Association of metabolic syndrome with comorbid major depressive disorder in remitted schizophrenia: a cross-sectional study

To estimate the prevalence of comorbid major depressive disorder (MDD) among adults with remitted schizophrenia and to examine whether metabolic syndrome (MetS) is associated with this comorbidity after accounting for key clinical and sociodemographic factors. In this cross-sectional study, 218 adults with remitted DSM-5 schizophrenia were evaluated in a tertiary outpatient clinic (July 2022–July 2023). Depressive symptoms were screened using the Calgary Depression Scale for Schizophrenia (CDSS; cut-off ≥ 7), and DSM-5 MDD was confirmed using the Structured Clinical Interview for DSM-5 (SCID-5). MetS was defined per NCEP ATP III criteria using anthropometric measures obtained at the study visit and laboratory values from medical records within the preceding 6 months. Group comparisons and sequential multivariable logistic regression models specified a priori were fitted. Model 1 adjusted for age, sex, smoking status, illness duration, and antipsychotic treatment category (first-generation, second-generation, clozapine, and combination therapy). Model 2 (primary) additionally included PANSS positive symptom severity. Sensitivity analyses included adjustment for antidepressant use and replacement PANSS positive with PANSS total score. Comorbid MDD was identified in 33.0% of participants. Overall MetS prevalence was 39.0%, and MetS was more frequent in participants with MDD than those without (55.6% vs. 30.8%, p < 0.01). In Model 1, MetS was associated with comorbid MDD (OR = 2.91, 95% CI: 1.57–5.40, p = 0.001). In the primary model, MetS remained associated with MDD after additionally adjusting for PANSS positive symptom severity (OR = 3.60, 95% CI: 1.85–6.99, p < 0.001), and higher PANSS positive scores were also associated with MDD (per-point OR = 1.17, 95% CI: 1.09–1.25, p < 0.001). After additional adjustment for antidepressant use, the MetS–MDD association remained significant (OR = 3.30, 95% CI: 1.66–6.55, p = 0.001), and antidepressant use was also associated with MDD (OR = 3.55, 95% CI: 1.73–7.29, p = 0.001). In the alternative model using PANSS total, the MetS–MDD association remained statistically significant (OR = 3.82, 95% CI: 1.92–7.59, p < 0.001). MDD is common among remitted patients with schizophrenia and is significantly associated with MetS. Given the cross-sectional design and the timing window for metabolic measurements, temporality cannot be established; therefore, clinical implications should emphasize screening for depressive symptoms alongside cardiometabolic risk monitoring. Longitudinal studies are warranted to clarify directionality and mechanisms.