Exploring the relationship between stress/distress reduction, inflammatory markers and relapse in relapsing remitting Inflammatory Bowel Disease (IBD)

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Inflammatory bowel disease (IBD) is a chronic, autoimmune, inflammatory condition. Biomedical models stipulate that inflammation levels and disease complications correlate with abdominal pain (Basso et al., 2015; Docherty et al., 2011); however, psychoneuroimmunological frameworks are helpful to conceptualise IBD symptomatology. IBD patients demonstrate dysregulated endocrine and immunological responses (Mackner et al., 2010; Pellissier et al., 2010). Additionally, in IBD it appears that there are bidirectional relationships between symptoms and psychological function (Sweeney et al,. 2018). The brain-gut axis provides a physiological framework for these relationships (Bonaz & Bernstein, 2013). A recent systematic review has demonstrated the bidirectional relationship between psychological factors and disease progression (Fairbrass et al., 2021); although it did not investigate biological markers of disease activity. Cross-sectional studies have identified associations between pro-inflammatory cytokines and depression, but there is a limited understanding of the directionality of inflammation and depressive symptoms in IBD (Moulton et al., 2019).Studies have suggested that hypothalamic-pituitary-adrenal (HPA) axis activity is correlated with the progression of IBD (Sun et al., 2019). Moreover, HPA axis hyperactivity is a consistent biological marker of depression (Gold et al., 2015; Iob et al., 2020; Pariante & Lightman, 2008; Stetler et al., 2013), therefore it is plausible that the depression symptoms in IBD patients may contribute to HPA axis hyperactivity. However, many studies investigating the area are underpowered and demonstrate conflicting results. The literature needs to establish standard ways of measuring key biomarkers and requires larger sample sizes.The primary supervisor, Prof Rona Moss-Morris, has done extensive research in IBD populations, including a randomised-controlled trial of a transdiagnostic online cognitive-behavioural therapy intervention. She and her team have developed an online CBT program, COMPASS, tailored to treat illness-related distress in the context of long-term conditions. COMPASS is delivered over 3 months, and RCT data demonstrate its effectiveness at reducing anxiety and depression in people with IBD However, to date there has been no investigations regarding the effectiveness of COMPASS (and other CBT interventions) at influencing critical disease biomarkers via psychoneuroimmunological pathways.Moreover, the second supervisor Dr Valeria Mondelli is a lead researcher in the field of psychoneuroimmunology and has investigated the relationship between inflammatory biomarkers, such as cortisol and peripheral immune biomarkers, with key disease factors such as treatment response (Mondelli et al., 2015; Enache et al., 2021), environmental stressors (Zajkowska et al., 2021), disease symptoms (McLaughlin et al., 2021) and severity of psychological symptoms (Murri et al., 2016; Sforzini et al., 2019).Dr Joanna Hudson has been added as a third supervisor. Alongside Prof Rona Moss-Morris, she was instrumental in the development of COMPASS.The aim of the thesis is to investigate the relationship between psychosocial factors, inflammatory biomarkers and reductions in illness-related distress following an online CBT investigation.Firstly, a systematic review will establish what is currently known about the relationships between mental and physical health outcomes and inflammatory biomarkers in IBD and clarify gaps in the literature.The second aim is to investigate cross-sectionally the associations between the identified inflammatory biomarkers and key psychosocial and clinical variables.The third aim is to investigate reductions in distress following an online CBT intervention (COMPASS) in IBD patients and to explore if reductions in distress are associated with reductions in inflammatory markers related to disease flares at post-intervention and 1year follow up.