Assessment of causal link between psychological factors and symptom exacerbation in inflammatory bowel disease: a systematic review utilising Bradford Hill criteria and meta-analysis of prospective cohort studies.
BACKGROUND
Psychological stress is a prevalent factor in inflammatory bowel disease (IBD) with detrimental effects on patients' quality of life and possibly disease course. Although the aetiology of symptom exacerbation in IBD has been explored, determining any causation between psychological stress and symptom worsening remains challenging and requires a methodologically rigorous approach.


AIM
The aim of this systematic review with meta-analysis was to determine a causal relationship between psychological stress and symptom exacerbation in IBD, subsequently utilising Bradford Hill's criteria (approach never used in this topic area before) to evaluate the likelihood of causal associations.


METHODS
Medline, EMBASE, CINAHL and PsycInfo were searched for relevant studies up to July 20, 2019. Data extraction and quality appraisal were performed by two independent reviewers. Results of all retained papers were presented as a narrative synthesis. A random-effect meta-analysis was conducted on studies meeting the criteria for meta-analysis. Bradford Hill criteria were applied to assess the causality of the relationship between all psychological factors and symptom exacerbation.


RESULTS
The searches yielded 2472 potential articles. Nineteen clinical prospective cohort studies were eligible for the narrative review with five suitable for the meta-analysis. Meta-analysis showed depression, anxiety and perceived stress did not have a statistically significant association with an increased risk of symptom exacerbation. Four of the Bradford Hill criteria were met which indicates that there is weak to moderate evidence of a causal association between all the psychological factors and disease activity. Inconsistent results and a dearth of studies using the same tools for measuring psychological factors suggest the need for more research to be done to facilitate more conclusive findings.


CONCLUSIONS
This original review utilising Bradford Hill criteria in addition to meta-analysis to evaluate the causality of relationship between psychological factors and symptom exacerbation in IBD provides evidence that psychological factors have a weak to moderate causal involvement in IBD symptom exacerbation. However, when combining this finding with the outcomes of the meta-analysis, we can say that the results were inconclusive. Interventions to reduce the associated psychological impact should be part of the treatment plan for patients with IBD.


SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42012003143.
['Schoultz|Mariyana|M|0000-0003-3780-8110', 'Beattie|Michelle|M|', 'Gorely|Trish|T|', 'Leung|Janni|J|']
D015984:Causality D006801:Humans D015212:Inflammatory Bowel Diseases D011446:Prospective Studies D011788:Quality of Life D000067251:Symptom Flare Up
Psychological factors Symptom exacerbation Inflammatory bowel disease Systematic review Meta-analysis Crohn’s disease Ulcerative colitis