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Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies

  • S. Hempel (a1), D. Chambers (a1), A.-M. Bagnall (a1) and C. Forbes (a1)



The aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is still unknown. The identification of risk factors for CFS/ME is of great importance to practitioners.


A systematic scoping review was conducted to locate studies that analysed risk factors for CFS/ME using multiple predictors. We searched for published and unpublished literature in 11 electronic databases, reference lists of retrieved articles and guideline stakeholder submissions in conjunction with the development of a forthcoming national UK guideline. Risk factors and findings were extracted in a concise tabular overview and studies synthesized narratively.


Eleven studies were identified that met inclusion criteria: two case-control studies, four cohort studies, three studies combining a cohort with a case-control study design, one case-control and twin study and one cross-sectional survey. The studies looked at a variety of demographic, medical, psychological, social and environmental factors to predict the development of CFS/ME. The existing body of evidence is characterized by factors that were analysed in several studies but without replication of a significant association in more than two studies, and by studies demonstrating significant associations of specific factors that were not assessed in other studies. None of the identified factors appear suitable for the timely identification of patients at risk of developing CFS/ME within clinical practice.


Various potential risk factors for the development of CFS/ME have been assessed but definitive evidence that appears meaningful for clinicians is lacking.


Corresponding author

*Address for correspondence: Dr S. Hempel, Centre for Reviews and Dissemination, University of York, York YO10 5DD, UK. (Email:


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Afari, N, Buchwald, D (2003). Chronic fatigue syndrome: a review. American Journal of Psychiatry 160, 221236.
Bagnall, A-M, Hempel, S, Chambers, D, Orton, V, Forbes, C (2005). The Investigation and Management of Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME) in Children and Adults – Systematic Review. University of York, Centre for Reviews and Dissemination: York.
Bell, KM, Cookfair, D, Bell, DS, Reese, P, Cooper, L (1991). Risk factors associated with chronic fatigue syndrome in a cluster of pediatric cases. Reviews of Infectious Diseases 13 (Suppl. 1), S32S38.
Candy, B, Chalder, T, Cleare, AJ, Peakman, A, Skowera, A, Wessely, S, Weinman, J, Zuckerman, M, Hotopf, M (2003). Predictors of fatigue following the onset of infectious mononucleosis. Psychological Medicine 33, 847855.
Candy, B, Chalder, T, Cleare, AJ, White, PD, Hotopf, M (2002). Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review. British Journal of General Practice 52, 844851.
Chalder, T, Goodman, R, Wessely, S, Hotopf, M, Meltzer, H (2003). Epidemiology of chronic fatigue syndrome and self reported myalgic encephalomyelitis in 5–15 year olds: cross sectional study. British Medical Journal 327, 654655.
Chambers, D, Bagnall, A-M, Hempel, S, Forbes, C (2006). Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): an updated systematic review. Journal of the Royal Society of Medicine 99, 506520.
Cope, H, Mann, A, Pelosi, A, David, A (1996). Psychosocial risk factors for chronic fatigue and chronic fatigue syndrome following presumed viral illness: a case-control study. Psychological Medicine 26, 11971209.
Department of Health (2002). A Report of the CFS/ME Working Group: Report to the Chief Medical Officer of an Independent Working Group. Department of Health: London.
Fukuda, K, Straus, SE, Hickie, I, Sharpe, MC, Dobbins, JG, Komaroff, AL, and the International CFS Study Group (1994). The chronic fatigue syndrome: a comprehensive approach to its definition and study. Annals of Internal Medicine 121, 953959.
Heim, C, Wagner, D, Maloney, E, Papanicolaou, DA, Solomon, L, Jones, JF, Unger, ER, Reves, WC (2006). Early adverse experiences and risk for chronic fatigue syndrome. Archives of General Psychiatry 63, 12581266.
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, 575.
Huibers, MJ, Bleijenberg, G, van Amelsvoort, LG, Beurskens, AJ, van Schayck, CP, Bazelmans, E, Knottnerus, A (2004 a). Predictors of outcome in fatigued employees on sick leave: results from a randomised trial. Journal of Psychosomatic Research 57, 443449.
Huibers, MJ, Kant, IJ, Knottnerus, JA, Bleijenberg, G, Swaen, GM, Kasl, SV (2004 b). Development of the chronic fatigue syndrome in severely fatigued employees: predictors of outcome in the Maastricht cohort study. Journal of Epidemiology and Community Health 58, 877882.
Jason, LA, Richman, JA, Rademaker, AW, Jordan, KM, Plioplys, AV, Taylor, RR, McCready, W, Huang, C-F, Plioplys, S (1999). A community-based study of chronic fatigue syndrome. Archives of Internal Medicine 159, 21292137.
Kato, K, Sullivan, PF, Evengard, B, Pedersen, NL (2006). Premorbid predictors of chronic fatigue. Archives of General Psychiatry 63, 12671272.
Prins, JB, van der Meer, JWM, Bleijenberg, G (2006). Chronic fatigue syndrome. Lancet 367, 346355.
Reyes, M, Dobbins, JG, Mawle, AC, Steele, L, Gary, HE Jr., Malani, H, Schmid, S, Fukuda, K, Stewart, J, Nisenbaum, R, Reeves, WC (1996). Risk factors for chronic fatigue syndrome: a case-control study. Journal of Chronic Fatigue Syndrome 2, 1733.
Reyes, M, Nisenbaum, R, Hoaglin, DC, Unger, ER, Emmons, C, Randall, B, Stewart, JA, Abbey, S, Jones, JF, Gantz, N, Minden, S, Reeves, WC (2003). Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Archives of Internal Medicine 163, 15301536.
Sharpe, MC, Archard, LC, Banatvala, JE, Borysiewicz, LK, Clare, AW, David, A, Edwards, RHT, Hawton, DM, Lambert, HP, Lane, RJM, McDonald, EM, Mowbray, JF, Pearson, DJ, Peto, TEA, Preedy, VR, Smith, AP, Smith, DG, Taylor, DJ, Wessely, S, White, PD (1991). A report – chronic fatigue syndrome: guidelines for research. Journal of the Royal Society of Medicine 84, 118121.
Viner, R, Hotopf, M (2004). Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study. British Medical Journal 329, 941.
Wessely, S, Chalder, T, Hirsch, S, Pawlikowska, T, Wallace, P, Wright, DJ (1995). Postinfectious fatigue: prospective cohort study in primary care. Lancet 345, 13331338.
Wessely, S, Chalder, T, Hirsch, S, Wallace, P, Wright, D (1997). The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study. American Journal of Public Health 87, 14491455.
White, PD (2004). What causes chronic fatigue syndrome? British Medical Journal 329, 928929.
White, PD, Thomas, JM, Amess, J, Crawford, DH, Grover, SA, Kangro, HO, Clare, AW (1998). Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever. British Journal of Psychiatry 173, 475481.
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.



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