A life-course approach for examining the impact of air pollutants on adolescent anxiety and depression and the role of DNA methylation

Abstract

Background and Aim: Anxiety and depression are common in adolescents; yet, their etiology is poorly understood. Air pollutants are widely recognized for their ability to adversely impact neurodevelopment and elicit changes to the epigenome. It is unclear whether pollution-related epigenome changes impact mental health. Methods: The Infinium MethylationEPIC BeadChip was used to assess whole blood DNA methylation from 159 adolescents (age 12). Fine particulate matter (PM2.5) and elemental carbon attributable to traffic (ECAT), a surrogate of diesel exhaust, were measured using validated land use regression and satellite-based spatio-temporally resolved prediction models, respectively. Three exposure windows were investigated: early-life (birth), recent (12 months prior to yr. 12 visit), and lifetime average. Anxiety and depression were assessed by child report with the Spence Children's Anxiety Scale and Child Depression Inventory-2 at age 12. Regression and distributed lag models controlled for sex, race, age, and household income. Results: Five CpG sites, mapping to 5 genes, were differentially methylated as a result of recent PM2.5 exposure (FDR < 0.05). Distributed lag models suggest significant cumulative effects for most of the CpGs (4 out of 5) with the timing of exposure being an important factor for three CpG sites. The top hit (cg08349910, FDR=0.03) annotates to the gene SRGAP3 which is ubiquitously expressed in the developing nervous system. We observed the methylation status of cg08349910 to be associated with increased symptoms of generalized anxiety, social phobia, and total anxiety. Controlling for ECAT or including an interaction between ECAT and PM2.5 did not change these findings. Additional analyses are being conducted to include nitrogen dioxide and ozone. Conclusions: These data suggest methylation at specific CpGs may serve as biomarkers for particulate matter exposure and identify children at increased risk for anxiety and depression. Keywords: Air pollution, DNA methylation, Mental health