Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man

Kalafatakis, K., Russell, G. M., Harmer, C. J., Munafo, M. R., Marchant, N., Wilson, A., Brooks, J. C. ORCID: https://orcid.org/0000-0003-3335-6209, Durant, C., Thakrar, J., Murphy, P., Thai, N. J. and Lightman, S. L. (2018) Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man. Proceedings of the National Academy of Sciences of the United States of America, 115 (17). E4091-E4100. ISSN 0027-8424

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Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.

Item Type: Article
Additional Information: ACKNOWLEDGMENTS. We thank the clinicians from the Pharmacy of the Bristol Royal Infirmary for their crucial contribution in the randomization process of the study and for realizing its double-blind, placebo-controlled nature. We also thank all the scientists at the Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology and the Clinical Research and Imaging Centre of the University of Bristol for their support and assistance in completing this work. We especially appreciate the assistance of Dr. Kristin Schmidt (University of Oxford) in optimizing the technicalities of the neurobehavioral investigation. Funding for this work was provided by the Medical Research Council (DCS Grant MR/J0125481/1) and the Wellcome Trust (Grant 089647/Z/09/Z).
Uncontrolled Keywords: emotional processing,fmri study,glucocorticoid rhythmicity,human brain,general,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1000
Faculty \ School: Faculty of Social Sciences > School of Psychology
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Depositing User: LivePure Connector
Date Deposited: 10 Feb 2022 14:30
Last Modified: 23 Oct 2022 03:32
URI: https://ueaeprints.uea.ac.uk/id/eprint/83406
DOI: 10.1073/pnas.1714239115


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