Irritable Bowel Syndrome: Whitehead WE

Chiarioni G, Palsson OS, Whitehead WE. · No affiliation provided · World J Gastroenterol. · Pubmed #19009639 links to  free full text

Abstract: Hypnosis is a therapeutic technique that primarily involves attentive receptive concentration. Even though a small number of health professionals are trained in hypnosis and lingering myths and misconceptions associated with this method have hampered its widespread use to treat medical conditions, hypnotherapy has gained relevance as an effective treatment for irritable bowel syndrome not responsive to standard care. More recently, a few studies have addressed the potential influence of hypnosis on upper digestive function and disease. This paper reviews the efficacy of hypnosis in the modulation of upper digestive motor and secretory function. The present evidence of the effectiveness of hypnotherapy as a treatment for functional and organic diseases of the upper bowel is also summarized, coupled with a discussion of potential mechanisms of its therapeutic action.

Whitehead WE. · No affiliation provided · Am J Gastroenterol. · Pubmed #17897338 No free full text.

Abstract: Twin studies have traditionally been used to assess the heritability of diseases such as irritable bowel syndrome (IBS) by comparing concordance rates in monozygotic twins (identical genetic endowment) to dizygotic twins (half of genes shared). Wojczynski et al. used twins in a novel way-they studied monozygotic twins who were discordant for IBS (but who shared identical genes) to show that the comorbidity of IBS with major depressive disorder could NOT be due to genetic influences. This paradigm provides the most rigorous method for separating genetic from environmental influences and should be adopted by other researchers. However, the authors' conclusion that major depressive disorder and IBS are part of the same pathophysiological process is questioned on the basis of (a) incomplete co-occurrence of IBS and major depressive disorder (13-45% co-occurrence) and (b) lack of specificity-the authors show that chronic widespread pain (related to fibromyalgia) and chronic fatigue are also strongly associated with IBS. This study provides precise, generalizable estimates from a large population-based study for the comorbidity of IBS with major depressive disorder, chronic widespread pain, and chronic fatigue.

Whitehead WE. · No affiliation provided · Gastroenterology. · Pubmed #15188156 No free full text.

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Whitehead WE. · No affiliation provided · Gastroenterology. · Pubmed #12612895 No free full text.

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Chiarioni G, Whitehead WE. · Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7080, USA. · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #18521115 No free full text.

Abstract: Biofeedback is a form of treatment that has no adverse effects and can be provided by physician extenders. The therapy relies on patients' ability to learn how to influence their bodily functions through dedicated machinery and teaching. This Review provides a comprehensive overview of all potential therapeutic applications of biofeedback for functional constipation, fecal incontinence, functional anorectal pain, IBS, functional dyspepsia, and aerophagia. Practical clinical applications of biofeedback therapy supported by randomized, controlled trials (RCTs) are limited to fecal incontinence and dyssynergic defecation. For fecal incontinence, RCTs suggest that biofeedback combining strength training and sensory discrimination training is effective in approximately 75% of patients and is more effective than placebo. However, verbal feedback provided by a therapist during extended digital examination may be equally effective, and children whose fecal incontinence is associated with constipation plus fecal impaction do no better with biofeedback than medical management. For dyssynergic defecation, RCTs show that biofeedback combining pelvic floor muscle relaxation training, practice in defecating a water-filled balloon, and instruction in effective straining is effective in approximately 70% of patients who have failed to respond to laxative treatment. For both incontinence and dyssynergic defecation, the benefits of biofeedback last at least 12 months.

Chitkara DK, van Tilburg MA, Blois-Martin N, Whitehead WE. · UNC Center for Functional GI and Motility Disorders, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7555, USA. · Am J Gastroenterol. · Pubmed #18177446 No free full text.

Abstract: BACKGROUND: Irritable bowel syndrome (IBS) is a common disorder that occurs in adults. The natural history of symptoms and risk factors that contribute to IBS may begin in childhood. The aim of this systematic review was to determine what early life factors contribute to the development of IBS in adolescents and adults. METHODS: A computer-assisted search of the PubMed database from 1966 to 2007 was performed. The selection criteria were: (a) studies conducted in adolescents or adults with IBS that (b) investigate premorbid factors occurring specifically during the childhood period and are (c) associated with the outcomes of symptoms, quality of life, health-care utilization, and interferences with work or disability. RESULTS: Twenty-five articles met inclusion criteria. The studies were categorized into articles examining the persistence of childhood gastrointestinal symptoms into adulthood, affluent childhood socioeconomic status and adult IBS, infantile and childhood trauma associated with the development of adult IBS, and social learning of illness behavior as predictors of adult IBS. CONCLUSION: Pediatricians should be aware of potentially modifiable childhood risk factors and should consider interventions such as early symptom management of recurrent functional abdominal pain with cognitive therapies and parent education about social learning of illness behavior. Early treatment may have a long-term impact. Research examining the effect of affluent childhood socioeconomic status and early childhood trauma in the evolution of functional gastrointestinal disorders may help identify causative factors of IBS.

