Unsaturated fatty acids mediate the bidirectional link between psoriasis and depression: Evidence from observational and mendelian randomization studies
Abstract
Background: Depression is a prevalent and debilitating comorbidity of psoriasis. While the epidemiological association between the two conditions is well established, the causal relationship and the underlying biological mechanisms remain insufficiently understood.
Objectives: To evaluate the causal association between psoriasis and depression, as well as the mediating function of circulating unsaturated fatty acids (UFAs).
Methods: We combined cross-sectional analysis of 211 psoriasis patients, high-throughput serum metabolomics, and bidirectional Mendelian randomization (MR) using large-scale genome-wide association studies (9267 psoriasis cases; 170,756 depression cases). Multivariable MR analyses were adjusted for body mass index (BMI) and smoking. Two-step MR mediation was used to assess the role of UFA phenotypes.
Results: Clinically significant depressive symptoms (PHQ-9 ≥ 10) were present in 32.7% of patients and were independently associated with higher BMI, smoking, special site involvement, and higher PASI scores. MR analyses indicated a robust bidirectional causal relationship between psoriasis and depression, independent of BMI and smoking. Serum metabolomics revealed reduced omega-3 PUFAs (DHA, DPA, ETA) and elevated MUFAs in psoriasis patients with depression. Mediation MR identified the DHA-to-total fatty acid ratio as a key causal intermediary from psoriasis to depression, whereas depression liability altered PUFA/MUFA ratios to promote psoriasis risk.…
How strong is the evidence?
Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 211 participants or records.
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