Decreased memory performance in healthy humans induced by stress-level cortisol treatment
Abstract
BACKGROUND: Glucocorticoids (GCs) can regulate hippocampal metabolism, physiologic functions, and memory. Despite evidence of memory decreases during pharmacological GC treatment, and correlations between memory and cortisol levels in certain disease conditions, it remains unclear whether exposure to the endogenous GC cortisol at levels seen during physical and psychological stress in humans can inhibit memory performance in otherwise healthy individuals. METHODS: Randomized, double-blind, placebo-controlled comparison of 2 fixed oral doses of cortisol (40 mg/d and 160 mg/d using split doses to approximate circadian rhythm) given for 4 days to matched groups of healthy subjects (n = 51). Lower-dose treatment approximated cortisol exposure during mild stress, whereas the higher dose approximated cortisol exposure during major stress. Cognitive testing and plasma sampling were done at baseline, after 1 and 4 days of treatment, and after a 6-day washout period, hypothesizing dose-dependent decreases in verbal declarative memory. RESULTS: Cortisol treatment at the higher dose produced reversible decreases in verbal declarative memory without effects on nonverbal memory, sustained or selective attention, or executive function. A significant interaction between time and treatment condition for paragraph recall was explained by treatment-induced differences in performance after 4 treatment days, with lower immediate and delayed recall performance during higher-dose cortisol treatment compared with lower-dose treatment and placebo. CONCLUSIONS: Several days of exposure to cortisol at doses and plasma concentrations associated with physical and psychological stress in humans can-similar to pharmacological GC treatment-reversibly decrease specific elements of memory performance in otherwise healthy individuals.
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Several studies have highlighted deleterious effects of exogenous glucocorticoids on cognition.
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From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [426]
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- Authors
- Newcomer, J. W.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Newcomer, J. W.
- ORCID
- Newcomer, J. W.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1999-06-01
- Volume
- 56
- Issue
- 6
- Pages
- 527-533
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2089435641
- Cited by
- 546
- References
- 67
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 6 · 2023: 9 · 2022: 12 · 2021: 11 · 2020: 9 · 2019: 18 · 2018: 11 · 2017: 14 · 2016: 13 · 2015: 18 · 2014: 18 · 2013: 24 · 2012: 19
- FWCI
- 12.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p60dk020579-35, 5k02mh001510-05)
- National Institute of Mental Health (MH-01510)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK20579)
- National Center for Research Resources (5M01 RR-00036, M01RR000036)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- cortisol, glucocorticoids, verbal declarative memory, memory impairment, stress, dose-dependent effects, hippocampus, healthy volunteers, pharmacological stress
- MeSH terms
- Adult, Circadian Rhythm, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Hydrocortisone, Male, Memory, Memory Disorders, Placebos, Mental Recall, Stress, Physiological, Stress, Psychological
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