Brecht Geeraerts

Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatisation?

Background: Gastric sensorimotor dysfunction, psychosocial factors and somatisation are all implicated in symptom generation in functional dyspepsia (FD). Aim: To determine the relative contribution of each of these factors to overall dyspeptic symptom severity and weight loss in FD. Methods: In 201 consecutive tertiary care patients with FD (mean age 40.1 (SD 12.6) years), gastric sensorimotor function was studied using barostat (sensitivity, compliance and accommodation). Psychosocial factors (depression and anxiety disorders, positive and negative affect, perceived stress, alexithymia and history of abuse), somatisation and co-morbid irritable bowel syndrome (IBS) and chronic fatigue symptoms were assessed using self-report questionnaires. Variables were correlated with dyspepsia symptom severity (DSS) and weight loss. Hierarchical multiple linear regression was used to identify determinants of DSS and weight loss. Results: Multiple linear regression identified the following determinants of DSS: gastric sensitivity (β = 0.77, p = 0.25), depression (β = 0.12, p = 0.06) and somatisation (β = 0.48, p<0.0001) (controlling for age and occupation, R2 = 0.29, p<0.0001). The effect of depression on DSS is partially mediated by somatisation. Gastric sensitivity (β = 2.87, p = 0.08), history of childhood sexual abuse (β = 9.37, p = 0.0006), depression (β = 0.19, p = 0.24) and somatisation (β = 0.67, p = 0.01) are independent determinants of weight loss (controlling for gender and occupation, R2 = 0.42, p<0.0001). The effect of depression on weight loss is fully mediated by somatisation. Conclusion: Symptom severity and weight loss in FD are determined by psychosocial factors (depression, abuse history) and somatisation, and only to a lesser extent by gastric sensorimotor function. The importance of psychosocial factors and somatisation compared to gastric sensorimotor function is most pronounced in hypersensitive patients.

Relationship between anxiety and gastric sensorimotor function in functional dyspepsia.

Objective: To investigate the relationship between anxiety and gastric sensorimotor function in patients with (hypersensitive) functional dyspepsia (FD). Comorbidity between FD and anxiety disorders is high. In FD, epigastric pain is associated with gastric hypersensitivity and neuroticism, a personality trait related to anxiety. Experimentally induced anxiety in healthy volunteers is associated with changes in sensorimotor function of the proximal stomach. Methods: A total of 139 patients with FD (n = 102 women) underwent a barostat investigation to determine gastric compliance, meal accommodation, and thresholds for discomfort and pain. Anxiety was measured by the State-Trait Anxiety Inventory (STAI) scale (anxiety as a stable personality trait) and the STAI-State scale (momentary anxiety). The anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A) was filled out to detect comorbid anxiety disorders. Results: Hyper- and normosensitive patients had similar anxiety scores, but gastric compliance was significantly lower in hypersensitive patients (11.4 versus 32.8 ml/mm Hg; p < .001). In the whole patient group, no significant correlations between STAI scores and gastric sensorimotor function were found. In hypersensitive patients (n = 53, 43 women), state anxiety was negatively correlated with discomfort threshold (&rgr; = −.49; p = .001), pain threshold (&rgr; = −.48; p = .02), and gastric compliance (&rgr; = −.46; p = .002). These results were confirmed by multiple linear and logistic regression analyses. Conclusion: In hypersensitive patients with FD, state anxiety is significantly and negatively correlated with discomfort threshold, pain threshold, and compliance. These results strengthen the hypothesis that anxiety is important in FD, especially in hypersensitive patients. FD = functional dyspepsia; STAI = State-Trait Anxiety Inventory; HADS-A = Hospital Anxiety and Depression Scale-Anxiety subscale; FGID = functional gastrointestinal disorders; IBS = irritable bowel syndrome; CNS = central nervous system; MDP = minimal distending pressure; WMW test = Wilcoxon Mann-Whitney test; OR = odds ratio; ANS = autonomic nervous system; EMS = emotional motor system; PAG = periaqueductal grey; LC = locus coeruleus; HPA-axis = hypothalamo-pituitary-adrenal axis; ASI = anxiety sensitivity index; VSI = visceral sensitivity index.

Abnormal Regional Brain Activity During Rest and (Anticipated) Gastric Distension in Functional Dyspepsia and the Role of Anxiety: A H 2 15 O-PET Study

