Causal role of immune cells in major depressive disorder and bipolar disorder: Mendelian randomization (MR) study

Abstract Major depressive disorder (MDD) and bipolar disorder (BD) are prevalent psychiatric conditions linked to inflammatory processes. This study employs a two-sample Mendelian randomization (MR) approach to investigate the relationship between immune cells and the risk of MDD and BD. Rigorous sensitivity analyses are conducted to assess the reliability, heterogeneity, and horizontal pleiotropy of the findings. The study reveals a significant association between immune cell profiles and the susceptibility to MDD and BD. Specifically, 29 immunophenotypes exhibit a substantial connection with MDD risk, including CD27 on IgD⁺ CD38⁻ unswitched memory B cell (inverse variance weighting (IVW): odds ratio(OR) [95%]: 1.017[1.007 to 1.027], p = 0.001), CD27 on IgD⁺ CD24⁺ (IVW: OR [95%]: 1.021 [1.011 to 1.031], p = 4.821×10 − 5), CD4 on Central Memory CD4⁺ T cell(IVW: OR [95%]:0.979 [0.963 to 0.995], p = 0.011) and the other 25 immunophenotypes. Additionally, 35 immunophenotypes demonstrate a significant association with BD risk, such as CD33br HLA DR⁺ AC AC (IVW: OR [95%]: 1.022[1.007 to 1.036], p = 0.007), CD28⁺ CD45RA- CD8br %T cell RC (IVW: OR [95%]: 1.024 [1.008 to 1.041], p = 0.004) CD62L on CD62L⁺ myeloid DC MFI (IVW: OR [95%]:0.926 [0.871 to 0.985], p = 0.014)), and the other 32 immunophenotypes. This MR study provides robust evidence supporting a causal relationship between immune cells and the susceptibility to MDD and BD, offering valuable insights for future clinical investigations.