Hostname: page-component-cd4964975-8cclj Total loading time: 0 Render date: 2023-03-29T13:12:16.132Z Has data issue: true Feature Flags: { "useRatesEcommerce": false } hasContentIssue true

Risk markers for both chronic fatigue and irritable bowel syndromes: a prospective case-control study in primary care

Published online by Cambridge University Press:  15 April 2009

W. T. Hamilton
Academic Unit of Primary Health Care, University of Bristol, Bristol, UK
A. M. Gallagher
Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Bart's and the London, Queen Mary School of Medicine and Dentistry, London, UK
J. M. Thomas
Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Bart's and the London, Queen Mary School of Medicine and Dentistry, London, UK
P. D. White*
Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Bart's and the London, Queen Mary School of Medicine and Dentistry, London, UK
*Address for correspondence: Professor P. D. White, Centre for Psychiatry, St Bartholomew's Hospital, LondonEC1A 7BE, UK. (Email:



Fatigue syndromes and irritable bowel syndrome (IBS) often occur together. Explanations include being different manifestations of the same condition and simply sharing some symptoms.


A matched case-control study in UK primary care, using data collected prospectively in the General Practice Research Database (GPRD). The main outcome measures were: health-care utilization, specific symptoms and diagnoses. Risk markers were divided into distant (from 3 years to 1 year before diagnosis) and recent (1 year before diagnosis).


A total of 4388 patients with any fatigue syndrome were matched to two groups of patients: those attending for IBS and those attending for another reason. Infections were specific risk markers for both syndromes, with viral infections being a risk marker for a fatigue syndrome [odds ratios (ORs) 2.3–6.3], with a higher risk closer to onset, and gastroenteritis a risk for IBS (OR 1.47, compared to a fatigue syndrome). Chronic fatigue syndrome (CFS) shared more distant risk markers with IBS than other fatigue syndromes, particularly other symptom-based disorders (OR 3.8) and depressive disorders (OR 2.3), but depressive disorders were a greater risk for CFS than IBS (OR 2.4). Viral infections were more of a recent risk marker for CFS compared to IBS (OR 2.8), with gastroenteritis a greater risk for IBS (OR 2.4).


Both fatigue and irritable bowel syndromes share predisposing risk markers, but triggering risk markers differ. Fatigue syndromes are heterogeneous, with CFS sharing predisposing risks with IBS, suggesting a common predisposing pathophysiology.

