Genetic evidence on the crucial role of immune cells in postpartum depression: Mendelian randomization analysis

This study aimed to investigate the potential causal relationship between specific immunophenotypes and postpartum depression (PPD).

Using Mendelian randomization (MR) analysis based on publicly available genome-wide association study (GWAS) data, we assessed the causal effects of 731 immune cell traits on the risk of PPD. Immune cell subpopulations were classified, and multivariable MR was performed to account for potential pleiotropy. Functional enrichment analysis of risk-associated single nucleotide polymorphisms (SNPs) was conducted to identify relevant genes and biological pathways.

MR analysis identified 46 immune cells causally associated with PPD. After multiple testing correction, increased levels of immunoglobulin D (IgD⁺) B cells and CD25 on IgD^- CD38dim B cells remained significantly associated with reduced risk of PPD. These associations were robust across multiple sensitivity analyses. Functional enrichment of related SNPs revealed target genes highly expressed in brain tissues and enriched in pathways such as immunoglobulin complex, axon guidance, cell adhesion, and inflammatory response.

The present study provides genetic evidence that IgD⁺ B cells and CD25⁺ IgD^- CD38dim B cells exert protective effects against PPD through mechanisms involving immune regulation and neurodevelopment. These findings highlight the relevance of immune function in the pathophysiology of PPD and suggest promising targets for future therapeutic interventions.