OBJECTIVES:During gastric distension in hypersensitive functional dyspepsia (FD), activation was found in somatosensory cortex (SI/SII) and ventrolateral prefrontal cortex (vlPFC) but, contrary to controls, not in pregenual anterior cingulate (pACC). The aims of this article were to study (i) cortical activations and deactivations during distension and sham compared with baseline in FD, regardless of sensitivity status; (ii) differences in brain activity between health and FD during “no distension” conditions; and (iii) the relationship between anxiety and brain activity in FD.METHODS:Brain H215O-PET was performed in 25 FD patients (13 hypersensitive) during three conditions: baseline, distension at discomfort threshold, and sham. Brain activity was compared against healthy controls using SPM2.RESULTS:Discomfort threshold was lower; sensation scores in all conditions were higher in patients than controls. (i) Activations were similar to controls, except for a lack of pACC activation during distension in FD. Patients showed no dorsal pons and amygdala deactivation during distension and sham, respectively. (ii) Comparing baseline or sham activity showed the following differences: higher activity in SII/SI, insula, midcingulate (MCC), dorsolateral and ventrolateral PFC in controls; and higher activity in occipital cortex in FD. Differences in left lateral PFC were specific to sham. (iii) Anxiety correlated negatively with pACC and MCC and positively with dorsal pons activity.CONCLUSIONS:FD patients failed to activate pACC, to deactivate dorsal pons during distension, and to deactivate amygdala during sham; this may represent arousal–anxiety-driven failure of pain modulation. During baseline and sham, differences between patients and controls were found in sensory as well as affective–cognitive areas.

Functional dyspepsia: past, present, and future

Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder characterized by symptoms originating from the gastroduodenal region in the absence of underlying organic disease that readily explains the symptoms. The Rome II consensus, which defined FD as the presence of unexplained pain or discomfort in the epigastrium, had a number of drawbacks, including an unjustified focus on pain, inclusion of a large number of nonspecific symptoms, and an unclear position on overlap with gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). The Rome III consensus redefined FD as the presence of epigastric pain or burning, postprandial fullness or early satiation in the absence of underlying organic disease. Frequent overlap with GERD and IBS is acknowledged but does not exclude a diagnosis of FD. A subgroup classification into postprandial distress syndrome and epigastric pain syndrome was proposed. Ongoing studies will clarify the impact of this subdivision on clinical management and treatment outcomes.

Regional Brain Activity in Functional Dyspepsia: A H215O-PET Study on the Role of Gastric Sensitivity and Abuse History

BACKGROUND & AIMS Differences in brain activity between health and functional dyspepsia (FD) have been reported; it is unclear whether this is influenced by gastric hypersensitivity or abuse history. Therefore, we aimed to determine the influence of gastric sensitivity and abuse history on gastric sensation scores and brain activity in homeostatic-afferent, emotional-arousal, and cortical-modulatory brain regions in FD. METHODS Abuse history was assessed using a validated self-report questionnaire. H(2)(15)O positron emission tomography was performed in 25 FD patients (13 hypersensitive and 8 abused) during 3 conditions, that is, no distension, gastric distension at discomfort threshold, and sham distension. Data were analyzed in SPM2. Region of interest analysis was used to confirm differences in prehypothesized regions. RESULTS No association between hypersensitivity and abuse history was found. Gastric hypersensitivity was associated with significantly higher gastric sensation scores during baseline and sham. A condition-independent difference in ventral posterior cingulate activity was found between groups, as well as distension and sham-specific differences in brainstem and cingulate areas. Abuse history was associated with higher gastric sensation scores in all conditions and with differences in insular, prefrontal, and hippocampus/amygdala activity. CONCLUSIONS Gastric sensitivity and abuse history independently influence gastric sensation as well as brain activity in FD.

Influence of abuse history on gastric sensorimotor function in functional dyspepsia

Abstract  Patients with functional gastrointestinal disorders have elevated rates of sexual or physical abuse, which may be associated with altered rectal sensorimotor function in irritable bowel syndrome. The aim was to study the association between abuse history and gastric sensorimotor function in functional dyspepsia (FD). We studied gastric sensorimotor function with barostat (sensitivity, compliance and accommodation) and gastric emptying test in 233 consecutive FD patients from a tertiary care centre (162 women, mean age 41.6 ± 0.9). Patients filled out self‐report questionnaires on history of sexual and physical abuse during childhood or adulthood. Eighty‐four patients (out of 198, 42.4%) reported an overall history of abuse [sexual and physical in respectively 30.0% (60/200) and 20.3% (42/207)]. FD patients reporting general as well as severe childhood sexual abuse have significantly lower discomfort thresholds during gastric distension [respectively 10.5 ± 0.4 vs 7.5 ± 1.0 mmHg above minimal distending pressure (MDP), P = 0.014 and 10.5 ± 0.4 vs 6.6 ± 1.2 mmHg above MDP, P = 0.007]. The corresponding intra‐balloon volume was also significantly lower (respectively 579 ± 21 vs 422 ± 59 mL, P = 0.013 and 579 ± 19 vs 423 ± 79 mL, P = 0.033). Gastric accommodation was significantly more pronounced in patients reporting rape during adulthood (91 ± 12 vs 130 ± 40 mL, P = 0.016). Abuse history was not associated with differences in gastric emptying. A history of abuse is associated with alterations in gastric sensorimotor function in FD. Particularly sexual abuse, rather than physical abuse, may influence gastric sensitivity and motor function.