Original Articles
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Afari, N, Buchwald, D (2001). A review of the evidence for overlap among unexplained medical conditions. Annals of Internal Medicine 134, 868881.Google Scholar
Aggarwal, VR, McBeth, J, Zakrzewska, JM, Lunt, M, Macfarlane, GJ (2006). The epidemiology of chronic syndromes that are frequently unexplained: do they have common associated factors? International Journal of Epidemiology 35, 468476.CrossRefGoogle ScholarPubMed
Buchwald, DS, Rea, TD, Katon, WJ, Russo, JE, Ashley, RL (2000). Acute infectious mononucleosis: characteristics of patients who report failure to recover. American Journal of Medicine 101, 531537.CrossRefGoogle Scholar
Cameron, OG (2001). Interoception: the inside story – a model for psychosomatic processes. Psychosomatic Medicine 63, 697710.CrossRefGoogle Scholar
CFS/ME Working Group (2002). A Report of the CFS/ME Working Group: Report to the Chief Medical Officer of an independent working group. Department of Health: London.Google Scholar
Craig, AD (2002). How do you feel? Interoception: the sense of the physiological condition of the body. Nature Reviews Neuroscience 3, 655666.CrossRefGoogle Scholar
Euba, R, Chalder, T, Deale, A, Wessely, S (1996). A comparison of the characteristics of chronic fatigue syndrome in primary and tertiary care. British Journal of Psychiatry 168, 121126.CrossRefGoogle ScholarPubMed
Gallagher, A, Thomas, J, Hamilton, W, White, PD (2004). The incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001. Journal of the Royal Society of Medicine 97, 571575.CrossRefGoogle ScholarPubMed
Hall, GH, Hamilton, WT, Round, AP (1998). Increased illness experience preceding chronic fatigue syndrome: a case control study. Journal of the Royal College of Physicians of London 32, 4448.Google ScholarPubMed
Hamilton, W, Hall, GH, Round, AP (2001). Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case control study. British Journal of General Practice 51, 553558.Google ScholarPubMed
Hamilton, WT, Gallagher, AM, Thomas, JM, White, PD (2005). The prognosis of different fatigue diagnostic labels: a longitudinal survey. Family Practice 22, 383388.CrossRefGoogle ScholarPubMed
Harvey, SB, Wadsworth, M, Wessely, S, Hotopf, M (2008). Etiology of chronic fatigue syndrome: testing popular hypotheses using a national birth cohort study. Psychosomatic Medicine 70, 488495.CrossRefGoogle ScholarPubMed
Heim, C, Wagner, D, Maloney, E, Papanicolaou, DA, Solomon, L, Jones, JF, Unger, ER, Reeves, WC (2006). Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Archives of General Psychiatry 63, 12581266.CrossRefGoogle ScholarPubMed
Hickie, I, Davenport, T, Wakefield, D, Vollmer-Conna, U, Cameron, B, Vernon, SD, Reeves, WC, Lloyd, A; Dubbo Infection Outcomes Study Group (2006). Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. British Medical Journal 333, 575580.CrossRefGoogle ScholarPubMed
Jones, R, Latinovic, R, Charlton, J, Gulliford, M (2006). Physical and psychological co-morbidity in irritable bowel syndrome: a matched cohort study using the General Practice Research Database. Alimentary Pharmacology and Therapeutics 24, 879886.CrossRefGoogle ScholarPubMed
Kato, K, Sullivan, P, Evengård, B, Pedersen, NL (2009). A population-based twin study of functional somatic syndromes. Psychological Medicine 39, 497505.CrossRefGoogle ScholarPubMed
Lawrie, S, Manders, D, Geddes, J, Pelosi, A (1997). A population-based incidence study of chronic fatigue. Psychological Medicine 27, 343353.CrossRefGoogle ScholarPubMed
Moss-Morris, R, Spence, M (2006). To ‘Lump’ or to ‘Split’ the functional somatic syndromes: can infectious and emotional risk factors differentiate between the onset of chronic fatigue syndrome and irritable bowel syndrome? Psychosomatic Medicine 68, 463469.CrossRefGoogle ScholarPubMed
Pawlikowska, T, Chalder, T, Hirsch, S, Wallace, P, Wright, D, Wessley, S (1995). Population based study of fatigue and psychological distress. British Medical Journal 308, 763766.CrossRefGoogle Scholar
Petersen, I, Thomas, JM, Hamilton, WT, White, PD (2006). Risk and predictors of fatigue after infectious mononucleosis in a large primary care cohort. Quarterly Journal of Medicine 99, 4955.CrossRefGoogle Scholar
Phillips, ML, Gregory, LJ, Cullen, S, Cohen, S, Ng, V, Andrew, C, Giampietro, V, Bullmore, E, Zelaya, F, Amaro, E, Thompson, DG, Hobson, AR, Williams, SCR, Brammer, M, Aziz, Q (2003). The effect of negative emotional context on neural and behavioural responses to oesophageal stimulation. Brain 126, 669684.CrossRefGoogle ScholarPubMed
Raine, R, Carter, S, Sensky, T, Black, N (2004). General practitioners' perceptions of chronic fatigue syndrome and beliefs about its management, compared with irritable bowel syndrome: qualitative study. British Medical Journal 328, 13541357.CrossRefGoogle ScholarPubMed
Spiller, R (2007). Irritable bowel syndrome. Lancet 369, 15861588.CrossRefGoogle ScholarPubMed
Thabane, M, Kottachchi, DT, Marshall, JK (2007). Systematic review and meta-analysis: the incidence and prognosis of post-infectious irritable bowel syndrome. Alimentary Pharmacology and Therapeutics 26, 535544.CrossRefGoogle ScholarPubMed
Vollmer-Conna, U, Aslakson, E, White, PD (2006). An empirical delineation of the heterogeneity of chronic unexplained fatigue. Pharmacogenetics 7, 355364.CrossRefGoogle ScholarPubMed
Wessely, S (1997). Chronic fatigue syndrome: a 20th century illness? Scandinavian Journal of Work, Environment and Health 23, 1734.Google ScholarPubMed
Wessely, S, Chalder, T, Hirsch, S, Pawlikoska, T, Wallace, P, Wright, D (1995). Postinfectious fatigue: prospective cohort study in primary care. Lancet 345, 13331338.CrossRefGoogle ScholarPubMed
Wessely, S, Nimnuan, C, Sharpe, MC (1999). Functional somatic syndromes: one or many? Lancet 354, 936939.CrossRefGoogle ScholarPubMed
Wessely, S, White, PD (2004). There is only one functional somatic syndrome. British Journal of Psychiatry 185, 9596.CrossRefGoogle ScholarPubMed
White, PD, Thomas, JM, Kangro, HO, Bruce-Jones, WD, Amess, J, Crawford, DH, Grover, SA, Clare, AW (2001). Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis. Lancet 358, 19461954.CrossRefGoogle ScholarPubMed
WHO (1992). The ICD-10 Classification of Mental and Behavioural Disorders; Clinical Descriptions and Diagnostic Guidelines. World Health Organization: Geneva.Google Scholar
Wiens, S (2005). Interoception in emotional experience. Current Opinion in Neurology 18, 442447.CrossRefGoogle ScholarPubMed