Abstract
This article reviews the current state of research in chronic fatigue syndrome (CFS). The evolving definition, prevalence, and prognosis of this controversial illness are presented. We review studies examining psychiatric, personality, and psychosocial etiology for CFS. The evidence for pathophysiology in CFS is also presented, and studies investigating viral, immune, neuroimaging, neuroendocrine, and central and autonomic nervous system abnormalities in CFS are assessed. Current evidence indicates that CFS is multidetermined and heterogeneous and that subgrouping patients according to factors such as psychiatric state and symptom onset may be fruitful. The current state of treatment for CFS is reviewed, and the challenges for research aimed at resolving this prototypical mind/body problem are discussed.
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References
Greenberg DB: Neurasthenia in the 1980s: Chronic mononucleosis, chronic fatigue syndrome, and anxiety and depressive disorders.Psychosomatics. 1990,31:129–137.
Sharpe MC, Archrd LC, Bantavala JE, et al: A report—Chronic fatigue syndrome: Guidelines for research.Journal of the Royal Society of Medicine. 1991,84:118–121.
Wessely S: Old wine and new bottles: Neurasthenia and ‘ME’.Psychological Medicine. 1990,20:35–53.
Wessely S: The history of chronic fatigue syndrome. In Straus SE (ed),Chronic Fatigue Syndrome. New York: Marcel Dekker, 1994, 3–44.
Holmes GP, Kaplan JE, Gantz NM, et al: Chronic fatigue syndrome: A working case definition.Annals of Internal Medicine. 1988,108:387–389.
Schluederberg A, Straus SE, Peterson P, et al: Chronic fatigue syndrome research. Definition and medical outcome assessment.Annals of Internal Medicine. 1992,117:325–331.
Fukuda K, Straus SE, Hickie I, et al: The chronic fatigue syndrome: A comprehensive approach to its definition and study.Annals of Internal Medicine. 1994,121:953–959.
Goldenberg DL: Fibromyalgia and its relation to chronic fatigue syndrome, viral illness and immune abnormalities.Journal of Rheumatology. 1989,16:91–93.
Lloyd AR, Wakefield D, Boughton C, Dwyer J: Prevalence of chronic fatigue syndrome in an Australian population.Medical Journal of Australia. 1990,153:522–528.
Lewis G, Wessely S: The epidemiology of fatigue: More questions than answers.Journal of Epidemiology and Community Health. 1992,46:92–97.
Smets EMA, Garssen B, Bonke B, de Haes JCMJ: The Multidimensional Fatigue Inventory (MFI): Psychometric qualities of an instrument to assess fatigue.Journal of Psychosomatic Research. 1995,39:315–319.
Ray C, Weir WRC, Phillips S, Cullen S: Development of a measure of symptoms in chronic fatigue syndrome: The Profile of Fatigue-Related Symptoms.Psychology and Health. 1992,7:27–43.
Komaroff AL: Clinical presentation and evaluation of fatigue and chronic fatigue syndrome. In Straus SE (ed),Chronic Fatigue Syndrome. New York: Marcel Dekker, 1994, 61–84.
Shafran SD: The chronic fatigue syndrome.American Journal of Medicine. 1991,90:730–739.
Euba R, Chadler T, Deale A, Wessely S: A comparison of the characteristics of chronic fatigue syndrome in primary and tertiary care.British Journal of Psychiatry. 1996,168:121–126.
Buchwald D, Umali P, Umali J, et al: Chronic fatigue and chronic fatigue syndrome: Prevalence in a Pacific Northwest health care system.Annals of Internal Medicine. 1995,123:81–88.
CDC surveillance summary for chronic fatigue syndrome—Four U.S. cities.Morbidity and Mortality Weekly Report. 1997,46(SS-2).
Bates DW, Schmitt W, Buchwald D, et al: Prevalence of fatigue and chronic fatigue syndrome in a primary care practice.Archives of Internal Medicine. 1993,153:2759.
Jason LA, Taylor R, Wagner L, et al: Estimating rates of chronic fatigue syndrome from a community-based sample: A pilot.American Journal of Community Psychiatry. 1995,23:557–568.
Jason LA, Wagner L, Rosenthal S, et al: Estimating the prevalence of chronic fatigue syndrome among nurses.American Journal of Medicine. 1998,105:91S-93S.
Steele L, Dobbins JG, Fukuda K, et al: The epidemiology of chronic fatigue in San Francisco.American Journal of Medicine. 1998,105:83S-90S.
