Shafiee Arman, Nakhaee Zahra, Amini Mohammad Javad, Abianeh Fatemeh Esmailpur, Goodarzi Mana, Omran Samira Parvizi, Hajishah Hamed, Sadeghi Dina, Nejad Aida Rezaei, Bakhtiyari Mahmood
Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran.
Student Research Committee, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran.
J Neurovirol. 2025 Apr;31(2):145-153. doi: 10.1007/s13365-025-01246-x. Epub 2025 Mar 26.
Human herpesviruses (HHVs) are lifelong pathogens that can reactivate under stress or immunological changes. Depression has been implicated as both a potential trigger for and a consequence of HHV reactivation. This study investigates the bidirectional relationship between HHV reactivation and depression through a systematic review and meta-analysis.
This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD42024565616). A search of PubMed, Web of Science, Embase, and Scopus identified studies published through March 5, 2024.
Nineteen studies, representing a total sample size of 94,194 participants, were included in the meta-analysis. The pooled odds ratio (OR) demonstrated a significant association between HHV reactivation and depression (OR = 1.33; 95% CI: 1.07-1.64; p < 0.001; I = 92%). Subgroup analyses revealed significant associations for Epstein-Barr virus (EBV) (OR = 1.99; 95% CI: 1.80-2.20) and herpes simplex virus 2 (HSV-2) (OR = 1.83; 95% CI: 1.32-2.55), while cytomegalovirus (CMV) and HSV-1 showed non-significant associations. A secondary meta-analysis found a significant association between pre-morbid depression and EBV reactivation (OR = 2.18; 95% CI: 1.48-3.21) as well as varicella-zoster virus (VZV) reactivation (HR = 1.09; 95% CI: 1.06-1.13). Sensitivity analyses confirmed the robustness of the findings, and no substantial publication bias was detected.
This study provides evidence of a bidirectional relationship between HHV reactivation and depression, highlighting depression as both a risk factor for and a potential consequence of HHV reactivation.
人类疱疹病毒（HHV）是终身性病原体，可在压力或免疫变化下重新激活。抑郁症被认为既是HHV重新激活的潜在触发因素，也是其后果。本研究通过系统评价和荟萃分析调查HHV重新激活与抑郁症之间的双向关系。
本系统评价和荟萃分析遵循PRISMA指南，并在PROSPERO（CRD42024565616）中注册。检索了PubMed、科学网、Embase和Scopus，以确定截至2024年3月5日发表的研究。
荟萃分析纳入了19项研究，总样本量为94194名参与者。合并优势比（OR）显示HHV重新激活与抑郁症之间存在显著关联（OR = 1.33；95%CI：1.07 - 1.64；p < 0.001；I = 92%）。亚组分析显示，爱泼斯坦 - 巴尔病毒（EBV）（OR = 1.99；95%CI：1.80 - 2.20）和单纯疱疹病毒2型（HSV - 2）（OR = 1.83；95%CI：1.32 - 2.55）存在显著关联，而巨细胞病毒（CMV）和HSV - 1显示无显著关联。二次荟萃分析发现，病前抑郁症与EBV重新激活（OR = 2.18；95%CI：1.48 - 3.21）以及水痘 - 带状疱疹病毒（VZV）重新激活（HR = 1.09；95%CI：1.06 - 1.13）之间存在显著关联。敏感性分析证实了研究结果的稳健性，未检测到实质性的发表偏倚。
本研究提供了HHV重新激活与抑郁症之间双向关系的证据，突出了抑郁症既是HHV重新激活 的危险因素，也是其潜在后果。
