The cortisol awakening response: More than a measure of HPA axis function

• Published in: Neuroscience and biobehavioral reviews Vol. 35; no. 1; pp. 97 - 103
• Main Authors: Clow, Angela, Hucklebridge, Frank, Stalder, Tobias, Evans, Phil, Thorn, Lisa
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.09.2010; Elsevier
• Subjects: Adrenal sensitivity to ACTH; Adrenocorticotropic hormone; Animals; Behavioral psychophysiology; Biological and medical sciences; CAR; Cortisol awakening response; Flip-flop switching; Fundamental and applied biological sciences. Psychology; Hippocampus; Humans; Hydrocortisone - physiology; Hypothalamo-Hypophyseal System - physiology; Pituitary-Adrenal System - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Sleep - physiology; Sleep inertia; Suprachiasmatic nucleus; Wakefulness - physiology; Suprachiasmatic nucleus; Cortisol awakening response; Flip-flop switching; CAR; Hippocampus; Sleep inertia; Adrenal sensitivity to ACTH; Corticosteroid; Hypothalamohypophysoadrenal axis; Steroid hormone; Central nervous system; Antiinflammatory agent; Hypothalamus; Review; Hydrocortisone; Glucocorticoid; Encephalon; Sensitivity; Adrenocorticotropic hormone; Sleep; Adenohypophyseal hormone; Adrenal hormone; Awakening; Sleep wake cycle
• ISSN: 0149-7634; 1873-7528; 1873-7528
• DOI: 10.1016/j.neubiorev.2009.12.011

In most healthy people morning awakening is associated with a burst of cortisol secretion: the cortisol awakening response (CAR). It is argued that the CAR is subject to a range physiological regulatory influences that facilitate this rapid increase in cortisol secretion. Evidence is presented for reduced adrenal sensitivity to rising levels of ACTH in the pre-awakening period, mediated by an extra-pituitary pathway to the adrenal from the suprachiasmatic nucleus (SCN). A role for the hippocampus in this pre-awakening regulation of cortisol secretion is considered. Attainment of consciousness is associated with ‘flip-flop’ switching of regional brain activation, which, it is argued, initiates a combination of processes: (1) activation of the hypothalamic pituitary adrenal (HPA) axis; (2) release of pre-awakening reduced adrenal sensitivity to ACTH; (3) increased post-awakening adrenal sensitivity to ACTH in response to light, mediated by a SCN extra-pituitary pathway. An association between the CAR and the ending of sleep inertia is discussed.