Depression’s Shadow in First-Onset Schizophrenia: Mapping the Burden and Clinical Significance in Drug-Naïve Patients

Background: Severe depressive symptoms (SDS) are common in patients with schizophrenia (SZ) and are associated with poor prognosis, reduced quality of life, and an increased risk of suicide. However, the prevalence of SDS and its key associated factors in first-onset drug-naïve patients with SZ remain unclear. Methods: This cross-sectional study enrolled 320 inpatients diagnosed with SZ according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), including 164 males and 156 females, aged 18 to 60 years, with a mean disease duration of 2.18 years. The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), anxiety symptoms were evaluated using the Hamilton Anxiety Rating Scale (HAMA), and SDS were assessed using the Hamilton Depression Rating Scale (HAMD). A history of suicide attempts was obtained through standardized interviews. The Kolmogorov-Smirnov test was used to assess the normality of continuous variables. Bonferroni correction was applied to all between-group comparisons of continuous and categorical variables. Univariate analyses and multivariable logistic regression were performed to identify factors independently associated with SDS. A sensitivity analysis excluding patients with a disease duration greater than 12 months was conducted to assess the robustness of the findings. Results: Among the 320 patients with SZ, 159 (49.7%) met the criteria for comorbid SDS. After adjustment for age, sex, disease duration, and marital status, multivariable logistic regression analysis demonstrated that higher PANSS scores (OR = 1.045, 95% CI: 1.024 to 1.067, p < 0.001), higher HAMA scores (OR = 1.284, 95% CI: 1.198 to 1.376, p < 0.001), and a history of suicide attempts (OR = 1.513, 95% CI: 1.222 to 1.875, p < 0.001) were independently associated with comorbid SDS. Excluding patients with a disease duration greater than 12 months (n = 138) did not materially alter the results. Furthermore, a combined model incorporating these three variables demonstrated excellent discriminatory performance, with an area under the receiver operating characteristic curve (AUC) of 0.937 (95% CI: 0.904 to 0.958, p < 0.001). Conclusions: Severe depressive symptoms are highly prevalent among first-onset, drug-naïve patients with schizophrenia and are independently associated with more severe psychotic symptoms, greater anxiety severity, and a history of suicide attempts. These findings provide important evidence to support early screening and targeted interventions for this vulnerable patient population.