Systematic review of the comorbidity of irritable bowel syndrome with other disorders: What are the causes and implications?
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.
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Psychological co-morbidity may have an impact on gastrointestinal function and vice versa.
“it is becoming increasingly understood how psychological co-morbidity may have an impact on gastrointestinal function, [30, 31, 32, 33] and vice versa, [34, 35]”
From Efficacy of psychological therapies for irritable bowel syndrome: systematic review and network meta-analysis (2020) · cites this paper as [32]
Many IBS patients meet diagnostic criteria for other functional disorders.
“Many IBS patients have at least one co-morbid somatic complaint and many meet diagnostic criteria for other functional disorders.”
From Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes (2010) · cites this paper as [4]
Studies of IBS among patients with chronic fatigue syndrome have reported a prevalence ranging from 35-92%.
“Studies of IBS among patients with chronic fatigue syndrome have reported a prevalence ranging from 35-92%.”
From Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes (2010) · cites this paper as [4]
Many IBS patients have at least one co-morbid somatic complaint.
“Many IBS patients have at least one co-morbid somatic complaint and many meet diagnostic criteria for other functional disorders.”
From Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes (2010) · cites this paper as [4]
Studies are consistent in finding that the overlap among FMS, CFS, CPP, sexual dysfunction, sleep disturbances and IBS is greater than expected based on their separate prevalence rates.
“The studies are consistent in their finding that the overlap among these disorders is greater than expected based on their separate prevalence rates.”
From Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes (2010) · cites this paper as [4]
Patients with more than 1 disorder have greater disease severity, higher rates of psychopathology, and more severely impaired health-related quality of life than those with only 1 disorder.
“In addition, patients with more than 1 disorder have greater disease severity, higher rates of psychopathology, and more severely impaired health-related quality of life than those with only 1 disorder.4”
From Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes (2010) · cites this paper as [4]
There is substantial overlap between IBS and other functional gastrointestinal disorders, such as functional dyspepsia.
“There is substantial overlap between IBS and other FGID, such as functional dyspepsia.”
From Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes (2010) · cites this paper as [4]
Studies of IBS among CFS patients have reported a prevalence ranging from 35-92% with a median of 51%.
“Studies of IBS among CFS patients have reported a prevalence ranging from 35-92%34-38 with a median of 51%.4”
From Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes (2010) · cites this paper as [4]
Many IBS patients have at least 1 co-morbid somatic complaint and many of them meet diagnostic criteria for other gastrointestinal and extraintestinal functional disorders.
“In summary, many IBS patients have at least 1 co-morbid somatic complaint and many of them meet diagnostic criteria for other gastrointestinal and extraintestinal functional disorders.”
From Irritable Bowel Syndrome and Co-morbid Gastrointestinal and Extra-gastrointestinal Functional Syndromes (2010) · cites this paper as [4]
Whitehead et al. reported in a systematic review that between one quarter and one third of IBS patients meet criteria for somatization disorder, much higher than in the normal population.
“Furthermore, in the systemic review, Whitehead et al. (20) reported that between a quarter and a third of patients with IBS meet the criteria for somatization disorder, which is much higher than in the normal population.”
From Psychosocial Distress and Somatic Symptoms in Community Subjects With Irritable Bowel Syndrome: A Psychological Component Is the Rule (2009) · cites this paper as [20]
Psychological and psychiatric comorbidity is common among patients with IBS.
“It is well known that psychological and psychiatric comorbidity is common among patients with IBS (17,20,40).”
From Psychosocial Distress and Somatic Symptoms in Community Subjects With Irritable Bowel Syndrome: A Psychological Component Is the Rule (2009) · cites this paper as [20]
The definition of PPPD paralleled work in other areas of medicine where functional disorders were defined by their core physical symptoms and not associated psychological features.
“The definition of PPPD paralleled work in other areas of medicine where functional disorders (e.g., the functional gastrointestinal disorders [25, 91] and fibromyalgia [93, 94]) were defined by their core physical symptoms and not associated psychological features.”
