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 To conduct a systematic review with meta-analysis to determine a causal relationship between psychological stress and symptom exacerbation in IBD. Methods A systematic review was conducted to identify, evaluate and summarise the literature relating to determining a causal relationship between different psychological factors and symptom exacerbation in IBD while utilising Bradford Hill criteria and meta-analysis. Data extraction and quality appraisal was performed by two independent reviewers. Hazard ratios (HR) were pooled where appropriate. Results The searches yielded 2472 potential articles. Nineteen clinical prospective cohort studies were eligible for the systematic review and only five for the meta-analysis. All of the Bradford Hill criteria were met which is a strong evidence supporting a causal association between all the psychological factors and disease activity. Meta-analysis showed depression, anxiety and perceived stress to be associated with increased risk of symptom exacerbation in IBD with perceived stress being statistically significant (HR 1.36 95 % [CI], 1.13, 1.65). Conclusions Current evidence indicates that psychological factors perceived stress is independently associated with symptom exacerbation in IBD and interventions reducing the impact of psychological factors should be part of the treatment plan for patients with IBD.