Anonymous00303, Irvine EJ, Whitehead WE, Chey WD, Matsueda K, Shaw M, Talley NJ, Veldhuyzen van Zanten SJ. · Division of Gastroenterology, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. · Gastroenterology. · Pubmed #16678567 No free full text.

Abstract: This document addresses the design of trials to assess the efficacy of new treatments for functional gastrointestinal disorders (FGID), emphasizing trials in irritable bowel syndrome and dyspepsia, because most research has been undertaken in these conditions. The double-blind, randomized, placebo-controlled, parallel group trial remains the preferred design. Randomized withdrawal designs, although encouraged by the European Agency for the Evaluation of Medicinal Products, have the same potential disadvantages as a crossover design, including carryover effects, unmasking (unblinding), and overestimation of the potential benefit for clinical practice. Innovative trial designs that evaluate intermittent (on demand) treatment are likely to become more common in the future. Investigators should include as broad a spectrum of patients as possible and should report recruitment strategies, inclusion/exclusion criteria, and attrition data. The primary analysis should be based on the proportion of patients in each treatment arm who satisfy an a priori treatment responder definition, or a prespecified clinically meaningful change in a patient-reported symptom improvement measure. Such measures of improvement are psychometrically validated subjective global assessments or a change from baseline in a validated symptom severity questionnaire. It is unethical to change the responder definition after a trial begins. Data analysis should address all patients enrolled, using an intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include an analysis of harms data and secondary outcome measures to support or explain the primary outcome. Trials should be registered in a public location, prior to initiation, and should be published even if the results are negative or inconclusive.

Drossman DA, Camilleri M, Mayer EA, Whitehead WE. · UNC Center for Functional GI and Motility Disorders, Division of Digestive Diseases, University of North Carolina, Chapel Hill, USA. · Gastroenterology. · Pubmed #12454866 No free full text.

This publication has no abstract.

Whitehead WE, Palsson O, Jones KR. · Division of Digestive Diseases and Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina 27599, USA. · Gastroenterology. · Pubmed #11910364 No free full text.

Abstract: BACKGROUND & AIMS: Comorbid or extraintestinal symptoms occur frequently with irritable bowel syndrome and account for up to three fourths of excess health care visits. This challenges the assumption that irritable bowel is a distinct disorder. The aims of this study were to (1) assess comorbidity in 3 areas: gastrointestinal disorders, psychiatric disorders, and nongastrointestinal somatic disorders; and (2) evaluate explanatory hypotheses. METHODS: The scientific literature since 1966 in all languages cited in Medline was systematically reviewed. RESULTS: Comorbidity with other functional gastrointestinal disorders is high and may be caused by shared pathophysiological mechanisms such as visceral hypersensitivity. Psychiatric disorders, especially major depression, anxiety, and somatoform disorders, occur in up to 94%. The nongastrointestinal nonpsychiatric disorders with the best-documented association are fibromyalgia (median of 49% have IBS), chronic fatigue syndrome (51%), temporomandibular joint disorder (64%), and chronic pelvic pain (50%). CONCLUSIONS: Multivariate statistical analyses suggest that these are distinct disorders and not manifestations of a common somatization disorder, but their strong comorbidity suggests a common feature important to their expression, which is most likely psychological. Some models explain the comorbidity of irritable bowel with other disorders by suggesting that each disorder is the manifestation of varying combinations of interacting physiological and psychological factors. An alternative hypothesis is that the irritable bowel diagnosis is applied to a heterogeneous group of patients, some of whom have a predominantly psychological etiology, whereas others have a predominantly biological etiology, and that the presence of multiple comorbid disorders is a marker for psychological influences on etiology.

Whitehead WE. · Department of Medicine, University of North Carolina at Chapel Hill, 27599-7080, USA. · Am J Med. · Pubmed #10588171 No free full text.

