Association of Depression With Incident Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

Background Individuals with a history of depression/depressive symptoms are suspected to be at increased risk of incident inflammatory bowel diseases (IBDs). Methods We systematically searched MEDLINE/PubMed, Embase, and Scopus databases for longitudinal studies examining the association between depression/depressive symptoms and subsequent new-onset IBD (ie, Crohn's disease and ulcerative colitis). We included studies in which the exposure was a confirmed diagnosis of depression/depressive symptoms measured through a validated scale. To limit concerns of diagnostic bias and reverse causality, and support temporality between exposure and outcomes, we synthesized estimates corresponding to the longest time lag reported. Two authors extracted study data independently and assessed each study's risk of bias. Maximally adjusted relative risk (RR) estimates were synthesized using random- and fixed-effects models. Results Of 5307 records, 13 studies (8 cohort and 5 nested case-control studies; 9 million individuals) fulfilled the eligibility criteria. Depression was significantly associated with incident Crohn's disease (RRrandom, 1.17; 95% confidence interval, 1.02-1.34; 7 studies, 17 676 cases) and ulcerative colitis (RRrandom, 1.21; 95% confidence interval, 1.10-1.33; 6 studies, 28 165 cases). The primary studies considered pertinent confounders. Several years, on average, separated exposure and outcomes. No evidence of important heterogeneity or publication bias was found. Summary estimates were at low risk of bias, and results were confirmed in multiple sensitivity analyses. No firm conclusions could be drawn regarding a dilution of the association over time. Conclusions Individuals with a history of depression may show small-to-moderate increased risk of IBD even when depression is diagnosed several years before new-onset IBD. Further epidemiological and mechanistic studies should clarify whether these associations are causal.Lay Summary Depression has recently been associated with the development of several chronic diseases. History of depression may be a factor increasing moderately the risk to develop inflammatory bowel disease in the future even when depression is diagnosed several years before new-onset inflammatory bowel disease.