Causal relationship between inflammatory cytokines and posttraumatic stress disorder: a Mendelian randomization study and potential mechanism analysis

Background: Post-traumatic stress disorder (PTSD) is a complex condition linked to inflammation. The causality between inflammatory cytokines and PTSD risk remains unclear.
Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) study using genome-wide association study (GWAS) data from 41 inflammatory cytokines and PTSD. Additional analyses included differential gene expression, protein–protein interaction, and functional enrichment to explore underlying mechanisms.
Results: MR analysis indicated that higher levels of stem cell factor (SCF) and interleukin-4 (IL-4) are associated with a reduced risk of PTSD. Genes POGZ and LRIG2 were identified as mediators, implicated in the TGF-beta signalling pathway.
Conclusion: Our findings suggest a protective role of certain cytokines against PTSD and highlight potential molecular mediators. This knowledge could inform future therapeutic strategies for PTSD.

This study identifies a protective link between specific inflammatory cytokines, namely stem cell factor (SCF) and interleukin-4 (IL-4), and reduced risk of posttraumatic stress disorder (PTSD), highlighting new avenues for PTSD prevention.
Through detailed gene analysis, POGZ and LRIG2 genes are shown to be key mediators in the interaction between cytokines and PTSD risk, offering potential therapeutic targets.
Findings emphasize the role of TGF-beta signalling in PTSD, with implications for developing targeted treatments addressing both inflammation and neuroprotective pathways.

This study identifies a protective link between specific inflammatory cytokines, namely stem cell factor (SCF) and interleukin-4 (IL-4), and reduced risk of posttraumatic stress disorder (PTSD), highlighting new avenues for PTSD prevention.
Through detailed gene analysis, POGZ and LRIG2 genes are shown to be key mediators in the interaction between cytokines and PTSD risk, offering potential therapeutic targets.
Findings emphasize the role of TGF-beta signalling in PTSD, with implications for developing targeted treatments addressing both inflammation and neuroprotective pathways.