title: Abnormalities of the HPA axis in affective disorders: clinical subtypes and potential treatments.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited.
authors.affiliation: 1Department of Psychological Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Porter
authors.affiliation: 2School of Neurology, Neurobiology and Psychiatry, University of Newcastle, Newcastle upon Tyne, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Gallagher