Epigenetics, air pollution, and childhood mental health

项目摘要 焦虑和抑郁是世界上最令人衰弱的疾病之一，并增加了 晚年不良健康后果的风险，包括慢性焦虑和抑郁，实质 虐待和自杀。焦虑和抑郁也是最常见的精神障碍 在4-5岁出现症状的青少年中。然而，我们仍然有一个 对青少年焦虑、抑郁的病因及发病机制认识不足 牵涉其中。空气污染物因其影响中枢神经系统的能力而被广泛认识。 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 对环境刺激的敏感性和针对炎症和氧化应激的研究 多种途径已经确定了暴露在空气污染物中会导致DNA甲基化的变化。 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- 宽平台可能有助于识别暴露和影响的新生物标记物，否则可能 有针对性地被忽视。这项提案的目标是确定是否 暴露于细颗粒物(PM2.5)和与交通有关的空气污染(陷阱) 童年和青春期对表观基因组的影响以及DNA甲基化的变化 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)和健康结局 测量环境(家)研究出生队列，我们将：1)进行不偏不倚 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)确定独特的和与污染相关的 DNA甲基化特征与焦虑和抑郁有关。此外，我们还将 在第三个独立的出生队列中复制我们的发现，Viva项目(n=652)，具有类似的 社会人口学特征和可用空气污染与神经发育结局 数据。这项研究设计基于三个公认的出生队列，其中近两个 数十年的后续行动，将允许对空气污染进行纵向和横断面分析， DNA甲基化和精神健康评估，所有这些都会增加 我们研究的概括性。

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.