Defecatory urge increases cognitive control and intertemporal patience in healthy volunteers

Background: Past research has demonstrated that moderate urge to urinate improves inhibitory control, specifically among participants with higher behavioral inhibition sensitivity (BIS). The effect was absent when the urge exceeded intolerable level. The present research examines whether rectal distension-induced urge to defecate has similar effects. Methods: The moderate and high defecatory urge were induced by rectal distension in healthy volunteers (n=35), while they completed Stroop task and monetary delay discounting task. The difference of average reaction time between incongruent and congruent trials in the Stroop task (Stroop interference) and the preference for larger-later rewards in the delay discounting task were the primary outcomes. Key Results: Participants with high BIS (n=17) showed greater ability to inhibit their automatic response tendencies, as indexed by their Stroop interference, under moderate urge relative to no urge (128±41 ms vs. 202±37 ms, t64=2.07; p=0.021, Cohen’s d: 0.44), but not relative to high urge (154±45 ms, t64=1.20; p=0.12, Cohen’s d: 0.30). High BIS participants also showed a higher preference for larger-later reward in the delay discounting task under high (odds ratio = 1.51 [1.02–2.25], p=0.039) relative to no urge, but not relative to moderate urge (odds ratio = 1.02 [0.73–1.42], p = 0.91). In contrast, rectal distension did not influence performance on either of the tasks in participants with low BIS (n=18). Conclusions and inference: These findings may be interpreted as a ‘spill-over’ effect of inhibition of the urge to defecate to volitional cognitive control among healthy participants with high BIS

Cumulative Effects of Psychologic Distress, Visceral Hypersensitivity, and Abnormal Transit on Patient-reported Outcomes in Irritable Bowel Syndrome

Background & Aims: Little is known about the link between pathophysiologic factors and symptoms of irritable bowel syndrome (IBS), or whether these factors have cumulative effects on patient-reported outcomes (PROs). We investigated whether pathophysiologic alterations associated with IBS have cumulative or independent effects on PROs. Methods: We performed a retrospective analysis of data from 3 cohorts of patients with IBS (n = 407; 74% female; mean age, 36 ± 12 years), based on Rome II or Rome III criteria, seen at a specialized unit for functional gastrointestinal disorders in Sweden from 2002 through 2014. All patients underwent assessments of colonic transit time (radiopaque markers); compliance, allodynia, and hyperalgesia (rectal barostat); anxiety and depression (Hospital Anxiety and Depression scale), as pathophysiologic factors. Dysfunction was defined by available normal values. PROs included IBS symptom severity, somatic symptom severity, and disease-specific quality of life. Results: Allodynia was observed in 36% of patients, hyperalgesia in 22%, accelerated colonic transit in 18%, delayed transit in 7%, anxiety in 52%, and depression in 24%: each of these factors was associated with severity of at least 1 symptom of IBS. Rectal compliance was not associated with more severe symptoms of IBS. At least 3 pathophysiologic factors were present in 20% of patients, 2 in 30%, 1 in 31%, and none in 18%. With increasing number of pathophysiologic abnormalities, there was a gradual increase in IBS symptom severity (P < .0001) and somatic symptom severity (P < .0001), and a gradual reduction in quality of life (P < .0001). Conclusion: Visceral hypersensitivity, including allodynia and hyperalgesia, abnormal colonic transit, and psychologic factors are all associated with IBS symptoms. These factors have a cumulative effect on gastrointestinal and nongastrointestinal symptoms, as well as on quality of life, in patients with IBS and are therefore relevant treatment targets

Cortisol and Subjective Stress Responses to Acute Psychosocial Stress in Fibromyalgia Patients and Control Participants

OBJECTIVE: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction may play a role in fibromyalgia (FM) pathogenesis, but remains understudied in this disorder. Furthermore, early childhood adversities (ECA) are common in FM, but whether they moderate stress reactivity is unknown. Hence, we investigated cortisol and subjective responses to acute psychosocial stress in FM and controls, while adjusting for ECA. METHODS: Twenty-seven female FM patients and 24 age-matched female controls were recruited in a tertiary care center and through advertisements, respectively. The Childhood Trauma Questionnaire was used to measure ECA history. Salivary cortisol levels and subjective stress ratings were measured at multiple time points before and after the Trier Social Stress Test (TSST) was administered. RESULTS: Significant main effects of group [F(1,43)=7.04, p=0.011, lower in FM] and ECA [F(1,43)=5.18, p=0.028, higher in participants with ECA] were found for cortisol responses. When excluding controls with ECA (n=5), a significant group-by-time interaction was found [F(6,39)=2.60, p=0.032], driven by a blunted response to the stressor in FM compared with controls (p=0.037). For subjective stress responses, a significant main effect of group [F(1,45)=10.69, p=0.002, higher in FM] and a trend towards a group-by-time interaction effect [F(6,45)=2.05, p=0.078, higher in FM 30 minutes before and 30 and 75 minutes after the TSST, and impaired recovery (difference immediately after - 30 minutes after the TSST) in FM] were found. CONCLUSIONS: Blunted cortisol responsivity to the TSST was observed in FM patients compared with controls without ECA. FM patients had higher subjective stress levels compared with controls, particularly at baseline and during recovery from the TSST. In FM patients, ECA history was not associated with cortisol or subjective stress levels, or with responsivity to the TSST. Future research should investigate the mechanisms underlying HPA axis dysregulation in FM

Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: Consistent findings from five different patient cohorts

Objective Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms. Design We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression. Results In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial η2: 0.047-0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05). Conclusions A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs

