Psoriasis is frequently accompanied by depression. However, the role of specific symptom domains, including cognitive-affective and somatic symptoms, as well as potential metabolic mediators between psoriasis and depression, remains unclear.
Methods
We analyzed data from the National Health and Nutrition Examination Survey (NHANES, n = 14,964) and the Health and Retirement Study (HRS, n = 4364). Depressive symptoms were classified into cognitive-affective and somatic domains. Cross-sectional associations were evaluated in NHANES, and longitudinal symptom trajectories were identified in HRS using group-based trajectory modeling. Based on genome-wide association study summary statistics, bidirectional and two-step Mendelian randomization (MR) were performed to assess causality and identify plasma metabolite mediators.
Results
In NHANES, total depressive symptoms (OR = 1.03, 95% CI: 1.01-1.06, P = 0.018) and somatic symptoms (OR = 1.08, 95% CI: 1.03-1.12, P = 0.003) showed positive associations with psoriasis, but not cognitive-affective symptoms. In HRS, persistently high trajectories of total (OR = 1.58, 95% CI: 1.08-2.32, P = 0.018) was associated with psoriasis, with no significant association for the cognitive-affective and somatic domains after full adjustment. MR supported a causal relationship of psoriasis on depression and identified sphingomyelin (d17:2/16:0, d18:2/15:0) and urate as mediators, accounting for 10.2% and 6.8% of the total effect, respectively.
Conclusion
Depressive symptoms were linked to psoriasis in both cross-sectional and longitudinal analyses. Lipid and antioxidant-related pathways involving sphingomyelin and urate may mediate the relationship between psoriasis and depression, offering potential targets for intervention.
