The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures

To examine published data regarding patient cohorts with the recently defined chronic fatigue syndrome.

Review of thirty-two peer-assessed research publications that included full disclosure of the methodology employed; classification of the findings as confirmed, contradictory, or non-duplicated.

Research studies have confirmed that the majority of patients with the chronic fatigue syndrome: 1) are white middle-aged women, 2) have a high prevalence of current major depression and somatization disorder, 3) have abnormal personality traits, 4) believe that their fatigue has a physical cause, and 5) show mild abnormalities of humoral immunity. Contradictory data have been presented with regard to: 1) the time of onset of depressive disorders, 2) the etiologic role of herpetic and enteroviral infections, 3) the presence of abnormal cellular immunity, and 4) the clinical utility of immunoglobulin therapy. Non-duplicated research has indicated 1) hypothalamic-pituitary-adrenal axis dysfunction, 2) abnormalities on magnetic resonance images of the brain, 3) altered cytokine production, and 4) the possibility of retroviral infection.

As presently defined, the chronic fatigue syndrome has many of the clinical and biological features associated with depressive and somatoform disorders. A specific etiologic role for infections or immune dysfunction has not been confirmed.