Executive functions in urban Hispanic/Latino youth: exposure to mixture of arsenic and pesticides during childhood

项目摘要/摘要 神经发育障碍(NDD)在美国和世界范围内呈上升趋势，但仍 在西班牙裔/拉丁裔儿童中诊断不足，部分原因是对环境风险因素的研究不足。 无机砷(As)是一种已知的神经毒物，暴露水平较高。长期的杀虫剂水平也是 神经毒性，在产前暴露时会影响儿童的认知。但相对的贡献是 较低水平的砷和慢性常用农药(毒死蜱和拟除虫菊酯)在城市的暴露 西班牙裔/拉丁裔青年尚不清楚。儿童时期的暴露如何影响执行功能也没有被很好地理解。 (EF)在青春期，一个关键的易感性窗口，由大脑区域的成熟支撑，如 前额叶皮质。砷和农药主要积累在以EF为主的脑区。综合效应 与单独检查相比，会产生更多的神经元减少和大脑区域的更大堆积。 EF结构域的缺陷是NDD的基础。虽然有生物学上的理由和证据表明 协会，没有关于儿童毒死蜱的独立和混合影响的纵向研究， 拟除虫菊酯和低水平砷对城市西班牙裔/拉丁裔青少年EF的影响。这项提议将对 蒙得维的亚的一群学生，蒙得维的亚是一个高度城市化的南美城市，暴露在许多污染物中。《敬礼》 环境蒙得维的亚(SAM)队列提供了实现拟议目标的绝佳机会，通过提供 暴露于砷、毒死蜱和拟除虫菊酯的生物标记物，EF的多项测量(七个域和三个 来自NIH认知工具箱的综合分数)，以及在家庭和 对421名11-18岁的参与者进行了邻里水平调查。目标1将评估AS暴露的关联性 儿童期和青春期青春期EF。目标2将评估毒死蜱和 儿童和青春期拟除虫菊酯类农药对青春期EF的影响。目标3将调查 应用新的混合统计模型研究三种暴露组合对青春期EF的影响 效果。实现这些目标将对来自美国和美国的城市拉美裔/拉美裔儿童产生积极影响 拉丁美洲：(1)为研究弱势群体中的非处方药的环境风险因素奠定基础 城市社区，(2)更好地认识到现实世界共同暴露于污染物的影响，以及(3) 为教育方案提供信息，使照顾者、卫生和教育系统获得更好的信息 提供适当的护理以及预防方案，以降低这两个社区的风险 不成比例地暴露在环境毒物中并受其影响。

Project Summary/Abstract Neurodevelopmental disabilities (NDD) are on the rise in the United States and worldwide but remain underdiagnosed among Hispanic/Latino children partly due to insufficient research on environmental risk factors. Inorganic arsenic (As) is a known neurotoxicant at higher exposure levels. Chronic levels of pesticides are also neurotoxic, affecting child cognition when exposure occurs in the prenatal period. But the relative contribution of lower levels of As and chronic common-use pesticide (chlorpyrifos and pyrethroids) exposure in urban Hispanic/Latino youth is unclear. It is also not well understood how childhood exposures affect executive function (EF) during adolescence, a critical window of susceptibility underpinned by the maturation of brain areas like the prefrontal cortex. As and pesticides accumulate mostly in EF-dominated brain regions. Combined effects produce more decreases in neurons and larger accumulations in brain regions than when examined individually. Deficits in domains of EF underlie NDDs. While there is a biological rationale and evidence of the proposed association, there are no longitudinal studies of the independent and mixture effects of childhood chlorpyrifos, pyrethroids, and low-level As, exposure on EF of urban Hispanic/Latino adolescents. This proposal will leverage a school cohort in Montevideo, a highly urban, South American city with exposure to many pollutants. The Salud Ambiental Montevideo (SAM) cohort provides an excellent opportunity to fulfill the proposed aims by providing biomarkers of exposure to As, chlorpyrifos and pyrethroids, multiple measures of EF (seven domains and three composite scores from the NIH Cognitive Toolbox), and rich contextual factors collected at the family and neighborhood levels on 421 participants aged 11-18 years. Aim 1 will estimate the association of As exposure in childhood and adolescence on adolescent EF. Aim 2 will estimate the association of chlorpyrifos and pyrethroids exposure in childhood and adolescence on adolescent EF. Aim 3 will investigate the association of the three exposures combined on EF during adolescence by employing novel statistical models of mixture effects. Accomplishing these aims will have a positive impact on urban Hispanic/Latino children from the US and Latin America by: (1) Laying a foundation of research on environmental risk factors for NDDs in disadvantaged urban communities, (2) A better recognition of the effects of real-world co-exposures to pollutants and (3) informing educational programs that will lead to better-informed caregivers, health and education systems to provide appropriate care, as well as preventive programs to lower exposure among communities that are both disproportionately exposed to and affected by environmental toxicants.