Causal effects of depression on prostatitis: a two-step Mendelian randomisation study with immune cell mediation

Depression has a significant global impact. Previous studies have suggested a link between depression and prostate diseases. However, these studies are often observational and may be influenced by confounding factors and reverse causality. This research aimed to explore the potential causal relationship between depression and prostate diseases using Mendelian randomisation (MR) and to assess the mediating role of immune cell phenotypes.

We utilised MR methods with genome-wide association studies (GWAS) data. The analysis was conducted in two phases: (a) a two-sample MR to investigate the impact of depression on prostate diseases; and (b) a two-step MR to evaluate the mediating effect of 731 immune cell phenotypes. Depression data were obtained from an extensive GWAS involving 480 359 participants across multiple European cohorts. Prostate disease data, including prostatitis, prostate cancer, and benign prostatic hyperplasia, were obtained from European-based GWAS. Independent single nucleotide polymorphisms related to depression were selected based on genome-wide significance criteria. Various MR methods, including inverse variance weighting, weighted median, MR-Egger, MR-PRESSO, MR-Robust, and MR-RAPS, were employed to ensure robust causal inference.

The MR analysis revealed a potential causal relationship between depression and an increased risk of prostatitis (odds ratio = 1.606, P = 8.35E-04). Sensitivity analysis confirmed the robustness of these findings. Additionally, a two-step MR analysis identified CD24+ CD27+ %lymphocytes as a potential mediator, with a mediation effect of 0.108 (P = 0.03), accounting for 22.78% of the total effect.

This study offers novel genetic evidence for the causal relationship between depression and prostatitis, with immune cells identified as potential mediators in this process. These findings highlight the importance of psychological factors in developing prostatitis and suggest that immune cells could be novel therapeutic targets.