Abstract: Subgroups of patients with irritable bowel syndrome (IBS) are likely to respond differently to existing and evolving therapies. The following criteria for subgrouping may be considered: (1) Patients with different predominant bowel habits respond differently to treatment (antidepressants, 5HT3-antagonists, psychotherapy). (2) Postprandial exacerbation of pain or other gastrointestinal symptoms is seen in approximately half of patients with IBS and may identify patients who are more responsive to some classes of drugs (e.g., those targeted at motility). (3) Women appear to respond differently from men to 5HT3-antagonists, and there may be gender differences in gastrointestinal physiology. (4) There is more overlap in the diagnosis of functional dyspepsia and IBS than would be predicted by chance, and both are associated with hyperalgesia to intraluminal distention.

Ringel Y, Whitehead WE, Toner BB, Diamant NE, Hu Y, Jia H, Bangdiwala SI, Drossman DA. · Department of Medicine, Division of Digestive Diseases and Nutrition, and the UNC Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, 27599-7080, USA. · Gut. · Pubmed #15138210 links to  free full text

Abstract: BACKGROUND: Patients with irritable bowel syndrome (IBS) have reduced pain thresholds for rectal distension. In addition, the prevalence of sexual/physical abuse in referred IBS patients is high and is associated with greater pain reporting, poorer health status, and poorer outcome. This lead to a hypothesis that abuse history may sensitise patients to report pain at a lower threshold. AIM: To compare rectal pain thresholds in women with IBS who had a history of severe abuse to IBS women with no history of abuse. METHODS: We studied 74 IBS patients with a history of severe physical and/or sexual abuse and 85 patients with no history of abuse. Abuse history was assessed by a previously validated self-report abuse screening questionnaire. Rectal sensory thresholds were assessed using an electronic barostat and determined by the ascending method of limit (AML) and by the tracking technique. RESULTS: IBS patients with a history of severe abuse had significantly higher rectal pain thresholds, as measured by AML (F (1, 111) = 6.06; p = 0.015) and the tracking technique (F (1, 109) = 5.21; p = 0.024). Patients with a history of severe abuse also reported a significantly higher threshold for urgency to defecate (F (1, 113) = 11.23; p =.001). CONCLUSION: Severe sexual/physical abuse is associated with higher urge and pain thresholds for rectal distension in IBS patients. This suggests that the greater pain reporting and poorer health status in IBS patients with abuse history are not related to increased rectal pain sensitivity. Further studies are needed to determine the causes of these findings.

Drossman DA, Toner BB, Whitehead WE, Diamant NE, Dalton CB, Duncan S, Emmott S, Proffitt V, Akman D, Frusciante K, Le T, Meyer K, Bradshaw B, Mikula K, Morris CB, Blackman CJ, Hu Y, Jia H, Li JZ, Koch GG, Bangdiwala SI. · UNC Center for Functional GI and Motility Disorders, Division of Digestive Diseases, University of North Carolina at Chapel Hill, 27599-7080, USA. · Gastroenterology. · Pubmed #12851867 No free full text.

Abstract: BACKGROUND & AIMS: Studies of antidepressants and psychological treatments in functional bowel disorders (FBD) are methodologically limited. The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy (CBT) against education (EDU) and desipramine (DES) against placebo (PLA) in female patients with moderate to severe FBD (irritable bowel syndrome, functional abdominal pain, painful constipation, and unspecified FBD). We also evaluated the amenability of clinically meaningful subgroups to these treatments. METHODS: This randomized, comparator-controlled, multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD. Participants received psychological (CBT vs. EDU) or antidepressant (DES vs. PLA) treatment for 12 weeks. Clinical, physiologic, and psychosocial assessments were performed before and at the end of treatment. RESULTS: The intention-to-treat analysis showed CBT as significantly more effective than EDU (P = 0.0001; responder rate, 70% CBT vs. 37% EDU; number needed to treat [NNT ], 3.1). DES did not show significant benefit over PLA in the intention-to-treat analysis (P = 0.16; responder rate, 60% DES vs. 47% PLA; NNT, 8.1) but did show a statistically significant benefit in the per-protocol analysis (P = 0.01; responder rate, 73% DES vs. 49% PLA; NNT, 5.2), especially when participants with nondetectable blood levels of DES were excluded (P = 0.002). Improvement was best gauged by satisfaction with treatment. Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms, abuse history, no depression, and diarrhea-predominant symptoms; CBT was beneficial over EDU for all subgroups except for depression. CONCLUSIONS: For female patients with moderate to severe FBD, CBT is effective and DES may be effective when taken adequately. Certain clinical subgroups are more or less amenable to these treatments.

Palsson OS, Turner MJ, Johnson DA, Burnett CK, Whitehead WE. · University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7080 USA. · Dig Dis Sci. · Pubmed #12452403 No free full text.

