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Abnormalities of the HPA axis in affective disorders: clinical subtypes and potential treatments

  • Richard J. Porter (a1) and Peter Gallagher (a2)
<span class='bold'>Background:</span>

New evidence is emerging regarding abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function in subtypes of affective disorders. Adverse effects of HPA axis dysregulation may include dysfunction of monoaminergic transmitter systems, cognitive impairment and peripheral effects. Newer treatments specifically targeting the HPA axis are being developed.

<span class='bold'>Objective:</span>

To review these developments focusing particularly on the glucocorticoid receptor (GR) antagonist mifepristone.

<span class='bold'>Method:</span>

A selective review of the literature.

<span class='bold'>Results:</span>

The function of GRs is increasingly being defined. The role of corticotrophin-releasing hormone (CRH) and dehydroepiandrosterone (DHEA) in the brain is also increasingly understood. HPA axis function is particularly likely to be abnormal in psychotic depression and bipolar disorder, and it is in these conditions that trials of the GR antagonist mifepristone are being focused. CRH antagonists and DHEA are also being investigated as potential treatments.

<span class='bold'>Conclusion:</span>

Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited.

Corresponding author
Richard J. Porter, MB BS, MD, MA, DipObst, MRCPsych, Department of Psychological Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch 8140, New Zealand. Tel: +64-3-372-0400; Fax: +64-3-372-0407; E-mail:
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Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
  • URL: /core/journals/acta-neuropsychiatrica
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