The serum trace metal signature distinguishes patients with psychiatric disorders from healthy controls

Mental health disorders (MHD) are conditions marked by disturbances in thinking, mood, or behavior that can cause significant distress or impair daily functioning. Diagnosis remains challenging, particularly in precision medicine, due to the scarcity of reliable biomarkers as objective diagnostic tools and external validators. This study investigates essential trace metals, cofactors in vital enzymes, as potential biomarkers for MHD. A total of 168 patients with mood spectrum disorders (MSD), schizophrenia spectrum disorders (SSD), and personality disorders (PD) and 61 healthy controls (HC) were evaluated for serum levels of zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg), as well as transferrin (TF), transferrin saturation (% TF-sat), ferritin (F), and Cu/Zn, Cu/Mg, Fe/Cu ratios. Principal Component Analysis (PCA) and regression models assessed the relationship between these biological variables and MHD. Zn levels were lower in patients, particularly in the PD group. Fe, TF, and % TF-sat were also lower in patients, with the SSD group showing the greatest decrease. Mg levels were similarly lower in patients than in controls. Zn, Fe, Fe/Cu, and TF showed protective effects against MHD, with odds ratios ranging from 0.22 to 0.50. The Cu/Zn ratio was higher in all patients’ groups. The Cu component, including Cu, Cu/Zn, and Cu/Mg levels, was linked to an 84% increase in the odds of having an MHD. This study highlights the potential of trace metals as adjunctive biomarkers in psychiatry, supporting clinical diagnosis and offering new insights into psychiatric pathophysiology.