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.