The DOI matches its Crossref record; 76 of the 76 references it cites were found in a registry or an index.
Pathophysiology of hypercortisolism in depression
Abstract
OBJECTIVE: The mechanisms mediating hypercortisolemia in depression remain controversial. Adopting the biomarker strategy, we studied adrenocorticotropin (ACTH) and cortisol dynamics in hypercortisolemic and non-hypercortisolemic depressed in-patients, and in normal volunteers. METHOD: Deconvolution analysis of 24-h pulsatile secretion, approximate entropy (ApEn) estimation of secretory regularity, cross-ApEn quantitation of forward and reverse ACTH-cortisol synchrony, and cosine regression of 24-h rhythmicity. RESULTS: Hypercortisolemia was strongly associated with melancholic and psychotic depressive subtypes. Hypercortisolemic patients had elevated ACTH and cortisol secretion, mediated chiefly by increased burst masses. Basal ACTH secretion was increased, ACTH half-life was reduced, and mean 24-h ACTH concentration was normal. Cortisol secretion was increased in a highly irregular pattern (high ApEn), with high ACTH --> cortisol cross-ApEn (impaired feedforward coupling). Cortisol-mediated feedback on the secretory pattern of ACTH was normal. Hypercortisolemic depressed patients had normal programming of the central hypothalamo-pituitary-adrenal (HPA) axis pulse generator: ACTH pulse frequency, cortisol pulse frequency, circadian acrophases, and ApEn of ACTH secretion were normal. Responsiveness of the adrenal cortex to endogenous ACTH was normal. Non-hypercortisolemic patients resembled hypercortisolemic patients on ACTH regulatory parameters but had low total cortisol secretion. CONCLUSION: Increased ACTH secretion occurs in depressed in-patients regardless of cortisolemic status, confirming central HPA axis overdrive in severe depression. Depressive hypercortisolemia results from an additional change in the adrenal cortex that causes ACTH-independent, disorderly basal cortisol release, a sign of physiological stress in melancholic/psychotic depression.
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In the citing paper
“some depressives show reduced sensitivity to glucocorticoid “fast feedback” (Young et al. 1993) and/or to dexamethasone negative feedback (Carroll et al. 1981), although these findings depend upon depressive subtype, being most common in melancholic and psychotic cases (Carroll et al. 2007).”
From Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression (2008) · cites this paper as Carroll et al. 2007
In the citing paper
“chronic conditions such as coronary artery disease, fibromyalgia, rheumatoid arthritis, and mood disorders such as Major Depressive Disorder (MDD) and Post Traumatic Stress Disorder (PTSD) have also been associated with abnormally high CORT levels and metabolic disruptions ( 5-13 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [8]
In the citing paper
“in hypercortisolism, it is not only that CORT levels are higher than normal, but in some cases, they also display abnormal rhythmicity. This varies depending on whether the underlying condition is associated with Cushing's syndrome, depression, PTSD, acute inflammation following major surgery, or chronic inflammatory diseases (e.g., rheumatoid arthritis) ( 2, 5-13, 57-60 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [8]
In the citing paper
“many of these conditions are accompanied by a disruption of normal glucose metabolism while preserving some degree of CORT rhythmicity.”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [8]
In the citing paper
“As suggested by Hosseinichimeh et al. (2015) and Carroll et al. (2007), cortisol levels are typically low from 8:00 pm to 4:00 am, peak between 4:00 am and 12:00 pm, and then decline back to minimal levels from 12:00 pm until 8:00 pm.”
From Model Predictive Controller to Regulate Cortisol Levels in Individuals With Adrenal Insufficiency (2026) · cites this paper as Carroll et al. (2007)
In the citing paper
“To validate the models, we used a dataset by Carroll and colleagues which included plasma ACTH and cortisol concentrations of 17 healthy subjects (8). The datasets reported the concentrations every 10 minutes for a 24 hour period”
From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [8]
In the citing paper
“The degradation rate, w3, is 0.009 [1/min] and it is found by using the half-life of the cortisol concentration reported in the literature (8).”
