Prenatal air pollution and neurodevelopment: a longitudinal neuroimaging study of mechanisms and early risk for ADHD in Puerto Rican children

产前空气污染和神经发育：波多黎各儿童 ADHD 机制和早期风险的纵向神经影像研究

• 批准号: 10647635
• 负责人: Claudia I Lugo-Candelas
• 金额: $ 62.54万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-17 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10647635
• 关键词: Accounting; Address; Air; Air Pollution; Attention deficit hyperactivity disorder; Behavior; Behavior assessment; Brain; Child; Child Health; Childhood; Corpus Callosum; Data; Development; Diameter; Disadvantaged; Disparate; Environmental Exposure; Epidemiology; Family; Female; Generations; Genetic; Genetic Risk; Heritability; Home; Human; IL17 gene; Impairment; Infant; Inflammation; Inflammatory Response; Interleukin-6; Intervention; Interview; Knowledge; Link; Literature; Magnetic Resonance Imaging; Measures; Mediating; Mental disorders; Mothers; Neurodevelopmental Disorder; Newborn Infant; Outcome; Participant; Particulate Matter; Pattern; Phenotype; Pollution; Predisposition; Pregnancy; Prevention; Puerto Rican; Recording of previous events; Reporting; Research; Research Design; Risk; Role; Running; Scanning; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Socioeconomic Status; Substance abuse problem; Symptoms; Testing; Time; Toddler; United States National Institutes of Health; Work; Youth; actigraphy; cohort; epidemiology study; fetal; fine particles; follow-up; frontal lobe; indexing; infancy; inflammatory marker; intergenerational; male; mobile sensor; neighborhood disadvantage; neural circuit; neurodevelopment; neuroimaging; neurotoxicity; offspring; pollutant; poor sleep; postnatal; preclinical study; predictive modeling; prenatal; prenatal influence; sex; sleep difficulty; socioeconomics; spatiotemporal; transmission process; white matter

This study aims to examine the neurodevelopmental consequences (specifically risk for ADHD phenotypes) of prenatal maternal air pollution exposure and to examine two potential mechanisms, prenatal maternal inflammation and offspring sleep disruptions. Epidemiological studies support this association; however, studies have yet to determine (1) important exposure periods, (2) pollutant exposure effects independent of socio-economic status and adversity, (3) offspring sex effects, and (4) the underlying mechanisms. Air pollution exposure is often higher in disadvantaged communities; studies that do not consider the socioeconomic and adversity history of participants run the risk of reporting confounded effects. We will address gaps by examining the influence of prenatal PM2.5 exposure on neurodevelopment (via MRI) while controlling for postnatal PM2.5, critical environmental aspects (intergenerational adversity, SES, family functioning), and polygenetic ADHD risk. We will examine offspring brain white matter twice, in infancy (~2 weeks) and in childhood (2-9 yrs). We will work within a two-generation, epidemiological cohort of Puerto Ricans that has been followed since 2000 and carefully characterized for adversity, family functioning, and psychiatric illness. We will study BYS-ECHO children (Generation 2; G2's), who are currently being scanned during infancy (UH3OD023328) and propose to re-assess white matter development in toddlerhood (n=84; 12-24 mos) or childhood (n=98; 6-9yrs). We will index the effects of mother’s prenatal PM2.5 exposure estimated using highly resolved spatio-temporal prediction models (and supplemented by real-time air quality data via portable sensors in a sub-sample) on G2’s ADHD-related neurocircuitry and phenotypes, while controlling for the aforementioned variables. The overarching aim of this study is to examine the neurodevelopmental consequences of prenatal PM2.5 exposure and test two proposed underlying mechanisms: (Aim1) prenatal maternal inflammation, OR (Aim 2) sleep deficits in offspring (measured via in-home actigraphy assessments). Maternal inflammation is a prenatal mechanism, thus we hypothesize in Aim 1 that neurocircuitry alterations will be present in both infancy and toddler/childhood MRIs. Because offspring sleep is a postnatal mechanism, in this alterative (Aim 2) hypothesis we predict alterations in ADHD neurocircuitry in toddler/childhood, but not in newborns. It is also possible we find support for both aims, in which case we would be uniquely poised to examine cumulative and interactive effects. We will also test the moderating role of infant sex (Aim 3), and based on pre-clinical studies, hypothesize that males would demonstrate more susceptibility to prenatal air pollution. This study will be the first to utilize infant longitudinal neuroimaging to understand prenatal air pollution exposure. We will be uniquely able to disassociate the effects of prenatal PM2.5 exposure from those of postnatal factors and PM2.5 on brain development, and to test two putative mechanisms, both of which are potential modifiable targets for intervention.

本研究旨在检查神经发育后果（特别是 ADHD 表型的风险） 产前母亲空气污染暴露并检查两种潜在机制，产前母亲 炎症和后代睡眠中断。流行病学研究支持这种关联；然而， 研究尚未确定 (1) 重要的暴露时间，(2) 污染物暴露影响独立于 社会经济地位和逆境，(3) 后代性别影响，(4) 潜在机制。空气污染 弱势社区的暴露程度往往较高；不考虑社会经济因素的研究 参与者的逆境历史存在报告混杂效应的风险。我们将通过以下方式解决差距 检查产前 PM2.5 暴露对神经发育的影响（通过 MRI），同时控制 产后 PM2.5、关键环境因素（代际逆境、SES、家庭功能）以及 多基因多动症风险。我们将检查后代大脑白质两次，一次是在婴儿期（约两周），一次是在 童年（2-9岁）。我们将在两代波多黎各人的流行病学队列中工作，他们已经 自 2000 年以来一直对其进行追踪，并仔细描述逆境、家庭功能和精神疾病的特征。 我们将研究 BYS-ECHO 儿童（第 2 代；G2），他们目前正在婴儿期接受扫描 （UH3OD023328）并建议重新评估幼儿时期的白质发育（n=84；12-24 个月）或 童年（n=98；6-9岁）。我们将使用高度估计的方法对母亲产前 PM2.5 暴露的影响进行索引 解析时空预测模型（并通过便携式实时空气质量数据进行补充 子样本中的传感器）对 G2 的 ADHD 相关神经回路和表型进行研究，同时控制 上述变量。本研究的总体目标是检查神经发育 产前 PM2.5 暴露的后果并测试两个拟议的潜在机制：（目标 1）产前 母体炎症，或（目标 2）后代睡眠不足（通过家庭体动记录仪评估进行测量）。 母体炎症是一种产前机制，因此我们在目标 1 中假设神经回路改变 将出现在婴儿期和幼儿/儿童 MRI 中。因为后代睡眠是一种后天机制， 在这个替代（目标 2）假设中，我们预测幼儿/儿童期 ADHD 神经回路的改变，但不是 在新生儿中。我们也有可能找到对这两个目标的支持，在这种情况下，我们将有独特的准备 检查累积效应和交互效应。我们还将测试婴儿性别的调节作用（目标 3），以及 根据临床前研究，假设男性对产前空气更敏感 污染。这项研究将是第一个利用婴儿纵向神经影像来了解产前空气的研究 污染暴露。我们将能够将产前 PM2.5 暴露的影响与那些影响区分开来。 后天因素和 PM2.5 对大脑发育的影响，并测试两种假定的机制，这两种机制都是 潜在的可修改干预目标。