Association of Elevated Urinary Cadmium Levels with Schizophrenia and Treatment Response on Negative Symptom Remission

Schizophrenia is a severe mental disorder where negative symptoms remain a major therapeutic challenge. Growing evidence suggests that environmental factors, including heavy metals, may contribute to its pathogenesis. This study investigated the dual role of urinary cadmium as both a risk factor for schizophrenia and a predictor of treatment response. In this case-control study of 34 schizophrenia patients and 33 healthy controls, we found that patients had significantly higher baseline urinary cadmium levels than controls (P < 0.0001). Firth’s logistic regression revealed a dramatically increased risk of schizophrenia in individuals with high cadmium levels, even after adjusting for age, BMI, and lifestyle factors (Adjusted OR = 569.65, 95% CI: 32.60–48771.81, P < 0.001). The diagnostic performance of urinary cadmium was robust, with an AUC of 0.79. Critically, in the longitudinal analysis of patients, baseline log-transformed cadmium levels were significantly and negatively correlated with the 8-week improvement in PANSS negative scores (r = -0.44, P = 0.01), indicating that higher cadmium exposure predicted poorer outcomes. This was confirmed by multiple linear regression, which showed that baseline cadmium was an independent predictor for diminished improvement in negative symptoms (Adjusted β = -5.60, P = 0.04) after controlling for initial symptom severity, chlorpromazine treatment and other covariates. In conclusion, elevated urinary cadmium appears to be a powerful risk factor for schizophrenia and, innovatively, a potential prognostic biomarker for poor response of negative symptoms to treatment. These findings underscore the importance of environmental neurotoxicants in the clinical course of schizophrenia and suggest that cadmium screening could aid in risk stratification and tailoring individualized therapies.