Abstract
Schizophrenia patients with depressive symptoms may represent a distinct clinical subtype with unique metabolic features. This study investigated divergent metabolic-psychopathological patterns in first-episode drug-naïve schizophrenia (FEDN-SCZ) patients stratified by depressive symptoms. We recruited 289 FEDN-SCZ patients and 128 healthy controls. Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and depressive symptoms were evaluated with the 24-item Hamilton Depression Rating Scale (HAMD-24). Patients were stratified into subgroups based on HAMD-24 cut-off scores. Metabolic parameters, including uric acid (UA), fasting glucose, glycated hemoglobin (HbA1c), fasting insulin, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol, were systematically measured. FEDN-SCZ patients exhibited marginally higher UA levels than healthy controls (p = 0.050), with elevated levels observed in patients with depressive symptoms compared to those without (351.41 vs. 317.64 µmol/L, p = 0.047). The UA-PANSS association was moderated by depressive status (significant interactions for negative, general, and total PANSS scores, all p < 0.05), with simple slopes significant only in the depression group. Multiple regression analyses revealed subgroup-specific predictors: in the depressive subgroup, higher UA was associated with greater symptom severity, while HDL-C showed a protective effect; in non-depressive patients, glycemic indices (HbA1c and glucose) emerged as significant predictors (p < 0.05). The UA-psychopathology association was exclusive to FEDN-SCZ patients with depressive symptoms, while non-depression patients were characterized by glucose and energy dysregulation. These findings underscore the importance of stratified management strategies addressing both psychiatric and metabolic health.