Abstract: Hypnosis improves irritable bowel syndrome (IBS), but the mechanism is unknown. Possible physiological and psychological mechanisms were investigated in two studies. Patients with severe irritable bowel syndrome received seven biweekly hypnosis sessions and used hypnosis audiotapes at home. Rectal pain thresholds and smooth muscle tone were measured with a barostat before and after treatment in 18 patients (study I), and treatment changes in heart rate, blood pressure, skin conductance, finger temperature, and forehead electromyographic activity were assessed in 24 patients (study II). Somatization, anxiety, and depression were also measured. All central IBS symptoms improved substantially from treatment in both studies. Rectal pain thresholds, rectal smooth muscle tone, and autonomic functioning (except sweat gland reactivity) were unaffected by hypnosis treatment. However, somatization and psychological distress showed large decreases. In conclusion, hypnosis improves IBS symptoms through reductions in psychological distress and somatization. Improvements were unrelated to changes in the physiological parameters measured.

Drossman DA, Patrick DL, Whitehead WE, Toner BB, Diamant NE, Hu Y, Jia H, Bangdiwala SI. · UNC Center for Functional GI and Motility Disorders, Division of Digestive Diseases, University of North Carolina, Chapel Hill 27599-7080, USA. · Am J Gastroenterol. · Pubmed #10763950 No free full text.

Abstract: OBJECTIVE: There has been growing interest in the investigation of health-related quality of life (HRQOL) among patients with gastrointestinal (GI) disorders. We recently reported on the development and preliminary validation of the IBS-QOL, a specific quality-of-life measure for irritable bowel syndrome (IBS). The aim of this study was to determine the longitudinal construct validity (responsiveness) of the IBS-QOL. METHODS: Female patients enrolled in a multicenter treatment trial for functional bowel disorders were studied pre- and posttreatment with the IBS-QOL and other health status measures. Based on the response to treatment for several variables (pain/14-day score, daily function, and days in bed/3 months), patients were stratified into Responders, Partial Responders, and Nonresponders. Change scores in the IBS-QOL were then statistically compared with changes in the other variables to determine their correlation and whether Responders were significantly different from non- and Partial Responders on the IBS-QOL. RESULTS: There was a significant correlation between change scores on the IBS-QOL and the other measures of treatment effect (Pain/14 days, r = 0.25, p < 0.002; Sickness Impact Profile [SIP] Total Score, r = 0.28, p < 0.0004). In addition, the IBS-QOL scores significantly differentiated Responders from Nonresponders for most of the variables tested (regression trend test for Pain/14 days, p < 0.04; SIP Total, p < 0.0001; SIP Physical, p < 0.0001; SIP Psychosocial, p < 0.002, and SIP Eating, p < 0.04). CONCLUSION: The IBS-QOL is responsive to treatment in a referral-based clinical population of patients with functional bowel disorders.

Dorn SD, Morris CB, Hu Y, Toner BB, Diamant N, Whitehead WE, Bangdiwala SI, Drossman DA. · UNC Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7080, USA. · J Clin Gastroenterol. · Pubmed #19623100 No free full text.

Abstract: BACKGROUND: The implications of the Rome III recommendations to change the irritable bowel syndrome (IBS) subtype criteria for stool pattern are unknown. AIM: (1) Determine the level of agreement between Rome II and Rome III subtypes and (2) compare the behaviors of Rome II and Rome III subtypes over time. METHODS: Female patients (n=148) with Rome II defined IBS were prospectively tracked over 5 consecutive 3-month periods. At baseline, bowel habit reports on questionnaires were used to subclassify patients into Rome II and Rome III subtypes. Over the subsequent 15 months, bowel habit reports on diary cards were used to subclassify patients based on previously derived surrogate criteria into Rome II and Rome III IBS subtypes. RESULTS: The level of agreement between Rome II and Rome III subtype assignments was quite high (86.5%; kappa 0.79). The behavior of Rome II and Rome III subtypes over time was also similar in terms of subtype prevalence, subtype stability, and the proportion of subjects who met criteria for alternating irritable bowel syndrome. CONCLUSIONS: Rome II and Rome III IBS subtypes are in high agreement and behave similarly over time. Therefore, studies that used Rome II subtype criteria and studies that will use Rome III criteria will define comparable populations.

Kanazawa M, Palsson OS, Thiwan SI, Turner MJ, van Tilburg MA, Gangarosa LM, Chitkara DK, Fukudo S, Drossman DA, Whitehead WE. · Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, North Carolina, USA. · Am J Gastroenterol. · Pubmed #18684175 No free full text.

