No Evidence for a Causal Association Between Depression and Herpes Zoster or Post-Herpetic Neuralgia: A Mendelian Randomization Study

Xuerong Zhang,* Yuqing Chen,* Jingrun Lin,* Weibing Guo, Hongchun Zhou, Xueying Yang, Qiong Zhao Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiong Zhao, Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, People’s Republic of China, Tel +86-177-2425-0727, Email [email protected] Xueying Yang, Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, People’s Republic of China, Tel +86-188-0204-0810, Email [email protected]: Observational studies have suggested a correlation between depression and herpes zoster (HZ), as well as post-herpetic neuralgia (PHN); however, the causal relationship remains unclear. This study aimed to assess the causal relationships between depression and HZ and PHN via a two-sample bidirectional Mendelian randomization (MR) approach.Methods: We collected data for major depressive disorder (MDD, 246,363 cases/561,190 controls), depressive status (442,840 individuals), HZ (7,132 cases/480,316 controls) and PHN (490 cases/435,371 controls) from genome-wide association studies (GWASs) in European populations, along with depression-related consultations (430 cases/2,152 controls) and zoster infections (2,209 cases/166,603 controls), for validation analysis in East Asian populations. We employed inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and MR-PRESSO for our analysis.Results: Although suggestive, no statistically significant associations were found between genetic MDD and the risk of HZ (IVW, OR: 1.190, 95% CI: 0.984– 1.439, P=0.073) or PHN (IVW, OR: 0.820, 95% CI: 0.428– 1.570, P=0.549) in Europeans. The same was true for depressive status and HZ (IVW, OR: 1.688, 95% CI: 0.820– 3.477, P=0.155) or PHN risk (IVW, OR: 9.535, 95% CI: 0.227– 400.820, P=0.237). In East Asians, genetic depression-related consultation did not significantly affect the risk of herpes infection (IVW, OR: 0.976, 95% CI: 0.922– 1.033, P=0.401). No reverse causality was observed.Conclusion: A comprehensive MR study suggested that depression is not causally related to susceptibility to HZ or PHN, and vice versa. Future studies should focus on how environmental/clinical, not genetic factors that cause depression affect the risk of HZ and PHN.Keywords: depression, herpes zoster, post-herpetic neuralgia, mendelian randomization