From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [8]
In the citing paper
“Yet these two are biological parameters which should not be very different across individuals (For instance, the half-life of ACTH for healthy individuals reported in (8) is 19.9 minutes with a relatively tight standard deviation of 4 minutes).”
From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [8]
In the citing paper
“In typical circadian oscillations, the hormone is at the minimum level between 8 p.m. and 4 a.m. It increases to a maximum level between 4 a.m. and 12 p.m. then it declines to a minimum level from 12 p.m. to 8 p.m. (8).”
From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [8]
In the citing paper
“These values are in the correct range when compared to averages of healthy individual data from (8, 47) as reported in (27) which found 3.06 ng/ml for cortisol, 21 pg/ml for ACTH, and 7.66 pg/ml for CRH providing further confidence in the overall plausibility of the results.”
From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [8]
In the citing paper
“Early attempts of establishing objective markers for diagnosing depression based on hormone levels and patterns produced by the HPA axis have not been successful [9, 12, 43].”
From Patient specific modeling of the HPA axis related to clinical diagnosis of depression (2017) · cites this paper as [9]
In the citing paper
“The data come from a study described by Carroll et al. [9], where healthy controls and depressive humans were included.”
From Patient specific modeling of the HPA axis related to clinical diagnosis of depression (2017) · cites this paper as [9]
In the citing paper
“The secretion of cortisol has been studied in many cases revealing both circadian and ultradian oscillations in the concentration [8, 9, 10, 16, 41].”
From Patient specific modeling of the HPA axis related to clinical diagnosis of depression (2017) · cites this paper as [9]
In the citing paper
“However, it is commonly believed that depression is caused by malfunctions in the Hypothalamic-Pituitary-Adrenal (HPA) axis - a coupled endocrine system [9, 12, 20, 40].”
From Patient specific modeling of the HPA axis related to clinical diagnosis of depression (2017) · cites this paper as [9]
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“…some depressives show reduced sensitivity to glucocorticoid ‘‘fast feedback’’ (Young et al. 1993) and/ or to dexamethasone negative feedback (Carroll et al. 1981), although these findings depend upon depressive subtype, being most common in melancholic and psychotic cases (Carroll et al. 2007).”
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Metadata
- Authors
- Carroll, B. J., Cassidy, F., Naftolowitz, D., Tatham, N. E., Wilson, W. H., Iranmanesh, A., Liu, P. Y., & Veldhuis, J. D.
- Affiliations
- Duke Medical Center (US)
- Salem VA Medical Center (US)
- Mayo Clinic (US)
- Corresponding author
- Carroll, B. J.
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2007-01-15
- Volume
- 115
- Issue
- s433
- Pages
- 90-103
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- OpenAlex
- W2129968987
- Cited by
- 317
- References
- 75
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 12 · 2023: 50 · 2022: 8 · 2021: 15 · 2020: 16 · 2019: 17 · 2018: 14 · 2017: 14 · 2016: 12 · 2015: 18 · 2014: 11 · 2013: 13 · 2012: 18
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh039593-10)
- U.S. Public Health Service (M0100585)
- National Institute of Mental Health (P30MH040159, P30 MH 40159)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK060717)
- National Center for Research Resources (M01RR000030, M01 RR 30, M01RR000585)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 2R01 MH-39593)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- hypercortisolism, depression, ACTH secretion, cortisol secretion, hypothalamic-pituitary-adrenal axis, pulsatile secretion, approximate entropy, endogenous depression, psychotic depression, circadian rhythm, stress response
- MeSH terms
- Adolescent, Adrenocorticotropic Hormone, Adult, Aged, Circadian Rhythm, Cushing Syndrome, Major Depressive Disorder, Electroencephalography, Female, Humans, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Diagnostic and Statistical Manual of Mental Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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