Patients diagnosed with inflammatory bowel disease (IBD) were 9 times as likely to develop depression over the next decade compared with the general population and unaffected siblings of patients with IBD were almost 2 times as likely to develop depression in a retrospective cohort analysis published in The Journal of Gastroenterology and Hepatology.1 A bidirectional relationship was also found with patients with depression being at twofold increased risk for developing IBD.

“This research reveals a clinical overlap between both conditions, and is the first study to investigate the 2-way association between IBD and depression in siblings,” said study coauthor Bing Zhang, MD, a gastroenterologist with Keck Medicine of University of Southern California (USC).2 Dr Zhang hypothesized that many factors may contribute to the bidirectional nature of the disorders, including environmental stressors, gut microbiome, and genetics.

Researchers used the Taiwanese National Health Insurance Research Database to investigate depression risk among 422 patients diagnosed with IBD (175 patients with ulcerative colitis, 247 with Crohn disease), 537 of their unaffected siblings, and 2148 healthy patients.

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Over an 11-year follow-up period, new-onset depression was diagnosed among 78 IBD patients (18.5%), 26 unaffected siblings (4.8%), and 54 adults in the control group (2.5%). The risk for depression was approximately 9-fold higher in patients with IBD than in the control group (Table). Unaffected siblings were also at increased risk.

Table. Risk for New-Onset Depression by IBD Status

GroupAdjusted OR for Depressiona
IBD patients9.43 (95% CI, 6.43–13.81; P <.001)
Unaffected siblings1.82 (95% CI, 1.14–2.91; P =.013)
Control groupReference
OR, odds ratio; IBD, inflammatory bowel disease
aAdjusted for age, sex, monthly income, urbanization, Charlson comorbidity index, medical comorbidities, and all-cause clinical visits.

Risk of IBD Among Patients With Depression

Conversely, patients with depression were also at risk for IBD development, according to data from 25,552 patients with depression, 26,147 unaffected siblings, and 104 588 healthy controls without depression. During the follow-up period, 18 patients with depression developed IBD (0.70/1000) as did 25 (0.96/1000) unaffected siblings and 58 (0.55/1000) healthy controls. The adjusted odds ratio for IBD among patients with depression and their unaffected siblings were 1.87 (95% CI, 1.07–3.26; P =.028) and 1.69 (95% CI, 1.05–2.69; P = 0.029), respectively.

Surprising Findings

While the finding that people with IBD are more prone to depression is understandable given the constant gastrointestinal symptoms associated with IBD, Dr Zhang said. “And the elevated depression risk among siblings of IBD patients may reflect caregiver fatigue if the siblings have a role in caring for the patient.”

However, the finding that patients with depression were prone to IBD was surprising and may be explained by the gut-brain axis, Dr Zhang explained. Inflammation of the brain, which plays a role in depression, may be linked to inflammation of the gastrointestinal tract, which is characteristic of IBD. Dr Zhang suggested that siblings may share a genetic susceptibility to these diseases.

Dr Zhang hopes that the study findings will encourage health care professionals to take both family history and the relationship between gastrointestinal and mood disorders into consideration when evaluating or treating patients with either IBD or depression.


1. Zhang B, Wang HE, Bai YM, et al. Bidirectional association between inflammatory bowel disease and depression among patients and their unaffected siblings. J Gastroenterol Hepatol. 2022 Apr 17. doi:10.1111/jgh.15855

2. New study shows link between inflammatory bowel disease and depression. News release. University of Southern California. June 1, 2022. Accessed June 3, 2022.