Association of psychiatric comorbidities with chronic urticaria: a nested case-control study in the All of Us research program.

Background: Chronic urticaria (CU) is characterized by recurring itchy hives lasting more than six weeks, with or without angioedema. Although CU patients are known to have an increased likelihood of psychiatric comorbidities, research exploring this connection in diverse populations remains limited. Objectives: This study investigates the association between CU and psychiatric disorders using the All of Us (AoU) database, a nationwide initiative designed to enhance research in underrepresented populations. Methods: We conducted a nested case-control study among US adults in the AoU program from May 6, 2018 to February 26, 2025. SNOMED codes were used to identify CU cases that were then matched 4:1 to controls by age, sex, ethnicity, and smoking status. Psychiatric comorbidities were assessed using logistic regression models adjusted for hypothyroidism, systemic lupus erythematosus, and rheumatoid arthritis. Results: We identified 1171 CU cases and 4684 matched controls. CU was significantly associated with increased odds of ADHD (OR, 3.61; 95% CI, 2.62-4.96), anxiety (OR, 3.48; 95% CI, 3.03-3.99), depression (OR, 3.26; 95% CI, 2.84-3.75), dysthymia (OR, 3.67; 95% CI, 2.89-4.66), insomnia (OR, 3.27; 95% CI, 2.77-3.86), psychological stress (OR, 3.92; 95% CI, 3.09-4.96), PTSD (OR, 3.25; 95% CI, 2.53-4.17), and substance use disorder (OR, 2.13; 95% CI, 1.74-2.62). Conclusions: These findings highlight the psychiatric burden associated with CU and demonstrates the importance of routine psychiatric screenings for CU patients to allow early intervention. Prospective studies investigating additional psychiatric disorders and underlying mechanisms will help clarify meaningful associations and guide appropriate psychiatric screening and management.