Causal Relationship Between Post-Traumatic Stress Disorder and Immune Cell Traits: A Mendelian Randomization Study

IntroductionPost-traumatic stress disorder (PTSD) is a debilitating psychological disorder that occurs after exposure to catastrophic-level experiences. Although alterations in immune function have been identified in individuals with PTSD, the causal relationship between the two remains unclear.MethodsTo investigate the causal relationship between PTSD and immune function, we conducted the forward and backward two-sample Mendelian randomization (MR) analyses, based on summary-level genome-wide association studies (GWAS) data on PTSD and immune cell traits.ResultsFor the forward MR analysis, PTSD was found to reduce the levels of CD62L- dendritic cell (DC) (beta = -0.254, FDR = 0.01), CD86+ myeloid DC (beta = -0.238, FDR = 0.014), CD62L- myeloid DC (beta = -0.26, FDR = 0.01), CD62L- CD86+ myeloid DC absolute count (beta = -0.264, FDR = 0.024), and CD62L- CD86+ myeloid DC (beta = -0.328, FDR = 0.002). In contrast, PTSD was observed to increase the level of CD28- CD8dim T-cell absolute count (beta = 0.27, FDR = 0.029). For the backward MR analysis, the odds ratio (OR) for CD33 on CD33dim HLA DR+ CD11b- in relation to PTSD risk was found to be 1.045 (95% CI = 1.021-1.069, FDR = 0.008). The OR for FSC-A on HLA DR+ CD8br was 1.048 (95% CI = 1.018-1.079, FDR = 0.039) and for CCR2 on CD14- CD16+ monocyte was 1.059 (95% CI = 1.027-1.092, FDR = 0.008). No significant pleiotropy was detected in both forward and backward MR analyses.ConclusionThe bidirectional MR study shed light on the intricate interplay between immune function and PTSD. The identification of a bidirectional causal relationship between T cells and PTSD opens new avenues for considering innovative approaches to the prevention and early intervention of PTSD. We explored the causal relationship between post-traumatic stress disorder (PTSD) and immune cells using a Mendelian randomization study approach on the basis of publicly available genome-wide association studies (GWAS) data. The results revealed that PTSD affects some immune cell levels, whereas individual immune cells also increase the risk of developing PTSD. This demonstrates the complex relationship between PTSD and immune function. image