INTRODUCTION: Emerging evidence suggests that ambient air pollution may affect the developing brain and contribute to an increased risk of mental health problems. However, most studies have focused on prenatal or early postnatal periods of exposure, with less attention given to the dynamic neurodevelopment period of early adolescence. Moving forward, it is necessary to consider additional periods of exposure, such as adolescence, and the biological mechanisms that may drive potential neurotoxicological effects. This project aimed to investigate whether 1-year exposure to ambient fine particulate matter (PM) and nitrogen dioxide (NO) at 9-10 years of age was associated with (1) concurrent prefrontal white matter connectivity at ages 9-10 years and (2) emotional health problems at ages 9-10 years as well as 1 year later. Lastly, we hypothesized that poor prefrontal white matter connectivity might be an intermediate marker (i.e., mediator) for the association between 1-year ambient exposure and mental health outcomes. 2.5 2
METHODS: We leveraged data from the multisite, nationwide Adolescent Brain Cognitive Development Study (ABCD Study; N = 11,880), with cross-sectional data on diffusion-weighted imaging at 9-10 years (baseline visit) and longitudinal emotional health outcomes at 9-10 (baseline visit) and 10-11 years (1-year follow-up). Based on residential addresses at ages 9-10 years, novel hybrid spatiotemporal exposure models were applied to estimate 1-year average ambient exposure to PMand NO. Diffusion tensor imaging (DTI) was used to measure white matter microstructure in tracts that innervate the prefrontal cortex. Emotional behavioral problems were measured based on caregiver reports using the Child Behavioral Checklist (CBCL). Mixed-effect two-pollutant models were fit using both PMand NOand adjusted for the study site, several potential sociodemographic and lifestyle characteristics, and magnetic resonance imaging (MRI) precision variables when necessary. For emotional health outcomes, longitudinal models included interaction terms for pollutant-by-time for both pollutants. Sensitivity analyses were conducted that also accounted for the number of years the child resided at the residential address, as well as adjusting for prenatal PMand NOexposures. 2.5 2 2.5 2 2.5 2
RESULTS: The final analytic sample included 7,546 participants with DTI data and 9,334 participants with emotional behavior data. The annual exposures to PMand NOacross 21 study sites were 7.66 μg/m[1.72-15.90 μg/m] and 18.61 ppb [0.73-37.94 ppb], respectively. Annual exposure to PMwas found to be significantly related to prefrontal structural connectivity, including fractional anisotropy (FA) in the right superior longitudinal fasciculus and widespread differences in mean diffusivity (MD) in the corpus callosum, bilateral uncinate fasciculus, left cingulum-hippocampal region, left anterior thalamic radiation, and left superior longitudinal fasciculus. The observed associations between PMand MD were negative and nonlinear, with greater decreases in MD seen at higher exposure levels. Annual exposure to NOwas found to have significant, negative linear associations with FA in the right anterior thalamic radiation, left uncinate fasciculus, and corpus callosum. In terms of emotional behavior, 1-year PMannual exposure was related to slightly less internalizing, anxiety/depression, and aggression problems at the 1-year follow-up. Similarly, 1-year NOannual exposure was related to slightly less internalizing and total problems at the 1-year follow-up. Although some of these associations were statistically significant, small parameter estimates suggest these noted effects on emotional outcomes may not be of clinical importance. Given the later findings, the required conditions to test mediation formally were not met. 2.5 2 2.5 2.5 2 2.5 2 3 3
CONCLUSIONS: Our analyses indicate that white matter microstructure is uniquely associated with annual exposure to PMand NOat ages 9-10 years. Against our hypotheses, annual exposure was not related to more emotional problems at ages 9-10 years or after a 1-year follow-up period. These findings suggest air pollution exposure levels below US national ambient air quality standards may have important implications for child white matter development and add to the literature suggesting neurotoxicity at low exposure levels of air pollution may be critical to include in the continuing review and risk assessment for the National Ambient Air Quality Standard. 2.5 2
