Psychological Medicine

Original Articles

Does hypocortisolism predict a poor response to cognitive behavioural therapy in chronic fatigue syndrome?

A. D. L. Robertsa1a2, M.-L. Charlera2, A. Papadopoulosa3, S. Wesselya1a2a3, T. Chaldera1a2 and A. J. Clearea1a2a3 c1

a1 King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, UK

a2 Chronic Fatigue Syndrome Research and Treatment Unit, Maudsley Hospital, London, UK

a3 National Affective Disorders Unit, Maudsley and Bethlem Royal Hospitals, London, UK


Background There is evidence that patients with chronic fatigue syndrome (CFS) have mild hypocortisolism. The clinical significance of this is unclear. We aimed to determine whether hypocortisolism exerted any effect on the response of CFS to cognitive behavioural therapy (CBT).

Method We measured 24-h urinary free cortisol (UFC) in 84 patients with Centers for Disease Control and Prevention (CDC)-defined CFS (of whom 64 were free from psychotropic medication) who then received CBT in a specialist, tertiary out-patient clinic as part of their usual clinical care. We also measured salivary cortisol output from 0800 to 2000 h in a subsample of 56 psychotropic medication-free patients.

Results Overall, 39% of patients responded to CBT after 6 months of treatment. Lower 24-h UFC output was associated with a poorer response to CBT but only in psychotropic medication-free patients. A flattened diurnal profile of salivary cortisol was also associated with a poor response to CBT.

Conclusions Low cortisol is of clinical relevance in CFS, as it is associated with a poorer response to CBT. Hypocortisolism could be one of several maintaining factors that interact in the persistence of CFS.

(Received July 25 2008)

(Revised May 21 2009)

(Accepted May 27 2009)

(Online publication July 17 2009)


c1 Address for correspondence: Dr A. J. Cleare, Department of Psychological Medicine, Section of Neurobiology of Mood Disorders, Institute of Psychiatry, 103 Denmark Hill, London SE5 8AF, UK. (Email: