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.

Public Health Relevance

These studies will ascertain how environmental exposures may be responsible for the neurodevelopmental and neurobehavioral disorders that are seen in the U.S. overall and in our target population. An understanding of how epigenetic mechanisms may be responsible for mediating the effects of prenatal exposures on these adverse health outcomes will allow targeted interventions to prevent long-term effects on children's health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES009600-14
Application #
8382560
Study Section
Special Emphasis Panel (ZES1-LKB-G)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
14
Fiscal Year
2012
Total Cost
$186,484
Indirect Cost
$88,240
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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Lovinsky-Desir, Stephanie; Jung, Kyung Hwa; Jezioro, Jacqueline R et al. (2017) Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter. Clin Epigenetics 9:65
Jung, Kyung Hwa; Torrone, David; Lovinsky-Desir, Stephanie et al. (2017) Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children. Respir Res 18:63
Jung, Kyung Hwa; Lovinsky-Desir, Stephanie; Yan, Beizhan et al. (2017) Effect of personal exposure to black carbon on changes in allergic asthma gene methylation measured 5 days later in urban children: importance of allergic sensitization. Clin Epigenetics 9:61
Perera, Frederica; Nolte, Emily L Roen; Wang, Ya et al. (2016) Bisphenol A exposure and symptoms of anxiety and depression among inner city children at 10-12 years of age. Environ Res 151:195-202
Miller, Rachel L; Yan, Zhonghai; Maher, Christina et al. (2016) Impact of prenatal polycyclic aromatic hydrocarbon exposure on behavior, cortical gene expression and DNA methylation of the Bdnf gene. Neuroepigenetics 5:11-18
Engel, Stephanie M; Bradman, Asa; Wolff, Mary S et al. (2016) Prenatal Organophosphorus Pesticide Exposure and Child Neurodevelopment at 24 Months: An Analysis of Four Birth Cohorts. Environ Health Perspect 124:822-30

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