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Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment

Nature Reviews Gastroenterology & Hepatology volume 19, pages 717–726 (2022)Cite this article

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Abstract

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a chronic, relapsing immune-mediated disease with a varying and sometimes severe disease course. IBD is often diagnosed in early adulthood and can lead to a substantial decline in quality of life. It has been suggested that patients with IBD are at increased risk of depression and anxiety, but it is still unclear to what extent these diseases co-occur and in what sequence they arise. This Review summarizes the literature on the degree of co-occurrence of IBD with depression and anxiety and the temporal relationship between these diseases. We also discuss the effect of psychological stress on the onset and course of IBD. In addition, we outline the possible mechanisms underlying the co-occurrence of IBD and depression and anxiety, which include changes in brain signalling and morphology, increases in peripheral and intracerebral pro-inflammatory cytokines, impairment of the nitric oxide pathway, changes in vagal nerve signalling, gut dysbiosis and genetics. Finally, we examine the possible effects of treatment of depression and anxiety on the risk and course of IBD, the influence of psychological interventions on IBD, and the effects of IBD treatment on psychiatric comorbidity.

Key points

  • Depression and anxiety are common comorbidities in inflammatory bowel disease (IBD), but the prevalence varies across studies owing to heterogeneity in study populations and assessment tools for depression and anxiety.

  • The relationship between IBD and depression and anxiety seems to be bidirectional.

  • The mechanisms behind the relationship between IBD and depression and anxiety include increased pro-inflammatory cytokines, vagal nerve signalling, gut dysbiosis and changes in brain signalling and morphology.

  • Antidepressants and behavioural therapies show not only effectiveness in the treatment of depression and anxiety but might also alleviate IBD symptoms or decrease the risk of relapse, although evidence is still limited.

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Fig. 1: Population-based studies illustrating the temporal relationship between inflammatory bowel disease and depression and anxiety.
Fig. 2: Potential mechanisms linking inflammatory bowel disease, depression and anxiety.

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Acknowledgements

T.J. received funding from the Danish National Research Foundation (DNRF148) and the Lundbeck Foundation (R313-2019-857). The funding sources had no role in the development of this article.

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Authors and Affiliations

  1. Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark

    Tania H. Bisgaard, Kristine H. Allin & Tine Jess

  2. Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark

    Kristine H. Allin & Tine Jess

  3. Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Laurie Keefer

  4. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Ashwin N. Ananthakrishnan

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T.J., K.H.A., L.K. and A.N.A. made a substantial contribution to discussion of content and reviewed/edited the manuscript before submission. T.H.B. researched data for the article, made a substantial contribution to discussion of content, wrote the article and reviewed/edited the manuscript before submission.

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Correspondence to Tine Jess.

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A.N.A. served on scientific advisory boards for Gilead and Abbvie. L.K. is a consultant to Abbvie and Pfizer and has equity ownership in Trellus Health, Inc. The other authors declare no competing interests.

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Nature Reviews Gastroenterology and Hepatology thanks David Gracie, Antonina Mikocka-Walus and Giovanni Monteleone for their contribution to the peer review of this work.

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The manuscript is based on a MEDLINE search using the terms: “inflammatory bowel disease” OR “Crohn’s diseases” OR “ulcerative colitis” AND “depression” OR “anxiety” combined with “epidemiology”, “incidence”, “prevalence”, “antidepressants”, “microbiome”, “microbiota”, “gut-brain axis”, “genetics”. The initial search yielded 529 results, and 132 articles were included for full article screening. Additional articles were identified through search of reference lists.

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Bisgaard, T.H., Allin, K.H., Keefer, L. et al. Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment. Nat Rev Gastroenterol Hepatol 19, 717–726 (2022). https://doi.org/10.1038/s41575-022-00634-6

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