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

  • A. D. L. Roberts (a1) (a2), M.-L. Charler (a2), A. Papadopoulos (a3), S. Wessely (a1) (a2) (a3), T. Chalder (a1) (a2) and A. J. Cleare (a1) (a2) (a3)...

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).


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.


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.


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.

Corresponding author
*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:
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AT Beck , C Ward , M Mendelson (1961). Beck Depression Inventory (BDI). Archives of General Psychiatry 4, 561571.

DJ Buysse , CF Reynolds 3rd, TH Monk , SR Berman , DJ Kupfer (1989). The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Research 28, 193213.

R Cevik , A Gur , S Acar , K Nas , AJ Sarac (2004). Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones. BMC Musculoskeletal Disorders 5, 47.

T Chalder , G Berelowitz , S Hirsch , T Pawlikowska , P Wallace , S Wessely , D Wright (1993). Development of a fatigue scale. Journal of Psychosomatic Research 37, 147153.

AJ Cleare (2004). The HPA axis and the genesis of chronic fatigue syndrome. Trends in Endocrinology and Metabolism 15, 5559.

AJ Cleare , D Blair , S Chambers , S Wessely (2001 a). Urinary free cortisol in chronic fatigue syndrome. American Journal of Psychiatry 158, 641643.

AJ Cleare , E Heap , GS Malhi , S Wessely , V O'Keane , J Miell (1999). Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet 353, 455458.

AJ Cleare , J Miell , E Heap , S Sookdeo , L Young , GS Malhi , V O'Keane (2001 b). Hypothalamo-pituitary-adrenal axis function in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy. Journal of Clinical Endocrinology and Metabolism 86, 35453554.

A Deale , T Chalder , S Wessely (2000). Illness beliefs and treatment outcome in chronic fatigue syndrome. Journal of Psychosomatic Research 45, 7783.

DP Goldberg , B Blackwell (1970). Psychiatric illness in general practice: a detailed study using a new method of case identification. British Medical Journal 2, 439443.

C Heim , UM Nater , E Maloney , R Boneva , JF Jones , WC Reeves (2009). Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction. Archives of General Psychiatry 66, 7280.

WK Jerjes , AJ Cleare , S Wessely , PJ Wood , NF Taylor (2005). Diurnal patterns of salivary cortisol and cortisone output in chronic fatigue syndrome. Journal of Affective Disorders 87, 299304.

WK Jerjes , TJ Peters , NF Taylor , PJ Wood , S Wessely , AJ Cleare (2006). Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome. Journal of Psychosomatic Research 60, 145153.

JC Mundt , IM Marks , K Shear , JH Griest (2002). The Work and Social Adjustment Scale: a simple measure of impairment in functioning. British Journal of Psychiatry 180, 461464.

UM Nater , LS Youngblood , JF Jones , ER Unger , AH Miller , WC Reeves , C Heim (2008). Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome. Psychosomatic Medicine 70, 298305.

J Prins , G Bleijenberg , E Bazelmans , L Elving , T de Boo , H Severens , G van der Wilt , P Spinhoven , J van der Meer (2001). Cognitive behaviour therapy for chronic fatigue syndrome: a multicenter randomised controlled trial. Lancet 357, 841847.

L Quarmby , KA Rimes , A Deale , S Wessely , T Chalder (2007). Cognitive-behaviour therapy for chronic fatigue syndrome: comparison of outcomes within and outside the confines of a randomised controlled trial. Behaviour Research and Therapy 45, 10851094.

ADL Roberts , S Wessely , T Chalder , A Papadopoulos , AJ Cleare (2004). Salivary cortisol response to awakening in chronic fatigue syndrome. British Journal of Psychiatry 184, 136141.

M Sharpe , T Chalder , I Palmer , S Wessely (1997). Chronic fatigue syndrom. A practical guide to assessment and management. General Hospital Psychiatry 19, 185199.

P Whiting , AM Bagnall , AJ Sowden , JE Cornell , CD Mulrow , G Ramirez (2001). Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. Journal of the American Medical Association 286, 13601368.

F Wolfe , H Smythe , M Yunus , R Bennett , C Bombardier , D Goldenberg , P Tugwell , S Campbell , M Abeles , P Clark , A Fam , S Farber , J Feichtner , C Franklin , R Gatter , D Hamaty , J Lessard , A Lichtbroun , A Masi , G McGain , W Reynolds , T Romano , I Russell , R Sheon (1990). The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis and Rheumatism 33, 160173.

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Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
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