IRRITABLE BOWEL SYNDROME

Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls

T O C Kilkens¹, A Honig², M A van Nieuwenhoven³, W J Riedel⁴, R-J M Brummer³

¹ Brain and Behaviour Institute, and Nutrition and Toxicology Research Institute Maastricht, University Hospital Maastricht, Maastricht, the Netherlands
² Brain and Behaviour Institute, and Department of Psychiatry, University Hospital Maastricht, Maastricht, the Netherlands
³ Nutrition and Toxicology Research Institute Maastricht, and Department of Gastroenterology, University Hospital Maastricht, Maastricht, the Netherlands
⁴ Brain and Behaviour Institute, University Hospital Maastricht, Maastricht, the Netherlands, and Department of Psychiatry, University of Cambridge, Cambridge, UK

Correspondence to:
Correspondence to:
MsT O C Kilkens
Maastricht University, Department of Psychiatry and Neuropsychology, Dr Tanslaan 10, 6229 ET, Maastricht, the Netherlands; T.Kilkens{at}pn.unimaas.nl

Background: Serotonin, a key denominator of the brain-gut axis, is involved in the regulation of gastrointestinal motility, secretion, and perception as well as cognition and mood.

Aim: To assess the effects of an acutely lowered serotonin synthesis, using the acute tryptophan depletion (ATD) method, on visceral perception, affective memory performance, and mood in diarrhoea predominant irritable bowel syndrome patients (d-IBS) and controls.

Methods: In a randomised, double blind, crossover design, 14 d-IBS patients and fourteen matched controls were studied under ATD and placebo conditions, respectively. Perception of urge and pain was scored during rectal distensions. Affective memory performance, mood, and biochemical parameters of serotonergic metabolism were simultaneously assessed.

Results: ATD significantly decreased plasma tryptophan (67.0 (2.0) v 24.9 (2.0) µmol/l) and 5-hydroxyindole acetic acid concentrations (29.9 (1.0) v 15.8 (0.6) nmol/l). ATD was associated with significantly increased urge scores specifically in the lower pressure range and overall increased pain scores. ATD significantly lowered the perceptual threshold for first perception compared with placebo (patients 10.6 (1.2) v 13.6 (0.8) mm Hg, controls 12.6 (1.3) v 15.7 (1.2) mm Hg) but not for maximal tolerable discomfort (patients 50.5 (3.6) v 51.6 (3.3) mm Hg, controls 50.9 (3.3) v 48.8 (2.9) mm Hg). ATD induced a significant shift in affective memory bias towards preferential loss of positive material but no significant changes in mood. ATD did not differentially affect the patient or control group.

Conclusions: We have provided evidence that serotonergic modulation by ATD affects both visceral perception as well as cognition in d-IBS and controls. Simultaneous measurement of brain and gut function and the application of ATD contribute to the elucidation of the complex pathophysiology of IBS.

Abbreviations: ATD, acute tryptophan depletion; CNS, central nervous system; CSF, cerebrospinal fluid; IBS, irritable bowel syndrome; d-IBS, diarrhoea predominant irritable bowel syndrome; PI-IBS, postinfectious irritable bowel syndrome; EC, enterochromaffin; 5-HIAA, 5-hydroxyindole acetic acid; LNAAs, large neutral amino acids; 5-HT, 5-hydroxytryptamine; ppp, platelet poor plasma; POMS, profile of mood states; MINI, mini international neuropsychiatric interview; HAM, Hamilton depression rating scale; SCL, symptom checklist; HADS, hospital anxiety and depression rating scale

Keywords: irritable bowel syndrome; brain-gut axis; serotonin; tryptophan depletion; visceral perception

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