Evidence that stress contributes to inflammatory bowel disease: Evaluation, synthesis, and future directions

Background: There is a long but inconsistent history of observations suggesting that psychologic stress contributes to the course of ulcerative colitis (UC) and Crohn's disease (CD). This study evaluated the strength of evidence for a causal link between stress, depression, and inflammatory bowel disease course. Methods: Literature review and unstructured qualitative analysis of all reported prospective studies of stress or depression and disease outcomes and randomized controlled studies (RCTs) of stress reduction interventions. Results: Although results remain inconsistent, prospective studies support a role for psychologic stress in the course of UC and for depressive symptoms in the course of CD. RCTs do not support the benefit of stress reduction for unselected patients with CD. UC has not been studied with adequately designed RCTs. Animal models suggest mechanisms whereby stress can exacerbate preexisting inflammatory disease, especially through increased epithetial permeability. Conclusions: A synthesis of the literature is presented suggesting approaches to reconcile apparently contradictory findings. Recommendations for further research emphasize refinements to avoid type II error and to identify subgroups of patients who are most likely to experience stress-related effects on illness or to benefit from stress reduction intervention.