Exploring the Biopsychosocial Model in Irritable Bowel Syndrome : with emphasis on stress, comorbidities and fatigue

Abstract: BackgroundIrritable bowel syndrome (IBS) is a common, chronic, relapsing, and sometimes disabling, symptombased disorder of gut brain interactions. It has got a female predominance and occurs in all ages, with a slight decrease among elderly. The IBS symptoms can affect everyday work and social life in addition to an increased use of health care resources. Most IBS patients are diagnosed and helped in primary health care (PHC). For many patients, available treatment is insufficient. It is known that both extraintestinal symptoms such as fatigue, as well as comorbidities such as mood disorders, chronic pain syndromes, and insomnia contribute to the illness burden, often to a larger extent than the gastrointestinal symptoms as such.Even though the pathophysiology of IBS is not completely known, it is now conceptualized as a disorder of altered brain-gut interactions, where a biopsychosocial model helps in understanding the symptoms. Exposure to stress is thought to play an important role overall in the pathology of IBS, as well as immune activation at least in a subgroup of patients.This thesis aimed to gain deeper understanding of the biopsychosocial mechanisms of IBS and its associations with stress, comorbidities, and fatigue.Methods Study I and II are based on the Twin cities IBS study population, which included IBS patients and a control group of other patients without gastrointestinal complaints from ten PHC centres in the county of Östergötland. Alongside demographics, psychosocial questionnaires and a GI symptom diary, it included analyses of hair cortisol concentrations (HCC) evaluated in study I, and data on self-rated health as well as diagnoses of comorbidities, and number of health care contacts from a regional registry, evaluated for study II.Study III of this thesis is based on the Brain-Gut study with a population of secondary care IBS patients, and healthy controls (HC). It included self-rated measures of fatigue impact on the daily life and early adverse life events, as well as measures of circulating TNF-α, and analyses of resting-state functional magnetic resonance imaging of brain areas within a mesocorticolimbic circuitry of known relevance for fatigue.Results Study I: Perceived stress was higher in the IBS group while a considerable portion of IBS patients had low levels of HCC. No association between perceived stress and HCC was seen in either group.Study II: IBS patients had lower self-rated health and more PHC utilization than the non-IBS patients. Good self-rated health was independently associated with younger age, higher sense of coherence and less gastrointestinal pain in both groups. In IBS, PHC utilization was associated with comorbidities in general, and sleep disorders in particular.Study III: Fatigue impact on daily life, and TNF- α were higher in IBS patients than in HC. In IBS, further an association was seen between fatigue impact on the one hand, and TNF- α, emotional abuse in childhood, as well as altered mesocorticolimbic connectivity on the other.Conclusion In conclusion this thesis firstly emphasizes that IBS patients in many ways, including health outcomes, consists a vulnerable group of PHC patients. We add evidence for a possible suppression of the stress response system in a substantial portion of IBS patients.Further, comorbid sleep disorders seem to be particularly associated with excess PHC utilization in IBS and could possibly be a target for treatment interventions. Moreover, alongside treating gastrointestinal pain, efforts to improve the individuals’ sense of coherence could be one way to achieve better self-rated health in both IBS and non-IBS patients.Finally, we suggest that fatigue in IBS is associated with immune activation, central alterations and to some extend also previous childhood trauma.