The role of air pollution in emotional neurodevelopment and risk for psychiatric disorders

项目摘要 室外空气污染，包括细颗粒物(PM2.5；及其成分)和二氧化氮(NO2)， 在城市地区无处不在，是一种神经毒物。新出现的毒理学和流行病学证据表明 空气污染可能会导致情绪行为问题的增加，并与各种精神疾病有关 儿童、青少年和成人的健康障碍。这些最新发现阐明了以下必要性：1) 检查产前和儿童期暴露的长期影响；2)确定临床前神经成像生物标记物 与精神健康风险有关的神经回路的神经毒理效应；以及3)调查这些效应 在儿童后期和青春期，因为这是识别和干预那些有风险的人的好时机 精神障碍。我们建议进行第一项纵向研究，以考察产前和儿童时期的空气污染 暴露影响参与情绪处理和调节的皮质边缘回路，以及 从儿童后期到青春期早期的内化和外化精神病理学。 我们的假设是，产前和儿童期接触空气污染会增加精神健康的风险。 青春期通过皮质边缘神经回路和情绪发育的改变而导致的精神障碍。至 检验我们的假设，拟议的项目将产生终身住宅空气污染暴露估计和 利用皮质边缘神经回路、情绪和心理健康数据的全面神经成像，来自 在全国范围内登记的9至10岁儿童(N=11,873)是多民族和不同地理位置的队列 青少年脑认知发展的纵向研究。使用多模式神经成像，我们将 阐明产前和儿童接触空气污染对结构变化的影响(目标1)和 大脑皮质边缘环路的功能(目标2)--儿童时期至 青春期早期。在目标3中，我们将研究产前和儿童接触空气污染如何影响 情绪问题的发展和随后的精神健康障碍的风险通过使用这两种方式：a) 维度量表和b)精神健康诊断标准(根据《精神诊断和统计手册》 紊乱)。作为一个探索性的子目标，我们还将研究皮质边缘改变的潜在调节作用 9-10年在发育过程中暴露于空气污染与随后的内化和 11-12岁的外化精神病理学。这项研究主要集中在长期产前和 儿童时期接触PM2.5和NO2；然而，我们也计划探索这些暴露的不同时间效应 以及其他环境污染物(即臭氧、PM组分)的潜在神经毒性影响。大型的， ABCD儿童的社会人口学和地理多样性样本处于合适的年龄进行评估 精神病理学的临床前标志物。这为更可靠和更具普遍性的发现提供了巨大的希望 有可能影响政策，并将早期神经成像生物标记物确定为早期 干预。

Project Abstract Outdoor air pollution, including fine particulate matter (PM2.5; and its constituents) and nitrogen dioxide (NO2), is ubiquitous in urban areas and is a neurotoxicant. Emerging toxicological and epidemiological evidence suggests that air pollution may contribute to increases in emotional behavioral problems and is linked to various mental health disorders in children, adolescents, and adults. These recent findings have elucidated the need to: 1) examine long-term effects of prenatal and childhood exposure; 2) identify pre-clinical neuroimaging biomarkers of neurotoxicological effects in neural circuitry implicated in mental health risk; and 3) investigate these effects in late-childhood and adolescence, as it is an opportune time to identify and intervene for those at risk for psychiatric disorders. We propose the first longitudinal study to examine how prenatal and childhood air pollution exposure impacts corticolimbic circuitry involved in emotion processing and regulation, and the onset of internalizing and externalizing psychopathology during the transition from late-childhood to early adolescence. Our hypothesis is that prenatal and childhood air pollution exposure contribute to increased risk for mental health disorders during adolescence through alterations in corticolimbic neural circuitry and emotional development. To test our hypothesis, the proposed project will create lifetime residential air pollution exposure estimates and leverage comprehensive neuroimaging of corticolimbic neural circuitry, emotion, and mental health data, from a multi-ethnic and geographically diverse cohort of 9- to 10-year-old children (N=11,873) enrolled in the nationwide longitudinal Adolescent Brain Cognitive Development (ABCD) study. Using multi-modal neuroimaging, we will elucidate the effects of prenatal and childhood air pollution exposure on changes in the structure (Aim 1) and function (Aim 2) of corticolimbic circuitry underlying emotional processing and regulation from late-childhood to early adolescence. In Aim 3, we will examine how prenatal and childhood air pollution exposure influences the development of emotional problems and subsequent risk for mental health disorders by using both: a) dimensional scales and b) mental health diagnostic criteria (based on Diagnostic and Statistical Manual of Mental Disorders). As an exploratory sub-aim, we will also examine a potential mediation of corticolimbic alterations at 9-10 yrs in the link between air pollution exposure during development and subsequent risk for internalizing and externalizing psychopathology at ages 11-12 yrs. This study is primarily focused on long-term prenatal and childhoodPM2.5 and NO2 exposure; however, we also plan to explore differential timing effects of these exposures as well as the potential neurotoxic effects of other ambient pollutants (i.e. ozone, PM components). The large, sociodemographic and geographic diverse sample of children from ABCD are at an opportune age to evaluate pre-clinical markers of psychopathology. This provides great promise for more robust and generalizable findings that have the potential to impact policy as well as identify early neuroimaging biomarkers as targets for early intervention.