Chronic fatigue and chronic fatigue syndrome: shifting boundaries and attributions

  • Andrew R. Lloyd
    Requests for reprints should be addressed to Andrew Lloyd, MD, Inflammation Research Unit, School of Pathology, University of New South Wales, 2052, Australia
    The Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, New South Wales, Australia

    Department of Infectious Diseases, Prince Henry Hospital, Little Bay, New South Wales, Australia
    Search for articles by this author


      The subjective symptom of “fatigue” is one of the most widespread in the general population and is a major source of healthcare utilization. Prolonged fatigue is often associated with neuropsychological and musculoskeletal symptoms that form the basis of several syndromal diagnoses including chronic fatigue syndrome, fibromyalgia, and neurasthenia, and is clearly not simply the result of a lack of force generation from the muscle. Current epidemiologic research in this area relies predominantly on self-report data to document the prevalence and associations of chronic fatigue. Of necessity, this subjective data source gives rise to uncertain diagnostic boundaries and consequent divergent epidemiologic, clinical, and pathophysiologic research findings. This review will highlight the impact of the case definition and ascertainment methods on the varying prevalence estimates of chronic fatigue syndrome and patterns of reported psychological comorbidty. It will also evaluate the evidence for a true postinfective fatigue syndrome.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lewis G.
        • Wessely S.
        The epidemiology of fatigue.
        J Epidemiol Community Health. 1992; 46: 92-97
        • Hickie I.
        • Hadzi-Pavlovic D.
        • Ricci C.
        Reviving the diagnosis of neurasthenia.
        Psychol Med. 1997; 27: 989-994
        • Lloyd A.R.
        • Hales J.P.
        • Gandevia S.C.
        Muscle strength, endurance and recovery in the post-infection fatigue syndrome.
        J Neurol Neurosurg Psychiatry. 1988; 51: 1316-1322
        • Lloyd A.R.
        • Gandevia S.C.
        • Hales J.P.
        Muscle endurance, twitch properties, voluntary activation and perceived exertion in normal subjects and patients with chronic fatigue syndrome.
        Brain. 1991; 114: 85-98
        • Muscio B.
        Is a fatigue test possible?.
        Br J Psychol. 1921; 12: 31-46
        • Cox B.
        • Blaxter M.
        • Buckle A.
        • et al.
        The health and lifestyles survey. Health Promotion Research Trust, London1987
        • Shepherd M.
        • Cooper B.
        • Brown A.
        • Kalton G.
        Psychiatric Illness in General Practice. 2nd edition. Oxford University Press, Oxford1981
        • Kroenke K.
        • Wood D.R.
        • Mangelsdorf A.D.
        • Meier N.J.
        • Powell J.B.
        Chronic fatigue in primary care.
        JAMA. 1988; 260: 929-934
        • David A.
        • Pelosi A.
        • McDonald E.
        • Stephens D.
        • Ledger D.
        • Rathbone R.
        • Mann A.
        Tired, weak or in need of rest.
        BMJ. 1990; 301: 1199-1202
        • Hickie I.
        • Hooker A.W.
        • Hadzi-Pavlovic D.
        • Bennett B.K.
        • Wilson A.J.
        • Lloyd A.R.
        Fatigue in selected primary care settings.
        Med J Aust. 1996; 164: 585-588
        • Bates D.W.
        • Schmitt W.
        • Buchwald D.
        • Ware N.C.
        • Lee J.
        • Thoyer E.
        • et al.
        Prevalence of fatigue and chronic fatigue syndrome in a primary care practice.
        Arch Intern Med. 1993; 153: 2759-2765
        • Pawlikowska T.
        • Chalder T.
        • Hirsch S.R.
        • Wallace P.
        • Wright D.J.M.
        • Wessely S.C.
        Population based study of fatigue and psychological distress.
        BMJ. 1994; 308: 763-766
        • Buchwald D.
        • Umali P.
        • Umali J.
        • Kith P.
        • Pearlman T.
        • Komaroff A.
        Chronic fatigue and chronic fatigue syndrome.
        Ann Intern Med. 1995; 123: 81-88
        • Wessely S.
        • Chalder T.
        • Hirsch S.
        • Pawlikowska T.
        • Wallace P.
        • Wright D.J.M.
        Postinfectious fatigue.
        Lancet. 1995; 345: 1333-1338
        • Fukuda K.
        • Straus S.E.
        • Hickie I.
        • et al.
        Chronic fatigue syndrome.
        Ann Intern Med. 1994; 121: 953-959
        • Lloyd A.
        • Wakefield D.
        • Dwyer J.
        • Boughton C.
        What is myalgic encephalomyelitis?.
        Lancet. 1988; i: 1286-1287
        • Lloyd A.
        • Hickie I.
        • Boughton C.R.
        • Spencer O.
        • Wakefield D.
        The prevalence of chronic fatigue syndrome in an Australian population.
        Med J Aust. 1990; 53: 522-528
        • Holmes G.P.
        • Kaplan J.E.
        • Gantz N.M.
        • et al.
        Chronic fatigue syndrome.
        Ann Intern Med. 1988; 108: 387-389
        • Sharpe M.C.
        • Archard L.C.
        • Banatvala J.E.
        • et al.
        A report—chronic fatigue.
        J R Soc Med. 1991; 84: 118-121
      1. Gunn W, Connell D, Randall B. Epidemiology of chronic fatigue syndrome: the Centers for Disease Control Study. In: Kleinman A, Straus SE (eds). Chronic Fatigue Syndrome. Ciba Foundation symposium; vol 173. Chichester: John Wiley, 1993:83–101.

