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Circadian regulation of cortisol after hippocampal damage in humans
Abstract
Background There is substantial evidence that the hippocampus (HC) regulates the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. Damage to the HC in animals produces a transient alteration in diurnal and stress-related HPA activity. This study was designed to examine the effects of HC damage on basal cortisol secretion in humans.Methods Salivary cortisol was measured in 22 patients with HC damage (12 with bilateral damage and 10 with unilateral damage), 7 brain-damaged comparison participants, 10 healthy, age-matched comparison participants, and 6 of the patients' caregivers. Salivary cortisol samples were taken immediately after awakening, 30 min after awakening, at 8:00 am, 11:00 am, 3:00 pm, 6:00 pm, and at bedtime on a single day. Brain-injured patients underwent a structural magnetic resonance imaging scan to examine quantitative volumes of the HC.Results Both bilateral and unilateral HC damage abolished the cortisol response to awakening documented in the comparison groups. Caregivers of bilateral HC patients showed a reduced response to awakening. The remainder of the circadian pattern was not affected in the HC patients; all groups showed a significant diurnal variation. There was no association between HC volume and cortisol secretion.Conclusions Hippocampal damage in humans abolishes the cortisol response to awakening, whereas the remainder of the diurnal cycle is unaffected in these patients. These data suggest a unique role of the HC in the control of basal cortisol secretion.
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“We assessed the cortisol response to awakening in the elderly, which has been recently reported to be associated with HC integrity such that HC damage predicts lower levels of cortisol in response to awakening (Buchanan et al., 2004;Wolf et al., 2005).”
From Self-esteem, locus of control, hippocampal volume, and cortisol regulation in young and old adulthood (2005) · cites this paper as Buchanan et al., 2004
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Valk, S. L., Engert, V., Puhlmann, L. M. C., Linz, R., Caldirou, B., Bernasconi, A., Bernasconi, N., Bernhardt, B. C., & Singer, T. (2024) · eLife · doi:10.7554/elife.87634.2
Valk, S. L., Engert, V., Puhlmann, L. M. C., Linz, R., Caldirou, B., Bernasconi, A., Bernasconi, N., Bernhardt, B. C., & Singer, T. (2024) · eLife · doi:10.7554/elife.87634.3
Metadata
- Authors
- Buchanan, T. W., Kern, S., Allen, J. S., Tranel, D., & Kirschbaum, C.
- Affiliations
- University of Iowa (US)
- Technische Universität Dresden (DE)
- Corresponding author
- Buchanan, Tony W.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 56
- Issue
- 9
- Pages
- 651-656
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2005834680
- Cited by
- 206
- References
- 61
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 12 · 2019: 7 · 2018: 6 · 2017: 5 · 2016: 16 · 2015: 12 · 2014: 18 · 2013: 13 · 2012: 15
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P01NS019632)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hippocampal lesions, cortisol, circadian rhythm, diurnal variation, hypothalamic-pituitary-adrenal axis, cortisol awakening response, salivary cortisol, caregivers, hippocampal volume, brain injury
- MeSH terms
- Adult, Aged, Aged, 80 and over, Brain Damage, Chronic, Circadian Rhythm, Demography, Female, Hippocampus, Humans, Hydrocortisone, Functional Laterality, Male, Middle Aged, Saliva, Time Factors, Reproducibility of Results, Case-Control Studies, Caregivers, Area Under Curve
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