Epstein–Barr virus infection increases the risk of depression: A cross-sectional study and Mendelian randomization analysis

Abstract

Depression, a common psychiatric disorder with multiple causes, has been increasingly linked to viral infections, especially herpesviruses. Epstein-Barr virus (EBV), is a widely infecting Herpesviridae virus. Although some studies have suggested that EBV may be associated with depression, a causal relationship remains unclear. This study aims to explore this link via NHANES data and GWAS findings. We conducted a cross-sectional analysis of 730 NHANES participants aged 18‐‐19 years and used weighted regression to assess the link between EBV levels and depression. Subsequently, we conducted univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses with GWAS data from 27,568 depression cases and 457,030 controls and used associated SNPs as instrumental variables to explore the causality and mediators of the EBV-depression association. After controlling for various factors, a significant link between EBV antibody levels and depression persisted, with a nonlinear association (P < 0.001). UVMR analysis revealed a positive causal effect of EBV on depression (OR = 1.008, 95 % CI 1.004–1.012, P < 0.001), implying that it could be a risk factor for depression. The MVMR suggested that IL-6 and CRP may serve as intermediary factors in this process. Cross-sectional studies have revealed a significant link between EBV infection and depression. Furthermore, MR studies have implicated a potential causal role of EBV in the pathogenesis of depression. These findings could inform depression treatment strategies for EBV-infected individuals and provide new insights into the pathogenesis of depression.