Abstract: OBJECTIVES: Irritable bowel syndrome (IBS) patients show pain hypersensitivity and hypercontractility in response to colonic or rectal distention. Aims were to determine whether predominant bowel habits and IBS symptom severity are related to pain sensitivity, colon motility, or smooth muscle tone. METHODS: One hundred twenty-nine patients classified as IBS with diarrhea (IBS-D, N = 44), IBS with constipation (IBS-C, N = 29), mixed IBS (IBS-M, N = 45), and unspecified IBS (IBS-U, N = 11) based on stool consistency, and 30 healthy controls (HC) were studied. A manometric catheter containing a 600-mL capacity plastic bag was positioned in the descending colon. Pain threshold was assessed using a barostat. Motility was assessed for 10 min with the bag minimally inflated (individual operating pressure [IOP]), 10 min at 20 mmHg above the IOP, and for 15-min recovery following bag inflation. Motility was also recorded for 30 min following an 810-kcal meal. RESULTS: Compared with HC, IBS patients had lower pain thresholds (medians 30 vs 40 mmHg, P < 0.01), but IBS subtypes were not different. IBS symptom severity was correlated with pain thresholds (rho =-0.36, P < 0.001). During distention, the motility index (MI) was significantly higher in IBS compared with HC (909 +/- 73 vs 563 +/- 78, P < 0.01). Average barostat bag volume at baseline was higher (muscle tone lower) in HC compared with IBS-D and IBS-M but not compared with IBS-C. The baseline MI and bag volume differed between IBS-D and IBS-C and correlated with symptoms of abdominal distention and dissatisfaction with bowel movements. Pain thresholds and MI during distention were uncorrelated. CONCLUSIONS: Pain sensitivity and colon motility are independent factors contributing to IBS symptoms. Treatment may need to address both, and to be specific to predominant bowel habit.

van Tilburg MA, Palsson OS, Levy RL, Feld AD, Turner MJ, Drossman DA, Whitehead WE. · Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina, USA. · BMC Complement Altern Med. · Pubmed #18652682 links to  free full text

Abstract: BACKGROUND: Functional Bowel Disorders (FBD) are chronic disorders that are difficult to treat and manage. Many patients and doctors are dissatisfied with the level of improvement in symptoms that can be achieved with standard medical care which may lead them to seek alternatives for care. There are currently no data on the types of Complementary and Alternative Medicine (CAM) used for FBDs other than Irritable Bowel Syndrome (IBS), or on the economic costs of CAM treatments. The aim of this study is to determine prevalence, types and costs of CAM in IBS, functional diarrhea, functional constipation, and functional abdominal pain. METHODS: 1012 Patients with FBD were recruited through a health care maintenance organization and followed for 6 months. Questionnaires were used to ascertain: Utilization and expenditures on CAM, symptom severity (IBS-SS), quality of life (IBS-QoL), psychological distress (BSI) and perceived treatment effectiveness. Costs for conventional medical care were extracted from administrative claims. RESULTS: CAM was used by 35% of patients, at a median yearly cost of $200. The most common CAM types were ginger, massage therapy and yoga. CAM use was associated with female gender, higher education, and anxiety. Satisfaction with physician care and perceived effectiveness of prescription medication were not associated with CAM use. Physician referral to a CAM provider was uncommon but the majority of patients receiving this recommendation followed their physician's advice. CONCLUSION: CAM is used by one-third of FBD patients. CAM use does not seem to be driven by dissatisfaction with conventional care. Physicians should discuss CAM use and effectiveness with their patients and refer patients if appropriate.

Grover M, Kanazawa M, Palsson OS, Chitkara DK, Gangarosa LM, Drossman DA, Whitehead WE. · Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, NC 27599-7080, USA. · Neurogastroenterol Motil. · Pubmed #18482250 No free full text.

