Human endogenous retroviruses type W (HERV-) activation and schizophrenia: A meta-analysis

Objective: Human endogenous retroviruses (HERV) are the remnants of infections that occurred million years ago. They gradually integrated into the human genome, comprising 8 % of it. There are growing reports suggesting their potential role in various diseases, including schizophrenia. Schizophrenia, a serious psychiatric disorder, is caused by the interaction of genetic and environmental factors. In the present paper, we investigated studies focusing on the association between schizophrenia and HERV-W. Methods: We registered this study at PROSPERO (registration number: CRD42022301122). The entire steps of this study were based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. We searched PubMed, Scopus, Web of Science, and Google Scholar up to 1 August 2022. Heterogeneity was estimated through I2 statistics, and the association was measured using the first estimate and penalization methods. Results: Finally, 13 eligible studies were analyzed, including 698 cases and 728 controls. The overall odds ratio indicated a significant association in both the first estimate (OR = 9.34, 95 % CI = 4.92-17.75; P = 0.002) and penalization (OR = 7.38, 95% CI = 4.15-13.10; P = 0.003) methods. In the subgroup analysis, among HERV-W fragments, the HERV-W envelope protein or RNA (OR = 11.41, 95 % CI: 5.67-22.97; P = 0.03) showed the strongest association with schizophrenia. Conclusion: Our meta-analysis showed that HERV-W is significantly associated with schizophrenia. More studies are required to determine the pathophysiological mechanism and the diagnostic, prognostic, and therapeutic value of HERV-W in schizophrenia.