Elemental Exposure and Attention-Deficit Hyperactivity Disorder Risk in Population Aged 6–16 Years: Associations and Potential Mediation by Oxylipins

The etiology of attention-deficit hyperactivity disorder (ADHD) is complex and multifactorial. Meanwhile, heavy metals have been associated with circulating oxylipins, which play crucial roles in regulating inflammatory response. Therefore, this case-control study was performed to evaluate the relationships among elemental exposure, oxylipin alterations, and ADHD risk. We also applied an integrated analytical approach to elucidate the mediating role of oxylipins in the association between elemental exposure and the risk of ADHD. All 40 elements were detected in over 75% of the 561 children, and a total of 125 oxylipins were detected in the cohort of 151 individuals. Logistic regression identified 14 elemental exposures significantly associated with ADHD risk. These were further refined to 11 key elements via elastic net regression for subsequent mixture analyses. The Bayesian kernel machine regression results indicated that the combined exposure levels of these elements were associated with increased odds of ADHD within the 25th-75th compared to the 50th percentile level. The quantile g-computation model also revealed a positive association between the elemental mixture level and ADHD risk, with an odds ratio (95% confidence intervals) of 1.72 (1.56, 1.90) for each quartile of the mixture concentration. Changes in four oxylipins were found to be correlated with three elemental levels. In the framework for mixed mediation analysis, the oxylipin risk score mediated 13.3% of the association between the element risk score and ADHD. This discovery not only broadens our understanding of the etiology of ADHD but also provides guidance for future research endeavors.