Abstract
BACKGROUND: Numerous clinical studies have investigated the association between schizophrenia and psoriasis, but the findings remain inconsistent. METHODS: We employed Mendelian randomization (MR) methods to evaluate the causal relationship between schizophrenia and psoriasis and its subtypes. Inverse variance weighting was used as the primary approach for MR analysis, complemented by inverse magnetic resonance analysis and sensitivity testing. To identify potential mediators, we applied a two-step MR approach. Additionally, pathway and functional enrichment analyses were conducted to uncover possible mechanisms linking schizophrenia and psoriasis. RESULTS: MR analysis indicated an association between schizophrenia and psoriasis (OR: 1.0010; p = 0.008). Subtype analyses revealed that genetic susceptibility increased the risk of developing psoriasis vulgaris (OR: 1.18; 95% CI: 1.03-1.34; p = 0.016) but was not significantly associated with arthropathy (OR: 1.04; 95% CI: 0.97-1.12; p = 0.292). Emotional states such as tenseness, tiredness, and misery fulfil the criteria of the MR two-step approach and can be considered as potential mediators of the association between schizophrenia and psoriasis vulgaris. Pathway and functional enrichment analyses suggested the involvement of oxidative stress-driven hypothalamic-pituitary-adrenal (HPA) axis pathways in the link between schizophrenia and psoriasis. CONCLUSION: Our MR study established a significant association between schizophrenia and psoriasis vulgaris, identifying tenseness, tiredness, and misery as potential mediators. Pathway and functional enrichment analyses indicated that oxidative stress in the HPA axis may represent a shared mechanism underlying schizophrenia and psoriasis.