Cited by 416Stress Responses and CortisolTreatment of Major DepressionAdrenal Hormones and Disorders

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Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression

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Barden, Nicholas·2004·Journal of Psychiatry and Neuroscience

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Abstract

Major alterations of the hypothalamic-pituitary-adrenocortical (HPA) system that can be reversed by successful antidepressant therapy are often seen in depressed patients. Persuasive evidence points to the involvement of a dysfunctional glucocorticoid receptor (GR) system in these changes. Support for this also comes from studies of transgenic mice that express an antisense RNA, complementary to the GR mRNA, and have numerous neuroendocrine characteristics of human depression as well as altered behaviour. Many of these neuroendocrine and behavioural characteristics of the transgenic mice can be reversed by antidepressants. A possible explanation for this is that the antidepressant-induced increase in GRs renders the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of antidepressant drugs.

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Authors: Barden, N.
Affiliations: Centre hospitalier de l'Université Laval (CA)
Corresponding author: Barden, Nicholas
Venue: Journal of Psychiatry and Neuroscience
Publisher: Canadian Science Publishing
Published: 2004-05
Volume: 29
Issue: 3
Pages: 185-193
ISSN: 1180-4882 (ISSN-L)
1488-2434
DOI: 10.1139/jpn.0421
PMC: PMC400688
OpenAlex: W20284704
Cited by: 416
References: 99
Citations by year: 2026: 7 · 2025: 11 · 2024: 16 · 2023: 10 · 2022: 20 · 2021: 18 · 2020: 27 · 2019: 21 · 2018: 25 · 2017: 12 · 2016: 22 · 2015: 17 · 2014: 23 · 2013: 20 · 2012: 19
FWCI: 7.53
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.nrcresearchpress.com/page/about/CorporateTextAndDataMining (tdm)
Locations: Journal of Psychiatry and Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
PubMed
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: hypothalamic-pituitary-adrenal axis, depression, glucocorticoid receptor, antidepressant action, HPA axis dysregulation, glucocorticoid feedback, neuroendocrine dysfunction, antidepressant drug development
MeSH terms: Antidepressive Agents, Major Depressive Disorder, Humans, Hypothalamo-Hypophyseal System, Hypothalamus, Pituitary-Adrenal System, RNA, Antisense, Mutation, Missense

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Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression

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