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Prednisolone suppression test in depression: prospective study of the role of HPA axis dysfunction in treatment resistance

  • Mario F. Juruena (a1), Carmine M. Pariante (a2), Andrew S. Papadopoulos (a3), Lucia Poon (a3), Stafford Lightman (a4) and Anthony J. Cleare (a5)...

Abstract

Background

People with severe depressive illness have raised levels of cortisol and reduced glucocorticoid receptor function.

Aims

To obtain a physiological assessment of hypothalamic–pituitary–adrenal (HPA) axis feedback status in an in-patient sample with depression and to relate this to prospectively determined severe treatment resistance.

Method

The prednisolone suppression test was administered to 45 in-patients with depression assessed as resistant to two or more antidepressants and to 46 controls, prior to intensive multimodal in-patient treatment.

Results

The patient group had higher cortisol levels than controls, although the percentage suppression of cortisol output after prednisolone in comparison with placebo did not differ. Nonresponse to in-patient treatment was predicted by a more dysfunctional HPA axis (higher cortisol levels postprednisolone and lower percentage suppression).

Conclusions

In patients with severe depression, HPA axis activity is reset at a higher level, although feedback remains intact. However, prospectively determined severe treatment resistance is associated with an impaired feedback response to combined glucocorticoid and mineralocorticoid receptor activation by prednisolone.

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Copyright

Corresponding author

Correspondence: Dr Anthony J. Cleare, Section of Neurobiology of Mood Disorders, PO 74, Institute of Psychiatry, 103 Denmark Hill, London SE5 8AF, UK. Email: a.cleare@iop.kcl.ac.uk

Footnotes

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The study was supported by Fundacao Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), the National Alliance for Research on Schizophrenia and Depression (NARSAD), the Medical Research Council (MRC) and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Trust and Institute of Psychiatry (King's College London). This research has been supported by a 2003 and 2005 NARSAD Young Investigator Award and a 2004 MRC Clinician Scientist Fellowship to C.M.P.; by a 2003 CAPES Fellowship Award and a 2006 NARSAD Young Investigator Award to M.F.J.; and by the NIHR Biomedical Research Centre at South London and Maudsley NHS Trust and Institute of Psychiatry (King's College London).

Declaration of interest

None.

Footnotes

References

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Prednisolone suppression test in depression: prospective study of the role of HPA axis dysfunction in treatment resistance

  • Mario F. Juruena (a1), Carmine M. Pariante (a2), Andrew S. Papadopoulos (a3), Lucia Poon (a3), Stafford Lightman (a4) and Anthony J. Cleare (a5)...

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Prednisolone suppression test in depression: prospective study of the role of HPA axis dysfunction in treatment resistance

  • Mario F. Juruena (a1), Carmine M. Pariante (a2), Andrew S. Papadopoulos (a3), Lucia Poon (a3), Stafford Lightman (a4) and Anthony J. Cleare (a5)...
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