An MRI Study of the Effects of Prenatal and Early Childhood PAH Exposure on Brain Maturation and Its Mediating Influences on Adverse Adolescent Outcomes

EPA Grant Number: R836154C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R836154
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: The Columbia Center for Children’s Environmental Health
Center Director: Perera, Frederica P.
Title: An MRI Study of the Effects of Prenatal and Early Childhood PAH Exposure on Brain Maturation and Its Mediating Influences on Adverse Adolescent Outcomes
Investigators: Peterson, Bradley S , Bansal, Ravi
Current Investigators: Peterson, Brad
Institution: Columbia University in the City of New York , Children's Hospital Los Angeles , Columbia University Mailman School of Public Health
Current Institution: Columbia University in the City of New York
EPA Project Officer: Louie, Nica
Project Period: September 1, 2015 through August 31, 2019
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text |  Recipients Lists
Research Category: Health , Children's Health

Objective:

Specific Aim 1: Evaluate the effects of prenatal and early postnatal exposure to PAH on each of those measures of brain structure, function, and metabolism at age 9-12 (pre-adolescence).

Specific Aim 2: Acquire new anatomical MRI scans at age 15-17 in this same cohort to assess the correlations of early PAH exposure with measures of brain structure in adolescence.

Specific Aim 3: Assess whether early exposure to high levels of PAH significantly disrupt the normal changes in brain structure from childhood through adolescence, and whether those children with the most disrupted anatomical changes experience the greatest degree of adverse outcomes in adolescence.

Approach:

In this project, investigators will evaluate the effects of prenatal and early postnatal exposure to PAH on each of those measures of brain structure, function, and metabolism at age 9-12 (preadolescence), and how the PAH-related disturbances in brain measures mediate CEBA outcomes at age 15-17 (in adolescence -- outcomes that are being assessed in Projects 1 & 2). In addition, we will acquire new anatomical MRI scans at 15-17 years of age (adolescence) in this same cohort to assess the correlations of early PAH exposure with measures of brain structure in adolescence. The new anatomical MRI scans, together with the anatomical scans already collected in preadolescence at ages 9-12, will allow us to assess whether early exposure to high levels of PAH significantly disrupt the normal changes in brain structure within self-regulatory systems from childhood through adolescence, and whether those children with the most disrupted anatomical changes experience the greatest degree of conduct disturbances, substance use, and depression, persistent ADHD symptoms, and adiposity measures, at 15-17 years of age.

This information will help us understand whether the adverse organizational effects of early life PAH exposure continue to derail brain development later in life, or whether any compensatory neuroplastic effects occur during this time of transition that help to mitigate those adverse effects. This knowledge can be translated to education and policy and exploited to aid the future development of therapeutic interventions.

Rationale:

The Columbia Center for Children’s Environmental Health (CCCEH) has followed a birth cohort of low-income, African-American and Latino children in New York City into their pre-adolescent years to assess the impact of environmental toxicants on health and development. In a pilot study of MRI measures in 40 of these children at 7-9 years of age, abnormalities were identified in anatomical measures of white matter throughout the entire left cerebral hemisphere that were linearly associated with prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH). Those white matter abnormalities were in turn linearly associated with measures of cognitive, emotional, behavioral, and adiposity (CEBA) problems at the time of MRI scan. Under separate funding, the CCCEH has collected brain-based MRI measures and neurobehavioral outcomes in 350 preadolescent children of the CCCEH cohort, between 9 and 12 years of age. The MRI dataset in 9-12 year olds includes state-of-the-art measures of brain structure (anatomical MRI), function (functional MRI), anatomical connectivity and white matter integrity (Diffusion Tensor Imaging, or DTI), and neurometabolite concentrations (MR Spectroscopy, or MRS).

Progress and Final Reports:

2016 Progress Report


Main Center Abstract and Reports:

R836154    The Columbia Center for Children’s Environmental Health

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836154C001 The Impact of PAH Exposure on Adolescent Neurodevelopment: Disruption of Self-Regulatory Processes
R836154C002 The Impact of PAH Exposure on Childhood Growth Trajectories and Visceral Adipose Tissue
R836154C003 An MRI Study of the Effects of Prenatal and Early Childhood PAH Exposure on Brain Maturation and Its Mediating Influences on Adverse Adolescent Outcomes