        • Schluederberg A.
        • Straus S.E.
        • Peterson P.
        • et al.
        NIH conference. Chronic fatigue syndrome research. Definition and medical outcome assessment.
        Ann Intern Med. 1992; 117: 325-331
        • Jason L.A.
        • Taylor R.
        • Wagner L.
        • Holden J.
        • Ferrari J.R.
        Estimating rates of chronic fatigue syndrome form a community-based sample.
        Am J Community Psychol. 1995; 23: 557-568
        • Wessely S.
        • Chalder T.
        • Hirsch S.
        • Wallace P.
        • Wright D.
        The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome.
        Am J Public Health. 1997; 87: 1449-1455
        • Wolfe F.
        • Smythe H.A.
        • Yunus M.B.
        • et al.
        The American College of Rheumatology 1990 criteria for the classification of fibromyalgia.
        Arthritis Rheum. 1990; 33: 160-172
        • Goldenberg D.L.
        • Simms R.W.
        • Geiger A.
        • Komaroff A.L.
        High frequency of fibromyalgia in patients with chronic fatigue seen in primary care practice.
        Arthritis Rheum. 1990; 33: 381-387
        • Taerk G.S.
        • Toner B.B.
        • Salit I.E.
        • et al.
        Depression in patients with neuromyasthenia (benign myalgic encephalomyelitis).
        Int J Psychiatry Med. 1987; 17: 49-56
        • Kruesi M.J.P.
        • Dale J.
        • Straus S.E.
        Psychiatric diagnoses in patients who have chronic fatigue syndrome.
        J Clin Psychiatry. 1989; 50: 53-56
        • Hickie I.
        • Lloyd A.
        • Wakefield D.
        • Parker G.
        The psychiatric status of patients with chronic fatigue syndrome.
        Br J Psychiatry. 1990; 156: 534-540
      2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R). 3rd rev. ed. Washington DC: American Psychiatric Association, 1987.

        • Wood G.
        • Bentall R.
        • Gopfert M.
        • Edwards R.
        A comparative pyschiatric assessment of patients with chronic fatigue syndrome and muscle disease.
        Psychol Med. 1991; 21: 619-628
        • Wessely S.
        • Powell R.
        Fatigue syndromes.
        J Neurol Neurosurg Psychiatry. 1989; 52: 940-948
        • Katon W.
        • Buchwald D.
        • Simon G.
        • et al.
        Psychiatric illness in patients with chronic fatigue and rheumatoid arthritis.
        J Gen Intern Med. 1991; 6: 277-285
        • Hotopf M.H.
        • Wessely S.
        Viruses, neurosis, and fatigue.
        J Psychosom Res. 1994; 38: 499-514
        • White P.D.
        • Thomas J.M.
        • Amess J.
        • et al.
        The existence of a fatigue syndrome after glandular fever.
        Psychol Med. 1995; 25: 907-916
        • White P.D.
        • Grover S.A.
        • Kangro H.O.
        • et al.
        The validity and reliability of the fatigue syndrome which follows glandular fever.
        Psychol Med. 1995; 25: 917-924