Acute psychological or physiological stress elicits an adaptive neuroendocrine response through the sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis. However, prolonged chronic stress disrupts diurnal cortisol rhythms, induces glucocorticoid receptor down-regulation, and perpetuates sterile systemic inflammation.
Diurnal Cortisol Rhythms and the Cortisol Awakening Response (CAR)
In healthy physiology, cortisol follows a precise circadian rhythm: peaking approximately 30–45 minutes post-awakening (the Cortisol Awakening Response) to mobilize glucose substrates, and declining gradually throughout the afternoon to reach a nadir around midnight. Chronic allostatic load blunts the morning peak and produces an elevated evening nadir, disturbing sleep onset and nocturnal cellular repair.