Cortisol/DHEA ratio and hippocampal volume: A pilot study in major depression and healthy controls
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Structural imaging studies investigating the relationship between hippocampal volume (HCV) and peripheral measures of glucocorticoids (GCs) have produced conflicting results in both normal populations and in individuals with MDD, raising the possibility of other modulating factors. In preclinical studies, dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS; together abbreviated, DHEA(S)) have been shown to antagonize the actions of GCs on the central nervous system. Therefore, considering the relationship of HCV to both of these hormones simultaneously may be important, although it has rarely been done in human populations. Using high-resolution magnetic resonance imaging (MRI), the present pilot study examined the relationship between morning serum cortisol, DHEA(S), and HCV in nineteen normal controls and eighteen unmedicated subjects with Major Depressive Disorder (MDD). Serum cortisol and DHEA(S) were not significantly correlated with HCV across all subjects (cortisol: r=-0.165, p=0.33; DHEA: r=0.164, p=0.35; DHEAS: r=0.211, p=0.22, respectively). However, the ratios of cortisol/DHEA(S) were significantly negatively correlated with HCV in combined group (Cortisol/DHEA: r=-0.461, p=0.005; Cortisol/DHEAS: r=-0.363, p=0.03). Significant or near-significant correlations were found between some hormonal measurements and HCV in the MDDs alone (DHEA: r=0.482, p=0.059; DHEAS: r=0.507, p=0.045; cort/DHEA: r=-0.589, p=0.02; cort/DHEAS: r=-0.424p=0.10), but not in the controls alone (DHEA: r=0.070, p=0.79; DHEAS: r=0.077, p=0.77; cort/DHEA: r=-0.427, p=0.09; cort/DHEAS: r=-0.331, p=0.19). However, Group (MDDs vs controls) did not have a significant effect on the relationship between cortisol, DHEA(S), and their ratios with HCV (p>0.475 in all analyses). Although the exact relationship between serum and central steroid concentrations as well as their effects on the human hippocampus remains not known, these preliminary results suggest that the ratio of cortisol to DHEA(S), compared to serum cortisol alone, may convey additional information about "net steroid activity" with relation to HCV.
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Higher baseline cortisol and higher cortisol-to-DHEA ratios have been linked to smaller hippocampal and medial prefrontal cortex volumes in healthy control and major depressive disorder samples.
“higher baseline cortisol levels as well as higher cortisol/dehydroepiandrosterone (DHEA) ratios have been linked to smaller hippocampal and mPFC volumes amongst HC and MDD samples (79,80)”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [80]
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- Authors
- Jin, R. O., Mason, S., Mellon, S. H., Epel, E. S., Reus, V. I., Mahan, L., Rosser, R. L., Hough, C. M., Burke, H. M., Mueller, S. G., & Wolkowitz, O. M.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Wolkowitz, Owen M.
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 72
- Pages
- 139-146
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC5203799
- OpenAlex
- W2463146849
- Cited by
- 41
- References
- 50
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 3 · 2017: 3
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH083784)
- National Center for Research Resources (UL1RR024131)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- cortisol/DHEA ratio, hippocampal volume, major depressive disorder, dehydroepiandrosterone sulfate, dehydroepiandrosterone, glucocorticoids, neuroendocrine regulation, hippocampal atrophy, serum cortisol, neurosteroids, untreated depression, healthy controls, neuroimaging biomarkers, neuroendocrine markers, neuroinflammation, neurodegeneration
- MeSH terms
- Aged, Dehydroepiandrosterone, Depressive Disorder, Major, Major Depressive Disorder, Female, Hippocampus, Humans, Hydrocortisone, Magnetic Resonance Imaging, Male, Middle Aged, Pilot Projects, Dehydroepiandrosterone Sulfate, Healthy Volunteers
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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