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Spiller, R., Aziz, Q., Creed, F., Emmanuel, A., Houghton, L., Hungin, P., Jones, R., Kumar, D., Rubin, G., Trudgill, N., et al. (2007) · Gut · doi:10.1136/gut.2007.119446 · Cited by 818 · see citing works
Whorwell, P. J., Altringer, L., Morel, J., Bond, Y., Charbonneau, D., O'Mahony, L., Kiely, B., Shanahan, F., & Quigley, E. M. M. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00734.x · Cited by 799 · see citing works
Management of functional somatic syndromes
Henningsen, P., Zipfel, S., & Herzog, W. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60159-7 · Cited by 741 · see citing works
Assessment and manifestation of central sensitisation across different chronic pain conditions
Arendt‐Nielsen, L., Morlion, B., Perrot, S., Dahan, A., Dickenson, A., Kress, H. G., Wells, C., Bouhassira, D., & Drewes, A. M. (2018) · European Journal of Pain · doi:10.1002/ejp.1140 · Cited by 695 · see citing works
“Furthermore, IBS is frequently occurring together with other disorders involving CS (Whitehead et al., 2002).”
BackgroundAnxiety disorders and comorbid medical illness
Roy-Byrne, P. P., Davidson, K. W., Kessler, R. C., Asmundson, G. J. G., Goodwin, R. D., Kubzansky, L., Lydiard, R. B., Massie, M. J., Katon, W., Laden, S. K., et al. (2008) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2007.12.006 · Cited by 668 · see citing works
“[32] Whitehead WE, Palsson O, Jones KR.”
Immune Activation in Patients With Irritable Bowel Syndrome
Liebregts, T., Adam, B., Bredack, C., Röth, A., Heinzel, S., Lester, S., Downie–Doyle, S., Smith, E., Drew, P., Talley, N. J., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.01.046 · Cited by 660 · see citing works
The Effects of Psychological Stress on Depression
Yang, L., Zhao, Y., Wang, Y., Liu, L., Zhang, X., Li, B., & Cui, R. (2015) · Current Neuropharmacology · doi:10.2174/1570159x1304150831150507 · Cited by 589 · see citing works
“Depression is not only highly comorbid with anxiety disorders [4], but is also closely associated with dementia [5], type 2 diabetes, coronary artery disease [6], Parkinson’s disease, epilepsy, pain, cancers [7], aging [8], osteoporosis [9] and irritable bowel syndrome [10].”
BackgroundFord, A. C., Talley, N. J., Schoenfeld, P. S., Quigley, E. M. M., & Moayyedi, P. (2009) · Gut · doi:10.1136/gut.2008.163162 · Cited by 582 · see citing works
Rao, A. V., Bested, A. C., Beaulne, T. M., Katzman, M. A., Iorio, C., Berardi, J. M., & Logan, A. C. (2009) · Gut Pathogens · doi:10.1186/1757-4749-1-6 · Cited by 577 · see citing works
“It is also true that LcS has been shown to reduce small intestinal bacterial overgrowth and the subjective reporting of the passage of gas in patients with IBS [29].”
BackgroundInfluentialDe Palma, G., Lynch, M. D. J., Lu, J., Dang, V. T., Deng, Y., Jury, J., Umeh, G., Miranda, P. M., Pigrau Pastor, M., Sidani, S., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf6397 · Cited by 505 · see citing works
“Fecal microbiota from IBS-D patients with moderate anxiety induces anxiety-like behavior in recipient mice Psychiatric comorbidities such as anxiety and depression affect 50 to 90% of patients with all subtypes of IBS (35), including IBS-D (20).”
BackgroundAllen, A. P., Hutch, W., Borre, Y. E., Kennedy, P. J., Temko, A., Boylan, G., Murphy, E., Cryan, J. F., Dinan, T. G., & Clarke, G. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.191 · Cited by 513 · see citing works
“…studies, speci fi c probiotic strains have shown potential for symptom alleviation in irritable bowel syndrome (IBS), 8,9 a stress-related brain – gut axis disorder associated with high rates of psychopathology 10 as well as altered hypothalamic – pituitary – adrenal axis activity 11 and cognition.”
Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact
Hungin, A. P. S., Chang, L., Locke, G. R., Dennis, E. H., & Barghout, V. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02463.x · Cited by 494 · see citing works
Labus, J. S., Bolus, R., Chang, L., Wiklund, I., Naesdal, J., Mayer, E. A., & Naliboff, B. D. (2004) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2004.02007.x · Cited by 475 · see citing works
Ford, A. C., Lacy, B. E., Harris, L. A., Quigley, E. M. M., & Moayyedi, P. (2019) · American Journal of Gastroenterology · doi:10.1038/s41395-018-0222-5 · Cited by 467 · see citing works
“Psychiatric conditions including depression, anxiety, and somatization often coexist in IBS (5,6).”
