Hypothalamo-pituitary-adrenal function in patients with depressive disorders is correlated with baseline cytokine levels, but not with cytokine responses to hydrocortisone
Abstract
Dysfunction of the hyopthalamo-pituitary adrenal (HPA) system is frequently found in major depression. In addition, signs of non-specific inflammatory system activation have been reported. However, very little is known about interactions between the HPA and immune systems in depressive patients. To assess HPA system function, we performed a combined dexamethasone suppression and corticotropin-releasing hormone stimulation (DEX/CRH) test in 14 depressive patients. Moreover, baseline nocturnal plasma levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured. In addition, the system was challenged with an intraveneous pulsatile injection of hydrocortisone (1 mg/kg body weight in total) and again cytokine levels were measured across one night. Baseline TNF-alpha levels were negatively correlated with the amount of ACTH released upon CRH stimulation during the DEX/CRH test. Acute hydrocortisone administration suppressed TNF-alpha and IL-6 levels independently of baseline HPA system activity. We conclude that chronic HPA system overactivity in depressed patients might compromise the production of inflammatory cytokines under baseline conditions. However, the responsivity of the cytokine production to acutely administered glucocorticoids does not seem to correlate with the state of the HPA system.
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Another study found that cytokine levels in depressed patients with evidence of glucocorticoid resistance and glucocorticoid excess were low, suggesting that glucocorticoid sensitivity in depressed subjects is maintained or possibly increased during depressive illness.
“another study found that cytokine levels in depressed patients with evidence of glucocorticoid resistance and glucocorticoid excess were low, suggesting that glucocorticoid sensitivity in depressed subjects is maintained or possibly increased during depressive illness.86”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [86]
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- Authors
- Schuld, A., Schmid, D. A., Haack, M., Holsboer, F., Friess, E., & Pollmächer, T.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Schuld, Andreas
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 37
- Issue
- 6
- Pages
- 463-470
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W1978114036
- Cited by
- 32
- References
- 23
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2014: 2 · 2013: 3
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- hypothalamic-pituitary-adrenal axis, major depressive disorder, depressive disorders, cytokines, interleukin-6, TNF-α, cortisol, glucocorticoid response, ACTH, dexamethasone suppression test, corticotropin-releasing hormone stimulation, inflammation
- MeSH terms
- Interleukin-6 Inhibitors, Adrenocorticotropic Hormone, Adult, Aged, Circadian Rhythm, Corticotropin-Releasing Hormone, Depressive Disorder, Major, Major Depressive Disorder, Dexamethasone, Drug Administration Schedule, Female, Glucocorticoids, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Injections, Male, Middle Aged, Pituitary-Adrenal System, Severity of Illness Index, Time Factors, Tumor Necrosis Factor-alpha, Interleukin-6, Diagnostic and Statistical Manual of Mental Disorders
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