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Predictors of new onsets of irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia: the lifelines study

  • Rei Monden (a1), Judith G. M. Rosmalen (a1), Klaas J. Wardenaar (a1) and Francis Creed (a2)



It has been claimed that functional somatic syndromes share a common etiology. This prospective population-based study assessed whether the same variables predict new onsets of irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS) and fibromyalgia (FM).


The study included 152 180 adults in the Dutch Lifelines study who reported the presence/absence of relevant syndromes at baseline and follow-up. They were screened at baseline for physical and psychological disorders, socio-demographic, psycho-social and behavioral variables. At follow-up (mean 2.4 years) new onsets of each syndrome were identified by self-report. We performed separate analyses for the three syndromes including participants free of the relevant syndrome or its key symptom at baseline. LASSO logistic regressions were applied to identify which of the 102 baseline variables predicted new onsets of each syndrome.


There were 1595 (1.2%), 296 (0.2%) and 692 (0.5%) new onsets of IBS, CFS, and FM, respectively. LASSO logistic regression selected 26, 7 and 19 predictors for IBS, CFS and FM, respectively. Four predictors were shared by all three syndromes, four predicted IBS and FM and two predicted IBS and CFS but 28 predictors were specific to a single syndrome. CFS was more distinct from IBS and FM, which predicted each other.


Syndrome-specific predictors were more common than shared ones and these predictors might form a better starting point to unravel the heterogeneous etiologies of these syndromes than the current approach based on symptom patterns. The close relationship between IBS and FM is striking and requires further research.

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This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.

Corresponding author

Author for correspondence: Rei Monden, E-mail:


