Unveiling the Interplay of EBV, HSV-1, and Inflammatory Biomarkers in Psychiatric Disorders


Akgül Ö., DEMİREL Ö. F., Tosun İ., KAVLA Y., KIRPINAR M. M., Sapmaz B., ...More

Journal of Clinical Medicine, vol.14, no.19, 2025 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 14 Issue: 19
  • Publication Date: 2025
  • Doi Number: 10.3390/jcm14196730
  • Journal Name: Journal of Clinical Medicine
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Directory of Open Access Journals
  • Keywords: Epstein–Barr Virus (EBV), Herpes Simplex Virus type 1 (HSV-1), immunopsychiatry, inflammatory biomarkers, psychiatric disorders
  • Istanbul University Affiliated: Yes

Abstract

Background/Objectives: Schizophrenia (SCH), bipolar disorder (BPD), and major depressive disorder (MDD) are increasingly viewed as neuroimmune disorders shaped by viral exposure and inflammation. Disorder-specific immunovirological profiles, however, remain 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 normality; 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 immunovirological 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 disorder 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.