Project Summary/Abstract Human exposure to environmental contaminants is ubiquitous, and there is growing concern that exposure to some may be linked with the rise in neurobehavioral problems in children. Given the lack of conclusive evidence for many environmental toxicants, there is a critical need for well-designed longitudinal studies of prenatal and postnatal exposure with long-term follow-up to address focused questions about the impact of these chemicals, especially on neurobehavioral endpoints. We will study two chemical classes to which nearly all of the US population are exposed, polybrominated diphenyl ethers (PBDEs) and perfluorinated chemicals (PFCs), that have been used as flame retardants and surfactants, respectively. Among an established cohort of typically developing pre-adolescent children within the Health Outcomes and Measures of the Environment (HOME) Study, we will determine associations between prenatal and childhood exposure to these persistent pollutants and internalizing behaviors including anxiety, depression and social impairment. We will also obtain neuroimaging outcomes to examine associations with exposure. The HOME Study enrolled women during pregnancy and has thus far followed offspring until age 8y. We will extend follow-up to include a study visit at 11-12y to study associations in the pre-adolescent period. Prenatal exposures were measured using maternal pregnancy and newborn specimens with multiple childhood samples currently being analyzed. Over 97% of participating women had detectable levels of PBDEs and PFCs during pregnancy; comparable with nationally reported levels. We hypothesize that exposures to these chemicals subtly alter the brain to produce neurobehavioral deficits that will be evident in increased internalizing symptoms and adverse changes in anatomical structure, neurochemistry, organization of white matter tracts, and connectivity of neural networks. Aim 1: To determine the impact of prenatal and childhood exposures to PBDEs and PFCs on internalizing symptoms in a longitudinal birth cohort of 11-12 year old children. Aim 2: To determine the impact of prenatal and childhood exposures to PBDEs on brain structure, organization, and function in a longitudinal birth cohort of 11-12 year old children. Exploratory aim (EA): To determine the impact of prenatal and childhood exposures to PFCs on brain structure, organization, and function in a longitudinal birth cohort of 11-12 year old children. Aim 3: To determine the potential mediational impact of brain structure, organization and function in the relationship between prenatal and childhood exposures to PBDEs and internalizing symptoms in a longitudinal birth cohort of 11-12 year old children. Aim 4: To identify appropriate statistical methodologies to determine the association of single and multiple PBDE and PFC exposures with neurodevelopment across multiple developmental stages.