A considerable amount of research has been devoted to investigating the nature and causes of CFS without arriving at firm conclusions. Unfortunately, most of these studies have suffered from methodological shortcomings, principally in patient selection. Patients have often been recruited from tertiary care clinics, using various diagnostic criteria, which have been inconsistently applied. Only a minority of studies have included comparison groups of patients with diagnoses of depression or anxiety disorders. Furthermore, because most studies have used a case-control design, it is often impossible to know whether the findings they report are causes or consequences of the illness (for instance, as the result of reduced activity or sleep disturbance).

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