Reyes M, Nisenbaum R, Stewart G, Reeves WC: Update: Wichita population-based study of fatiguing illness. InProceedings of the Fourth International AACFS Research Conference. Cambridge, MA, 1998.
McCluskey DR: Pharmacological approaches to the therapy of chronic fatigue syndrome. In Bock BR, Whelan J (eds),Chronic Fatigue Syndrome. New York: Wiley, 1993, 280–297.
Vercoulen JHMM, Swanink CMA, Fennis JF, et al: Prognosis in chronic fatigue syndrome: A prospective study on the natural course.Journal of Neurology, Neurosurgery, and Psychiatry. 1996,60:489–494.
Joyce J, Hotopf M, Wessely S: The prognosis of chronic fatigue and chronic fatigue syndrome: A systematic review.Quarterly Journal of Medicine. 1997,90:223–233.
Hedrick TE: Summary of risk factors for chronic fatigue syndrome is misleading. [Letter to the Editor].Quarterly Journal of Medicine. 1997,90:723–725.
Bonner D, Ron M, Chalder T, Butler S, Wessely S: Chronic fatigue syndrome: A follow-up study.Journal of Neurology, Neurosurgery, and Psychiatry. 1994,57:617–621.
Ray C, Jefferies S, Weir WR: Coping and other predictors of outcome in chronic fatigue syndrome: A 1-year follow-up.Journal of Psychosomatic Research. 1997,43:405–415.
Levine PH, Snow PG, Ranum BA, Paul C, Holmes MJ: Epidemic neuromyasthenia and chronic fatigue syndrome in West Otago, New Zealand. A 10-year follow-up.Archives of Internal Medicine. 1997,157:750–754.
Johnson H:Osler’s Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic. New York: Crown Publishers, 1996.
Bates DW, Buchwald D, Lee J, et al: Clinical laboratory findings in patients with chronic fatigue syndrome.Archives of Internal Medicine. 1995,155:97–103.
Natelson BH, Ellis SP, O’Braonain PJ, DeLuca J, Tapp WN: Frequency of deviant immunological test values in chronic fatigue syndrome.Clinical and Diagnostic Laboratory Immunology. 1995,2:238–240.
Manu P, Lane TJ, Matthews DA: Chronic fatigue and chronic fatigue syndrome: Clinical epidemiology and aetiological classification. In Bock GR, Whelan J (eds).Chronic Fatigue Syndrome. Chichester, UK: Wiley, 1993, 23–42.
Stewart DE: Emotional disorders misdiagnosed as physical illness: Environmental hypersensivity, candidiasis hypersensitivity, and chronic fatigue syndrome.International Journal of Mental Health 1990,19:56–68.
David AS, Wessely S, Pelosi AJ: Postviral fatigue syndrome: Time for a new approach.British Medical Bulletin. 1988,296:696–699.
Solomon GF: Psychoneuroimmunology and chronic fatigue syndrome: Toward new models of disease.Journal of Chronic Fatigue Syndrome. 1995,1:3–7.
Manu P, Affleck G, Tennen H, Morse PA, Escobar JI: Hypochondriasis influences quality of life outcomes in patients in chronic fatigue syndrome.Psychotherapy and Psychosomatics. 1996,65:76–81.
Shorter E:From Paralysis to Fatigue: A History of Psychosomatic Illness in the Modern Era. New York: Free Press, 1992.
Manu P, Lane TJ, Matthews DA: The frequency of chronic fatigue syndrome in patients with symptoms of persistent fatigue.Annals of Internal Medicine. 1988,109:554–556.
Abbey SE, Garfinkle PE: Chronic fatigue syndrome and depression: Cause, effect, or covariate.Reviews of Infectious Diseases. 1991,18(Suppl. 1):S73-S83.
Lane TJ, Manu P, Matthews DA: Depression and somatization in the chronic fatigue syndrome.American Journal of Medicine. 1991,91:335–344.
Taerk GS, Toner BB, Salit IE, Garfinkel PE, Oersky S: Depression in patients with neuromyasthenia (benign myalgic encephalomyelitis).International Journal of Psychiatry. 1987,17:49–56.
Wessely S, Chadler T, Hirsch S, Wallace P, Wright D: Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: A prospective study in primary care.American Journal of Psychiatry. 1996,153:1050–1059.
Wells KB, Golding JM, Burnam MA: Chronic medical conditions in a sample of the general population with anxiety, affective, and substance use disorders.American Journal of Psychiatry. 1989,146:1440–1446.
