Chronic Fatigue Syndrome


Chronic fatigue syndrome represents an operationally defined condition with substantial, disabling and prolonged fatigue as its main symptom. It has a prevalence of about 1% and makes a substantial public health impact.

Keywords: CFS; myalgic encephalomyelitis; ME; postviral fatigue syndrome; chronic fatigue and immune dysfunction syndrome (CFIDS)

Figure 1.

Components of hypothalamic–pituitary–adrenal axis and serotonergic input; sites of negative feedback are shown with the − sign. CRH, corticotrophin‐releasing hormone; ACTH, adrenocorticotrophic hormone; AVP, arginine vasopressin; MR, mineralocorticoid receptors; GR, glucocorticoid receptors; 5‐HT, 5‐hydroxytryptamine (serotonin); 5‐HIAA, 5‐hydroxyindoleacetic acid. Letters relate to the sites of proposed abnormalities in chronic fatigue syndrome, listed in Table .

Figure 2.

Predisposing, precipitating and perpetuating factors in the generation of acute, subacute and chronic fatigue. The model separates those considered to be risk factors or triggers, and those that may be responsible for fatigue perpetuation in chronic fatigue syndrome. Factors interact substantially and may be more important in some patients than in others (e.g. chronic fatigue after viral infections is more likely with previous psychological disorder and prolonged convalescence). EBV, Epstein–Barr virus; 5‐HT, 5‐hydroxytryptamine (serotonin).

Figure 3.

Time course of improvement in chronic fatigue syndrome during and after 13 sessions of either cognitive behavioural therapy (CBT) or relaxation therapy as a control intervention. (a) Disability, measured using the physical function subscale of the medical outcomes survey short form 36 (SF‐36) (0 = maximum disability; 100 = no disability). (b) Fatigue, scored on a 13‐item scale (13 = maximum fatigue; 0 = no fatigue). Pre, pretreatment; mid, midtreatment; post, posttreatment. Adapted from Deale A .



Cleare AJ, Bearn J, Allain T et al. (1995) Contrasting neuroendocrine responses in depression and chronic fatigue syndrome. Journal of Affective Disorders 35: 283–289.

Cleare AJ, Heap E, Malhi GS et al. (1999) Low‐dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet 353: 455–458.

Cope H, David A, Pelosi A and Mann A (1994) Predictors of chronic ‘post viral’ fatigue. Lancet 344: 864–868.

Deale A, Chalder T, Marks I and Wessely S (1997) A randomised controlled trial of cognitive behaviour versus relaxation therapy for chronic fatigue syndrome. American Journal of Psychiatry 154(3): 408–414.

Deale A (1998) Cognitive Behaviour Therapy for Chronic Fatigue Syndrome: outcome of a randomised controlled trial. PhD thesis, University of London.

Fulcher KY and White PD (1997) Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. British Medical Journal 314: 1647–1652.

Hotopf M, Noah N and Wessely S (1996) Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study. Journal of Neurology, Neurosurgery and Psychiatry 60: 504–509.

McKenzie R, O'Fallon A, Dale J et al. (1998) Low‐dose hydrocortisone treatment of chronic fatigue syndrome: results of a placebo controlled study of its efficacy and safetly. Journal of the American Medical Association 280: 1061–1066.

Sharpe M, Hawton K, Simkin S et al. (1996) Cognitive behaviour therapy for chronic fatigue syndrome; a randomized controlled trial. British Medical Journal 312: 22–26.

Vercoulen J, Swanink C, Zitman F et al. (1996) Fluoxetine in chronic fatigue syndrome; a randomized, double‐blind, placebo‐controlled study. Lancet 347: 858–861.

Wearden A, Morriss R, Mullis R et al. (1998) double‐blind, placebo controlled treatment trial of fluoxetine and a graded exercise programme for chronic fatigue syndrome. British Journal of Psychiatry 172: 485–490.

Wessely S, Chalder T, Hirsch S et al. (1995) Post infectious fatigue: a prospective study in primary care. Lancet 345: 1333–1338.

Further Reading

Demitrack M (1997) Neuroendocrine correlates of chronic fatigue syndrome: a brief review. Journal of Psycholosomatic Research 31: 69–82.

Fox R (1998) A Research Portfolio on Chronic Fatigue Syndrome. London: Royal Society of Medicine Press.

Komaroff A and Fagioli L (1996) Medical assessment of fatigue and chronic fatigue syndrome. In: Demitrack M and Abbey S (eds) Chronic Fatigue Syndrome: An Integrative Approach to Evaluation and Treatment, pp. 154–184. New York: Guildford Press.

Lloyd AR, Wakefield D and Hickie I (1993) Immunity and the pathophysiology of chronic fatigue syndrome. In: Kleinman A and Straus S (eds) Chronic Fatigue Syndrome, pp. 176–187. Chichester, UK: John Wiley.

Moss‐Morris R, Petrie K, Large R and Kydd R (1996) Neuropsychological deficits in chronic fatigue syndrome: artefact or reality? Journal of Neurology, Neurosurgery and Psychiatry 60: 474–477.

Royal College of Physicians (1996) Chronic Fatigue Syndrome: Report of a Committee of the Royal Colleges of Physicians, Psychiatrists and General Practitioners. London: RCP.

Wessely S (1995) The epidemiology of chronic fatigue syndrome. Epidemiologic Reviews 17: 139–151.

Wessely S, Hotopf M and Sharpe M (1998) Chronic Fatigue and its Syndromes. Oxford: Oxford University Press.

White P (1997) The relationship between infection and fatigue. Journal of Psychosomatic Research 43: 346–350

Wright J and Beverley D (1998) Chronic fatigue syndrome. Archives of Disease in Childhood 79: 368–374.

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Cleare, Anthony James, and Wessely, Simon(Apr 2001) Chronic Fatigue Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0002207]