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Glucocorticoids and glucocorticoid receptors: mediators of fatigue?

Published online by Cambridge University Press:  24 June 2014

A. J. Cleare
A. J. Cleare*
Affiliation:
Section of Neurobiology of Mood Disorders, Division of Psychological Medicine, The Institute of Psychiatry, London, UK and Affective Disorders Unit, Maudsley Hospital, London, UK
*
Anthony J Cleare, Section of Neurobiology of Mood Disorders, Division of Psychological Medicine, Institute of Psychiatry, London SE5 8AF, UK. Tel: 020 78485130; Fax: 020 78485408; E-mail: [email protected]
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Abstract

Fatigue is a common problem; when chronic and disabling, subjects can be categorized as having chronic fatigue syndrome (CFS). Whilst it is most likely a multifactorial condition of biopsychosocial origin, the nature of the pathophysiological component remains unclear. There has been a wealth of interest in the possible hypothalamo–pituitary–adrenal (HPA) axis dysfunction in CFS, and whether such changes may mediate fatigue. On balance, there appears to be reduced cortisol output in a proportion of patients, together with heightened negative feedback and glucocorticoid receptor function. There is evidence for impaired adrenocorticotropic hormone (ACTH) and cortisol responses to a variety of challenges. However, there is no evidence for a specific or uniform dysfunction of the HPA axis. Evidence that these changes may be related to symptom production comes from randomized controlled trials of glucocorticoid replacement therapy, which have shown improvements in fatigue and disability. Given the many factors that may impinge on the HPA axis in CFS, such as inactivity, sleep disturbance, psychiatric comorbidity, medication and ongoing stress, it seems likely that there is not a single or specific change to the HPA axis in CFS and that the observed HPA axis disturbances are of multifactorial etiology. This is further supported by a comparison of neuroendocrine findings in other conditions in which fatigue is prominent, showing both similarities and differences with the pattern in CFS.

Keywords

chronic fatigue syndromeCortisolhydrocortisonehypothalmo–pituitary–adrenal axisneuroendocrine
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 15 , Issue 6 , December 2003 , pp. 341 - 353
Copyright
Copyright © 2003 Blackwell Munksgaard

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