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. Antecedentes: El Trastorno de Estr & eacute;s Postraum & aacute;tico (TEPT) es una condici & oacute;n compleja relacionada con la inflamaci & oacute;n. La causalidad entre las citoquinas inflamatorias y el riesgo de TEPT no est & aacute;n esclarecidas.M & eacute;todos: Condujimos un estudio bidireccional de aleatorizaci & oacute;n Mendeliana (AM) de dos muestras utilizando datos de estudios de asociaci & oacute;n de todo el genoma (GWAS en sus siglas en ingles) de 41 citoquinas inflamatorias y TEPT. Los an & aacute;lisis adicionales incluyeron expresi & oacute;n gen & eacute;tica diferencial, interacci & oacute;n prote & iacute;na-prote & iacute;na y enriquecimiento funcional para explorar los mecanismos subyacentes.Resultados: El an & aacute;lisis de AM indicaron que niveles m & aacute;s altos de factor de c & eacute;lulas madre (SCF en sus siglas en ingles) e interleukina-4 (IL-4) se asociaban con un menor riesgo de TEPT. Se identificaron los genes POGZ y LRIG2 como mediadores, implicados en la v & iacute;a de se & ntilde;alizaci & oacute;n TGF-beta.Conclusi & oacute;n: Nuestros hallazgos sugieren un papel protector de ciertas citoquinas contra el TEPT y destacan los posibles mediadores moleculares. Este conocimiento podr & iacute;a orientar futuras estrategias terap & eacute;uticas para el TEPT.