T O C Kilkens

Maastricht University, Maestricht, Limburg, Netherlands

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Publications (14)106.74 Total impact

  • Michiel A van Nieuwenhoven, Tessa O C Kilkens
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    ABSTRACT: Irritable bowel syndrome (IBS) patients suffer from visceral hypersensitivity and show increased activity in the brain emotional arousal network following a rectal stimulus, compared with controls. Serotonergic activity can be decreased by acute tryptophan depletion (ATD), which increases visceral perception and also increases activity in the brain's emotional arousal network during rectal stimulation. Treatment with a serotonin reuptake inhibitor such as citalopram is effective in some IBS patients. Hence, serotonergic modulation alters visceral perception. However, it is not clear whether serotonergic modulation alters rectal motor function. The aims of the study were to evaluate the effect of the administration of ATD and citalopram on rectal motor function in diarrhea-predominant IBS (d-IBS) patients and controls using a barostat procedure. Following a randomized, double-blind placebo-controlled crossover design, an ATD and citalopram experiment was conducted. Fourteen d-IBS patients and 14 healthy, matched (age, sex, BMI) controls participated. Rectal volume (RV), adaptive relaxation (RAR), and compliance (RC) were determined using a barostat procedure. d-IBS patients showed significantly decreased RV (P<0.04), RAR (P<0.03), and RC (P=0.05) compared with the controls. ATD and citalopram did not influence RV, RAR, or RC significantly (all P's>0.1). d-IBS patients have disturbed rectal pressure-volume relations. Visceral perception in IBS is associated with both increased activity in the brain's emotional arousal network and decreased RC. Acutely decreasing or increasing serotonergic activity does not affect these characteristics in d-IBS patients or healthy controls. The pathophysiology in d-IBS contains both a rectal motor component and a central neuropsychologic component.
    European journal of gastroenterology & hepatology 08/2012; 24(11):1259-65. DOI:10.1097/MEG.0b013e3283583cf5 · 2.15 Impact Factor
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    ABSTRACT: Barostat methodology is widely used for assessing visceral perception. Different barostat protocols are described with respect to the measurement of rectal compliance and visceral perception. The choice of protocols affects the duration, which is normally 60-90 min, and accuracy of the procedure. This study aimed to shorten the procedure by using the semi-random distension protocol for both compliance and visceral perception measurement and a correction based on rectal capacity (RC) instead of minimal distension pressure (MDP). Twelve irritable bowel syndrome (IBS) patients (7 females) and 11 healthy controls (8 females) underwent a barostat procedure. Compliance was determined during both a staircase distension and a semi-random protocol. Visceral perception data were compared as a function of pressure or relative volume, corrected for MDP or RC, respectively. Compliance measurement using the semi-random protocol instead of the staircase distension protocol resulted in an overestimation in healthy volunteers, but not in IBS patients. The overall conclusion that IBS patients had a lower compliance compared to controls was not different between protocols. Data presentation of the visceral perception scores as a function of corrected volume instead of pressures corrected for MDP did not alter the conclusion that sensation scores in IBS patients were higher as compared to healthy controls. This study showed that barostat procedures may be shortened by approximately 20 min, without losing the ability to discriminate between healthy controls and IBS patients. A correction for RC instead of MDP may improve the accuracy of the procedure.
    Journal of Gastroenterology 02/2012; 47(8):896-903. DOI:10.1007/s00535-012-0543-x · 4.02 Impact Factor
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    ABSTRACT: 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. 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). 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. 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.
    Gut 03/2011; 60(9):1196-203. DOI:10.1136/gut.2010.213447 · 13.32 Impact Factor
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    ABSTRACT: Fermentation of dietary fibres by colonic microbes leads to the production of short chain fatty acids (mainly propionate, butyrate and acetate), which are utilized by the colonic mucosa. Previous studies showed positive effects of butyrate on parameters of oxidative stress, inflammation and apoptosis. Recent studies in rats, however, showed that butyrate increased visceral sensitivity. The aim of this study was to determine the effects of physiologically relevant concentrations of butyrate on visceral perception in healthy human subjects. Eleven healthy volunteers participated in this randomized double-blind, placebo controlled cross-over study. The study consisted of three periods of 1 week each, in which the volunteers daily self-administered rectal enemas containing 100, 50 mmol L(-1) butyrate, or placebo (saline) prior to sleeping. A rectal barostat measurement was performed at the start and the end of each test period for the measurement of pain, urge and discomfort. Butyrate treatment resulted in a dose-dependent reduction of pain, urge and discomfort throughout the entire pressure range of the protocol. At a pressure of 4 mmHg, 50 and 100 mmol L(-1) butyrate concentrations resulted in a 23.9% and 42.1% reduction of pain scores, respectively, and the discomfort scores decreased by 44.2% and 69.0% respectively. At a pressure of 67 mmHg, 50 and 100 mmol L(-1) of butyrate decreased the pain scores by 23.8% and 42%, respectively, and discomfort scores 1.9% and 5.2% respectively. Colonic administration of butyrate, at physiologically relevant concentrations, dose-dependently decreases visceral sensitivity in healthy volunteers.
    Neurogastroenterology and Motility 06/2009; 21(9):952-e76. DOI:10.1111/j.1365-2982.2009.01324.x · 3.42 Impact Factor
  • Gastroenterology 05/2009; 136(5). DOI:10.1016/S0016-5085(09)63331-X · 13.93 Impact Factor
  • Gastroenterology 04/2008; 134(4). DOI:10.1016/S0016-5085(08)60739-8 · 13.93 Impact Factor