Rao SM, Huber SJ, Bornstein RA: Emotional changes with multiple sclerosis and Parkinson’s disease.Journal of Consulting and Clinical Psychology. 1992,60:369–377.
Johnson SK, DeLuca J, Natelson BH: Assessing somatization disorder in chronic fatigue syndrome.Psychosomatic Medicine. 1996,58:50–57.
Katon W, Russo J: Somatic symptoms and depression.Journal of Family Practice. 1989,29:65–69.
Kirmayer LJ, Robbins JM, Drorkird M, Yaffe MJ: Somatization and the recognition of depression and anxiety in primary care.American Journal of Psychiatry. 1993,150:734–740.
Johnson SK, DeLuca J, Natelson BH: Depression in fatiguing illness: Comparing patients with chronic fatigue syndrome, multiple sclerosis, and depression.Journal of Affective Disorders. 1996,39:21–30.
Huber S, Freidenberg D, Paulson G, Shuttleworth E, Christy J: The pattern of depressive symptoms varies with progression of Parkinson’s disease.Journal of Neurology, Neurosurgery, and Psychiatry. 1990,53:275–278.
Stone AA, Broderick JE, Porter LS, et al: Fatigue and mood in chronic fatigue syndrome patients: Results of a momendatary assessment protocol examining fatigue and mood levels and diurnal patterns.Annals of Behavioral Medicine. 1994,16(3):228–234.
Ray C, Weir WR, Cullen S, Phillips S: Illness perception and symptom components in chronic fatigue syndrome.Journal of Psychosomatic Research. 1992,36:243–256.
Powell R, Dolan R, Wessely S: Attributions and self-esteem in depression and chronic fatigue syndrome.Journal of Psychosomatic Research. 1990,21:665–673.
Bearn J, Wessey S: Neurobiological aspects of the chronic fatigue syndrome.European Journal of Clinical Investigation. 1994,24:79–90.
David AS, Wessely S, Pelosi AJ: Postviral fatigue syndrome: Time for a new approach.British Medical Bulletin. 1988,296:696–699.
Ray C: Chronic fatigue syndrome and depression: Conceptual and methodological ambiguities.Psychological Medicine. 1991,21: 1–9.
Millon C, Salvato F, Blaney N, et al: A psychological assessment of chronic fatigue syndrome/chronic Epstein-Barr virus patients.Psychology and Health 1989,3:131–141.
Stricklin A, Sewell M, Austad C: Objective measurement of personality variables in epidemic neuromyasthenia patients.South African Medical Journal. 1988,77:31–34.
Blakely AA, Howard RC, Sosich RM, et al: Psychiatric symptoms, personality, and ways of coping in chronic fatigue syndrome.Psychological Medicine. 1991,21:347–362.
Pepper CM, Krupp LB, Friedberg F, Doscher C, Coyle PK: A comparison of neuropsychiatric characteristics in chronic fatigue syndrome, multiple sclerosis, and major depression.Journal of Neuropsychiatry and Clinical Neurosciences. 1993,5:200–205.
Johnson SK, DeLuca J, Natelson BH: Personality dimensions in the chronic fatigue syndrome: A comparison with multiple sclerosis and depression.Journal of Psychiatric Research. 1996,30:9–20.
Costa PT, McCare RR: Neuroticism, somatic complaints and disease: Is the bark worse than the bite?Journal of Personality. 1987,55:299–316.
David AS, Wessely S, Pelosi AJ: Chronic fatigue syndrome: Signs of a new approach.British Journal of Hospital Medicine. 1991,45:158–159.
Cope H, Mann A, Pelosi A, David A: Psychosocial risk factors for chronic fatigue and chronic fatigue syndrome following presumed viral illness: A case-control study.Psychological Medicine. 1996,26:1197–1209.
Robins L, Helzer J, Cottler L, Goldring E:National Institute of Mental Health Diagnostic Interview Schedule, Version Three Revised: DSM-III-R. St. Louis, MO: Washington University School of Medicine, 1989.
Spitzer RL, Williams JBW, Gibbon M:Instruction Manual for the Structural Clinical Interview for DSM-III-R. New York: New York State Psychiatric Institute, 1988.
Hickie I, Lloyd A, Wakefield D, Parker G: The psychiatric status of patients with chronic fatigue syndrome.British Journal of Psychiatry. 1990,156:534–540.
