Associations Between Major Depressive Disorder, Multimorbidity Burden, and Inflammatory Biomarkers (NLR, PLR, MLR,...

Background/Objectives: Major depressive disorder (MDD) frequently coexists with chronic diseases and inflammatory processes, particularly in primary care. The primary aim of this study was to investigate the association between MDD and multimorbidity burden (≥2 chronic diseases), while the secondary aim was to examine the relationship between MDD and routinely available inflammatory biomarkers. Methods: This retrospective cross-sectional study used electronic medical records from a Family Health Center in Türkiye between 1 January 2025 and 31 December 2025. Individuals aged ≥18 years with accessible records, complete laboratory data, and recorded sociodemographic/lifestyle variables were included. Patients were considered to have MDD if a psychiatrist-diagnosed MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), was recorded in the electronic medical system within the past year. Multimorbidity burden was defined as the total number of chronic diseases and was further dichotomized as ≥2 versus <2 for multivariable regression analysis. Inflammatory biomarkers were calculated from routine blood tests: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and monocyte-to-HDL cholesterol ratio (MHR). Group comparisons and logistic regression were performed to evaluate associations with MDD. Results: A total of 3006 patients were analyzed; 375 (12.5%) had MDD. Participants with MDD were older and more frequently female, had higher body mass index and waist circumference, and exhibited a substantially higher burden of chronic comorbidities. PLR was higher in the MDD group (p = 0.019), whereas MHR was lower (p = 0.004); NLR, MLR, and SII did not differ significantly. In multivariable analysis, increasing age (OR 1.029, 95% CI 1.019-1.039, p < 0.001), female sex (OR 2.659, 95% CI 1.949-3.636, p < 0.001), and multimorbidity (OR 2.162, 95% CI 1.650-2.833, p < 0.001) were independently associated with MDD, whereas PLR and MHR were not independently associated after adjustment. Conclusions: In this large real-world primary care cohort, MDD was common and strongly linked to multimorbidity. Although PLR and MHR differed significantly between groups, they were not independently associated with MDD after adjustment, suggesting that these differences may be driven by multimorbidity and related clinical factors rather than independent disease-specific effects.