Cortisol awakening response
The cortisol awakening response (CAR) is an increase between 38% and 75% in cortisol levels peaking 30–45 minutes after awakening in the morning in some people. This rise is superimposed upon the late-night rise in cortisol which occurs before awakening. While its purpose is uncertain, it may be linked to the hippocampus' preparation of the hypothalamic-pituitary-adrenal axis (HPA) in order to face anticipated stress.
Shortly after awakening, a sharp 38–75% (average 50%) increase occurs in the blood level of cortisol in about 77% of healthy people of all ages. The average level of salivary cortisol upon waking is roughly 15 nmol/l; 30 minutes later it may be 23 nmol/l, though there are wide variations. The cortisol awakening response reaches a maximum approximately 30 minutes after awakening though it may still be heightened by 34% an hour after waking. The pattern of this response to waking is relatively stable for any individual. Twin studies show its pattern is largely genetically determined since there is a heritability of 0.40 for the mean cortisol increase after awakening and 0.48 for the area under the cortisol rise curve.
Normally, the highest cortisol secretion happens in the second half of the night with peak cortisol production occurring in the early morning. Following this, cortisol levels decline throughout the day with lowest levels during the first half of the night. Cortisol awakening response is independent of this circadian variation in HPA axis activity; it is superimposed upon the daily rhythm of HPA axis activity, and it seems to be linked specifically to the event of awakening.
Cortisol awakening response provides an easy measure of the reactivity capacity of the HPA axis.
- Waking up earlier in the morning increases the response.
- Shift work: nurses working on morning shifts with very early awakening (between 4:00–5:30 a.m.) had a greater and prolonged cortisol awakening response than those on the late day shift (between 6:00–9:00 a.m.) or the night shift (between 11:00 a.m.–2:00 p.m.). However another study found that this greater response could be attributed to increased stress and impaired sleep quality before an early work shift ("when these factors were taken into account, the difference in CAR related to experimental condition was no longer significant").
- Naps: students taking a nap of one to two hours in the early evening hours (between 6:45–8:30 p.m.) had no cortisol awakening response, suggesting cortisol awakening response only occurs after night sleep.
- Waking up in the light: cortisol awakening response is larger when people wake up in light rather than darkness.
- Noise: there is no cortisol rise after nights with traffic-like low-frequency noise.
- Alarm clock vs. spontaneous waking: there is no difference on days when people woke up spontaneously or used the alarm clock.
- Aspirin has been found to reduce the response probably through an action upon ACTH.
- Morning types show a larger cortisol awakening response than evening types.
- Those suffering fatigue show a low rise and flat plateau.
- Those in pain: the response is reduced the more people are in pain.
- The lower a person's socioeconomic status, the higher their response. This might link to the material hardship that occurs with low socioeconomic status.
Cortisol awakening response is larger for those:
- Waking up to a working day compared to work-free weekend day.
- Experiencing chronic stress and worry.
- Overloaded with work.
- In acute stress. People taking part in a competitive ballroom dance tournament had an increased cortisol awakening response on the morning of their competition day but not their non-competition one.
- Worn down by burnout: some studies find an increased response, though other researchers find a decreased or normal response.
Cortisol is released from the adrenal glands following activation by ACTH release from the pituitary. The ACTH release creating the cortisol awakening response is strongly inhibited after intake of a low-dose dexamethasone. This is a synthetic glucocorticoid and this inhibition allows the detection of the presence of negative feedback from circulating cortisol that controls to ACTH-secreting cells of the pituitary.
In the hypothalamic-pituitary-adrenal axis the pituitary release of ACTH is regulated by the hypothalamus. This occurs through the hypothalamus's production of the hypophysiotropic hormone corticotropin-releasing hormone, the production of which is subject to circadian influence and the day/night cycle. In the cortisol awakening response, the hypothalamic-pituitary-adrenal axis is controlled by the hippocampus. For example, cortisol awakening response is absent in those with bilateral and unilateral hippocampus damage and hippocampal atrophy. Those with severe amnesia, and thus with presumed damage to the temporal lobe, also do not have it. Those with a larger hippocampus have a greater response.
The function of cortisol awakening response is unknown but it has been suggested to link with a stress-related preparation in regard to the upcoming day by the hippocampus. One hypothesis is: "that the cortisol rise after awakening may accompany an activation of prospective memory representations at awakening enabling individual's orientation about the self in time and space as well as anticipation of demands of the upcoming day... it is tempting to speculate that for the CAR, anticipation of these upcoming demands may be essential in regulating the CAR magnitude for the particular day. The hippocampus is, besides its established role in long-term memory consolidation, involved in the formation of a cohesive construct and representation of the outside world within the central nervous system processing information about space, time and relationships of environmental cues. This puts the hippocampus in a pivotal position for the regulation of the CAR."
- Elder, Greg J.; Wetherell, Mark A.; Barclay, Nicola L.; Ellis, Jason G. (2014). "The cortisol awakening response – Applications and implications for sleep medicine". Sleep Medicine Reviews. 18 (3): 215–224. doi:10.1016/j.smrv.2013.05.001. PMID 23835138.
