Metal exposure and internalizing and externalizing psychobehavioral problems in a Chinese early adolescent cohort

Our study aimed to assess cross-sectional and longitudinal associations between exposure to individual metals (vanadium [V], chromium [Cr], manganese [Mn], iron [Fe], cobalt [Co], nickel [Ni], copper [Cu], zinc [Zn], arsenic [As], molybdenum [Mo], cadmium [Cd], and lead [Pb]), and metal mixtures and internalizing (depression, anxiety, suicidality) and externalizing (aggression) psychobehavioral problems in adolescents.

This study consisted of 1,398 Chinese adolescents (mean age = 12.48 ± 0.48 years) with a 2-year follow-up period. Cross-sectional (baseline serum metal exposure vs. baseline outcomes) and longitudinal (baseline serum metal exposure vs. outcomes at 2-year follow-up) analyses were conducted. Regression models for single and multiple metals employed linear regression (aggression) and modified Poisson regression (depression/anxiety/suicidality). The effects of metal mixtures were analyzed using quantile g-computation (qgcomp) and Bayesian Kernel Machine Regression (BKMR). All analyses were sex-stratified (single-/multi-metal/BKMR models) and included interaction terms for single-/multi-metal/qgcompint models.

No significant associations of individual metals or metal mixtures with outcomes were observed in the overall sample. Sex-stratified analyses showed cross-sectional associations between iron (Fe), zinc (Zn), and aggression in males (β = -2.05, 95 % CI: -3.37 to -0.74; β = -1.80, 95 % CI: -3.08 to -0.53). Females showed a longitudinal association between vanadium (V) and depression (RR = 0.57, 95 % CI: 0.43 to 0.76). Interaction analysis revealed a significant Zn-by-sex interaction (FDR-P = 0.036), but qgcompint revealed no significant mixture-by-sex interactions. BKMR indicated null mixture effects in males, but inverse associations with new-onset depression/anxiety in females when all metals exceeded the 60th percentile, with vanadium(V) and arsenic(As) showing highest importance (PIPs: V = 0.994, As = 0.833).

These findings highlight sex-specific relationships between metals and psychobehavioral outcomes, warranting further validation.