Cortisol and The Brain: Look For the Pattern, Not the Level

Posted on:July 11, 2020
Last Updated: July 16, 2020
Time to read: 2 minutes

The article is based on the talk by Prof Stafford Lightman at RCPysch19.

Prof Lightman is Professor of medicine at Bristol Medical School (THS), Laboratories for Integrative Neuroscience and Endocrinology, Systems Neuroendocrinology Research Group, Bristol Neuroscience

Prof Lightman’s research involved studying the mechanisms through which the brain recognises environmental stress and disease, and the pathways it uses to initiate appropriate responses in physiological regulation and gene transcription. The group have been particularly interested in the way the body utilises rhythmic activation of neuroendocrine response systems such as the hypothalamo-pituitary-adrenal axis to provide digital as well as analogue signals to glucocorticoid responsive tissues throughout the body.

  • Cortisol is released in pulses which result in a dynamic ultradian rhythm of plasma cortisol. 
  • An oscillating pattern of plasma cortisol is vital in healthy brain responses – the glucocorticoid (GC) rhythm affects sleep behaviour, working memory performance, and how the brain responds when exposed to emotional stimuli.  

  • Smooth hormone levels in the blood are obtained with current GC replacement therapy, but this therapy does not replicate physiological pulsatile cortisol secretion.[Russell et al. 2014]  
  • The pulsatile activity of the HPA axis is crucial for an optimal response of GC-sensitive neural processes. The kinetics of oral drugs reveal non-pulsatile plasma cortisol levels throughout the day, with abnormal regulation of many GC-responsive genes.[Lightman & Conway-Campbell. 2010] 
  • Animal studies have shown that normal cognitive and metabolic function relies on dynamic oscillations of GCs, which maintain the response to stress. Current cortisol replacement therapy in humans is linked with psychopathological symptoms, and a new study investigated the pattern of GC dynamics in the brain for cognitive and behavioural processes.[Kalafatakis et al. 2018] 
  • The pattern of cortisol in the brain affects sleep quality and cognitive function. In a comparison study of patients who were given either a smooth profile (constant level) of cortisol vs a physiological pulsatile pattern of cortisol, the latter group had much better sleep quality and exhibited better memory performance.  
  • An investigation of emotional bias revealed those patients who received the physiological pulsatile infusion of cortisol had a much greater bias towards viewing happy faces rather than fearful faces, whereas those who received a constant infusion showed no difference in attentional bias between either face expression. 
  • In the future, new techniques of automated ambulatory hormone analysis should reveal changes in hormone dynamics associated with psychiatric disease. Publicly available datasets can be used to investigate surrogates of mental health at a population level.