Assessment of the causal influence of herpesvirus infections on the risk of depression phenotypes: A Mendelian randomization study

Objective

Previous findings of associations between herpesvirus infections and depression were mixed and did not implicate causality. This study used two-sample Mendelian randomization (MR) to clarify the causal impact of four symptomatic herpesvirus infections (shingles, chicken pox, cold sores, and mononucleosis) on three depression phenotypes, including depressive symptoms (DS), number of episodes with depressed mood (NEDM), and major depressive disorder (MDD).

Methods

Eligible SNPs were selected as instrumental variables (IVs). MR estimates were primarily based on the inverse variance weighted (IVW) method. Cochran's Q, MR-Egger intercept tests, and leave-one-out analyses were performed to assess the robustness of the results. False discovery rates (FDR) were calculated to correct the bias of multiple testing. Sensitivity analyses were performed by repeating the above process using IVs meeting a more relaxed threshold.

Results

Estimates of the main MR analyses suggested that shingles was associated with an increased risk of DS (IVW β = 0.040, FDR = 0.008) and NEDM (IVW β = 0.056, FDR = 0.003), which was supported by the sensitivity analyses. The effects of chicken pox on DS and NEDM were non-significant in the main analyses, whereas significant in the sensitivity analyses (for DS: IVW β = 0.063, FDR = 0.027; for NEDM: IVW β = 0.151, FDR = 0.039). None of the four herpesvirus infections was linked to MDD.

Conclusion

Our findings provide evidence that shingles is causally linked to specific depression phenotypes. Enhancing antiviral treatments and vaccination programs may promote the prevention of depression.