Cortical deactivations during gastric fundus distension in health: visceral pain-specific response or attenuation of ‘default mode’ brain function? A H215O-PET study

Abstract  Gastric distension activates a cerebral network including brainstem, thalamus, insula, perigenual anterior cingulate, cerebellum, ventrolateral prefrontal cortex and potentially somatosensory regions. Cortical deactivations during gastric distension have hardly been reported. To describe brain areas of decreased activity during gastric fundus distension compared to baseline, using data from our previously published study (Gastroenterology, 128, 2005 and 564). H215O‐brain positron emission tomography was performed in 11 healthy volunteers during five conditions (random order): (C1) no distension (baseline); isobaric distension to individual thresholds for (C2) first, (C3) marked, (C4) unpleasant sensation and (C5) sham distension. Subtraction analyses were performed (in SPM2) to determine deactivated areas during distension compared to baseline, with a threshold of Puncorrected_voxel_level < 0.001 and Pcorrected_cluster_level < 0.05. Baseline–maximal distension (C1–C4) yielded significant deactivations in: (i) bilateral occipital, lateral parietal and temporal cortex as well as medial parietal lobe (posterior cingulate and precuneus) and medial temporal lobe (hippocampus and amygdala), (ii) right dorsolateral and dorso‐ and ventromedial PFC, (iii) left subgenual ACC and bilateral caudate head. Intragastric pressure and epigastric sensation score correlated negatively with brain activity in similar regions. The right hippocampus/amygdala deactivation was specific to sham. Gastric fundus distension in health is associated with extensive cortical deactivations, besides the activations described before. Whether this represents task‐independent suspension of ‘default mode’ activity (as described in various cognitive tasks) or an visceral pain/interoception‐specific process remains to be elucidated.

The role of somatosensory cortical regions in the processing of painful gastric fundic distension: an update of brain imaging findings

Abstract  Painful gastric distension is processed in a network consisting of brainstem, thalamus, insula, anterior cingulate cortex, (lateral) orbitofrontal and prefrontal cortex, superior temporal cortex and cerebellum. However, the role of primary and secondary somatosensory cortical regions (SI/SII) in the processing of visceral sensation or pain in general and gastric sensation in particular remains unclear. The aim of this study was to localize activations in the SI/SII area from our previously published functional brain imaging studies on gastric distension more precisely, using newly available cytoarchitectonic probability maps of SI/SII, implemented in the SPM Anatomy toolbox. In healthy volunteers, we found two clusters to be overlapping with SII (mainly the OP4 subregion) and, to a lesser extent, SI, although this overlap was small in size. In functional dyspepsia patients, we found two clusters to be overlapping with SII (mainly OP4), of which the cluster in the right hemisphere also overlapped with SI. These findings were confirmed in a conjunction analysis of both groups. Activation in right SI/SII was significantly higher in healthy volunteers when formally compared to patients. These results provide more detailed information on the brain processing of gastric sensation, supporting the hypothesis that SI/SII are involved. This is in line with some previously published studies on visceral sensation, but at variance with some other studies. Methodological differences between the brain imaging studies on gastric distension may account for these somewhat discrepant findings.

Different regional brain activity during physiological gastric distension compared to balloon distension: a H215O‐PET study

Background  Stepwise gastric balloon distension progressively activates a ‘visceral pain neuromatrix’, ultimately inducing discomfort and pain. On the other hand, normal meal ingestion requires gastric volume expansion without induction of pain. The aim was to test the hypothesis that physiological gastric distension (liquid meal infusion) until maximal satiation elicits brain responses similar to balloon distension at discomfort threshold.

Role of endogenous opioids in the control of gastric sensorimotor function

Abstract  Endogenous opioids have been implicated not only in the process of feeding but also in the control of gastric sensitivity and gastric motor responses, and impairment of antinociceptive opioid pathways has been hypothesized to contribute to the pathogenesis of functional dyspepsia. Our aim was to study the effect of suppression of endogenous opioid action by naloxone on gastric sensorimotor function in healthy volunteers. During intravenous administration of saline or naloxone (0.4 mg intravenous bolus followed by continuous infusion 20 μg kg−1 h−1), sensitivity to gastric distension, gastric accommodation and fundic phasic contractility were evaluated by barostat in 15 subjects. Nutrient tolerance and meal‐related symptoms were assessed using a satiety drinking test (n = 13), and solid and liquid gastric emptying were evaluated by breath test (n = 14). Naloxone did not influence gastric compliance and sensitivity. No effect on preprandial gastric tone was found but meal‐induced accommodation was significantly inhibited by naloxone (P = 0.031). Subjects receiving naloxone demonstrated a higher motility index before (20.8 ± 2.4 vs 28.0 ± 1.9 mL s−1, P = 0.007) and after (15.2 ± 2.0 vs 22.7 ± 1.5 mL s−1, P = 0.0006) the meal. Naloxone significantly decreased the amount of food ingested at maximum satiety (715.4 ± 77.7 vs 617.3 ± 61.3 mL, P = 0.03). No effect of naloxone on gastric emptying was observed and intensity of postprandial symptoms was unchanged. These observations suggest that endogenous opioids are involved in the control of gastric accommodation and phasic contractility but not in the control of sensitivity to gastric distension or gastric emptying in healthy volunteers.