Review article: the economic impact of the irritable bowel syndrome
Canavan, C., West, J., & Card, T. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12938 · Cited by 458 · see citing works
Johnsen, P. H., Hilpüsch, F., Cavanagh, J. P., Leikanger, I. S., Kolstad, C., Valle, P. C., & Goll, R. (2018) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(17)30338-2 · Cited by 437 · see citing works
Gasbarrini, A., Corazza, G. R., Gasbarrini, G., Montalto, M., Stefano, M. D., Basilisco, G., Parodi, A., Usai–Satta, P., Satta, P. U., Vernia, P., et al. (2009) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2009.03951.x · Cited by 445 · see citing works
Chapman, C. R., & Vierck, C. J. (2017) · The Journal of Pain · doi:10.1016/j.jpain.2016.11.004 · Cited by 423 · see citing works
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Extra-intestinal and long term consequences of Giardia duodenalis infections
Halliez, M. C. M. (2013) · World Journal of Gastroenterology · doi:10.3748/wjg.v19.i47.8974 · Cited by 406 · see citing works
Microbes and the gut‐brain axis
Bercik, P., Collins, S. M., & Verdu, E. F. (2012) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2012.01906.x · Cited by 417 · see citing works
Neuroimaging of the brain–gut axis: From basic understanding to treatment of functional GI disorders
Mayer, E. A., Naliboff, B. D., & Craig, A. D. B. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.10.026 · Cited by 366 · see citing works
Kelly, J. R., Allen, A. P., Temko, A., Hutch, W., Kennedy, P. J., Farid, N., Murphy, E., Boylan, G., Bienenstock, J., Cryan, J. F., et al. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.11.018 · Cited by 355 · see citing works
Giloteaux, L., Goodrich, J. K., Walters, W. A., Levine, S. M., Ley, R. E., & Hanson, M. R. (2016) · Microbiome · doi:10.1186/s40168-016-0171-4 · Cited by 338 · see citing works
Fink, P., & Schröder, A. (2010) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2010.02.004 · Cited by 334 · see citing works
Macfarlane, G. J., Jones, G. T., & McBeth, J. (2006) · Elsevier eBooks · doi:10.1016/b0-443-07287-6/50081-3 · Cited by 335 · see citing works
Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications
Li, Z., Ruan, M., Chen, J., & Fang, Y. (2021) · Neuroscience Bulletin · doi:10.1007/s12264-021-00638-3 · Cited by 352 · see citing works
“It is well established that comorbidity of depression and gastrointestinal diseases is common [70, 71].”
BackgroundThe Incidence of Fibromyalgia and Its Associated Comorbidities
Weir, P. T., Harlan, G. A., Nkoy, F. L., Jones, S. S., Hegmann, K. T., Gren, L. H., & Lyon, J. L. (2006) · JCR Journal of Clinical Rheumatology · doi:10.1097/01.rhu.0000221817.46231.18 · Cited by 320 · see citing works
Fink, P., Toft, T., Hansen, M. S., Ørnbøl, E., & Olesen, F. (2007) · Psychosomatic Medicine · doi:10.1097/psy.0b013e31802e46eb · Cited by 314 · see citing works
“However, further studies are needed to identify why patients manifest different GI, MS, or CP variations of bodily distress or bodily distress disorder and other types of studies are needed to uncover the precise nature of the biological and physiological intrinsic mechanism involved (12,34,35).”
BackgroundEarly Life Risk Factors That Contribute to Irritable Bowel Syndrome in Adults: A Systematic Review
Chitkara, D. K., van Tilburg, M. A. L., Blois-Martin, N., & Whitehead, W. E. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2007.01722.x · Cited by 303 · see citing works
“In addition, comorbid extraintestinal symptom complaints, such as back pain, headache, limb pain, anxiety, and depression, are also common to both children and adults with functional gastrointestinal disorders (3, 8).”
BackgroundSelf-citationBlack, C. J., Thakur, E. R., Houghton, L. A., Quigley, E. M. M., Moayyedi, P., & Ford, A. C. (2020) · Gut · doi:10.1136/gutjnl-2020-321191 · Cited by 299 · see citing works
Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia)
Vierck, C. J. (2006) · Pain · doi:10.1016/j.pain.2006.06.001 · Cited by 294 · see citing works
“, 1995), irritable bowel syndrome (Whitehead et al., 2002) and interstitial cystitis (Clauw et al.”