Abstract: Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS), although the issue is still under debate. The aim of this study was to determine the prevalence of SIBO in those with IBS and its association with colonic motility, bowel symptoms and psychological distress. Sucrose hydrogen and methane breath tests were performed in 158 IBS patients and 34 healthy controls (HC). Thresholds for pain and urgency were tested by barostat in the descending colon. The motility index (MI) was calculated as the average area under the curve for all phasic contractions. Questionnaires assessed psychological distress, IBS symptom severity (IBS-SS), IBS quality of life (IBS-QOL) and self-reported bowel symptoms. Fifty-two of 158 (32.9%) IBS patients had abnormal breath tests compared with six of 34 (17.9%) HC (chi(2) = 0.079). SIBO (SIBO+) and non-SIBO (SIBO-) patients did not differ in the prevalence of IBS subtypes, IBS-SS, IBS-QOL and psychological distress variables. IBS patients had a greater post-distension increase in MI than HC, but there was no difference between SIBO+ and SIBO- patients. Predominant methane producers had higher urge thresholds (28.4 vs 18.3, P < 0.05) and higher baseline MI (461 vs 301.45, P < 0.05) than SIBO- IBS patients, and they reported more 'hard or lumpy stools' when compared with predominant hydrogen producers (P < 0.05) and SIBO- IBS patients (P < 0.05). SIBO is unlikely to contribute significantly to the pathogenesis of IBS. Methane production is associated with constipation.

Ringel Y, Drossman DA, Leserman JL, Suyenobu BY, Wilber K, Lin W, Whitehead WE, Naliboff BD, Berman S, Mayer EA. · UNC Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina, USA. · Gastroenterology. · Pubmed #18242208 No free full text.

Abstract: BACKGROUND & AIMS: Abuse history is common in irritable bowel syndrome (IBS) and is associated with greater pain reporting, psychologic distress, and poorer health outcome. These effects may be mediated by enhanced responses to aversive visceral stimuli. We investigated the effects of IBS and abuse history on pain reporting and brain activation in response to rectal distentions. METHODS: Ten female patients with IBS and 10 controls were included. Half of patients in each group reported a history of abuse. Brain functional magnetic resonance imaging (fMRI) images and pain ratings were obtained during rectal distentions. Statistical parametric mapping identified activation in subregions of the dorsal cingulate cortex and covariation with rated pain. RESULTS: (1) Distention-elicited pain correlated with anxiety and activation of the posterior (PCC) and middle (MCC) dorsal cingulate subregions. (2) Subjects with a history of abuse showed greater activation in the left MCC (P = .022; t = 5.61) and PCC (P = .033; t = 5.00) than subjects without abuse. (3) Those with IBS and abuse reported greater pain than all others (P = .004), had more activity in the left MCC (P = .021; t = 5.29) and PCC (P = .049; t = 4.81), and had less activity in the left supragenual anterior cingulate (sACC) (P = .01; t = 4.86). CONCLUSIONS: Pain ratings during rectal distention are associated with activation of dorsal cingulate regions implicated in homeostatic afferent processing, and prior abuse enhances this activation. Patients with IBS and abuse report more pain, greater MCC/PCC activation, and reduced activity of a region implicated in pain inhibition and arousal (sACC). These findings suggest a possible explanation for the clinical observation of greater pain reporting and poorer outcome in IBS patients with a history of abuse.

Whitehead WE, Palsson OS, Levy RR, Feld AD, Turner M, Von Korff M. · Center for Functional GI and Motility Disorders at the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7555, USA. · Am J Gastroenterol. · Pubmed #17900326 No free full text.

Abstract: BACKGROUND: Comorbid nongastrointestinal symptoms account for two-thirds of excess health-care costs in irritable bowel syndrome (IBS). OBJECTIVES: To determine whether IBS patients are at greater risk for specific comorbid disorders versus showing a general tendency to overreport symptoms; whether patients with inflammatory bowel disease (IBD) show patterns of comorbidity similar to IBS; whether comorbidity is explained by psychiatric disease; and whether excess comorbidity occurs in all IBS patients. METHODS: All 3,153 patients in a health maintenance organization with a diagnosis of IBS in 1994-1995 were compared to 3,153 age- and gender-matched controls, and to 571 IBD patients. All diagnoses in a 4-yr period beginning 1 yr before their index visit were categorized as gastrointestinal, psychiatric, or nongastrointestinal somatic. Nongastrointestinal somatic diagnoses were further divided into symptom-based versus biological marker-based diagnoses. RESULTS: Forty-eight of 51 symptom-based and 16 of 25 biomarker-based diagnoses were significantly more common in IBS versus controls. However, there were no unique associations. Bacterial, viral, and fungal infections and stroke were among diagnoses made more frequently in IBS. IBD patients were similar to controls. Greater somatic comorbidity was associated with concurrent psychiatric diagnosis. Only 16% of IBS patients had abnormally high numbers of comorbid diagnoses. CONCLUSIONS: Comorbidity in IBS is due to a general amplification of symptom reporting and physician consultation rather than a few unique associations; this suggests biased symptom perception rather than shared pathophysiology. Comorbidity is influenced by, but is not explained by, psychiatric illness. Excess comorbidity is present in only a subset of IBS patients.

