Project 2: Endocrine Disruptors, Epigenetic Mechanims and Neurodevelopment

17%的美国儿童被诊断出患有学习或行为障碍。我们正在提出相关的政策 产前暴露对常见内分泌干扰物多环芳烃影响的研究 碳氢化合物(PAH)和双酚A(BPA)对青春期早期神经发育障碍的影响，以及 表观遗传机制作为这些效应的中介。该项目利用了我们正在进行的队列研究 居住在纽约市低收入少数族裔社区的儿童，他们一直被 哥伦比亚儿童环境健康中心(CCCEH)自1998年以来，我们对杨格的新研究 兄弟姐妹(兄弟姐妹/Hermanos队列)。我们的队列提供了一个独特的机会来评估较长期 产前暴露于多环芳烃的后果，并首次评估产前暴露于双酚A的影响 通过青春期周围几年，阐明表观遗传机制在其神经行为影响中的作用。 目的1：确定产前暴露于内分泌干扰物PAH和BPA是否与 通过儿童诊断性评估评估青春期儿童的不良神经行为结果 精神病理学和认知功能。目标2：确定产前接触多环芳烃或双酚A是否 与脐带白细胞的表观遗传学变化有关(DNA甲基化通过基因验证 表达)在与内分泌紊乱和免疫失调相关的候选基因/途径中 已知对胎儿大脑发育至关重要，以及甲基化和基因表达改变是否 与目标1中描述的神经行为结果相关。目标3：使用地理信息系统，确定 哪些邻里层面的情况有助于神经行为结果和/或缓和个人层面的 暴露于多环芳烃或双酚A与儿童神经发育之间的联系(见目标1和2)。 了解影响儿童发育障碍的多因素病因和机制 学习成绩将为预防开辟新的途径。

17% of U.S. children have been diagnosed with a learning or behavior disorder. We are proposing policy relevant research on the contribution of prenatal exposures to the common endocrine disruptors, polycyclic aromatic hydrocarbons (PAH) and bisphenol A (BPA), to neurodevelopmental disorders in early adolescence, and epigenetic mechanisms as mediators of these effects. The project takes advantage of our ongoing cohort study of children residing in low-income, minority neighborhoods of New York City who have been followed by the Columbia Center for Children's Environmental Health (CCCEH) since 1998 and of our new study of younger siblings (Sibling/Hermanos cohort). Our cohorts provide a unique opportunity to evaluate the longer-term consequences of prenatal exposure to PAH and, for the first time, to assess the effect of prenatal BPA exposure through the peri-pubertal years, elucidating the role of epigenetic mechanisms in their neurobehavioral impacts. Aim1: Determine whether prenatal exposures to the endocrine disruptors PAH and BPA are associated with adverse neurobehavioral outcomes in peri-pubertal children, as measured by diagnostic assessment of child psychopathology and cognitive functioning. Aim 2: Determine whether prenatal exposure to PAH or BPA is associated with epigenetic changes in umbilical cord white blood cells (DNA methylation validated by gene expression) in candidate genes/pathways associated with endocrine disruption and immune dysregulation known to be critical in fetal brain development, and whether altered methylation and gene expression is associated with the neurobehavioral outcomes described in Aim 1. Aim 3: Using GIS, determine the extent to which neighborhood-level conditions contribute to neurobehavioral outcomes and/or moderate the individual-level associations between exposure to PAH or BPA and child neurodevelopment (as seen in Aims 1 and 2). Understanding of the multi-factorial etiology and mechanisms of developmental disorders that affect children's academic performance will open new avenues for prevention.