Examining the impact of common mental disorder symptoms, and the role of the gut-brain axis, in inflammatory bowel disease

Introduction:
The extent to which the brain-gut axis influences the natural history of inflammatory bowel disease (IBD) is unknown. Evidence supporting the effect of common mental disorders on adverse outcomes in IBD would help to target those individuals most at risk. This thesis aims to better understand the bidirectional nature of the brain-gut axis and characterise those individuals who should have targeted psychological support.

Methods:
A systematic review and meta-analysis of studies looking at the effect of common mental disorders on outcomes in IBD (brain-to-gut) and studies examining the effect of disease activity in IBD on psychological outcomes (gut to-brain) was conducted to assess the bidirectional effect of the brain-gut axis in IBD. Longitudinal follow-up studies helped to evaluate the relationship between common mental disorders and their cumulative impact on adverse events related to disease activity. Analysis of the natural trajectory of common mental disorder symptoms over time, enabled further characterisation of this IBD cohort, to identify those most vulnerable to the influence of gut-brain interactions. Data was also collected on healthcare utilisation, including gastroenterology and nurse-led clinic appointments, as well as endoscopic, and radiological investigations.

Results:
The brain-gut axis is bidirectional in its effects, and influences the natural history of both IBD and psychological health. The cumulative impact of increasing psychological burden lead to a worse course of disease, in those patients in biochemical remission at baseline. During longitudinal follow-up, the burden of both disease activity and presence of symptoms of a common mental disorder significantly increased the risk of morbidity (hazard ratio (HR) 2.48; 95% confidence interval (CI) 1.38-4.46) and mortality (HR 6.26; 95% CI 2.23-17.56), with the presence of psychological co-morbidity a poor prognostic marker. Those individuals with persistently high depression and anxiety scores had significantly
higher healthcare utilisation with more outpatient appointments, and radiological and endoscopic investigations, for IBD-related symptoms.

Conclusions:
The bidirectional effects of the gut-brain axis have an influential role in the natural progression of both physical and psychological health in IBD. Better characterisation of these patients identifies those most at risk for developing psychological co-morbidity and adverse disease outcomes from their IBD. This in turn helps target those in most need of early intervention, improves future study design, and highlights the need for a holistic, biopsychosocial care model in the management of patients with IBD.