Beyond Infection: The Interplay of Salivary Human Herpesvirus 6, Stress, and Host Factors in Major Depressive Disorder

Human Herpesvirus 6 (HHV-6) is a neurotropic virus associated with lifelong latency and stress-induced reactivation. Its role in major depressive disorder (MDD) remains unclear. This study investigated the association between HHV-6 infection and MDD and evaluated interaction effects with psychosocial and clinical factors. A cross-sectional study was conducted among 2403 university students in Thailand, including 52 participants with physician-diagnosed MDD and 2351 healthy controls. HHV-6 DNA was detected by quantitative polymerase chain reaction (qPCR) using saliva. Logistic regression and interaction analyses were performed. HHV-6 DNA was detected in 50.7% of participants. HHV-6 infection was not significantly associated with MDD (OR = 1.335, 95% CI: 0.766–2.328, p = 0.309). Multivariable analysis identified congenital disease, high-fat food consumption, stress, and depressive symptoms as independent predictors of MDD. Significant interaction effects were observed between HHV-6 and several factors. HHV-6 was not independently associated with MDD; however, exploratory interaction analyses identified potential relationships with selected psychosocial and host-related factors that require further validation.