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

K. Kalafatakis, G. M. Russell, C. J. Harmer, M. R. Munafo, N. Marchant, A. Wilson, J. C. Brooks, C. Durant, J. Thakrar, P. Murphy, N. J. Thai, S. L. Lightman*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

78 Citations (Scopus)
544 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)E4091-E4100
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
Early online date9 Apr 2018
Publication statusPublished - 24 Apr 2018

Structured keywords

  • Brain and Behaviour
  • Tobacco and Alcohol
  • Physical and Mental Health


  • Emotional processing
  • FMRI study
  • Glucocorticoid rhythmicity
  • Human brain


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