Taylor R, Jason LA: The effects of psychiatric instrumentation and scoring on psychiatric diagnoses for individuals with CFS.Psychology and Health: An International Journal. 1998,13:1087–1104.
Ware NC, Kleinman A: Culture and somatic experience: The social course of illness in neurasthenia and chronic fatigue syndrome.Psychosomatic Medicine. 1992,54:546–560.
Van Houdenhove B, Onghena P, Neerinckx E, Hellin J: Does high ‘action-proneness’ make people more vulnerable to chronic fatigue syndrome? A controlled psychometric study.Journal of Psychsomatic Research. 1995,39:633–640.
Magnusson AE, Nias DK, White PD: Is perfectionism associated with fatigue?Journal of Psychosomatic Research. 1996,41:377–383.
Surawy C, Hackman A, Hawton K, Sharpe M: Chronic fatigue syndrome: A cognitive approach.Behavioral Research Therapy. 1995,33:535–544.
Cope H, David A, Pelosi A, Mann A: Predictors of chronic ‘post viral’ fatigue.Lancet. 1994,344:864–868.
Shorter E: Sucker-punched again! Physicians meet the disease of the month syndrome.Journal of Psychiatric Research. 1995,39:115–118.
Schweitzer R, Robertson DL, Kelly B, Whiting J: Illness behavior of patients with chronic fatigue syndrome.Journal of Psychosomatic Research. 1993,38:41–49.
Lawrie SM, Manders DN, Geddes JR, Pelosi AJ: A population-based incidence study of chronic fatigue.Psychological Medicine. 1997,27:343–353.
Natelson BH, Johnson SK, DeLuca J, et al: Reducing heterogeneity in chronic fatigue syndrome: A comparison with depression and multiple sclerosis.Clinical Infectious Diseases. 1995,21:1204–1210.
Deale A, Chalder T, Marks I, Wessely S: Cognitive behavior therapy for chronic fatigue syndrome: A randomized controlled trial.American Journal of Psychiatry. 1997,154:408–414.
Buchwald D, Pearlman T, Umali J, Schmaling K, Katon W: Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals.American Journal of Medicine. 1996,101:364–370.
Bombardier CH, Buchwald D: Chronic fatigue, chronic fatigue syndrome, and fibromyalgia. Disability and health care use.Medical Care. 1996,34:924–930.
Petrie K, Moss-Morris R, Weinman J: The impact of catastrophic beliefs on functioning in chronic fatigue syndrome.Journal of Psychosomatic Research. 1995,39:31–37.
Cristodoulo C, DeLuca J, Lange G, Johnson SK, Natelson BH: Relationship between neuropsychological impairment and functional disability in patients with CFS.Journal of Neurology, Neurosurgery, and Psychiatry, 1998,64:431–434.
Komaroff AL: Clinical presentation and evaluation of fatigue and chronic fatigue syndrome. In Straus SE (ed),Chronic Fatigue Syndrome. New York: Marcel Dekker, Inc., 1994, 61–84.
Altay HT, Toner BB, Brooker H, et al: The neuropsychological dimensions of post-infectious neuromyasthenia (chronic fatigue syndrome): A preliminary report.International Journal of Psychiatry in Medicine. 1990,20(2):141–149.
DeLuca J, Johnson SK, Beldowicz D, Natelson BH: Neuropsychological impairments in chronic fatigue syndrome, multiple sclerosis, and depression.Journal of Neurology, Neurosurgery, and Psychiatry. 1995,58:38–43.
Grafman J: Neuropsychological features of chronic fatigue syndrome. In Straus SE (ed),Chronic Fatigue Syndrome. New York: Marcel Dekker, Inc., 1994, 263–283.
Smith AP, Behan PO, Bell W, Millar K, Bakheit M: Behavioral problems associated with the chronic fatigue syndrome.British Journal of Psychology. 1993,84:411–423.
Riccio M, Thompson C, Wilson B, Morgan RD, Lant AF: Neuropsychological and psychiatric abnormalities in myalgic encephalomyelitis: A preliminary report.British Journal of Clinical Psychology. 1992,31:111–120.
Sandman CA, Barron JL, Nackoul K, Goldstein J, Fidler F: Memory deficits associated with chronic fatigue syndrome.Biological Psychiatry. 1993,33:618–623.
Grafman J, Schwartz V, Dale JK, et al: Analysis of neuropsychological functioning in patients with chronic fatigue syndrome.Journal of Neurology, Neurosurgery, and Psychiatry. 1993,56:684–689.
