Exposure to multiple metals and adolescent major depressive disorder: a case-control study in China

Major depressive disorder (MDD) in adolescents is a common mental health problem with a complicated cause and increasing prevalence. Previous studies reported the impact of metals on adolescents with depressive symptoms, but limited evidence is available on the relationship between metals and adolescent MDD.

A total of 203 adolescents with MDD and 203 healthy controls were recruited for this case-control study. Urinary levels of 21 metals were measured using inductively coupled plasma mass spectrometry. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to identify metals for key metals, and conditional logistic regression and Bayesian Kernel Machine Regression (BKMR) were applied to assess individual and joint effects.

In the multi-metal model, higher urinary copper (Cu) and iron (Fe) levels were associated with increased MDD risk, whereas nickel (Ni) and iodine (I) inversely associated. BKMR analysis confirmed positive associations for Cu and Fe and protective effects for Ni and I. The combined metal exposure showed an overall negative association with MDD risk. These associations were consistent across several subgroups.

This research was the first case-control study to explore the relationship between urinary metal levels and adolescent MDD. Our study identified urinary Cu and Fe as risk factors for adolescent MDD, whereas urinary Ni and I were potential protective factors. These findings might provide new light on the future prevention of adolescent MDD.