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Bakken, I. J., Tveito, K., Gunnes, N., Ghaderi, S., Stoltenberg, C., Trogstad, L., … Magnus, P. (2014). Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: A population-based registry study from Norway 2008–2012. BMC Medicine, 12, 167.
Boeckxstaens, G. (2018). The emerging role of mast cells in irritable bowel syndrome. Gastroenterology & Hepatology, 14, 250.
Brugha, T. S., & Cragg, D. (1990). The list of threatening experiences: The reliability and validity of a brief life events questionnaire. Acta Psychiatrica Scandinavica, 82, 7781.
Chang, M. H., Hsu, J. W., Huang, K. L., Su, T. P., Bai, Y. M., Li, C. T., … Chen, M. H. (2015). Bidirectional association between depression and fibromyalgia syndrome: A nationwide longitudinal study. Journal of Pain, 16, 895902.
Costa, P., & McCrae, R. R. (1992). Revised NEO personality inventory (NEO-PI-R) and NEO five-factor inventory (NEO-FFI). Odessa, FL: Psychological Assessment Resources.
Creed, F. (2019). Review article: The incidence and risk factors for irritable bowel syndrome in population-based studies. Alimentary Pharmacology and Therapeutics, 50, 507516.
Creed, F. (2020) A review of the incidence and risk factors for fibromyalgia and chronic widespread pain in population-based studies. Pain, 161(6), 11691176.
Davis, J., & Goadrich, M. (2006). The relationship between Precision-Recall and ROC curves. In Proceedings of the 23rd international conference on Machine learning University of Wisconsin Madison.
Derogatis, L. R., Lipman, R. S., Rickels, K., Uhlenhuth, E. H., & Covi, L. (1974). The Hopkins Symptom Checklist (HSCL): A self-report symptom inventory. Behavioral Science, 19, 115.
Donnachie, E., Schneider, A., Mehring, M., & Enck, P. (2018). Incidence of irritable bowel syndrome and chronic fatigue following GI infection: A population-level study using routinely collected claims data. Gut, 67, 10781086.
Eekhout, I., De Vet, H. C. W., Twisk, J. W. R., Brand, J. P. L., De Boer, M. R., & Heymans, M. W. (2014). Missing data in a multi-item instrument were best handled by multiple imputation at the item score level. Journal of Clinical Epidemiology, 67, 335342.
Ehlin, A. G. C., Montgomery, S. M., Ekbom, A., Pounder, R. E., & Wakefield, A. J. (2003). Prevalence of gastrointestinal diseases in two British national birth cohorts. Gut, 52, 11171121.
Enck, P., Aziz, Q., Barbara, G., Farmer, A. D., Fukudo, S., Mayer, E. A., … Spiller, R. C. (2016). Irritable bowel syndrome. Nature Reviews Disease Primers, 2, 16014.
Friedman, J., Hastie, T., & Tibshirani, R.. (2010). Regularization paths for generalized linear models via coordinate descen. Journal of statistical software, 33(1), 1.
Grau, J., Grosse, I., & Keilwagen, J. (2015). PRROC: Computing and visualizing precision-recall and receiver operating characteristic curves in R. Bioinformatics, 31, 25952597.
Hamilton, W. T., Gallagher, A. M., Thomas, J. M., & White, P. D. (2009). Risk markers for both chronic fatigue and irritable bowel syndromes: A prospective case-control study in primary care. Psychological Medicine, 39, 19131921.
Haney, E., Smith, M. E. B., McDonagh, M., Pappas, M., Daeges, M., Wasson, N., & Nelson, H. D. (2015). Diagnostic methods for myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a national institutes of health pathways to prevention workshop. Annals of Internal Medicine, 162, 834.
Hanlon, P., Nicholl, B. I., Jani, B. D., Lee, D., McQueenie, R., & Mair, F. S. (2018). Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: A prospective analysis of 493 737 UK Biobank participants. The Lancet Public Health, 3, e323e332.
Harvey, S. B., Wessely, S., Kuh, D., & Hotopf, M. (2009). The relationship between fatigue and psychiatric disorders: Evidence for the concept of neurasthenia. Journal of Psychosomatic Research, 66, 445454.
Häuser, W., & Fitzcharles, M.-A. (2018) Facts and myths pertaining to fibromyalgia. Les Laboratoires Servier. Dialogues in Clinical Neuroscience, 20, 5362.
Hays, R. D., & Morales, L. S. (2001). The RAND-36 measure of health-related quality of life. Annals of Medicine, 33, 350357.
Holgate, S., Komaroff, A., Mangan, D., & Wessely, S. (2011). Chronic fatigue syndrome: Understanding a complex illness. Nature Reviews Neuroscience, 12, 539.
Honaker, J., King, G., & Blackwell, M. (2011). Amelia II: A program for missing data. Journal of Statistical Software, 45, 147.
Hulme, K., Hudson, J. L., Rojczyk, P., Little, P., & Moss-Morris, R. (2017). Biopsychosocial risk factors of persistent fatigue after acute infection: A systematic review to inform interventions. Journal of Psychosomatic Research, 99, 120129.
Jason, L. A., Richman, J. A., Rademaker, A. W., Jordan, K. M., Plioplys A, V., Taylor, R. R., … Plioplys, S. (1999). A community-based study of chronic fatigue syndrome. Archives of Internal Medicine, 159, 2129.
Joustra, M. L., Janssens, K. A. M., Bültmann, U., & Rosmalen, J. G. M. (2015). Functional limitations in functional somatic syndromes and well-defined medical diseases. Results from the general population cohort LifeLines. Journal of Psychosomatic Research, 79, 9499.
Klijs, B., Scholtens, S., Mandemakers, J., Snieder, H., Stolk, R., & Smidt, N. (2015). Representativeness of the LifeLines Cohort Study. ed. Ali, R. I.. PLos One, 10, e0137203.
The Lancet Gastroenterology & Hepatology (2018). Unmet needs of patients with irritable bowel syndrome. The Lancet Gastroenterology and Hepatology, 3, 587.
Lubrano, E., Iovino, P., Tremolaterra, F., Parsons, W. J., Ciacci, C., & Mazzacca, G. (2001). Fibromyalgia in patients with irritable bowel syndrome. An association with the severity of the intestinal disorder. International Journal of Colorectal Disease, 16, 211215.
Macfarlane, G. J., Barnish, M. S., & Jones, G. T. (2017). Persons with chronic widespread pain experience excess mortality: Longitudinal results from UK Biobank and meta-analysis. Annals of the Rheumatic Diseases, 76, 18151822.
Marrie, R. A., Yu, B. N., Leung, S., Elliott, L., Warren, S., Wolfson, C., … Fisk, J. D. (2012). The incidence and prevalence of fibromyalgia are higher in multiple sclerosis than the general population: A population-based study. Multiple Sclerosis and Related Disorders, 1, 162167.
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.
Roberts, E., Wessely, S., Chalder, T., Chang, C.-K., & Hotopf, M. (2016). Mortality of people with chronic fatigue syndrome: A retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) register. The Lancet, 387, 16381643.
Rosmalen, J. G. M., Bos, E. H., & De Jonge, P. (2012). Validation of the long-term difficulties inventory (LDI) and the list of threatening experiences (LTE) as measures of stress in epidemiological population-based cohort studies. Psychological Medicine, 42, 25992608.
Scholtens, S., Smidt, N., Swertz, M., Bakker, S., Dotinga, A., Vonk, J., … Stolk, R. (2015). Cohort Profile: LifeLines, a three-generation cohort study and biobank. International Journal of Epidemiology, 44, 11721180.
Sheehan, D., Lecrubier, Y., Sheehan, K., Amorim, P., Janavs, J., Weiller, E., … Dunbar, G. (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. The Journal of Clinical Psychiatry, 59(Suppl 2), 2233, quiz 34–57.
Sibelli, A., Chalder, T., Everitt, H., Workman, P., Windgassen, S., & Moss-Morris, R. (2016). A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset. Psychological Medicine, 46, 30653080.
Slim, M., Calandre, E. P., & Rico-Villademoros, F. (2015). An insight into the gastrointestinal component of fibromyalgia: Clinical manifestations and potential underlying mechanisms. Rheumatology International, 35, 433444.
Tibshirani, R. (1996). Regression shrinkage and selection via the lasso. Journal of the Royal Statistical Society: Series B (Methodological), 58, 267288.
Walitt, B., Katz, R. S., Bergman, M. J., & Wolfe, F. (2016). Three-quarters of persons in the US population reporting a clinical diagnosis of fibromyalgia do not satisfy fibromyalgia criteria: The 2012 National Health Interview Survey. PLoS ONE, 11 (6).
Warren, J. W., & Clauw, D. J. (2012). Functional somatic syndromes: Sensitivities and specificities of self-reports of physician diagnosis. Psychosomatic Medicine, 74, 891895.
Wessely, S., Nimnuan, C., & Sharpe, M. (1999). Functional somatic syndromes: One or many? The Lancet, 354, 936939.
Wolfe, F., Schmukler, J., Jamal, S., Castrejon, I., Gibson, K. A., Srinivasan, S., … Pincus, T. (2019). Diagnosis of fibromyalgia: Disagreement between fibromyalgia criteria and clinician-based fibromyalgia diagnosis in a university clinic. John Wiley and Sons Inc. Arthritis Care and Research, 71, 343351.


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Predictors of new onsets of irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia: the lifelines study

  • Rei Monden (a1), Judith G. M. Rosmalen (a1), Klaas J. Wardenaar (a1) and Francis Creed (a2)


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