Scheffers MK, Johnson R, Grafman J, Dale JK, Straus SE: Attention and short-term memory in chronic fatigue syndrome patients: An event-related potential analysis.Neurology. 1992,42:1667–1675.
Smith AP: Cognitive changes in myalgic encephalomyelitis. In Jenkins R, Mowbray JF (eds),Post-Viral Fatigue Syndrome. New York: Wiley, 1991, 179–194.
DeLuca J, Johnson SK, Natelson BH: Information processing efficiency in chronic fatigue syndrome and multiple sclerosis.Archives of Neurology. 1993,50:301–304.
Johnson SK, DeLuca J, Fiedler N, Natelson BH: Cognitive functioning in patients with chronic fatigue syndrome.Clinical Infectious Diseases. 1994,18:S84-S85.
Krupp LB, Sliwinski M, Masur DM, Friedberg F, Coyle PK: Cognitive functioning and depression in patients with chronic fatigue syndrome and multiple sclerosis.Archives of Neurology. 1994,51:705–710.
Ray C, Phillips L, Weir WR: Quality of attention in chronic fatigue syndrome: Subjective reports of everyday attention and cognitive difficulty, and performance on tasks of focused attention.British Journal of Clinical Psychology. 1993,32:357–364.
Johnson SK, DeLuca J, Diamond BJ, Natelson BH: Selective impairment of auditory processing in chronic fatigue syndrome: A comparison with multiple sclerosis and healthy controls.Perceptual Motor Skills. 1996,83:51–62.
Johnson SK, DeLuca J, Diamond BJ, Natelson B: Memory dysfunction in fatiguing illness: Interference and distraction in short-term memory.Cognitive Neuropsychiatry. 1998,3:269–285.
Wearden A, Appleby L: Cognitive performance and complaints of cognitive impairment in chronic fatigue syndrome (CFS).Psychological Medicine. 1997,27:81–90.
DeLuca J, Johnson SK, Ellis SP, Natelson BH: Cognitive functioning is impaired in chronic fatigue syndrome patients devoid of psychiatric disease.Journal of Neurology, Neurosurgery, and Psychiatry. 1997,62:151–155.
McDonald E, Cope H, David A: Cognitive impairment in patients with chronic fatigue: A preliminary study.Journal of Neurology, Neurosurgery, and Psychiatry. 1993,56:812–815.
Cope H, Pernet A, Kendall B, David A: Cognitive functioning and magnetic resonance imaging in chronic fatigue.British Journal of Psychiatry. 1995,167:86–94.
Johnson SK, Lange G, DeLuca J, Korn L, Natelson BH: The effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, multiple sclerosis, and depression.Applied Neuropsychology. 1997,4:145–153.
LaManca J, Sisto SA, DeLuca J, et al: The influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome.American Journal of Medicine. 1998,105:59S-65S.
DeLuca J, Johnson SK, Natelson BH: Sudden vs. gradual onset of chronic fatigue syndrome differentiates individuals on cognitive and psychiatric measures.Journal of Psychiatric Research. 1997,31:83–90.
Lutgendorf S, Klimas NG, Antoni M, Brickman A, Fletcher MA: Relationships of cognitive difficulties to immune measures, depression, and illness burden in chronic fatigue syndrome.Journal of Chronic Fatigue Syndrome. 1995,1:23–41.
Mawle AC, Steele L, Reyes M, Dobbins JG, Reeves WC:A Case-Control Study of Immunologic Parameters in Chronic Fatigue Syndrome (CFS) Patients. First Annual Meeting of the American Association for Chronic Fatigue. Miami, FL: 1994.
Mawle AC, Nisenbaum R, Dobbins JG, et al: Immune responses associated with chronic fatigue syndrome: A case control study.Journal of Infectious Diseases. 1997,175:136–141.
Hickie I, Lloyd A, Hadzi-Pavlovic D, et al: Can chronic fatigue syndrome be defined by distinct clinical features?Psychological Medicine. 1995,25:925–935.
Natelson BH, Ellis SP, O’Braonain PJ, DeLuca J, Tapp WN: Frequency of deviant immunological test values in chronic fatigue syndrome.Clinical and Diagnostic Lab Immunology. 1994,2:238–240.
Hay J, Jenkins FJ: Human herpes viruses and chronic fatigue syndrome. In Straus SE (ed),Chronic Fatigue Syndrome. New York: Marcel Dekker, Inc., 1994, 181–197.
