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The Role of Hypothalamic-Pituitary-Adrenal Axis in the Pathophysiology of Major Depression: A Translational Research Perspective of the Prednisolone Suppression Test

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Translational Research Methods for Major Depressive Disorder

Part of the book series: Neuromethods ((NM,volume 179))

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Abstract

Glucocorticoids mediate their actions, including feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis, through two distinct corticosteroid receptor subtypes: mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). Dexamethasone, specifically the dexamethasone suppression test (DST), was the first and most studied glucocorticoid for assessing HPA axis activity; unfortunately, it has pharmacodynamic and pharmacokinetic features that are very distinct from cortisol. We have developed a suppressive test using prednisolone, which is pharmacologically more similar to cortisol than dexamethasone and can therefore obtain a more physiological assessment of HPA axis regulation. We focus here the prednisolone suppression test (PST), summarizing the preclinical work, studies in healthy control subjects, and applications to date in clinical populations. We propose that prednisolone at the 5-mg dosage, together with the assessment of salivary cortisol, can be used to investigate both impaired and enhanced glucocorticoid-mediated negative feedback. The work undertaken to date suggests that, in depression, results using the PST differ from those of the DST, in that patients who are non-suppressors to dexamethasone show normal suppressive responses to prednisolone. Furthermore, preserved suppressive responses to prednisolone predict treatment response in previously difficult-to-treat depression, whereas prednisolone non-suppression is predictive of severe treatment resistance even to the most intensive treatments. We argue that the different results using the PST, which probes both MR and GR, and the DST, which probes only GR, suggest a dissociation between GR and MR function in depressive patients. Thus, we propose that the prednisolone suppression test may offer specific biological and clinical information related to its action at both the GR and the MR. Therefore, the relevance of HPA axis dysfunction in psychiatric disorders and the ability to distinguish “true” from “pseudo-” treatment-resistant depression suggest that the PST holds an important clinical tool.

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Authors and Affiliations

  1. Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Mario F. Juruena, Anthony J. Cleare & Allan H. Young

Authors
  1. Mario F. Juruena
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  2. Anthony J. Cleare
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  3. Allan H. Young
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Corresponding author

Correspondence to Mario F. Juruena .

Editor information

Editors and Affiliations

  1. Department of Psychiatry, Korea University Ansan Hospital, Ansan, Korea (Republic of)

    Yong-Ku Kim

  2. Deptartment of Speech Therapy, Isfahan University of Medical Sciences, Isfahan, Iran

    Meysam Amidfar

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Juruena, M.F., Cleare, A.J., Young, A.H. (2022). The Role of Hypothalamic-Pituitary-Adrenal Axis in the Pathophysiology of Major Depression: A Translational Research Perspective of the Prednisolone Suppression Test. In: Kim, YK., Amidfar, M. (eds) Translational Research Methods for Major Depressive Disorder. Neuromethods, vol 179. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2083-0_1

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  • DOI: https://doi.org/10.1007/978-1-0716-2083-0_1

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2082-3

  • Online ISBN: 978-1-0716-2083-0

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