Molecular mechanisms underlying psoriasis and depression: an integrated analysis using mendelian randomization, transcriptomics, and single-cell sequencing

Background: Psoriasis, an immune-mediated systemic inflammatory disease affecting skin, vessels, and joints, often co-occurs with depression. Routine depression screening is vital, as mood disorders link to inflammation, visible lesions, and functional limitations. Methods: The study integrated Mendelian randomization (MR), transcriptomics, and single-cell omics via public databases to explore comorbidity mechanisms. Results: ), enriched in IL-17/NF-κB/FoxO pathways, cholesterol metabolism, and synaptic cycling. They correlated with immune infiltration, ferroptosis, and specific cell localization. Folic acid (from CTD) targeted 3 genes. Conclusion: These 4 genes mediate comorbidity via inflammation, immune metabolism, and ferroptosis. Folic acid pathways have therapeutic value, laying a foundation for precision therapy.