The dopaminergic system in patients with functional dyspepsia analysed by single photon emission computed tomography (SPECT) and an alpha-methyl-para-tyrosine (AMPT) challenge test

Functional dyspepsia (FD) is a chronic condition characterized by upper abdominal symptoms without an identifiable cause. While the serotonergic system is thought to play a key role in the regulation of gut physiology, the role of the dopaminergic system, which is important in the regulation of visceral pain and stress, is under-studied. Therefore, this study investigated the dopaminergic system and its relationship with drinking capacity and symptoms in FD patients. In FD patients and healthy volunteers (HV) the dopaminergic system was investigated by in-vivo assessment of central dopamine D2 receptors (D2Rs) with [I-123]IBZM SPECT and by an acute, but reversible, dopamine depletion alpha-methyl-para-tyrosine (AMPT) challenge test. A nutrient drink test was performed to investigate the association between maximal ingested volume, evoked symptoms, and D2Rs. The HV subjects comprised 12 women and 8 men (mean age 31 +/- 3 years), and the FD patients comprised 5 women and 3 men (mean age 39 +/- 5 years). The FD patients had a lower left plus right average striatal binding potential (BPNP) for the caudate nucleus (p = 0.02), but not for putamen (p = 0.15), which in the FD patients was correlated with maximal ingested volume (r = 0.756, p = 0.03). The D2R BPNP in the putamen was correlated with nausea (r = 0.857, p = 0.01). The acute dopamine depletion test, however, failed to reveal differences in prolactin release between the FD patients and the HV subjects. These preliminary data suggest that chronic rather than acute alterations in the dopaminergic system may be involved in the pathogenesis of FD. Further studies are required to reproduce our novel findings and to evaluate to what extent the dopaminergic changes may be secondary to abnormalities in serotonergic pathway

Prevalence and impact of childhood adversities and post-traumatic stress disorder in women with fibromyalgia and chronic widespread pain.

OBJECTIVE: This study investigates the prevalence of different types of childhood adversities (CA) and posttraumatic stress disorder (PTSD) in female patients with Fibromyalgia or Chronic Widespread Pain (FM/CWP) compared to patients with Functional Dyspepsia (FD) and achalasia. In FM/CWP, we also investigated the association between CA and PTSD on the one hand and pain severity on the other. METHODS: Patient samples consisted of 154 female FM/CWP, 83 female FD and 53 female achalasia patients consecutively recruited from a tertiary care hospital. Well-validated self-report questionnaires were used to investigate CA and PTSD. RESULTS: Forty-nine per cent of FM/CWP patients reported at least 1 type of CA, compared to 39.7% of FD patients and 23.4% of achalasia patients (p < 0.01). The prevalence of CA did not differ significantly between FM/CWP and FD, but both groups had a higher prevalence of CA compared to both achalasia and healthy controls (p < 0.01). FM/CWP patients were six times more likely to report PTSD than both FD (p < 0.001) and achalasia (p < 0.001) patients. CONCLUSION: In FM/CWP, PTSD comorbidity, but not CA, was associated with self-reported pain severity and PTSD severity mediated the relationship between CA and pain severity. In summary, the prevalence of CA is higher in FM/CWP compared to achalasia, but similar to FD. However, PTSD is more prevalent in FM/CWP compared to FD and associated with higher pain intensity in FM/CWP. SIGNIFICANCE: As expected and has been shown in other functional disorders, we found elevated levels of childhood adversity in FM/CWP patients. Results of this study however suggest that the impact of childhood adversity (i.e. whether such events have led to the development of PTSD symptoms), rather than the mere presence of such adversity, is of crucial importance in FM/CWP patients. Screening for PTSD symptoms should be an essential part of the assessment process in patients suffering from FM/CWP, and both prevention and intervention efforts should take into account PTSD symptoms and their impact on pain severity and general functioning

Reply

Reply. We thank Drs Siah and Gwee for their interest in our study, in which we reported an exploratory factor analysis of Rome IV symptoms (Clevers et al), which we refer to as the Rome IV exploratory model (R4EM) similar to Siah and Gwee

Factor Analysis Defines Distinct Upper and Lower Gastrointestinal Symptom Groups Compatible With Rome IV Criteria in a Population-based Study

Background & Aims: The Rome IV criteria define functional gastrointestinal (GI) disorders by specific combinations of symptoms. It is possible to empirically evaluate these symptom combinations by factor analysis (a statistical procedure that groups variables that correlate). However, this analysis has not been performed for the Rome IV criteria, and factor analyses based on the previous versions of the Rome criteria did not use population-based data. We therefore investigated symptom grouping by the Rome IV questionnaire using factor analysis of a population-based sample. Methods: The Rome IV questionnaire was completed online in English by 5931 respondents from the United Kingdom, United States, and Canada (49% female, age range, 18–92 years). We performed an exploratory factor analysis on the Rome IV questions. Next, we performed a confirmatory factor analysis to compare the exploratory factor result to that of the Rome IV criteria. Results: The exploratory factor analysis identified 8 factors that accounted for 45% of the variance in response: constipation, diarrhea, irritable bowel syndrome, abdominal pain, heartburn, nausea or vomiting, globus, and other upper GI symptoms. Most factors corresponded to distinct functional GI disorders defined by the Rome IV criteria—exceptions included abdominal pain and upper GI symptoms. In confirmatory factor analysis, the exploratory model fitted slightly better than that based on the Rome IV criteria (root mean square error of approximation, 0.063 vs 0.077). Conclusions: We used factor analysis to identify distinct upper and lower GI symptom groups that are compatible with the Rome IV criteria. Our findings support the use of the Rome IV criteria in research and clinical practice as a basis for development of diagnostics and management of patients