Project 2: Endocrine Disruptors, Epigenetic Mechanims and Neurodevelopment

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.