The role of air pollution in emotional neurodevelopment and risk for psychiatric disorders

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Project Abstract Outdoor air pollution, including fine particulate matter (PM2.5; and its constituents) and nitrogen dioxide (NO2), is ubiquitous in urban areas and is a neurotoxicant. Emerging toxicological and epidemiological evidence suggests that air pollution may contribute to increases in emotional behavioral problems and is linked to various mental health disorders in children, adolescents, and adults. These recent findings have elucidated the need to: 1) examine long-term effects of prenatal and childhood exposure; 2) identify pre-clinical neuroimaging biomarkers of neurotoxicological effects in neural circuitry implicated in mental health risk; and 3) investigate these effects in late-childhood and adolescence, as it is an opportune time to identify and intervene for those at risk for psychiatric disorders. We propose the first longitudinal study to examine how prenatal and childhood air pollution exposure impacts corticolimbic circuitry involved in emotion processing and regulation, and the onset of internalizing and externalizing psychopathology during the transition from late-childhood to early adolescence. Our hypothesis is that prenatal and childhood air pollution exposure contribute to increased risk for mental health disorders during adolescence through alterations in corticolimbic neural circuitry and emotional development. To test our hypothesis, the proposed project will create lifetime residential air pollution exposure estimates and leverage comprehensive neuroimaging of corticolimbic neural circuitry, emotion, and mental health data, from a multi-ethnic and geographically diverse cohort of 9- to 10-year-old children (N=11,873) enrolled in the nationwide longitudinal Adolescent Brain Cognitive Development (ABCD) study. Using multi-modal neuroimaging, we will elucidate the effects of prenatal and childhood air pollution exposure on changes in the structure (Aim 1) and function (Aim 2) of corticolimbic circuitry underlying emotional processing and regulation from late-childhood to early adolescence. In Aim 3, we will examine how prenatal and childhood air pollution exposure influences the development of emotional problems and subsequent risk for mental health disorders by using both: a) dimensional scales and b) mental health diagnostic criteria (based on Diagnostic and Statistical Manual of Mental Disorders). As an exploratory sub-aim, we will also examine a potential mediation of corticolimbic alterations at 9-10 yrs in the link between air pollution exposure during development and subsequent risk for internalizing and externalizing psychopathology at ages 11-12 yrs. This study is primarily focused on long-term prenatal and childhoodPM2.5 and NO2 exposure; however, we also plan to explore differential timing effects of these exposures as well as the potential neurotoxic effects of other ambient pollutants (i.e. ozone, PM components). The large, sociodemographic and geographic diverse sample of children from ABCD are at an opportune age to evaluate pre-clinical markers of psychopathology. This provides great promise for more robust and generalizable findings that have the potential to impact policy as well as identify early neuroimaging biomarkers as targets for early intervention.