Akgül, ÖzerDemirel, Ömer FarukTosun, İlkerKavla, YasinKırkpınar, Mehmet MuratSapmaz, BurcuŞenyiğit, GülçinÇalışkan, ReyhanÖner, Yaşar Ali2025-11-042025-11-042025Akgül, Ö., Demirel, Ö. F., Tosun, İ., Kavla, Y., Kırkpınar, M. M., Sapmaz, B., Şenyiğit, G., Çalışkan, R., & Öner, Y. A. (2025). Unveiling the interplay of EBV, HSV-1, and ınflammatory biomarkers in psychiatric disorders. Journal of Clinical Medicine, 14(19), pp. 1-11. https://doi.org/10.3390/jcm141967302077-0383https://doi.org/10.3390/jcm14196730https://hdl.handle.net/20.500.13055/1160Background/Objectives: Schizophrenia (SCH), bipolar disorder (BPD), and major depres sive disorder (MDD) are increasingly viewed as neuroimmune disorders shaped by viral exposure and inflammation. Disorder-specific immunovirological profiles, however, re main poorly defined. Methods: In this cross-sectional study, we assessed Epstein–Barr Virus (EBV) and Herpes Simplex Virus type 1 (HSV-1) seropositivity and measured serum CRP, IL-6, and IL-1β in 708 participants: 110 with SCH, 121 with BPD, 135 with MDD, and 342 healthy controls (HC). Statistical analyses included Shapiro–Wilk tests for nor mality; Kruskal–Wallis with Bonferroni-adjusted Dunn post hoc comparisons; and logistic regression adjusted for age, sex, and marital status. Results: EBV seropositivity was higher in SCH (90.9%) than in HC (78.9%) (OR = 3.46, 95% CI: 1.68–7.12; p = 0.001) but not in BPD or MDD. HSV-1 seropositivity was elevated in BPD (83.5%) versus HC (67.0%) (OR = 2.29, 95% CI: 1.34–3.92; p = 0.003), with no differences in SCH or MDD. Inflammatory biomarkers were significantly increased in SCH and MDD compared to HC (p < 0.001), while BPD showed no differences. Conclusions: The findings delineate distinct immunovi rological patterns across major psychiatric disorders. Schizophrenia was characterized by EBV seropositivity accompanied by systemic inflammatory activation, bipolar disorder by HSV-1 seropositivity in the absence of inflammatory changes, and major depressive disor der by inflammatory dysregulation independent of viral exposure. These disorder-specific profiles highlight heterogeneity in neuroimmune pathways and underscore the potential relevance of biomarker-based stratification for generating hypotheses regarding targeted antiviral or anti-inflammatory interventions in psychiatric populations.eninfo:eu-repo/semantics/openAccessPsychiatric DisordersEpstein–Barr Virus (EBV)Herpes Simplex Virus Type 1 (HSV-1)Inflammatory BiomarkersImmunopsychiatryArticle10.3390/jcm141967301419111Q1PMID: 41095809Q1