BackgroundFunctional gastrointestinal disorders as a public health problem
Talley, N. J. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01097.x · Cited by 291 · see citing works
Role of serotonin in the pathophysiology of the irritable bowel syndrome
Crowell, M. D. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705762 · Cited by 289 · see citing works
The epidemiology of chronic generalized musculoskeletal pain
Gran, J. T. (2003) · Best Practice & Research Clinical Rheumatology · doi:10.1016/s1521-6942(03)00042-1 · Cited by 288 · see citing works
Eijsbouts, C. Q., Zheng, T., Kennedy, N. A., Bonfiglio, F., Anderson, C. A., Moutsianas, L., Holliday, J., Shi, J., Shringarpure, S., Agee, M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00950-8 · Cited by 290 · see citing works
Slyepchenko, A., Maes, M., Jacka, F. N., Köhler, C. A., Barichello, T., McIntyre, R. S., Berk, M., Grande, I., Foster, J. A., Vieta, E., et al. (2017) · Psychotherapy and Psychosomatics · doi:10.1159/000448957 · Cited by 278 · see citing works
The microbiome, immunity, and schizophrenia and bipolar disorder.
Dickerson, F., Severance, E., & Yolken, R. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.12.010 · Cited by 268 · see citing works
Functional Abdominal Pain in Childhood and Long-term Vulnerability to Anxiety Disorders
Shelby, G. D., Shirkey, K. C., Sherman, A. L., Beck, J. E., Haman, K., Shears, A. R., Horst, S. N., Smith, C. A., Garber, J., & Walker, L. S. (2013) · Pediatrics · doi:10.1542/peds.2012-2191 · Cited by 272 · see citing works
Central changes associated with chronic pelvic pain and endometriosis
Brawn, J., Morotti, M., Zondervan, K. T., Becker, C. M., & Vincent, K. (2014) · Human Reproduction Update · doi:10.1093/humupd/dmu025 · Cited by 274 · see citing works
“, 2007) and IBS (Whitehead et al., 2002), whilst endometriosis is associated with a variety of autoimmune and endocrine conditions including hypothyroidism, systemic lupus erythematosus and multiple sclerosis (Sinaii et al.”
Systematic review on the management of irritable bowel syndrome in North America
Brandt, L. J., Bjorkman, D. J., Fennerty, M. B., Locke, G. R., Olden, K. W., Peterson, W., Quigley, E. M. M., Schoenfeld, P., Schuster, M. M., & Talley, N. J. (2002) · The American Journal of Gastroenterology · doi:10.1016/s0002-9270(02)05657-5 · Cited by 275 · see citing works
Kim, Y., & Shin, C. (2018) · Current Neuropharmacology · doi:10.2174/1570159x15666170915141036 · Cited by 273 · see citing works
“More than 50% of IBS patients have comorbid depression or anxiety [23].”
BackgroundThe Role of Stress on Physiologic Responses and Clinical Symptoms in Irritable Bowel Syndrome
Chang, L. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.01.032 · Cited by 268 · see citing works
Aznar, L. A. M., Ral, P. C., Anta, R. M. O., Martín, J. J. D., Baladia, E., Basulto, J., Serrat, S. B., Altaba, I. I., López-Sobaler, A. M., Manera, M., et al. (2013) · PubMed · doi:10.3305/nutrhosp.v28in06.6691 · Cited by 268 · see citing works
Functional abdominal pain in childhood and adolescence increases risk for chronic pain in adulthood
Walker, L. S., Crish, S. D., Rippel, S., & Bruehl, S. P. (2010) · Pain · doi:10.1016/j.pain.2010.06.018 · Cited by 264 · see citing works
“Potential explanations for the overlap previously reported between FGIDs and chronic pain in adults include a shared dysfunction in the central nervous system [20], psychological influences [34], and contextual factors such as social reinforcement of pain behavior [18].”
BackgroundYeo, A., Boyd, P., Lumsden, S., Saunders, T., Handley, A., Stubbins, M., Knaggs, A., Asquith, S., Taylor, I., Bahari, B., et al. (2004) · Gut · doi:10.1136/gut.2003.035451 · Cited by 260 · see citing works
“31 39–43 There are few literature reports to date showing genetic evidence of a genetic risk factor in IBS (see above), although several twin studies based on questionnaires have shown that there is such a factor for the development of IBS.”
