Air pollution exposure and prefrontal connectivity in early adolescence

This New Investigator Award study is evaluating how fine-particle exposure affects the development of prefrontal connections and emotional behaviors during the transition from childhood to adolescence and whether this, in turn, contributes to greater risk for neuropsychiatric disorders.

Poster abstract for HEI Annual Conference 2023

Air Pollution Exposure and Prefrontal Connectivity and Emotional Outcomes in Early Adolescence

Megan M. Herting¹, Elisabeth Burnor¹, Hedyeh Ahmadi¹, Gabrielle Major¹, Elizabeth Romero¹, Sandrah P. Eckel¹, Kiros Berhane², Rob McConnell¹, Joel Schwartz³, Jiu-Chiuan Chen¹, William Gauderman, PhD¹

¹University of Southern California, Los Angeles, CA, USA; ²Columbia University, New York City, NY, USA; ³Harvard University, Cambridge, Massachusetts, USA

Background. We aim to investigate whether ambient PM_2.5 and NO₂ exposures at 9-10 years are associated with 1) prefrontal connectivity in youth ages 9-10 and 2) subsequent behavioral health problems and risk for neuropsychiatric disorders at ages 10-11 years.

Methods. The current study uses data from the nationwide Adolescent Brain Cognitive Development (ABCD) study℠ (N=11,873), with cross-sectional diffusion tensor imaging (DTI) at 9-10 years and longitudinal data on emotional health outcomes at 9-10 and 11-12 years. Based on residential addresses at ages 9-10, novel hybrid spatiotemporal exposure models were applied to estimate the annual average ambient exposures to PM_2.5 and NO₂. Prefrontal connectivity was measured using DTI in white matter tracts that innervate the prefrontal cortex. The Child Behavioral Checklist (CBCL) was used to measure internalizing and externalizing emotional problems. We used a directed acyclic graph to a priori identify a minimal sufficient adjustment set of variables, which included child’s age, sex, race/ethnicity, household income, child’s physical activity and screen time use, distance to roadways, perceived neighborhood quality, population density, and urbanicity for both aims, as well as the addition of MRI manufacturer, head motion, and child handedness as precision variables for MRI outcomes. Mixed-effects models were fit with both PM_2.5 and NO₂ to adjust for study site and socio-demographics. For DTI outcomes, data were stratified by brain hemisphere. For emotional health outcomes, longitudinal models included interaction terms for pollutant-by-time for both pollutants. All results were corrected for multiple comparisons.

Results. The mean annual exposures to PM_2.5 and NO₂ across 21 study sites were 7.62 ug/m³ [1.72–15.90 ug/m³] and 18.7 ppb [0.73–37.9 ppb], respectively. Significant negative associations were seen between PM_2.5 and mean diffusivity (MD) in four tracts in the left hemisphere, one tract in the right hemisphere, and in the corpus callosum (p<0.05). Negative but nonsignificant associations were also seen between NO₂ and MD in a total of six white matter tracts. The estimated exposure effects on CBCL outcomes were small, although PM_2.5-by-time was statistically significant for anxious/depressed (p<0.001) and aggressive behavior (p=0.05) and internalizing score (p=0.003), whereas NO₂-by-time interactions were statistically significant for internalizing problems (p=0.02).  

Conclusions.  Our analyses indicate that differences in white matter microstructure in adolescents may be associated with PM_2.5 in a hemisphere-specific manner, while longitudinal associations with emotional problems with PM_2.5 and NO₂ are negligible. These findings suggest that white matter microstructure, but not necessarily behavioral problems, may be associated with air pollution concentrations largely below U.S. national ambient air quality standards. The ultimate findings from our study may provide important epidemiologic data on developmental neurotoxicity at low exposure levels to inform the continuing review and risk assessment for the National Ambient Air Quality Standard.