Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder
Open accessAbstract
Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is believed to play a role in the pathophysiology of depression. To investigate mechanisms that may underlie this effect, we examined several indices of HPA axis function - specifically, diurnal cortisol slope, cortisol awakening response, and suppression of cortisol release following dexamethasone administration - in 26 pre-menopausal depressed women and 23 never depressed women who were matched for age and body mass index. Salivary cortisol samples were collected at waking, 30 min after waking, and at bedtime over three consecutive days. On the third day, immediately after the bedtime sample, participants ingested a 0.5mg dexamethasone tablet; they then collected cortisol samples at waking and 30 min after waking the following morning. As predicted, depressed women exhibited flatter diurnal cortisol rhythms and more impaired suppression of cortisol following dexamethasone administration than non-depressed women over the three sampling days. In addition, flatter diurnal cortisol slopes were associated with reduced cortisol response to dexamethasone treatment, both for all women and for depressed women when considered separately. Finally, greater self-reported depression severity was associated with flatter diurnal cortisol slopes and with less dexamethasone-related cortisol suppression for depressed women. Depression in women thus appears to be characterized by altered HPA axis functioning, as indexed by flatter diurnal cortisol slopes and an associated impaired sensitivity of cortisol to dexamethasone. Given that altered HPA axis functioning has been implicated in several somatic conditions, the present findings may be relevant for understanding the pathophysiology of both depression and depression-related physical disease.
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46% of the variability in diurnal cortisol slope in depressed individuals may be explained by their levels of glucocorticoid sensitivity.
“46% of the variability in diurnal cortisol slope in depressed individuals may be explained by their levels of glucocorticoid sensitivity”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Jarcho, Slavich, Tylova-Stein, Wolkowitz, & Burke, 2013
The Results (§3.3) state that glucocorticoid receptor sensitivity explained 46% of the variability in diurnal cortisol slope among depressed women. The claim extends that finding to depressed individuals generally, while the study reports it for women. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIndividuals with MDD have flatter diurnal cortisol slopes, indicating higher overall cortisol concentrations, than persons without MDD.
“In the context of depression, for example, individuals with MDD have been found to have flatter diurnal cortisol slopes (i.e., higher overall cortisol concentrations) than persons without MDD”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Jarcho, Slavich, Tylova-Stein, Wolkowitz, & Burke, 2013
Results §3.2 reports flatter diurnal cortisol slopes in women with MDD than in non-depressed women. It also reports no significant group difference in overall cortisol levels (p > 0.45), so the claim’s explanation that flatter slopes indicate higher overall concentrations is not supported. The study included only pre-menopausal women; the Discussion says whether the findings generalize to men remains unknown. (LLM, conf=0.91)
Experimental — accuracy not yet measured
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“Depression has also been associated with a flatter diurnal cortisol rhythm, but this has been investigated less often, and the available evidence is not very consistent [6].”
BackgroundMechanisms of brain glucocorticoid resistance in stress-induced psychopathologies
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- Authors
- Jarcho, M. R., Slavich, G. M., Tylova-Stein, H., Wolkowitz, O. M., & Burke, H. M.
- Affiliations
- University of California, Los Angeles (US)
- University of California, San Francisco (US)
- Corresponding author
- Jarcho, Michael R.
- Venue
- Biological Psychology
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 93
- Issue
- 1
- Pages
- 150-158
- ISSN
- 0301-0511 (ISSN-L)
- PMC
- PMC3687535
- OpenAlex
- W2057125010
- Cited by
- 134
- References
- 17
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 4 · 2023: 10 · 2022: 3 · 2021: 4 · 2020: 11 · 2019: 11 · 2018: 14 · 2017: 13 · 2016: 17 · 2015: 18 · 2014: 13 · 2013: 4
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biological Psychology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Institute of Mental Health (5K08MH75813-3, R01MH083784, T32MH019925, K08MH075813)
- National Center for Research Resources (UL1RR024131)
- California National Primate Research Center
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, diurnal cortisol rhythm, glucocorticoid resistance, hypothalamic-pituitary-adrenal axis, cortisol awakening response, dexamethasone suppression test, premenopausal women, depression severity, salivary cortisol, depression pathophysiology
- MeSH terms
- Adult, Circadian Rhythm, Major Depressive Disorder, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Saliva, Stress, Psychological
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