Schizophrenia with hypozincemia: Clinical features and symptom severity

Schizophrenia (SCZ) is a heterogeneous mental disorder with a complex and multifaceted pathophysiology. Current antipsychotic medications based on the hyperdopaminergic hypothesis, fail to achieve adequate symptom improvement in approximately 30 % of patients, indicating the need for novel treatment strategies grounded on homogenous pathophysiology defined by specific biomarkers. Accumulating evidence indicates the presence of zinc (Zn) deficiency in a subpopulation of individuals with SCZ, although its role in SCZ pathophysiology remains underexplored. In this study, we aimed to characterize the clinical features associated with hypozincemia in SCZ to identify a homogeneous subgroup that may benefit from tailored-made treatment with Zn supplementation. A cohort of 497 individuals with SCZ or schizoaffective disorder was classified into hypozincemia (<80.0 μg/dL) and non-hypozincemia groups. Between-group differences in clinical features were examined, and regression analysis was performed to determine the association between serum Zn levels and positive and negative syndrome scale (PANSS) scores. Hypozincemia was diagnosed in 68.0 % of the study participants. The hypozincemia group was characterized by older age, longer disease duration, more frequent hospitalizations, and higher PANSS scores compared with the non-hypozincemia group. After adjusting for age, hospitalization, and antipsychotic medication use, regression analysis demonstrated a significant negative correlation between serum Zn levels and the positive symptom subscale, general psychopathology subscale, and total score. These findings may enhance the understanding of the mechanisms underlying the clinical severity of SCZ and support the potential use of Zn supplementation to mitigate neuropsychiatric symptoms in patients with hypozincemia.