Prevalence of Gastroesophageal Reflux Disease and Proton Pump Inhibitor-Refractory Symptoms
Delshad, S. D., Almario, C. V., Chey, W. D., & Spiegel, B. M. R. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.12.014 · Cited by 253 · see citing works
Dysregulation of the hypothalamic‐pituitary‐adrenal (HPA) axis in irritable bowel syndrome
Chang, L., Sundaresh, S., Elliott, J. E., Anton, P. A., Baldi, P., Licudine, A., Mayer, M., Vuong, T., Hirano, M., Naliboff, B. D., et al. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01171.x · Cited by 250 · see citing works
Irritable bowel syndrome and surgery: A multivariable analysis☆
Longstreth, G. F., & Yao, J. F. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.02.020 · Cited by 248 · see citing works
Craske, M. G., Wolitzky-Taylor, K. B., Labus, J., Wu, S., Frese, M., Mayer, E. A., & Naliboff, B. D. (2011) · Behaviour Research and Therapy · doi:10.1016/j.brat.2011.04.001 · Cited by 243 · see citing works
Mayer, E. A. (2008) · New England Journal of Medicine · doi:10.1056/nejmcp0801447 · Cited by 243 · see citing works
Gut microbiota–brain axis in depression: the role of neuroinflammation
Carlessi, A. S., Borba, L. A., Zugno, A. I., Quevedo, J., & Réus, G. Z. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14631 · Cited by 243 · see citing works
Nellesen, D., Yee, K., Chawla, A., Lewis, B. E., & Carson, R. T. (2013) · Journal of Managed Care Pharmacy · doi:10.18553/jmcp.2013.19.9.755 · Cited by 242 · see citing works
Catassi, C., Alaedini, A., Bojarski, C., Bonaz, B. L., Bouma, G., Carroccio, A., Castillejo, G., de Magistris, L., Dieterich, W., Liberto, D. D., et al. (2017) · Nutrients · doi:10.3390/nu9111268 · Cited by 240 · see citing works
“Patients with IBS report a reduced quality of life and there is an associated economic and societal cost [60,61].”
BackgroundImpact of Functional Gastrointestinal Disorders on Survival in the Community
CHANG, J. Y., Locke, R. G., McNally, M. A., Halder, S. L. S., Schleck, C. D., Zinsmeister, A. R., & Talley, N. J. (2010) · The American Journal of Gastroenterology · doi:10.1038/ajg.2010.40 · Cited by 235 · see citing works
“19 ); depression (and suicidal ideation) is also associated (”
BackgroundSpiller, R. E., Humes, D. J., Campbell, E., Hastings, M. C., Neal, K. R., Dukes, G. E., & Whorwell, P. J. (2010) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2010.04402.x · Cited by 236 · see citing works
An Evidence-Based Systematic Review on the Management of Irritable Bowel Syndrome
Brandt, L. J., Chey, W. D., Foxx-Orenstein, A. E., Quigley, E. M. M., Schiller, L. R., Schoenfeld, P. S., Spiegel, B. M., Talley, N. J., & Moayyedi, P. (2009) · American Journal of Gastroenterology · doi:10.14309/00000434-200901001-00002 · Cited by 225 · see citing works
Walker, L. S., Sherman, A. L., Bruehl, S. P., Garber, J., & Smith, C. A. (2012) · Pain · doi:10.1016/j.pain.2012.03.026 · Cited by 225 · see citing works
Levy, R. L., Whitehead, W. E., Walker, L. S., Korff, M. V., Feld, A. D., Garner, M. D., & Christie, D. L. (2004) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2004.40478.x · Cited by 223 · see citing works
“This last observation may contribute to the development of multiple, extraintestinal symptoms that are frequently seen in association with IBS (2) and that account for two-third of their excess health-care costs in IBS patients (31).”
BackgroundResultSelf-citationEdwards, R. R., Ness, T. J., Weigent, D. A., & Fillingim, R. B. (2003) · Pain · doi:10.1016/j.pain.2003.09.005 · Cited by 220 · see citing works
“Relative to controls, patients with fibromyalgia (FM; Hurtig et al., 2001), whiplash (Kasch et al., 2001), headache (Bendtsen, 2000), temporomandibular disorder (TMD; Svensson et al., 2001), and irritable bowel syndrome (Whitehead et al., 2002) show enhanced pain sensitivity.”
