Project 3- An MRI Study of the Effects of Prenatal and Early Childhood PAH Exposure on Brain Maturation and Its Mediating Influences on Adverse Adolescent Outcomes

Project Summary: 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, we identified abnormalities 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, we have 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); we will now 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.