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: 10392444
• 负责人: Kelly J Brunst
• 金额: $ 61.33万
• 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/10392444
• 关键词: 12 year old; 5 year old; AIDS/HIV problem; Accounting; Acute; Adolescence; Adolescent; Adult; Affect; Affective; Age; Air Pollutants; Air Pollution; Anxiety; Area; Behavior; Behavioral; Biological; Biological Markers; Birth; Blood; Boston; Brain; Caliber; Carbon Black; Characteristics; Child; Childhood; Chronic; Cognitive; Complex; Consent; CpG Islands; Cross-Sectional Studies; DNA Methylation; DNA Sequence; Data; Development; Disease; Early Diagnosis; Elderly; Elements; Environment; Environmental Exposure; Epigenetic Process; Etiology; Exposure to; Follow-Up Studies; Functional disorder; Future; Gene Expression; Genetic Transcription; Goals; Health; Hypersensitivity; Inflammation; Inflammatory; Inhalation; Intervention; Life Cycle Stages; Link; Measures; Mental Depression; Mental Health; Mental disorders; Methylation; Molecular; Monitor; Nature; Neuraxis; Obsessive-Compulsive Disorder; Olfactory Nerve; Outcome; Outcome Measure; 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; base; 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; traffic-related air pollution; ultrafine particle; 12 year old; 5 year old; AIDS/HIV problem; Accounting; Acute; Adolescence; Adolescent; Adult; Affect; Affective; Age; Air Pollutants; Air Pollution; Anxiety; Area; Behavior; Behavioral; Biological; Biological Markers; Birth; Blood; Boston; Brain; Caliber; Carbon Black; Characteristics; Child; Childhood; Chronic; Cognitive; Complex; Consent; CpG Islands; Cross-Sectional Studies; DNA Methylation; DNA Sequence; Data; Development; Disease; Early Diagnosis; Elderly; Elements; Environment; Environmental Exposure; Epigenetic Process; Etiology; Exposure to; Follow-Up Studies; Functional disorder; Future; Gene Expression; Genetic Transcription; Goals; Health; Hypersensitivity; Inflammation; Inflammatory; Inhalation; Intervention; Life Cycle Stages; Link; Measures; Mental Depression; Mental Health; Mental disorders; Methylation; Molecular; Monitor; Nature; Neuraxis; Obsessive-Compulsive Disorder; Olfactory Nerve; Outcome; Outcome Measure; 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; base; 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; 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 焦虑和抑郁是全球最令人衰弱的疾病之一，并增加 后来生活不良健康结果的风险，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 在有症状的青少年中，早在4-5岁时就会出现。但是，我们仍然有一个 对青年焦虑和抑郁的病因的理解不足 涉及。空气污染物因影响中枢神经系统的能力而被广泛认可 并不利地影响儿童时期的神经发育。表观基因组特别是 对环境刺激和针对炎症和氧化应激的研究敏感 途径已确定导致暴露于空气污染物的DNA甲基化变化。 然而，氧化应激和炎症并不是空气污染涉及的唯一途径 神经毒性或心理健康疾病的病理生理学。因此，利用表观基因组 广泛的平台可能有助于识别新型的曝光和效果生物标志物，否则 通过有针对性的方法被忽视。该提议的目的是确定是否 暴露于精细颗粒物（PM2.5）和与交通相关的空气污染（陷阱） 童年和青春期会影响表观基因组以及DNA甲基化的变化 可用于识别患有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（CCAAP）和健康成果以及 环境的度量（家庭）研究出生队列，我们​​将：1）进行公正 范围均可搜索与PM2.5和陷阱相关的DNA甲基化生物标志物 从产前到12岁（n = 500）和2）识别与污染有关的独特和污染有关 DNA甲基化特征与焦虑和抑郁有关。此外，我们将 在第三个独立的出生队列中复制我们的发现，Viva项目（n = 652），类似 社会人口统计学特征以及可用的空气污染和神经发育结果 数据。研究设计，基于三个公认的出生队列，近两个 数十年的随访将允许对空气污染进行纵向和横截面分析， DNA甲基化和心理健康评估所有这些都将增加严格和 我们研究的概括性。