Neuroendocrine aspects of hypercortisolism in major depression

Parker, Karen J; Schatzberg, Alan F; Lyons, David M

doi:10.1016/s0018-506x(02)00016-8

Cited by 455Stress Responses and CortisolAdrenal Hormones and DisordersNeuroendocrine regulation and behavior

Neuroendocrine aspects of hypercortisolism in major depression

Parker, Karen J, Schatzberg, Alan F, Lyons, David M·2003·Hormones and Behavior

DOI 10.1016/s0018-506x(02)00016-8

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Abstract

A consistent finding in biological psychiatry is that hypothalamic-pituitary-adrenal (HPA) axis physiology is altered in humans with major depression. These findings include hypersecretion of cortisol at baseline and on the dexamethasone suppression test. In this review, we present a process-oriented model for HPA axis regulation in major depression. Specifically, we suggest that acute depressions are characterized by hypersecretion of hypothalamic corticotropin-releasing factor, pituitary adrenocorticotropic hormone (ACTH), and adrenal cortisol. In chronic depressions, however, enhanced adrenal responsiveness to ACTH and glucocorticoid negative feedback work in complementary fashion so that cortisol levels remain elevated while ACTH levels are reduced. In considering the evidence for hypercortisolism in humans, studies of nonhuman primates are presented and their utility and limitations as comparative models of human depression are discussed.

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The induction of anhedonia has been the primary focus in the chronic unpredictable/mild/variable stress model.
“The induction of anhedonia has been the primary focus in this model”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [40]
Hypercortisolism is the most consistent biological abnormality in major depression.
“has been the most consistent biological abnormality in this disorder [38, 40].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [40]
The chronic unpredictable/mild/variable stress model reproduces hypercortisolism found in 40-60% of patients with major depression.
“along with its important feature reproducing hypercortisolism, which is found in 40–60% of patients with major depression”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [40]

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Authors: Parker, K. J., Schatzberg, A. F., & Lyons, D. M.
Affiliations: Stanford Medicine (US)
Corresponding author: Parker, Karen J
ORCID: Parker, Karen J
Schatzberg, Alan F
Venue: Hormones and Behavior
Publisher: Elsevier BV
Published: 2003-01
Volume: 43
Issue: 1
Pages: 60-66
ISSN: 0018-506X (ISSN-L)
DOI: 10.1016/s0018-506x(02)00016-8
OpenAlex: W2093358121
Cited by: 455
References: 89
Citations by year: 2026: 8 · 2025: 4 · 2024: 13 · 2023: 12 · 2022: 23 · 2021: 18 · 2020: 18 · 2019: 18 · 2018: 25 · 2017: 18 · 2016: 19 · 2015: 17 · 2014: 27 · 2013: 27 · 2012: 22
FWCI: 7.82
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Hormones and Behavior (publishedVersion)
PubMed (publishedVersion)
Funders: School of Medicine, Stanford University
National Institute of Mental Health (MH-47573, R01MH050604, MH50604, R01MH047573)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords: hypercortisolism, major depressive disorder, hypothalamic-pituitary-adrenal axis, cortisol, corticotropin-releasing factor, ACTH, glucocorticoid negative feedback, dexamethasone suppression test, chronic depression, acute depression, neuroendocrinology
MeSH terms: Adrenocorticotropic Hormone, Animals, Corticotropin-Releasing Hormone, Major Depressive Disorder, Humans, Hydrocortisone, Neurosecretory Systems

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Neuroendocrine aspects of hypercortisolism in major depression

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