Mehmet Murat KIRPINAR, İrem YILDIRIM, Sarp YOLDAŞ, Furkan TOKSOY, Merve Rana ALTUNEL, Zeynep Özge DAĞOĞLU, Cana Aksoy POYRAZ, Ömer Faruk DEMİREL
Psychiatry and Behavioral Sciences - 2026;16(3):181-191
Objective: Increasing evidence suggests that inflammatory processes may play a role in the pathophysiology of mood disorders. However, the diagnostic utility of inflammatory biomarkers in distinguishing bipolar from unipolar depression remains unclear. Methods: This retrospective study included 810 inpatients diagnosed with bipolar disorder (n = 444) or unipolar depression (n = 366). Inflammatory markers, including CRP, neutrophil count, NLR, SII, and SIRI, were obtained within 24 hours of admission. Group comparisons, hierarchical logistic regression analyses, ROC analyses, and multivariable linear regression models were performed. Results: Inflammatory markers were significantly elevated in bipolar mania compared to depressive groups. In logistic regression analyses restricted to depressive episodes, higher NLR (OR = 1.21, p = .004), SII (OR = 1.0006, p = .003), and SIRI (OR = 1.21, p = .021) were associated with bipolar depression; however, effect sizes were modest. Clinical variables, including hospitalization history and treatment exposure, demonstrated stronger associations with diagnostic classification. ROC analyses revealed poor discriminative performance for all markers (AUCs ? 0.55). In linear regression models, hospitalization frequency, lithium, and antipsychotic use were not associated with inflammatory markers, whereas valproic acid use was associated with lower levels (all p < .001). Conclusion: Although inflammatory markers are associated with bipolar disorder, their ability to distinguish bipolar from unipolar depression is limited. These findings suggest that inflammatory biomarkers reflect state-dependent processes rather than stable diagnostic differences and therefore have limited value as standalone diagnostic tools.
