RATIONALE: Patients with major depression show hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, but the mechanisms underlying this abnormality are still unclear. OBJECTIVES: We have compared two synthetic glucorticoids, dexamethasone and prednisolone, in their ability to suppress the hypothalamic-pituitary-adrenal (HPA) axis in depressed patients. Dexamethasone probes glucocorticoid receptor (GR) function, while prednisolone probes both GR and mineralocorticoid receptor (MR) function. MATERIALS AND METHODS: We used a single-blind, repeated-measure design. We administered placebo, prednisolone (5 mg) or dexamethasone (0.5 mg), at 22:00, to 18 severe, treatment-resistant depressed inpatients (15 of them with a history of childhood trauma) and 14 healthy volunteers. On the following days, we collected salivary cortisol from 9:00 to 22:00. RESULTS: Depressed patients had higher salivary cortisol levels compared with controls, at baseline and after both prednisolone and dexamethasone (p<0.001). Consistent with previous studies, depressed inpatients showed impaired suppression by dexamethasone: based on the analysis of the areas under the curve (AUCs), suppression by dexamethasone (0.5 mg) was -85% in controls vs -46% in depressed patients (p=0.018). However, the same depressed patients showed normal suppression by prednisolone (5 mg): suppression was -41% in controls and -36% in depressed patients (p=0.6). CONCLUSIONS: We suggest that the additional effects of prednisolone on the MR explain the different responses to these glucocorticoids in the same depressed patients.
RATIONALE: Patients with major depression show hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, but the mechanisms underlying this abnormality are still unclear. OBJECTIVES: We have compared two synthetic glucorticoids, dexamethasone and prednisolone, in their ability to suppress the hypothalamic-pituitary-adrenal (HPA) axis in depressed patients. Dexamethasone probes glucocorticoid receptor (GR) function, while prednisolone probes both GR and mineralocorticoid receptor (MR) function. MATERIALS AND METHODS: We used a single-blind, repeated-measure design. We administered placebo, prednisolone (5 mg) or dexamethasone (0.5 mg), at 22:00, to 18 severe, treatment-resistant depressed inpatients (15 of them with a history of childhood trauma) and 14 healthy volunteers. On the following days, we collected salivary cortisol from 9:00 to 22:00. RESULTS: Depressed patients had higher salivary cortisol levels compared with controls, at baseline and after both prednisolone and dexamethasone (p<0.001). Consistent with previous studies, depressed inpatients showed impaired suppression by dexamethasone: based on the analysis of the areas under the curve (AUCs), suppression by dexamethasone (0.5 mg) was -85% in controls vs -46% in depressed patients (p=0.018). However, the same depressed patients showed normal suppression by prednisolone (5 mg): suppression was -41% in controls and -36% in depressed patients (p=0.6). CONCLUSIONS: We suggest that the additional effects of prednisolone on the MR explain the different responses to these glucocorticoids in the same depressed patients.
Authors: C C Gispen-de Wied; H D'Haenen; W M Verhoeven; H J Wynne; H G Westenberg; J H Thijssen; J M Van Ree Journal: Psychoneuroendocrinology Date: 1993 Impact factor: 4.905
Authors: C C Gispen-de Wied; L M Jansen; H J Wynne; W Matthys; R J van der Gaag; J H Thijssen; H van Engeland Journal: Psychoneuroendocrinology Date: 1998-04 Impact factor: 4.905
Authors: Christoph Anacker; Patricia A Zunszain; Livia A Carvalho; Carmine M Pariante Journal: Psychoneuroendocrinology Date: 2011-04 Impact factor: 4.905
Authors: Valeria Mondelli; Paola Dazzan; Nilay Hepgul; Marta Di Forti; Monica Aas; Alessandro D'Albenzio; Marco Di Nicola; Helen Fisher; Rowena Handley; Tiago Reis Marques; Craig Morgan; Serena Navari; Heather Taylor; Andrew Papadopoulos; Katherine J Aitchison; Robin M Murray; Carmine M Pariante Journal: Schizophr Res Date: 2009-09-13 Impact factor: 4.939