BackgroundSomatic comorbidities of irritable bowel syndrome: A systematic analysis
Riedl, A., Schmidtmann, M., Stengel, A., Goebel, M., Wisser, A.-S., Klapp, B. F., & Mönnikes, H. (2008) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2008.02.021 · Cited by 274 · see citing works
Matricon, J., Méleine, M., Gelot, A., Piche, T., Dapoigny, M. C., Muller, E., & Ardid, D. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12080 · Cited by 216 · see citing works
The Burden of Illness of Irritable Bowel Syndrome: Current Challenges and Hope for the Future
Hulisz, D. (2004) · Journal of Managed Care Pharmacy · doi:10.18553/jmcp.2004.10.4.299 · Cited by 215 · see citing works
“5% of IBS patients also suffered from GERD.(4,5) About 50% of IBS sufferers experience at least 1 comorbid non–GI-related symptom, such as headache, back pain, poor sleep, and fatigue.”
BackgroundInfluentialCremonini, F., & Talley, N. J. (2005) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2005.02.008 · Cited by 215 · see citing works
Wu, Y., Murray, G. K., Byrne, E. M., Sidorenko, J., Visscher, P. M., & Wray, N. R. (2021) · Nature Communications · doi:10.1038/s41467-021-21280-7 · Cited by 212 · see citing works
Comorbidity in Irritable Bowel Syndrome
Whitehead, W. E., Palsson, O. S., Levy, R. R., Feld, A. D., Turner, M., & Von Korff, M. (2007) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2007.01540.x · Cited by 210 · see citing works
“We have previously shown that excess comorbitity is the primary determinant of excess health-care costs associated with IBS (5), and we suggested that understanding the causes of comorbidity is critical both to improving the care of IBS patients and to reducing the burden on the health-care system which these patients…”
BackgroundResultInfluentialSelf-citationStress and visceral pain: From animal models to clinical therapies
Larauche, M. H., Mulak, A., & Taché, Y. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.04.020 · Cited by 212 · see citing works
Irritable bowel syndrome: Diagnosis and pathogenesis
El‐Salhy, M. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i37.5151 · Cited by 214 · see citing works
Comorbid Subjective Health Complaints in Low Back Pain
Hagen, E. M., Svensen, E., Eriksen, H. R., Ihlebæk, C., & Ursin, H. (2006) · Spine · doi:10.1097/01.brs.0000219947.71168.08 · Cited by 210 · see citing works
“to all somatic complaints as seen in patients with irritable bowel syndrome.(22,23) These patients have high scores on most other subjective health complaints,(22) including musculoskeletal pain, while our LBP patients did not report any higher levels of gastrointestinal complaints than the general population.”
BackgroundGastrointestinal issues in autism spectrum disorder
Hsiao, E. Y. (2014) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000029 · Cited by 209 · see citing works
“In fact, it is estimated that 60% of patients suffering from functional GI disorders exhibit comorbid major affective disorders.(79)”
BackgroundThe cost of treating anxiety: the medical and demographic correlates that impact total medical costs
Marciniak, M. D., Lage, M. J., Dunayevich, E., Russell, J. M., Bowman, L., Landbloom, R. P., & Levine, L. R. (2005) · Depression and Anxiety · doi:10.1002/da.20074 · Cited by 204 · see citing works
“…of psychiatric [Dinardo and Barlow, 1990; Pini et al., 1997; Roy et al., 1995] as well as medical comorbidities [Carr 1999; Lloyd et al., 2000; Whitehead et al., 2002] among individuals diagnosed with anxiety as well as research which has shown increased hospitalizations, emergency room…”
BackgroundGrundmann, O., & Yoon, S. L. (2010) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2009.06120.x · Cited by 210 · see citing works
Is Irritable Bowel Syndrome a Low-Grade Inflammatory Bowel Disease?
Berčík, P., Verdu, E. F., & Collins, S. M. (2005) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2005.02.007 · Cited by 207 · see citing works
“Comorbidity of psychiatric conditions is high and occurs in up to 94% of patients [48].”
