Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome
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Patients with chronic hypercortisolemia due to Cushing's syndrome (CS) exhibit cognitive dysfunction. Because glucocorticoid excess is associated with hippocampal damage in animals, and the hippocampus participates in learning and memory, we explored the relationships between hippocampal formation (HF) volume, memory dysfunction, and cortisol levels in 12 patients with CS. After magnetic resonance imaging, HF volume was determined using digital sum of track ball traces of dentate gyrus, hippocampus proper and subiculum, correcting for total intracranial volume. For 27% of the patients, HF volume fell outside the 95% confidence intervals for normal subject volume given in the literature. In addition, there were significant and specific correlations between HF volume and scores for verbal paired associate learning, verbal recall, and verbal recall corrected for full-scale IQ (r = 0.57 to 0.70, p < 0.05). HF volume was negatively correlated with plasma cortisol levels (r = -0.73, p < 0.05). These studies suggest an association between reduced HF volume, memory dysfunction, and elevated cortisol in patients with CS.
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In major depressive illness, as well as in Cushing's disease, the duration of the illness and not the age of the subjects predicts a progressive reduction in volume of the hippocampus.
“In major depressive illness, as well as in Cushing’s disease, the duration of the illness and not the age of the subjects predicts a progressive reduction in volume of the hippocampus, determined by structural magnetic resonance imaging (Starkman et al., 1992; Sheline et al., 1999).”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Starkman et al., 1992
Hypothalamus-pituitary-adrenal axis hyperactivity has been associated with hippocampal atrophy in aging and in Cushing's disease.
“Hypothalamus-pituitary-adrenal axis hyperactivity have been associated with hippocampal atrophy in aging (16) and in Cushing's disease (17).”
From Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly (2003) · cites this paper as [17]
In major depressive illness, as well as in Cushing's disease, the duration of the illness, and not the age of the subjects, predicts a progressive reduction in volume of the hippocampus.
“In major depressive illness, as well as in Cushing's disease, the duration of the illness, and not the age of the subjects, predicts a progressive reduction in volume of the hippocampus, determined by structural magnetic resonance imaging.103,112”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [112]
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- Authors
- Starkman, M. N., Gebarski, S. S., Berent, S., & Schteingart, D. E.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Starkman, Monica N.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 1992-11
- Volume
- 32
- Issue
- 9
- Pages
- 756-765
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2027066838
- Cited by
- 840
- References
- 14
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 9 · 2023: 18 · 2022: 18 · 2021: 25 · 2020: 22 · 2019: 22 · 2018: 17 · 2017: 25 · 2016: 25 · 2015: 40 · 2014: 31 · 2013: 34 · 2012: 29
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health (5r01mh043372-03)
- National Institute of Mental Health (R01-MH43372)
- National Center for Research Resources (MO1RR0042, M01RR000042)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Cushing's syndrome, memory impairment, hypercortisolism, plasma cortisol, glucocorticoid neurotoxicity, dentate gyrus, subiculum, word recall, cognitive impairment
- MeSH terms
- Adolescent, Adult, Aged, Brain Mapping, Cushing Syndrome, Female, Hippocampus, Humans, Hydrocortisone, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Mental Recall, Retention, Psychology, Verbal Learning, Visual Perception, Wechsler Scales, Neurocognitive Disorders
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