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The val158met Catechol-O-methyl-transferase (COMT) polymorphism is associated with irritable bowel syndrome-like symptoms
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
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(English)Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:umu:diva-3355OAI: oai:DiVA.org:umu-3355DiVA: diva2:142020
Available from: 2008-09-03 Created: 2008-09-03 Last updated: 2011-05-17Bibliographically approved
In thesis
1. The emotional motor system and gastrointestinal symptoms
Open this publication in new window or tab >>The emotional motor system and gastrointestinal symptoms
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is a significant comorbidity between anxiety/depression and functional gastrointestinal syndromes, such as irritable bowel syndrome (IBS) and functional dyspepsia. The pathophysiological link between emotions and the gut is not known. A model of an emotional motor system (EMS) which reacts to interoceptive and exteroceptive stress has been proposed. EMS consists of specific brain structures including anterior cingulate cortex (ACC), amygdala, hippocampus and hypothalamus and mediates their communication to the rest of the body (including the gastrointestinal tract) through the hypothalamus-pituitary-adrenal (HPA) axis, the autonomic nervous system (ANS) and by a pain modulation system. The aim of this thesis was to test the EMS model by studying the relationship between symptoms of anxiety and depression and IBS-like symptoms in patients with recurrent unipolar depression, in patients with IBS and in a sample of a normal Swedish population. The peripheral limb of EMS (ANS, HPA axis and the pain modulations system) was tested in patients with IBS and control subjects. Spectral heart rate variability was used to investigate ANS function in patients with refractory IBS and in healthy controls. The HPA axis function was tested by a weight adjusted low dose dexamethasone suppression test in control subjects. The influence of catecholamine degradation on pain modulation was tested by analyzing val158met catechol-o-methyl transferase (COMT) polymorphism in patients with IBS and in control subjects.

We found a significant relationship between symptoms of anxiety/depression and IBS-like symptoms in patients with recurrent unipolar depression, in patients with IBS and in a sample of the normal population. Interestingly, patients with recurrent unipolar depression in remission had no more IBS-like symptoms than controls, indicating that the gastrointestinal symptoms may resolve when depression is treated to remission.

Patients with IBS have an increased mid-frequency power in rest and in supine position (after tilt test) compared to healthy controls indicating an increased sympathetic ANS drive.

The symptoms of diarrhea and early satiety has in the litterature been associated to the stimulation of corticotropin releasing hormone (CRH) receptors and was also in our study related to HPA axis function tested by a low dose dexamethasone test. Interestingly both hypo- and hyperfunction of the HPA axis was related to these symptoms in control subjects.

The val158met COMT polymorphism was associated to IBS-like symptoms. Control subjects with IBS-like symptoms (defined by the upper quartile in total GSRS-IBS score) had a higher frequency of the met/met and a significantly lower frequency of the val/met genotype. Also patients with IBS tended to have a lower frequency of the heterozygous val/met genotype so we conclude that this genotype may be protective against IBS/IBS like symptoms. In addition, the val/val genotype in patients with IBS was associated to diarrhea symptoms.

Conclusions: Our results support the model of an emotional motor system in the genesis of functional gastrointestinal symptoms by the finding of the association of IBS-like symptoms and mood disturbances, and by finding alterations in the peripheral limbs of EMS (ANS, HPA axis and catecholamines) in subjects with IBS and IBS-like symptoms.

Place, publisher, year, edition, pages
Umeå: Medicin, 2008. 62 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1196
Keyword
Anxiety, ANS, autonomic nervous system, cortisol, DST, emotional motor system, functional, gastrointestinal symptoms, GSRS-IBS, gut, HADS, heart rate variability, HPA axis, IBS, irritable bowel syndrome, stress, unipolar depression, val158met COMT polymorphism
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-1802 (URN)978-91-7264-602-5 (ISBN)
Public defence
2008-09-19, Sal B, 1D, Tandläkarhögskolan, NUS, Umeå, 09:00 (English)
Opponent
Available from: 2008-09-03 Created: 2008-09-03 Last updated: 2010-01-18Bibliographically approved

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Adolfsson, RolfNorrback, Karl-Fredrik

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