Air Pollution Exposure, Prefrontal Connectivity, and Emotional Behavior in Early Adolescence

Abstract

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_2.5) and nitrogen dioxide (NO₂) 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.

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 PM_2.5 and NO₂. 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 PM_2.5 and NO₂ and 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 PM_2.5 and NO₂ exposures.

Results: The final analytic sample included 7,546 participants with DTI data and 9,334 participants with emotional behavior data. The annual exposures to PM_2.5 and NO₂ across 21 study sites were 7.66 μg/m³ [1.72-15.90 μg/m³] and 18.61 ppb [0.73-37.94 ppb], respectively. Annual exposure to PM_2.5 was 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 PM_2.5 and MD were negative and nonlinear, with greater decreases in MD seen at higher exposure levels. Annual exposure to NO₂ was 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 PM_2.5 annual exposure was related to slightly less internalizing, anxiety/depression, and aggression problems at the 1-year follow-up. Similarly, 1-year NO₂ annual 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.

Conclusions: Our analyses indicate that white matter microstructure is uniquely associated with annual exposure to PM_2.5 and NO₂ at 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.

Statement Figure.

Annual NO₂ exposure is associated with lower white matter connectivity in the prefrontal cortex of children ages 9–10. Higher NO₂ exposure was associated with lower fractional anisotropy in three of seven areas: the uncinate fasciculus (UNC), anterior thalamic radiation (ATR), and corpus callosum.

Figure 1.

Geographic distribution of Adolescent Brain Cognitive Development (ABCD) study sites. Study site abbreviations: CHLA = Children’s Hospital of Los Angeles, CUB = University of Colorado Boulder, FIU = Florida International University, LIBR = Laureate Institute for Brain Research, MUSC = Medical University of South Carolina, OHSU = Oregon Health and Science University, ROC = University of Rochester, SRI = SRI International, UCLA = University of California, Los Angeles, UCSD = University of California San Diego, UFL = University of Florida, UMB = University of Maryland Baltimore, UMICH = University of Michigan, UMN = University of Minnesota, UPMC = University of Pittsburgh Medical Center, UTAH = University of Utah, UVM = University of Vermont, UWM = University of Wisconsin-Milwaukee, VCU = Virginia Commonwealth University, WUSTL = Washington University in St. Louis, YALE = Yale University.

Figure 2.

Annual averages of daily PM_2.5 and NO₂ across the continental United States for the calendar year. Overlay of 21 ABCD study site locations included for visualization purposes. See Figure 1 for study site abbreviations.

Figure 3.

Correlation matrix of prenatal and annual average exposure at ages 9–10 years (baseline visit). Correlation values represent Spearman’s r correlations from complete pairwise comparisons between annual average PM_2.5, annual average NO₂, prenatal PM_2.5, and prenatal NO₂ using the full ABCD study dataset and those with high-quality prenatal exposure data (i.e., prenatal air pollution estimates for subjects without errors in reporting of prenatal addresses or errors in reporting percentage of time spent at address during the prenatal period). Sample sizes for comparisons: annual air pollution estimates: N = 11,189; annual air pollution estimates with prenatal air pollution: n = 7,504; prenatal air pollution: n = 7,848.

Figure 4.

Associations between annual average PM_2.5 and NO₂ exposure and PFC white matter fractional anisotropy (FA) at ages 9–10 years (baseline visit). (A) Visualization of white matter tracts showing significant effects of annual average PM_2.5 and NO₂ at ages 9–10 years from hemisphere-specific two-pollutant models predicting fractional anisotropy (FA) at ages 9–10 years, adjusting for a minimally sufficient set of covariates, including: child’s age, sex, race/ethnicity, total household income, child’s physical activity, child’s screen time use, distance to roadways, perceived neighborhood quality, population density, urban classification, and MRI precision variables (manufacturer, head motion, and child handedness). Anatomical details about each tract can be found in Appendix Table 2. (B) Plots of non-linear associations between annual average PM_2.5 and FA at ages 9–10 years and linear associations between annual average NO₂ and FA at ages 9–10 years for significant white matter tracts from hemisphere-specific two-pollutant LMMs adjusted for minimally sufficient set of covariates. Shaded bands represent 95% confidence intervals. Significant tracts for PM_2.5 effects were identified with a Type III analysis of variance (Satterthwaite method) comparing models with both a spline PM_2.5 term and a linear term for NO₂ to models with a linear term for NO₂ only (i.e., a “null” model). Significant tracts for NO₂ were identified using the P value associated with the linear NO₂ beta coefficient in models with both a spline PM_2.5 term and a linear term for NO₂. This P value was calculated using the Satterthwaite method for computing degrees of freedom and t statistics. Significance level was set a priori at P < 0.05 for all tests. Abbreviations: A = anterior; P = posterior; R = right hemisphere; L = left hemisphere; ATR = anterior thalamic radiation (green); SLF = superior longitudinal fasciculus (light blue); UNC = uncinate fasciculus (darker blue); CC = corpus callosum (red).

Commentary Figure 1.

ABCD Study sites.

Commentary Figure 2.

Associations between annual PM_2.5 and NO₂ exposure and prefrontal cortex white matter connectivity at ages 9–10. PM_2.5 was associated with no change or higher connectivity (A and B), whereas NO₂ was associated with lower connectivity (C). Higher mean diffusivity and lower fractional anisotropy indicate disease states. Nonsignificant changes are not shown. ATR = anterior thalamic radiation; CGH = cingulum (hippocampal); SLF = superior longitudinal fasciculus; UNC = uncinate fasciculus.

Commentary Figure 3.

Emotional behavior at ages 9–10 at baseline and 1-year follow-up. Left column (Time): emotional behavior changes at 1-year follow-up. Middle columns (PM_2.5 and NO₂): Associations between annual PM_2.5 and NO₂ exposure and emotional behavior at baseline. Right columns (PM_2.5×Time and NO₂×Time): Associations between exposure and emotional behavior at 1-year follow-up. Beta estimates are reported per 1-unit change in year and exposure. Estimates that are larger than 0 indicate increased emotional behavior problems.