Brain mediators of negative affect-induced physical symptom reporting in patients with functional somatic syndromes.

Functional somatic syndromes (FSS) include fibromyalgia, irritable bowel syndrome (IBS), and others. In FSS patients, merely viewing negative affective pictures can elicit increased physical symptoms. Our aim was to investigate the neural mechanisms underlying such negative affect-induced physical symptoms in FSS patients. Thirty patients with fibromyalgia and/or IBS and 30 healthy controls (all women) watched neutral, positive and negative affective picture blocks during functional MRI scanning and rated negative affect and physical symptoms after every block. We compared brain-wide activation during negative versus neutral picture viewing in FSS patients versus controls using robust general linear model analysis. Further, we compared neurologic pain signature (NPS), stimulus intensity-independent pain signature (SIIPS) and picture-induced negative emotion signature (PINES) responses to the negative versus neutral affect contrast and investigated whether they mediated between-group differences in affective picture-induced physical symptom reporting. More physical symptoms were reported after viewing negative compared to neutral pictures, and this effect was larger in patients than controls (p = 0.025). Accordingly, patients showed stronger activation in somatosensory regions during negative versus neutral picture viewing. NPS, but not SIIPS nor PINES, responses were higher in patients than controls during negative versus neutral pictures (p = 0.026). These differential NPS responses partially mediated between-group differences in physical symptoms. In conclusion, picture-induced negative affect elicits physical symptoms in FSS patients as a result of activation of somatosensory and nociceptive brain patterns, supporting the idea that affect-driven alterations in processing of somatic signals is a critical mechanism underlying FSS.

The Rome Foundation Global Epidemiology study: Research opportunities national and worldwide.

The Rome Foundation embarked on an ambitious multi-year, multinational population-based study to evaluate the prevalence of Rome IV-defined DGBI and their biopsychosocial impact on a worldwide scale. The consistency of the study findings attests to the scientific rigor of this effort, as evident in the publications that resulted from this international study. Dr. Sperber and colleagues report a subanalysis on the Rome IV Global Epidemiology internet survey of the 2012 adults in Israel. These data determined the national prevalence of Rome IV-defined DGBIs, and their associated healthcare utilization and sociodemographic and psychosocial variables. Importantly, they also permitted seamless comparison of the data in the rest of the world. The Israeli study highlights some of the strengths of the Global Epidemiology Study: the 2 respondents had a geographical spread representative of the country. The questionnaire in Israel was available to the participants online in four different languages used by the population in Israel: The database of the study is now available through the Rome Foundation Research Institute for use by academic and industry researchers. This unique gift from the Rome Foundation to the scientific community no doubt will further enhance our understanding of disorders of gut-brain interaction.

Transient hypopharyngeal intrabolus pressurization patterns: Clinically relevant or normal variant?

INTRODUCTION: In oropharyngeal dysphagia, impaired pharyngoesophageal junction (PEJ) opening is reflected by an elevated hypopharyngeal intrabolus pressure (IBP), quantifiable using pharyngeal high-resolution manometry with impedance (P-HRM-I). Transient intrabolus pressurization (TP) phenomena are not sustained and last for only a brief period. We hypothesized that TP patterns reflect impaired coordination between timing of hypopharyngeal bolus arrival and PEJ relaxation. METHODS: A retrospective audit was conducted of P-HRM-I datasets; 93 asymptomatic Controls and 214 Patients with differing etiological/clinical backgrounds were included. TP patterns were examined during 10ml liquid swallows. TP was defined by a simultaneous, non-sustained, pressurization wave spanning from the velo-/meso-pharynx to PEJ. The coordination between deglutitive pharyngeal bolus distension and PEJ relaxation timing was assessed using timing variables; (i) Distention-Contraction Latency (DCL, s) and (ii) PEJ Relaxation Time (RT, s). Resultant flow resistance was quantified (IBP, mmHg). RESULTS: TP swallows were observed in 87 (28%) cases. DCL was not significantly different in relation to TP, while PEJ relaxation time was shorter, and IBP was higher during TP swallows. In Patients RT-DCL time difference correlated with IBP (r -0.368, p < 0.01). CONCLUSION: Bolus distension and PEJ relaxation were miss-timed during TP swallows, impeding bolus flow and leading to a brief period of pressurization of the pharyngeal chamber by muscular propulsive forces. While TP swallows were identified in both Controls and Patients, increased IBPs were most apparent for Patient swallows indicating that the extent of IBP increase may differentiate pathological TP swallows.

A survey of functional dyspepsia in 361,360 individuals: Phenotypic and genetic cross-disease analyses.

BACKGROUND: Functional dyspepsia (FD) is a common gastrointestinal condition of poorly understood pathophysiology. While symptoms' overlap with other conditions may indicate common pathogenetic mechanisms, genetic predisposition is suspected but has not been adequately investigated. METHODS: Using healthcare, questionnaire, and genetic data from three large population-based biobanks (UK Biobank, EGCUT, and MGI), we surveyed FD comorbidities, heritability, and genetic correlations across a wide spectrum of conditions and traits in 10,078 cases and 351,282 non-FD controls of European ancestry. KEY RESULTS: In UK Biobank, 281 diagnoses were detected at increased prevalence in FD, based on healthcare records. Among these, gastrointestinal conditions (OR = 4.0, p < 1.0 × 10-300 ), anxiety disorders (OR = 2.3, p < 1.4 × 10-27 ), ischemic heart disease (OR = 2.2, p < 2.3 × 10-76 ), and infectious and parasitic diseases (OR = 2.1, p = 1.5 × 10-73 ) showed strongest association with FD. Similar results were obtained in an analysis of self-reported conditions and use of medications from questionnaire data. Based on a genome-wide association meta-analysis of genotypes across all cohorts, FD heritability was estimated close to 5% ( hSNP2  = 0.047, p = 0.014). Genetic correlations indicate FD predisposition is shared with several other diseases and traits (rg  > 0.344), mostly overlapping with those also enriched in FD patients. Suggestive (p < 5.0 × 10-6 ) association with FD risk was detected for 13 loci, with 2 showing nominal replication (p < 0.05) in an independent cohort of 192 FD patients. CONCLUSIONS & INFERENCES: FD has a weak heritable component that shows commonalities with multiple conditions across a wide spectrum of pathophysiological domains. This new knowledge contributes to a better understanding of FD etiology and may have implications for improving its treatment.

Chicago classification version 4.0© technical review: Update on standard high-resolution manometry protocol for the assessment of esophageal motility.

The Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). A key feature of CCv.4.0 is the more rigorous and expansive protocol that incorporates single wet swallows acquired in different positions (supine, upright) and provocative testing, including multiple rapid swallows and rapid drink challenge. Additionally, solid bolus swallows, solid test meal, and/or pharmacologic provocation can be used to identify clinically relevant motility disorders and other conditions (eg, rumination) that occur during and after meals. The acquisition and analysis for performing these tests and the evidence supporting their inclusion in the Chicago Classification protocol is detailed in this technical review. Provocative tests are designed to increase the diagnostic sensitivity and specificity of HRM studies for disorders of esophageal motility. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification, decrease the proportion of HRM studies that deliver inconclusive diagnoses and increase the number of patients with a clinically relevant diagnosis that can direct effective therapy. Another aim in establishing a standard manometry protocol for motility laboratories around the world is to facilitate procedural consistency, improve diagnostic reliability, and promote collaborative research.

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.