Nyrop KA, Palsson OS, Levy RL, Korff MV, Feld AD, Turner MJ, Whitehead WE. · Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, NC 27599-7080, USA. · Aliment Pharmacol Ther. · Pubmed #17593069 No free full text.

Abstract: AIM: To provide estimates of actual costs to deliver health care to patients with functional bowel disorders, and to assess the cost impact of symptom severity, recency of onset, and satisfaction with treatment. METHODS: We enrolled 558 irritable bowel (IBS), 203 constipation, 243 diarrhoea and 348 abdominal pain patients from primary care and gastroenterology clinics at a health maintenance organization within weeks of a visit. Costs were extracted from administrative claims. Symptom severity, satisfaction with treatment and out-of-pocket expenses were assessed by questionnaires. RESULTS: Average age was 52 years, 27% were males, and 59% participated. Eighty percent were seen in primary care clinics. Mean annual direct health care costs were $5049 for IBS, $6140 for diarrhoea, $7522 for constipation and $7646 for abdominal pain. Annual out-of-pocket expenses averaged $406 for treatment of IBS symptoms, $294 for diarrhoea, $390 for constipation and $304 for abdominal pain. Lower gastrointestinal costs comprised 9% of total costs for IBS, 9% for diarrhoea, 6.5% for constipation and 9% for abdominal pain. In-patient care accounted for 17.5% of total costs (15.2% IBS). CONCLUSION: Costs were affected by disease severity (increased), recent exacerbation of bowel symptoms (increased), and whether the patient was consulting for the first time (decreased).

Dorn SD, Palsson OS, Thiwan SI, Kanazawa M, Clark WC, van Tilburg MA, Drossman DA, Scarlett Y, Levy RL, Ringel Y, Crowell MD, Olden KW, Whitehead WE. · Center for Functional GI and Motility Disorders, University of North Carolina, Campus Box 7080, Chapel Hill, NC 27599-7080, USA. · Gut. · Pubmed #17483191 No free full text.

Abstract: OBJECTIVE: The aim was to determine whether lower visceral pain thresholds in irritable bowel syndrome (IBS) primarily reflect physiological or psychological factors. METHODS: Firstly, 121 IBS patients and 28 controls underwent balloon distensions in the descending colon using the ascending methods of limits (AML) to assess pain and urge thresholds. Secondly, sensory decision theory analysis was used to separate physiological from psychological components of perception: neurosensory sensitivity (p(A)) was measured by the ability to discriminate between 30 mm Hg vs 34 mm Hg distensions; psychological influences were measured by the report criterion-that is, the overall tendency to report pain, indexed by the median intensity rating for all distensions, independent of intensity. Psychological symptoms were assessed using the Brief Symptom Inventory (BSI). RESULTS: IBS patients had lower AML pain thresholds (median: 28 mm Hg vs 40 mm Hg; p<0.001), but similar neurosensory sensitivity (median p(A): 0.5 vs 0.5; p = 0.69; 42.6% vs 42.9% were able to discriminate between the stimuli better than chance) and a greater tendency to report pain (median report criterion: 4.0 ("mild" pain) vs 5.2 ("weak" pain); p = 0.003). AML pain thresholds were not correlated with neurosensory sensitivity (r = -0.13; p = 0.14), but were strongly correlated with report criterion (r = 0.67; p<0.0001). Report criterion was inversely correlated with BSI somatisation (r = -0.26; p = 0.001) and BSI global score (r = -0.18; p = 0.035). Similar results were seen for the non-painful sensation of urgency. CONCLUSION: Increased colonic sensitivity in IBS is strongly influenced by a psychological tendency to report pain and urge rather than increased neurosensory sensitivity.

Kanazawa M, Drossman DA, Shinozaki M, Sagami Y, Endo Y, Palsson OS, Hongo M, Whitehead WE, Fukudo S. · Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai 980-8575, Japan. · Biopsychosoc Med. · Pubmed #17371576 links to  free full text

