Is there a causal link between psychological disorders and functional gastrointestinal disorders?

ABSTRACT

Introduction

Psychological distress is associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD) but only evidence from prospective longitudinal and treatment studies can indicate whether the link between FGIDs and psychological distress is causal. Emerging evidence suggests underlying biological mechanisms may explain the association of psychological distress with FGIDs.

Areas covered

This review critically evaluates whether anxiety and/or depression and FGIDs are causally related including evidence for a temporal sequence, strength and specificity of the association, biological gradient, and biological plausibility.

Expert opinion

Accumulating evidence suggests that psychological factors are causal for symptoms in a subset of FGID patients and not explained by health care seeking behavior (brain-gut disorder). In other cases, psychological factors may arise secondary to intestinal disease (gut-brain disorder). Prospective population-based studies are needed in FGIDs other than IBS and FD to determine if a similar brain-gut and gut-brain syndrome exists. Treatment studies have not phenotyped FGIDs according to brain-gut versus gut-brain origins which may be important in understanding true treatment efficacy. Future research needs to unravel biological mechanisms that may explain the link between psychological factors and FGIDs but promising data in the area of the brain-gut–immune-microbe axis is emerging.

KEYWORDS:

• Psychological factors
• anxiety
• depression
• functional gastrointestinal disorders
• brain gut axis
• irritable bowel syndrome
• functional dyspepsia
• microbiome

Article highlights

• The evidence for a causal relationship between psychological factors and FGIDs is presented based upon the Bradford Hill criteria for assessing causation and includes evidence for a temporal sequence, strength, specificity and consistency of the association, biological gradient and biological plausibility.

• Promising data is reviewed in relation to the brain-gut–immune-microbe axis to explain the causal association of psychological factors and FGIDs in some individuals.

• Future research will need to focus on phenotyping all FGIDs according to brain- gut versus gut-brain origins, especially in treatment studies.

Declaration of interest

N Koloski receives research support from the Princess Alexandra Hospital, National Health & Medical Research Council of Australia Centre of Research Excellence in Digestive Health.

N Talley served as Chair of the Gastroduodenal Committee for Rome IV. He reports grants from Abbott Pharmaceuticals, Commonwealth Diagnostics, Viscera USA, non-financial support from HVN National Science Challenge NZ, grants and personal fees from GI therapies, personal fees from Adelphi values, Allergens PLC, Takeda, Ampligent, Progenity Inc, Sanofi-aventis, IM Health Sciences, Napo Pharmaceutical, Outpost Medicine, Samsung Bioepis, Synergy, Theravance, Yuhan, outside the submitted work; In addition, N Talley has a patent Biomarkers of IBS licensed, a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley, a patent Nestec European Patent licensed, and a patent Singapore Provisional Patent ‘Microbiota Modulation Of BDNF Tissue Repair Pathway’ issued. Committees: Australian Medical Council (AMC) [Council Member]; Australian Telehealth Integration Programme; MBS Review Taskforce; NHMRC Principal Committee (Research Committee) Asia Pacific Association of Medical Journal Editors. Boards: GESA Board Member, Sax Institute, Committees of the Presidents of Medical Colleges. Community group: Advisory Board, IFFGD (International Foundation for Functional GI Disorders). Miscellaneous: Avant Foundation (judging of research grants). N Talley acknowledges funding from the National Health and Medical Research Council (NHMRC) for the Centre for Research Excellence in Digestive Health. N Talley holds an NHMRC Investigator grant.

G Holtmann received unrestricted educational support from Bayer Ptd, Ltd and the Falk Foundation. Research support was provided via the Princess Alexandra Hospital, Brisbane by GI Therapies Pty Limited, Takeda Development Center Asia, Pty Ltd, Eli Lilly Australia Pty Limited, F.Hoffmann-La Roche Limited, MedImmune Ltd Celgene Pty Limited, Celgene International II Sarl, Gilead Sciences Pty Limited, Quintiles Pty Limited, Vital Food Processors Ltd, Datapharm Australia Pty Ltd Commonwealth Laboratories, Pty Limited, Prometheus Laboratories, Falk GmbH and Co Kg, Nestle Pty Ltd, Mylan, Allergan. Patent Holder: A biopsy device to take aseptic biopsies (US 20150320407 A1). G Holtmann is on the SERVATUS Advisory Panel. G Holtmann acknowledges funding from the National Health and Medical Research Council (NHMRC) for the Centre for Research Excellence in Digestive Health. G Holtmann holds an MRFF grant.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer would like to disclose that they have worked with Biocodex, Ipsen, Kyowa Kirin, Mayoly Spindler, MSD, Norgine and Tillotts pharma. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was funded by the National Health & Medical Research Council of Australia Center of Research Excellence in Digestive Health.