Project Summary

Mario Francisco Juruena, M.D. (Young Investigator 2006) of the Institute of Psychiatry/King's College London and the University of London, aims to study the role of the mineralocorticoid receptor in treatment-resistant depression. Studies have consistently described patients resistant to treatment as having elevated levels of the hormone cortisol. Elevated cortisol is linked to an abnormal function of the receptors for the hormone in the brain, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Although cortisol dysfunction is an important factor in the etiology of severe depressive illnesses, and one factor implicated in treatment resistance, little data exist as to the status of the MR in this illness. It has long been shown that there is a downregulation of GR function in depression. However, based on recent work by Dr. Juruena, he hypothesizes there is also an upregulation of the MR receptor in depression because there is a reduced suppression of cortisol after treatment with dexamethasone (a GR agonist), but a normal suppression after the administration of prednisolone (a mixed GR/MR agonist). Dr. Jureuena will investigate the effect of prednisolone both alone and in the presence of the MR antagonist spironolactone. The study should further define HPA axis dysfunction in treatment-resistant depression and provide data on the role of the understudied MR receptor for such patients.

Program Area: MOOD DISORDERS\Unipolar

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