Abstract: ABSTRACT: AIMS: To compare quality of life (QOL) for patients with irritable bowel syndrome (IBS) between the U.S. and Japan, it is indispensable to develop common instruments. The IBS-QOL, which is widely used in Western countries, was translated into Japanese as there has been a lack of Japanese disease-specific QOL measures for IBS. METHODS: The original 34 items of the IBS-QOL were translated from English into Japanese through two independent forward translations, resolution, back translation, and resolution of differences. Forty nine patients who had GI symptoms but did not have any organic diseases (including 30 IBS patients diagnosed by Rome II criteria) were recruited from Tohoku University Hospital in Sendai, Japan and completed a Japanese version of the IBS-QOL (IBS-QOL-J) concomitant with a Japanese version of the IBS severity index (IBSSI-J) twice within 7-14 days. RESULTS: The IBS-QOL-J demonstrated high internal consistency (Cronbach's alpha; 0.96) and high reproducibility (intraclass correlation coefficient; 0.92, p < 0.001). Convergent analyses confirmed that the overall score of IBS-QOL-J was significantly correlated with overall severity of IBS symptoms on the IBSSI-J (r = -0.36, p = 0.01) and with the individual items on the IBSSI-J that assess interference with life in general (r = -0.47, p = 0.001) and dissatisfaction with bowel habits (r = -0.32, p < 0.05). Eight patients who reported continuous abdominal pain in the past 6 months had significantly lower scores in the IBS-QOL-J than those who did not (53.7 +- 12.7 vs. 73.6 +- 19.5, p < 0.01). Age, sex, education or marital status did not affect scores on the measure. CONCLUSION: The IBS-QOL-J is a reliable instrument to assess the disease-specific QOL for IBS. Considering cross-cultural comparison, this measure is likely to be a valuable tool to investigate the QOL in Japanese patients with IBS.

Whitehead WE, Palsson OS, Feld AD, Levy RL, VON Korff M, Turner MJ, Drossman DA. · Center for Functional GI and Motility Disorders, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. · Aliment Pharmacol Ther. · Pubmed #16803612 No free full text.

Abstract: BACKGROUND: Studies suggest that the positive predictive value of the Rome II criteria for diagnosing irritable bowel syndrome can be enhanced by excluding red flag symptoms suggestive of organic diseases. AIM: We assessed the utility of red flags for detecting organic diseases in patients diagnosed irritable bowel syndrome by their physicians. METHODS: Systematic chart reviews were completed in 1434 patients with clinical diagnoses of irritable bowel syndrome, abdominal pain, diarrhoea or constipation, who also completed questionnaires to identify Rome II criteria for irritable bowel syndrome and red flag symptoms. RESULTS: The overall incidence of gastrointestinal cancer was 2.5% (but 1.0% in those with irritable bowel syndrome), for inflammatory bowel disease 2.0% (1.2% in irritable bowel syndrome), and for malabsorption 1.3% (0.7% in irritable bowel syndrome). Red flags were reported by 84% of the sample. The positive predictive value of individual red flags for identifying organic disease was 7-9%. Excluding any patient with a red flag improved the agreement between Rome II and clinical diagnosis by a modest 5%, but left 84% of patients who were diagnosed with irritable bowel syndrome by their physicians, without a diagnosis. CONCLUSIONS: Red flags may be useful for identifying patients who require additional diagnostic evaluation, but incorporating them into the Rome criteria would not improve sensitivity and would result in too many missed irritable bowel syndrome diagnoses.

Shinozaki M, Kanazawa M, Sagami Y, Endo Y, Hongo M, Drossman DA, Whitehead WE, Fukudo S. · Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Seiryo, Aoba, Sendai, Japan. · J Gastroenterol. · Pubmed #16799892 No free full text.

Abstract: BACKGROUND: Instruments for measuring the presence and severity of specific irritable bowel syndrome (IBS) symptoms, comparable to those used in Western countries, have been lacking in Japan. The aim of this study was to develop, validate, and confirm the reliability of the Japanese version of the Rome II modular questionnaire for IBS (RIIMQ-J) and the IBS severity index (IBSSI-J). METHODS: Forty-nine patients in the university hospital with chronic or recurrent abdominal pain and discomfort and/or altered bowel habits were enrolled. With Rome II criteria, 27 patients were diagnosed as having IBS, and the other 22 patients were evaluated as having other functional bowel disorders (FBDs). The English versions of RIIMQ and IBSSI were translated into Japanese. After back-translation and approval of the questionnaire, subjects completed both questionnaires twice within 14 days. RESULTS: Cronbach's alpha of the RIIMQ-J was high (0.72). The sensitivity of RIIMQ-J for the diagnosis of IBS was also high (89%). The specificity of RIIMQ-J for denial of IBS among patients with other FBD was satisfactory (73%). The IBSSI-J showed high internal consistency (0.69) and reproducibility (intraclass correlation coefficient, 0.86, P < 0.001). CONCLUSIONS: The RIIMQ-J and IBSSI-J are valid, reliable, and appropriate instruments for detecting and assessing the severity of IBS status in Japanese patients.