysiology of mental health disorders. Thus, utilizing an epigenome- wide platform may help identify novel biomarkers of exposure and effect which may otherwise be overlooked with a targeted approach. The goal of this proposal is to determine whether exposure to fine particulate matter (PM2.5) and traffic-related air pollution (TRAP) during childhood and adolescence impacts the epigenome and whether changes in DNA methylation can be used to identify children at increased risk for anxiety and depression. Using the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) and Health Outcomes and Measures of the Environment (HOME) study birth cohort, we will: 1) conduct an unbiased epigenome-wide search for DNA methylation biomarkers associated with PM2.5 and TRAP exposure prenatally through age 12 years (n=500) and 2) identify unique and pollution-related DNA methylation signatures associated with anxiety and depression. In addition, we will replicate our findings in a third, independent birth cohort, Project Viva (n=652), with similar sociodemographic characteristics and available air pollution and neurodevelopmental outcome data. The study design, based on three well-established birth cohorts with nearly two decades of follow-up, will allow for longitudinal and cross-sectional analyses of air pollution, DNA methylation, and mental health assessments all of which will increase the rigor and generalizability of our study.

项目摘要 焦虑和抑郁是世界上最令人衰弱的疾病之一， 晚年不良健康后果的风险，包括慢性焦虑和抑郁，物质 虐待和自杀焦虑和抑郁也是最常见的精神疾病 在症状早在4-5岁的青少年中。然而，我们仍然有一个 对青少年焦虑和抑郁的病因和机制认识不足 涉案空气污染物因其影响中枢神经系统的能力而被广泛认可 并对儿童时期的神经发育产生不利影响。表观基因组特别是 对环境刺激敏感以及针对炎症和氧化应激的研究 已经确定了暴露于空气污染物导致的DNA甲基化变化。 然而，氧化应激和炎症并不是空气污染的唯一途径 神经毒性或精神健康障碍的病理生理学。因此，利用表观基因组- 广泛的平台可以帮助识别暴露和影响的新生物标志物， 以有针对性的方式加以忽视。本提案的目的是确定是否 暴露于细颗粒物（PM2.5）和交通相关的空气污染（TRAP） 童年和青春期影响表观基因组， 可用于识别焦虑和抑郁风险增加的儿童。使用 辛辛那提儿童过敏和空气污染研究（CCAAPS）和健康结果， 环境措施（HOME）研究出生队列，我们将：1）进行公正的 全表观基因组搜索与PM2.5和TRAP相关的DNA甲基化生物标志物 产前暴露至12岁（n=500）和2）确定独特和污染相关 与焦虑和抑郁相关的DNA甲基化特征此外，我们会 在第三个独立的出生队列中复制了我们的发现，Viva项目（n=652）， 社会人口学特征和现有的空气污染和神经发育结果 数据研究设计基于三个成熟的出生队列， 几十年的跟踪，将允许对空气污染进行纵向和横向分析， DNA甲基化和心理健康评估，所有这些都将增加严格性， 我们研究的普遍性。