PROJECT SUMMARY / ABSTRACT More than one in five adolescents will experience a mental health disorder, including depression and anxiety, and the prevalence of these conditions is increasing. Among adolescents, depression and anxiety are linked to increased risk of suicide, a leading cause of death in this age group. Identifying underlying and modifiable contributors to these conditions is crucial as current research and interventions focus on screening and treatment rather than prevention. Here, we posit that air pollution, in addition to genetic susceptibility, social determinants, familial and school issues, and other factors, is a contributor to mental health disorders. Toxicological studies demonstrate that fine particulate matter (PM2.5) and traffic-related air pollution (TRAP) are neurotoxic, and epidemiologic studies consistently link these pollutants to reduced cognitive abilities and increased externalizing behaviors. However, few studies have prospectively evaluated the role of air pollution exposure on mental health disorders in childhood. Recently, we found that childhood air pollution exposure is associated with increased risk for depression and anxiety at age 12 years. However, the role of air pollution in the onset and persistence of mental health disorders during adolescence, and changes in brain structure, organization, and function linked to these outcomes, remain poorly understood. Therefore, we hypothesize that exposure to air pollution during critical periods of brain development, including adolescence, is associated with adverse mental health outcomes. We will leverage existing longitudinal data from the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) and the Health Outcomes and Measures of the Environment (HOME) Study, two prospective cohorts located in Cincinnati, Ohio, to address this hypothesis. Both cohorts have been followed from birth and evaluated with concordant measures of mental health and neuroimaging at age 12 years. We will conduct new follow-up at age 18 years to assess the onset and persistence of mental health outcomes through adolescence and apply validated models for PM2.5 and TRAP to characterize air pollution exposure from conception through age 18 years. We will also acquire novel neuroimaging outcomes, including brain -aminobutyric acid and glutathione concentrations accompanied by anatomical and functional magnetic resonance imaging. Our aims are to: 1) determine the association between exposure to PM2.5 and TRAP during distinct developmental periods and the onset and persistence of mental health outcomes in adolescence; 2) determine the association between exposure to PM2.5 and TRAP during distinct developmental periods and neuroimaging outcomes in late adolescence; and 3) determine whether changes in brain volume, organization, metabolism, and function mediate associations between PM2.5 and TRAP exposure and mental health outcomes. Examining air pollution as a novel and modifiable risk factor will provide critical data to guide primary prevention aimed at reducing the burden of mental health disorders in adolescence.

PROJECT NARRATIVE Depression and anxiety are common mental health disorders in adolescents, but factors that contribute to these outcomes are poorly understood. We will study how air pollution, which can affect brain development and function, may contribute to these disorders in adolescence by changing the structure, organization, metabolism, or function of the brain. We will combine two existing study populations with repeated measures of air pollution exposure and mental health outcomes from birth through adolescence to provide important information to guide future public health interventions.