Komaroff AL: Chronic fatigue syndromes: Relationship to chronic viral infections.Journal of Virology Research. 1988,21:3–10.
Komaroff AL: Clinical presentation and evaluation of fatigue and chronic fatigue syndrome. In Straus SE (ed),Chronic Fatigue Syndrome. New York: Marcel Dekker, Inc., 1994, 61–84.
Krueger G, Klueppelberg U, Hoffmann A, Ablashi DV: Clinical correlates of infection with human herpesvirus-6.In Vivo. 1994,8:457–486.
Patnaik M, Komaroff AL, Conley E, Ojo-Amize EA, Peter JB: Prevalence of IgM antibodies to human herpesvirus 6 early antigen (p41/38) in patients with chronic fatigue syndrome.Journal of Infectious Diseases. 1995,172:1364–1367.
Fekety R: Infection and chronic fatigue syndrome. In Straus SE (ed),Chronic Fatigue Syndrome. New York: Marcel Dekker, Inc., 1994, 101–179.
Mawle AC, Reyes M, Schmid DS: Is chronic fatigue syndrome an infectious disease?Infectious Agents and Disease. 1994,2:333–341.
Mawle AC, Nisenbaum R, Dobbins JG, et al: Seroepidemiology of chronic fatigue syndrome: A case-control study.Clinical Infectious Diseases. 1995,21:1386–1389.
Hotopf M, Noah N, Wessely S: Chronic fatigue and minor psychiatric morbidity after viral meningitis: A controlled study.Journal of Neurology, Neurosurgery, and Psychiatry. 1996,60:504–509.
Wessely S, Chalder T, Hirsch S, et al: Postinfectious fatigue: Prospective cohort study in primary care.Lancet. 1995,345:1333–1338.
Ayres JG, Flint N, Smith EG, et al: Post-infection fatigue syndrome following Q fever.Quarterly Journal of Medicine. 1998,91:105–123.
Suhadolnik RJ, Peterson DL, O’Brien K, et al: Biochemical evidence for a novel low molecular weight 2-5A-Dependent Rnase L in chronic fatigue syndrome.Journal of Interferon and Cytokine Research. 1997,17:377–385.
Suhadolnik RJ, Reichenbach NL, Hitzges P, et al: Changes in the 2–5A synthetase/RNase L antiviral pathway in a controlled clinical trial with Poly(I)-Poly(C12U) in chronic fatigue syndrome.In Vivo. 1994,8:599–604.
Vojdani A, Ghoneum M, Choppa PC, Magtoto L, Lapp CW: Elevated apoptotic cell population in patients with chronic fatigue syndrome: The pivotal role of protein kinase RNA.Journal of Internal Medicine. 1997,242:465–478.
Bell DS: Chronic fatigue syndrome update.Postgraduate Medicine. 1994,96:73–80.
Ablashi DV, Ablashi KL, Kramarsky B, et al: Viruses and chronic fatigue syndrome: Current status.Journal of Chronic Fatigue Syndrome. 1995,1:3–22.
Landay AL, Jessop C, Lenette ET, et al: Chronic fatigue syndrome: Clinical condition associated with immune activation.Lancet. 1991,338:707–712.
Klimas NG, Salvato FR, Morgan R, et al: Immunologic abnormalities in chronic fatigue syndrome.Journal of Clinical Microbiology. 1990,28:1403–1410.
Caligiuri M, Murray C, Buchwald D: Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome.Journal of Immunology. 1987,139:3306–3313.
Cannon JG, Angel JB, Abad LW, et al: Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome.Journal of Clinical Immunology. 1997,17:253–261.
Natelson BH, LeManca J, Denny T, et al: Immunological parameters in chronic fatigue syndrome, major depression, and multiple sclerosis.American Journal of Medicine. 1998,105:43S-49S.
Buchwald D, Wener MH, Pearlman T, Kith P: Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome.Journal of Rheumatology. 1997,24:372–376.
Strober W: Immunological functioning chronic fatigue syndrome. In Straus SE (ed),Chronic Fatigue Syndrome. New York: Marcel Dekker, Inc., 1994, 207–237.
Buchwald D, Ashley RL, Pearlman T, Kith P, Komaroff AL: Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.Journal of Medical Virology. 1996,50:25–30.
Natelson BH, Cohen JM, Brassloff I, Lee HJA: Controlled study of brain magnetic resonance imaging in patients with fatiguing illnesses.Journal of the Neurological Sciences. 1993,120:213–217.
Buchwald DPR, Cheney DI, Peterson B, et al: A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus Type 6 infection.Annals of Internal Medicine. 1992,116:103–113.
Schwartz RB, Garada BM, Komaroff AL, et al: Detection of intracranial abnormalities in patients with chronic fatigue syndrome: Comparison of MR imaging and SPECT.American Journal of Radiology. 1994,162:935–941.
Cope H, David AS: Neuroimaging in chronic fatigue syndrome.Journal of Neurology, Neurosurgery, and Psychiatry. 1996,60:471–477.
Lange G, DeLuca J, Lee HJ, Maldjian JA, Natelson BH: Cerebral abnormalities in chronic fatigue syndrome. Society for Neuroscience Conference. Washington, DC: 1997.
Ichise M, Salit IE, Abbey SE, et al: Assessment of regional cerebral perfusion by99Tcm-HMPAO SPECT in chronic fatigue syndrome.Nuclear Medicine Communications. 1992,13:767–772.
Schwartz RB, Komaroff AL, Garada BM, et al: SPECT imaging of the brain: Comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression.American Journal of Radiology. 1994,162:943–951.
Costa DC, Tannock C, Brostoff J: Brainstem profusion is impaired in chronic fatigue syndrome.Quarterly Journal of Medicine. 1995,88:767–773.
Prasher D, Smith A, Findley L: Sensory and cognitive event related potentials in myalgic encephalomyelitis.Journal of Neurology, Neurosurgery, and Psychiatry. 1990,53:247–253.
Sisto SA, Tapp W, Drastal S, Bergen M: Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome.Clinical Autonomic Research. 1995,5:139–143.
Cordero DL, Sisto SA, Tapp WN, et al: Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome.Clinical Autonomic Research. 1996,6:329–333.
Bou-Holaigah I, Rowe PC, Kan J, Calkins H: The relationship between neurally mediated hypotension and the chronic fatigue syndrome.Journal of the American Medical Association. 1995,274:961–967.
LaManca J, Peckerman A, Walker J, et al: Neurally mediated hypotension and cardiovascular response during head-up tilt in chronic fatigue syndrome.Medicine and Science in Sports and Exercise. 1998,30:S160.
Streeten DHP, Bell DS: Circulating blood volume in chronic fatigue syndrome.Journal of Chronic Fatigue Syndrome. 1998,4:3–11.
Boda WL, Natelson BH, Sisto SA, Tapp WN: Gait abnormalities in chronic fatigue syndrome.Journal of the Neurological Sciences. 1995,131:156–161.
McCully KK, Sisto SA, Natelson BH: Use of exercise for treatment of chronic fatigue syndrome.Sports Medicine. 1996,21:35–48.
Rosen SD, King JC, Wilkinson JB, Nixon PG: Is chronic fatigue syndrome synonymous with effort syndrome?Journal of the Royal Society of Medicine. 1990,83:761–764.
Lawrie SM, MacHale SM, Power MJ, Goodwin GM: Is chronic fatigue syndrome best understood as a primary disturbance of the sense of effort?Psychological Medicine. 1997,27:995–999.
Demitrack MA, Dale JK, Straus SE, et al: Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome.Journal of Clinical Endocrinology and Metabolism. 1991,73:1–11.
Demitrack MA: Neuroendocrine aspects of chronic fatigue syndrome. In Straus SE (ed),Chronic Fatigue Syndrome. New York: Marcel Dekker, Inc., 1994, 285–308.
Bakheit AMO, Behan PO, Dinan TG, Gray CE, O’Keane V: Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome.British Medical Journal. 1992,304:1010–1012.
Cleare AJ, Bearn J, McGregor A, et al: Contrasting neuroendocrine responses in depression and chronic fatigue syndrome.Journal of Affective Disorders. 1995,34:283–289.
Sharpe M, Hawton K, Clements A, Cowen PJ: Increased brain serotonin function in men with chronic fatigue syndrome.British Medical Journal. 1997,315:164–165.
Yatham LN, Morehouse RL, Chisholm BT, et al: Neuroendocrine assessment of serotonin (5-HT) function in chronic fatigue syndrome.Canadian Journal of Psychiatry. 1995,40:93–96.