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    ABSTRACT: Acute tryptophan depletion (ATD) studies have shown that serotonin plays a role in learning and memory processes. In this study, we performed a pooled analysis of nine ATD studies in order to examine the nature of the memory-impairing effects of ATD and mediating factors, such as gender, age and vulnerability for disease in which disturbed serotonin was hypothesized to play a role. All studies that were used in this pooled analysis assessed declarative episodic memory using a verbal learning task paradigm. Immediate recall, delayed recall, and delayed recognition scores were examined. A total of 211 participants were included in the analysis. The analysis revealed that ATD impaired not only delayed recall, but also immediate recall. The ATD-induced impairments were larger in females than in males. Furthermore, ATD did not interact with any other serotonergic vulnerability and age. This suggests that the only factor that actually has the properties of a serotonergic vulnerability factor for declarative memory performance is female gender. The findings provide further support for a critical role of serotonin in declarative episodic memory.
    Neuroscience & Biobehavioral Reviews 02/2007; 31(4):516-29. DOI:10.1016/j.neubiorev.2006.11.009 · 10.28 Impact Factor
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    T O C Kilkens, A Honig, D Fekkes, R-J M Brummer
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    ABSTRACT: 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. 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. 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. 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. 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.
    Alimentary Pharmacology & Therapeutics 12/2005; 22(9):865-74. DOI:10.1111/j.1365-2036.2005.02660.x · 5.48 Impact Factor
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    ABSTRACT: 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. 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. 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. ATD significantly decreased plasma tryptophan (67.0 (2.0) v 24.9 (2.0) mumol/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. 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.
    Gut 01/2005; 53(12):1794-800. DOI:10.1136/gut.2004.041657 · 13.32 Impact Factor
  • T O C Kilkens, L Hofstra, P J E H M Kitslaar
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    ABSTRACT: A 23-year-old woman had exercise-induced right leg symptoms. An extensive diagnostic workup including 2 surgical explorations was performed, but did not reveal the cause. Finally, high-resolution color-coded duplex scanning was performed, which demonstrated an isolated, nonthrombotic obstruction of the common femoral vein by a diaphragm-like membrane. Successful operative repair was accomplished with venotomy and excision of the membrane, with full relief from clinical signs and symptoms at 9-month follow-up.
    Journal of Vascular Surgery 11/2004; 40(4):815-8. DOI:10.1016/j.jvs.2004.07.042 · 2.98 Impact Factor
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    ABSTRACT: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with a high co-occurrence with affective dysregulation. Affective disorders have been associated with specific changes in the PUFA and cholesterol profile. In IBS, similar changes may be present as have been reported in patients with affective disorders. This exploratory study investigates (i) the level of affective dysregulation (AD) in IBS patients and healthy controls; (ii) PUFA and cholesterol profiles in IBS patients compared with controls; and (iii) associations between PUFA and cholesterol parameters with the level of AD. Blood samples were obtained for determination of the FA composition of plasma phospholipids and serum cholesterol in 23 diarrhea-predominant IBS patients and 23 healthy matched controls. AD was scored using the Symptom Check List depression scale, the Hospital Anxiety and Depression Scale, and the Hamilton Depression Rating Scale. The level of AD was higher in IBS patients compared with controls. PUFA and cholesterol profiles did not differ significantly between groups. Total n-3 PUFA and cholesterol were significantly negatively associated and the ratio of n-6 to n-3 PUFA and the ratio of arachidonic acid to EPA were significantly positively associated with the level of AD. The findings of the present study reveal that AD was higher in IBS patients compared with healthy controls and that changes in PUFA and cholesterol profiles were significantly associated with the level of AD. These results warrant further studies regarding the role of PUFA and cholesterol status in the co-occurrence of AD and functional gastrointestinal disorders.
    Lipids 06/2004; 39(5):425-31. DOI:10.1007/s11745-004-1247-x · 2.35 Impact Factor
  • Gastroenterology 04/2003; 124(4). DOI:10.1016/S0016-5085(03)82929-3 · 13.93 Impact Factor
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    ABSTRACT: Both central and peripheral serotonergic modulators are used in the treatment of irritable bowel syndrome. The majority of patients with irritable bowel syndrome presenting to a gastroenterologist demonstrate affective dysregulation. Serotonin may play a regulatory role in both gastrointestinal motility and sensitivity, as well as in affective dysregulation, in irritable bowel syndrome. To analyse, systematically, randomized controlled trials studying the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome, in order to elucidate baseline irritable bowel syndrome symptomatology and possible differential effects of serotonergic modulation on this symptomatology. A standardized qualitative analysis was performed of studies investigating the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome using a blind review approach. The studies were ranked according to their total quality score (maximum 100 points). Eleven studies fulfilled the entry criteria, six of which scored above 55 points. An association between gastroenterological and psychiatric changes was present in five of the six studies. The results strengthen the serotonergic association between gastroenterological and psychiatric symptoms. Adjusted guidelines for combined gastrointestinal and psychiatric assessments are recommended in order to further elucidate the serotonergic interaction between gastrointestinal and psychiatric symptoms.
    Alimentary Pharmacology & Therapeutics 02/2003; 17(1):43-51. DOI:10.1046/j.1365-2036.2003.01388.x · 5.48 Impact Factor
  • European Journal of Gastroenterology & Hepatology 01/1999; 11(12). DOI:10.1097/00042737-199912000-00308 · 2.15 Impact Factor

Publication Stats

225 Citations
106.74 Total Impact Points


  • 2005–2012
    • Maastricht University
      • • Department of Psychiatry & Neuropsychology
      • • Department of Internal Medicine
      Maestricht, Limburg, Netherlands
  • 2004–2005
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands