Different responses to dexamethasone and prednisolone in the same depressed patients
Abstract
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.
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The modified plasma cortisol assay was validated for salivary cortisol measurement, with reproducible calibration, good correlation with a published TR-FIA, analytical sensitivity of 0.2 nmol/l, and inter/intra assay precision below 10%.
“The plasma cortisol assay of the analyzer was suitably modified and then validated for these measurements. A set of 10 cortisol standards in saline were used in each assay to plot a calibration graph. This was highly reproducible with slope of (mean± SEM) 0.197 ± 0.004. The method correlated well with a previously published TR-FIA (Juruena et al., 2006). It had analytical sensitivity of 0.2 nmol/l”
From Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: The role of stress and of antipsychotic treatment (2010) · cites this paper as Juruena et al., 2006
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- Authors
- Juruena, M. F., Cleare, A. J., Papadopoulos, A. S., Poon, L., Lightman, S., & Pariante, C. M.
- Affiliations
- King's College London (GB)
- Bethlem Royal Hospital (GB)
- University of Bristol (GB)
- Corresponding author
- Pariante, Carmine M.
- Venue
- Psychopharmacology
- Published
- 2006-10-03
- Volume
- 189
- Issue
- 2
- Pages
- 225-235
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2080795205
- Cited by
- 147
- References
- 75
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 4 · 2017: 12 · 2016: 3 · 2015: 10 · 2014: 8 · 2013: 11 · 2012: 7
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- major depressive disorder, dexamethasone suppression test, hypothalamic-pituitary-adrenal axis, HPA axis hyperactivity, glucocorticoid receptor, mineralocorticoid receptor, salivary cortisol, treatment-resistant depression, childhood trauma
- MeSH terms
- Major Depressive Disorder, Dexamethasone, Female, Glucocorticoids, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Prednisolone, Receptors, Glucocorticoid, Saliva, Salivary Glands, Single-Blind Method, Receptors, Mineralocorticoid, Area Under Curve
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