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Four major hypotheses are reviewed.

1. Although CFS is often associated with viral infection, the presence of viruses has as yet not consistently been detected.

2. It is not clear whether anomalies of the HPA axis often observed in CFS are cause or the consequences of the disorder.

3. Immune dysfunction as the cause of CFS is thus far the weakest hypothesis.

4. The psychiatric and psychosocial hypothesis denies the existence of CFS as a disease entity. Accordingly, the fatigue symptoms are assumed to be the consequence of other (somatic) diseases.

Other possible causes of CFS are oxidative stress and genetic predisposition.

In CFS cognitive behavioral therapy is most commonly used. This therapy, however, appears to be ineffective in many patients.

The suggested causes of CFS and the divergent reactions to therapy may be explained by the lack of recognition of subgroups. Identification of subtypes may lead to more effective therapeutic interventions.

Source: World Journal of Biological Psychiatry. 2007 May 8; 1-7 [E-publication ahead of print], PMID: 17853290, Sanders P, Korf J. University Centre of Psychiatry, University of Groningen, Groningen, The Netherlands.