BackgroundEvidence-based clinical practice guidelines for irritable bowel syndrome
Fukudo, S., Kaneko, H., Akiho, H., Inamori, M., Endo, Y., Okumura, T., Kanazawa, M., Kamiya, T., Sato, K., Chiba, T., et al. (2014) · Journal of Gastroenterology · doi:10.1007/s00535-014-1017-0 · Cited by 207 · see citing works
“have at least one psychological disturbance [167].”
Spiegel, B. M. R., Farid, M., Esrailian, E., Talley, J., & Chang, L. (2010) · The American Journal of Gastroenterology · doi:10.1038/ajg.2010.47 · Cited by 206 · see citing works
Kuiken, S. D., Tytgat, G. N. J., & Boeckxstaens, G. E. (2003) · Clinical Gastroenterology and Hepatology · doi:10.1016/s1542-3565(03)70039-1 · Cited by 206 · see citing works
“The severity of IBS symptoms of abdominal bloating, flatulence, urgency, and the feeling of incomplete evacuation was scored before, at 2 weeks, and after 6 weeks of treatment on a self-rated scale, derived from the validated Gastrointestinal Symptom Rating Scale (GSRS), in which symptoms are rated on a 7-graded Liker…”
MethodKleykamp, B. A., Ferguson, M. C., McNicol, E., Bixho, I., Arnold, L. M., Edwards, R. R., Fillingim, R., Grol-Prokopczyk, H., Turk, D. C., & Dworkin, R. H. (2021) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2020.10.006 · Cited by 202 · see citing works
Fadgyas-Stanculete, M., Buga, A.-M., Popa-Wagner, A., & Dumitrascu, D. L. (2014) · Journal of Molecular Psychiatry · doi:10.1186/2049-9256-2-4 · Cited by 197 · see citing works
“Rates of co-morbidity with psychiatric disorders range from 54 to 94% in treatment-seeking patient with IBS [15-17].”
BackgroundMigraine, fibromyalgia, and depression among people with IBS: a prevalence study
Cole, J. A., Rothman, K. J., Cabral, H., Zhang, Y., & Farraye, F. A. (2006) · BMC Gastroenterology · doi:10.1186/1471-230x-6-26 · Cited by 196 · see citing works
The economic impact of irritable bowel syndrome
Inadomi, J. M., Fennerty, M. B., & Bjorkman, D. (2003) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.2003.t01-1-01736.x · Cited by 190 · see citing works
Intestinal Barrier Dysfunction in Irritable Bowel Syndrome: A Systematic Review
Hanning, N., Edwinson, A. L., Ceuleers, H., Peters, S. A., De Man, J. G., Hassett, L. C., De Winter, B. Y., & Grover, M. (2021) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756284821993586 · Cited by 197 · see citing works
Gut memories: Towards a cognitive neurobiology of irritable bowel syndrome
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There is only one functional somatic syndrome
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Evidence-based clinical practice guidelines for irritable bowel syndrome 2020
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“Comment: IBS shows high co-morbidity with extraintestinal disorders such as fibromyalgia, chronic fatigue syndrome, chronic pelvic pain, temporomandibular joint disease, interstitial cystitis, premenstrual syndrome, bronchial asthma, dementia [218], Parkinson’s disease [219], and psychological disturbance especially a…”
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Irritable bowel syndrome and chronic fatigue 3 years after acute giardiasis: historic cohort study
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- Authors
- Whitehead, W. E., Palsson, O., & Jones, K. R.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 122
- Issue
- 4
- Pages
- 1140-1156
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2145558296
- Cited by
- 1,116
- References
- 180
- Citations by year
- 2026: 26 · 2025: 16 · 2024: 29 · 2023: 27 · 2022: 63 · 2021: 53 · 2020: 53 · 2019: 49 · 2018: 50 · 2017: 51 · 2016: 63 · 2015: 51 · 2014: 64 · 2013: 55 · 2012: 54
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK031369, R01 DK31369)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Keywords
- irritable bowel syndrome, comorbidities, extraintestinal manifestations, functional gastrointestinal disorders, mental illness, depression, anxiety, somatoform disorders, fibromyalgia, chronic fatigue syndrome, temporomandibular disorders, chronic pelvic pain, visceral hypersensitivity, somatization, psychological etiology
- MeSH terms
- Mental Disorders, Colonic Diseases, Functional, Gastrointestinal Diseases, Humans, Psychophysiologic Disorders, Comorbidity
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