Supplementary Material for: Childhood-Onset Celiac Disease Autoimmunity and Risk of Depression and Anxiety Across the Lifespan: A Longitudinal Analysis of a Large Real-World Cohort

Purpose: Celiac disease is associated with various extraintestinal manifestations, including psychiatric and psychological comorbidities. We evaluated the risk of developing depression and anxiety among patients diagnosed with celiac disease autoimmunity (CDA). Methods: This retrospective case-control cohort study was conducted using the Clalit Healthcare Services population-based electronic database (~4.5 million individuals). Between January 1, 2008, and December 31, 2022, we identified subjects aged 1–80 years with a positive IgA anti–tissue transglutaminase test and a repeat measurement within 6–36 months. Depression and anxiety were identified over follow-up using ICD-9 diagnostic codes or by documented regular use of antidepressants or anxiolytics. Results: We identified 3,797 patients with CDA, and the cohort was matched in a 1:3 ratio with 11,387 healthy controls having a negative anti-tTG2 serology. Over a median 60 months follow up duration, 5.9% of CDA patients developed depression or anxiety, compared to 1.7% of the control group (HR 2.89, 95% CI 2.2–3.8, p 10 X ULN), older age at diagnosis, and female sex were independently associated with the risk of developing anxiety and depression among CDA patients (HR 1.82, 1.03, and 1.38, p-values 0.029, 0.018 and 0.038, respectively). Conclusions: CDA appears to increase the risk for anxiety and depression, particularly with very high baseline anti-tTG2 levels, advanced age at diagnosis and in females.