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

Lookup NU author(s): Dr Richard Porter, Dr Peter GallagherORCiD


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Background: 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. Objective: To review these developments focusing particularly on the glucocorticoid receptor (GR) antagonist mifepristone. Method: A selective review of the literature. Results: 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. Conclusion: Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited. © 2006 Blackwell Munksgaard.

Publication metadata

Author(s): Porter RJ, Gallagher P

Publication type: Review

Publication status: Published

Journal: Acta Neuropsychiatrica

Year: 2006

Volume: 18

Issue: 5

Pages: 193-209

Print publication date: 01/10/2006

ISSN (print): 0924-2708

ISSN (electronic): 1601-5215


DOI: 10.1111/j.1601-5215.2006.00152.x