Abstract
BACKGROUND AND AIM: Approximately 30% of inflammatory bowel disease (IBD) patients develop depression. Conversely, several studies reported increased IBD risk among patients with depression. Such bidirectional relationship has not been reported within one representative cohort, nor investigated among patients' family members. These associations may further implicate the gut-brain axis in IBD. METHODS: We conducted parallel retrospective cohort analyses to investigate depression risk among IBD patients and their unaffected siblings, and IBD risk among patients with depression and their unaffected siblings using the Taiwanese National Health Insurance Research Database. Individuals were followed up to 11 years for new-onset depression or IBD. Controls were matched to unaffected siblings based on predefined characteristics. RESULTS: To investigate depression risk among IBD - 422 IBD patients, 537 unaffected siblings, and 2148 controls were enrolled. During follow-up, 78 (18.5%) IBD patients, 26 (4.8%) unaffected siblings, and 54 (2.5%) controls developed depression. Adjusted odds ratios (ORs) for depression among IBD patients and unaffected siblings were 9.43 (95% CI 6.43-13.81; P < 0.001) and 1.82 (95% CI 1.14-2.91; P = 0.013), respectively. To investigate IBD risk among depression - 25 552 patients with depression, 26 147 unaffected siblings, and 104 588 controls were enrolled. During follow-up, 18 (0.70/1000) depression patients, 25 (0.96/1000) unaffected siblings, and 58 (0.55/1000) controls developed IBD. ORs for IBD among depression patients and unaffected siblings were 1.87 (95% CI 1.07-3.26; P = 0.028) and 1.69 (95% CI 1.05-2.69; P = 0.029), respectively. CONCLUSIONS: This population-based study elucidates bidirectional association between IBD and depression. Elevated risks for either disease among patients and their unaffected siblings suggest shared etiologic contributors, offering novel insight into the gut-brain axis' influence in IBD pathophysiology.