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John W. Newcomer, MD; Gregg Selke, BA; Angela K. Melson, MA; Tamara Hershey, PhD; Suzanne Craft, PhD; Katherine Richards, BA; Amy L. Alderson, MA

Arch Gen Psychiatry. 1999;56:527-533.

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.

From the Department of Psychiatry, Washington University School of Medicine (Drs Newcomer and Hershey, Mr Selke, and Mss Melson and Richards), and the Department of Psychology, Washington University (Dr Newcomer and Ms Alderson), St Louis, Mo; and the Department of Psychiatry and Behavioral Science, University of Washington, and the Geriatric Research, Education, and Clinical Center, Seattle/American Lake Veterans Affairs Medical Center, Seattle, Wash (Dr Craft).

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