Dissecting the potential causal relationship between immune cells and postpartum depression mediated by plasma metabolites: a mediated Mendelian randomization study

Introduction: Recent studies have shown that immune cells play an important role in PPD, but their causal relationship and potential metabolic mediators are still unclear. This study employed MR to investigate the causal relationships among immune cells, PPD, and potential metabolic mediators. Materials and methods: We collected genetic data from published GWAS, including 731 immune cell phenotypes and 1,400 plasma metabolites. The summary data of PPD were obtained from the FinnGen database. This study used MR analysis to explore the causal relationship between immune cells, blood metabolites, and PPD, supplemented by mediation analysis to identify potential mediating metabolites. Results: The results indicated that 23 immune cell phenotypes were causally related to PPD, with no evidence of reverse causality. Additionally, 36 metabolites exhibited a causal relationship with PPD. According to Mediation analysis, there are 11 plasma metabolites that may guide the intermediary between immune cells and PPD. Inosine levels mediated the causal relationship between CD45RA- CD4+ %T cell and PPD, with a mediation proportion of 30.1% and P = 0.032. Limitations: Our analysis utilized GWAS data derived from European populations, thus constraining the generalizability of our findings to other ethnic groups. Conclusion: This MR study provides new genetic evidence for the association of immune cell phenotype with PPD risk and highlights the mediator role of plasma metabolites. This finding further clarifies the pathogenesis of PPD and provides new insights into its diagnosis and treatment.