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

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

Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women

OBJECTIVE: Alterations in serotonin signalling within the brain–gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD. METHODS: 12 healthy females (19–25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24–50 years). RESULTS: In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C. CONCLUSIONS: The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology

The effects of an acute serotonergic challenge on brain-gut responses in irritable bowel syndrome patients and controls

Summary Background : Serotonin, a key denominator of the brain-gut axis is involved in the regulation of gastrointestinal function as well as cognition, mood and hypothalamic-pituitary-adrenal axis-mediated neuroendocrine responses. Aim : To assess the effects of an acutely increased serotonergic activity, using a 20 mg intravenous citalopram challenge test on visceral perception, affective memory performance, mood and neuroendocrine responses, respectively, in diarrhoea-predominant irritable bowel syndrome patients and controls. Methods : In a randomized, double-blind crossover design, 14 diarrhoea-predominant irritable bowel syndrome patients and 14 matched controls were studied under citalopram and placebo conditions, respectively. Visceral perception was scored in response to rectal distensions. Affective memory performance, mood, levels of adrenocorticotropic hormone, cortisol, prolactin and biochemical parameters of serotonergic metabolism were simultaneously assessed. Results : Visceral perception did not significantly differ between the citalopram and placebo condition. Citalopram administration enhanced affective memory performance because of a bias towards positive material but no significant changes in mood. Citalopram significantly increased plasma serotonin, adrenocorticotropic hormone and cortisol levels compared with placebo. Citalopram did not differentially affect the patient or control group. Conclusions : We have provided evidence that acutely increased serotonergic activity influences neuroendocrine responses and cognition in diarrhoea-predominant irritable bowel syndrome and controls without a significant effect on visceral perception

Tests examining skill outcomes in sport: A systematic review of measurement properties and feasibility

BackgroundA high level of participant skill is influential in determining the outcome of many sports. Thus, tests assessing skill outcomes in sport are commonly used by coaches and researchers to estimate an athlete&rsquo;s ability level, to evaluate the effectiveness of interventions or for the purpose of talent identification.ObjectiveThe objective of this systematic review was to examine the methodological quality, measurement properties and feasibility characteristics of sporting skill outcome tests reported in the peer-reviewed literature.Data SourcesA search of both SPORTDiscus and MEDLINE databases was undertaken.Study SelectionStudies that examined tests of sporting skill outcomes were reviewed. Only studies that investigated measurement properties of the test (reliability or validity) were included. A total of 22 studies met the inclusion/exclusion criteria.Study Appraisal and Synthesis MethodsA customised checklist of assessment criteria, based on previous research, was utilised for the purpose of this review.ResultsA range of sports were the subject of the 22 studies included in this review, with considerations relating to methodological quality being generally well addressed by authors. A range of methods and statistical procedures were used by researchers to determine the measurement properties of their skill outcome tests. The majority (95 %) of the reviewed studies investigated test&ndash;retest reliability, and where relevant, inter and intra-rater reliability was also determined. Content validity was examined in 68 % of the studies, with most tests investigating multiple skill domains relevant to the sport. Only 18 % of studies assessed all three reviewed forms of validity (content, construct and criterion), with just 14 % investigating the predictive validity of the test. Test responsiveness was reported in only 9 % of studies, whilst feasibility received varying levels of attention.LimitationsIn organised sport, further tests may exist which have not been investigated in this review. This could be due to such tests firstly not being published in the peer-review literature and secondly, not having their measurement properties (i.e., reliability or validity) examined formally.ConclusionsOf the 22 studies included in this review, items relating to test methodological quality were, on the whole, well addressed. Test&ndash;retest reliability was determined in all but one of the reviewed studies, whilst most studies investigated at least two aspects of validity (i.e., content, construct or criterion-related validity). Few studies examined predictive validity or responsiveness. While feasibility was addressed in over half of the studies, practicality and test limitations were rarely addressed. Consideration of study quality, measurement properties and feasibility components assessed in this review can assist future researchers when developing or modifying tests of sporting skill outcomes.<br /