Tune It Down to Live It Up? Rapid, Nongenomic Effects of Cortisol on the Human Brain

Abstract

The stress hormone cortisol acts on the brain, supporting adaptation and time-adjusted coping processes. Whereas previous research has focused on slow emerging, genomic effects of cortisol, we addressed the rapid, nongenomic cortisol effects on in vivo neuronal activity in humans. Three independent placebo-controlled studies in healthy men were conducted. We observed changes in CNS activity within 15 min after intravenous administration of a physiological dose of 4 mg of cortisol (hydrocortisone). Two of the studies demonstrated a rapid bilateral thalamic perfusion decrement using continuous arterial spin labeling. The third study revealed rapid, cortisol-induced changes in global signal strength and map dissimilarity of the electroencephalogram. Our data demonstrate that a physiological concentration of cortisol profoundly affects the functioning and perfusion of the human brain in vivo via a rapid, nongenomic mechanism. The changes in neuronal functioning suggest that cortisol acts on the thalamic relay of background as well as on task-specific sensory information, allowing focus and facilitation of adaptation to challenges.

Stress improves task processing efficiency in dual-tasks

“…Cortisol induces rapid changes in neuronal information processing [30] by acting on receptors at the neuronal membrane [31]. It has been shown previously that increases in dual-task performance similar to those observed in the current study are evident when punishments are provided in case of slow reaction times [22].…”

The hypothalamic–pituitary–adrenal–leptin axis and metabolic health: a systems approach to resilience, robustness and control

“…any effect occurring within 10 min precludes the time required for translocation, transcription and translation [34]. One recent study combining experimental cortisol infusion and neuroimaging techniques has confirmed that cortisol exerts rapid effects on neuronal activity; however, this technique does not yet provide an actual functional index of feedback signalling [30]. This study will provide the proof of concept for a systems-based index of rapid cortisol inhibitory feedback signalling.…”

“…These data suggest that this mathematical model may provide a unique window into the central nervous system mechanisms underlying HPA feedback control. Future studies might investigate this possibility by looking at the correlation between this model parameter and other purported measures of feedback signalling, such as the DST or neuroimaging during cortisol injections [30]. However, the results of DST may differ from feedback regulation by endogenous cortisol owing to differences in potency, receptor binding affinity, specificity of rapid glucocorticoid receptor mechanisms, access to brain receptors and time scales of the underlying neural mechanisms [24,31,34].…”

“…Several previous modelling approaches to the HPA have shown promise in this regard [27][28][29]. Whereas much research has focused on classical genomic glucocorticoid mechanisms, it is now becoming clear that rapid, non-transcriptional mechanisms may play a particularly important role in stress responses [30], negative feedback inhibition of the HPA, consolidation of aversive memories and food intake [26,31,32]. Socalled rapid effects appear to be mediated via G protein-coupled receptors in hypothalamic neuroendocrine cells [26,33] and are primarily distinguished through temporal criteria-i.e.…”

Altered Patterns of Heartbeat-Evoked Potentials in Depersonalization/Derealization Disorder

“…On the basis of previous reports on the effects of exogenous cortisol on blood perfusion in the thalamus (86), it was hypothesized that cortisol may act as a filter in the integration of exteroceptive and interoceptive sensory information (19). Biologically active cortisol is converted into inactive cortisone by the enzyme 11β-hydroxysteroid dehydrogenase type 2 (56).…”