Ottenweller JE, LaManca JL, Sisto SA, Guo W, Natelson BH: Endocrine hyporesponsiveness to exercise in patients with chronic fatigue syndrome.Integrative Physiological Behavioral Science. 1997,32:189.
Vercoulen JHMM, Swanink CMA, Zitman FG, et al: Randomized, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome.Lancet. 1996,347:858–861.
Zubieta JK, Demitrack MA, Shipley JE, et al: Sleep EEG in chronic fatigue syndrome: Comparison with major depression.Biological Psychiatry. 1993,33:74A.
Thase ME, Frank E, Kupfer DJ: Biological processes in major depression. In Beckham EE, Leber WR (eds),Handbook of Depression: Treatment, Assessment, and Research. Homewood, IL: Dorsey Press, 1985, 816–819.
Blondel-Hill E, Shafran SD: Treatment of the chronic fatigue syndrome.Drugs. 1993,46:639–651.
Strayer DR, Carter WA, Brodsky I, et al: A controlled clinical trial with a specifically configured RNA drug, Poly(I):Poly(C12U), in chronic fatigue syndrome.Clinical Infectious Diseases. 1994,18(Suppl. 1):S88-S95.
Butler S, Chalder T, Ron M, Wessely S: Cognitive-behavior therapy in the chronic fatigue syndrome.Journal of Neurology, Neurosurgery, and Psychiatry. 1991,54:153–158.
Lloyd A, Hickie I, Brockman A, et al: Immunological and psychologic therapy for patients with chronic fatigue syndrome.American Journal of Medicine. 1993,94:197–203.
Freidberg F, Krupp LB: A comparison of cognitive behavioral treatment for chronic fatigue syndrome and primary depression.Clinical Infectious Diseases. 1994,18(Suppl. 1):S105-S110.
Friedberg F: Chronic fatigue syndrome: A new clinical application.Professional Psychology: Research and Practice. 1996,27:487–494.
Sharpe M, Wessely S: Putting the rest cure to rest—again.British Medical Journal. 1998,316:796–800.
Sharpe M, Hawton K, Simkin S, et al: Cognitive-behaviour therapy for the chronic fatigue syndrome: A randomized controlled trial.British Medical Journal. 1996,312:22–26.
Fulcher KY, White PD: Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome.British Medical Journal. 1997,314:1647–1652.
Jason LA, Richman JA, Freidberg F, et al: Politics, science, and the emergence of a new disease: The case of chronic fatigue syndrome.American Psychologist. 1997,9:973–983.
Nixon PGF: Exhaustion: Cardiac rehabilitation’s starting point. In Maes S, Speilberger CD, Defares PB, Sarason IG (eds),Topics in Health Psychology. Chicester, England: John Wiley & Sons, 1988, 129–139.
Wessely S, David A, Butler S, Chalder T: Management of chronic (postviral) fatigue syndrome.Journal of the Royal College of General Practice. 1989,39:26–29.
Maclean G, Wessely S: Professional and popular views of chronic fatigue syndrome.British Medical Journal. 1994,308:776–777.
Jason LA, Ropacki MT, Santoro NB, et al: A screening scale for chronic fatigue syndrome: Reliability and validity.Journal of Chronic Fatigue Syndrome. 1997,3:39–59.
Hickie I, Hadzi-Pavlovic D, Ricci C: Reviving the diagnosis of neurasthenia.Psychological Medicine. 1997,27:989–994.
Wessely S: Chronic fatigue syndrome. Summary of a report of a joint committee of the Royal Colleges of Physicians, Psychiatrists, and General Practitioners.Journal of the Royal College of Physicians. 1996,30(6):497–504.
Webster R:Why Freud Was Wrong. New York: Basic Books, 1995.
Slater E, Glithero E: A follow-up of patients diagnosed as suffering from “hysteria”.Journal of Psychosomatic Research. 1965,9:9–13.
Mace CJ, Trimble MR: Ten-year prognosis of conversion disorder.British Journal of Psychiatry. 1996,169:282–288.
Showalter E:Histories: Hysterical Epidemics and Modern Culture. New York: Columbia University Press, 1997.
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Preparation of this manuscript was supported in part by NIH grant MH52810-03.
The authors would like to thank Amy Beam for assistance in manuscript preparation.
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Johnson, S.K., DeLuca, J. & Natelson, B.H. Chronic fatigue syndrome: Reviewing the research findings. ann. behav. med. 21, 258–271 (1999). https://doi.org/10.1007/BF02884843
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DOI: https://doi.org/10.1007/BF02884843