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）， 普遍存在于城市地区，是一种神经毒素。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，并与各种心理问题有关。 儿童、青少年和成人的健康障碍。这些最新的发现阐明了需要：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志物 神经系统中的神经毒理学效应与精神健康风险有关; 3）研究这些效应 在儿童后期和青少年时期，因为这是一个适当的时间来确定和干预那些有风险的人， 精神疾病我们提出了第一个纵向研究，以研究产前和儿童期的空气污染如何 暴露影响涉及情绪处理和调节的皮质边缘回路， 从童年后期到青春期早期的过渡期内在和外在的精神病理学。 我们的假设是，产前和儿童期的空气污染暴露有助于增加心理健康的风险 通过改变皮质边缘神经回路和情感发展，在青春期出现障碍。到 测试我们的假设，拟议的项目将创建终身住宅空气污染暴露估计， 利用皮质边缘神经回路、情绪和心理健康数据的综合神经成像， 在全国范围内招募的9至10岁儿童（N= 11，873）的多种族和地理多样性队列 青少年大脑认知发展（ABCD）纵向研究。使用多模态神经成像，我们将 阐明产前和儿童期空气污染暴露对结构变化的影响（目标1）， 功能（目标2）的皮质边缘电路的基础情绪处理和调节，从童年后期到 青春期早期在目标3中，我们将研究产前和儿童期空气污染暴露如何影响 发展情绪问题和随后的精神健康障碍的风险，通过使用：a） 维度量表和B）心理健康诊断标准（基于精神疾病诊断和统计手册） 疾病）。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介导， 9-10在发展过程中接触空气污染与随后内在化风险之间的联系， 在11-12岁的外化精神病理学。这项研究主要集中在长期的产前和 儿童期PM2.5和NO2暴露;然而，我们还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成分）的潜在神经毒性效应。大的， 来自ABCD儿童的社会人口和地理多样性样本正处于评估的适当年龄 精神病理学的临床前标志这为更有力和更普遍的发现提供了巨大的希望 有可能影响政策，并确定早期神经影像学生物标志物作为早期治疗的目标。 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.