Background: It has been proposed that depression plays a role in how psoriasis affects quality of life. However, primary data are limited. Objective: To investigate the role depression plays in how patients experience psoriasis. Methods: Cross-sectional study conducted between January and May 2005. Recruitment of 265 adults with prevalent psoriasis through Internet advertisements. Standardized assessment of depressive symptoms, health-related quality of life (HRQL), illness-related stress, and clinical severity of psoriasis using validated scales. Results: Thirty-two percent of all participants screened positive for depression. We observed a graded relationship between depressive symptoms and HRQL impairment (p < 0.001). Only 16.5% of those with high depression scores were currently treated for depression. Both dissatisfaction with antipsoriatic treatment and illness-related stress were highly associated with depression. After adjustment for HRQL, patients with more severe psoriasis were less likely depressed, although this association failed to reach statistical significance (multiadjusted odds ratio 0.37; 95% CI 0.13–1.02; p = 0.06). Conclusion: Patients with high subjective distress and low objective measures of psoriasis should be evaluated for depression.

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