- Wüst S, Wolf J, Hellhammer DH, Federenko I, Schommer N, Kirschbaum C (2000). "The cortisol awakening response - normal values and confounds". Noise Health. 2 (7): 79–88. PMID 12689474. Archived from the original on 2017-12-01. Retrieved 2009-08-22.CS1 maint: multiple names: authors list (link)
- Fries E, Dettenborn L, Kirschbaum C (April 2009). "The cortisol awakening response (CAR): facts and future directions". Int J Psychophysiol. 72 (1): 67–73. doi:10.1016/j.ijpsycho.2008.03.014. PMID 18854200.CS1 maint: multiple names: authors list (link)
- Hucklebridge F, Hussain T, Evans P, Clow A (2005). "The diurnal patterns of the adrenal steroids cortisol and dehydroepiandrosterone (DHEA) in relation to awakening". Psychoneuroendocrinology. 30 (1): 51–7. doi:10.1016/j.psyneuen.2004.04.007. PMID 15358442. S2CID 24499836.CS1 maint: multiple names: authors list (link)
- Wüst S, Federenko I, Hellhammer DH, Kirschbaum C (2000). "Genetic factors, perceived chronic stress, and the free cortisol response to awakening". Psychoneuroendocrinology. 25 (7): 707–20. doi:10.1016/s0306-4530(00)00021-4. PMID 10938450. S2CID 12858990.CS1 maint: multiple names: authors list (link)
- Tsigos C, Chrousos GP (2002). "Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress". J Psychosom Res. 53 (4): 865–71. doi:10.1016/S0022-3999(02)00429-4. PMID 12377295.
- Wilhelm I, Born J, Kudielka BM, Schlotz W, Wüst S (2007). "Is the cortisol awakening rise a response to awakening?". Psychoneuroendocrinology. 32 (4): 358–66. doi:10.1016/j.psyneuen.2007.01.008. PMID 17408865. S2CID 25044761.CS1 maint: multiple names: authors list (link)
- Schmidt-Reinwald A, Pruessner JC, Hellhammer DH, Federenko I, Rohleder N, Schürmeyer TH, Kirschbaum C (1999). "The cortisol response to awakening in relation to different challenge tests and a 12-hour cortisol rhythm". Life Sci. 64 (18): 1653–60. doi:10.1016/s0024-3205(99)00103-4. PMID 10328525.CS1 maint: multiple names: authors list (link)
- Kudielka BM, Kirschbaum C (2003). "Awakening cortisol responses are influenced by health status and awakening time but not by menstrual cycle phase". Psychoneuroendocrinology. 28 (1): 35–47. doi:10.1016/s0306-4530(02)00008-2. PMID 12445835. S2CID 23846041.
- Federenko I, Wüst S, Hellhammer DH, Dechoux R, Kumsta R, Kirschbaum C (2004). "Free cortisol awakening responses are influenced by awakening time". Psychoneuroendocrinology. 29 (2): 174–84. doi:10.1016/s0306-4530(03)00021-0. PMID 14604599. S2CID 29227742.CS1 maint: multiple names: authors list (link)
- Williams E, Magid K, Steptoe A (2005). "The impact of time of waking and concurrent subjective stress on the cortisol response to awakening". Psychoneuroendocrinology. 30 (2): 139–48. doi:10.1016/j.psyneuen.2004.06.006. PMID 15471612. S2CID 108257.CS1 maint: multiple names: authors list (link)
- Scheer FA, Buijs RM (1999). "Light affects morning salivary cortisol in humans". J Clin Endocrinol Metab. 84 (9): 3395–8. doi:10.1210/jcem.84.9.6102. PMID 10487717.
- Thorn L, Hucklebridge F, Esgate A, Evans P, Clow A (2004). "The effect of dawn simulation on the cortisol response to awakening in healthy participants". Psychoneuroendocrinology. 29 (7): 925–30. doi:10.1016/j.psyneuen.2003.08.005. PMID 15177708. S2CID 14394805.CS1 maint: multiple names: authors list (link)
- Waye KP, Clow A, Edwards S, Hucklebridge F, Rylander R (2003). "Effects of nighttime low frequency noise on the cortisol response to awakening and subjective sleep quality". Life Sci. 72 (8): 863–75. doi:10.1016/s0024-3205(02)02336-6. PMID 12493567.CS1 maint: multiple names: authors list (link)
- Watson S, Horton K, Bulmer S, Carlile J, Corcoran C, Gallagher P, Ferrier IN (2009). "Effect of aspirin on hypothalamic-pituitary-adrenal function and on neuropsychological performance in healthy adults: a pilot study". Psychopharmacology. 205 (1): 151–5. doi:10.1007/s00213-009-1525-4. PMID 19404617. S2CID 7312121.CS1 maint: multiple names: authors list (link)
- Kudielka BM, Federenko IS, Hellhammer DH, Wüst S (2006). "Morningness and eveningness: the free cortisol rise after awakening in "early birds" and "night owls"". Biol Psychol. 72 (2): 141–6. doi:10.1016/j.biopsycho.2005.08.003. PMID 16236420. S2CID 35202187.CS1 maint: multiple names: authors list (link)
- Kumari M, Badrick E, Chandola T; et al. (November 2009). "Cortisol secretion and fatigue: associations in a community based cohort". Psychoneuroendocrinology. 34 (10): 1476–85. doi:10.1016/j.psyneuen.2009.05.001. PMID 19497676. S2CID 35741736.CS1 maint: multiple names: authors list (link)
- Fabian LA, McGuire L, Page GG, Goodin BR, Edwards RR, Haythornthwaite J (2009). "The association of the cortisol awakening response with experimental pain ratings". Psychoneuroendocrinology. 34 (8): 1247–51. doi:10.1016/j.psyneuen.2009.03.008. PMC 2740898. PMID 19375866.CS1 maint: multiple names: authors list (link)
- Wright CE, Steptoe A (2005). "Subjective socioeconomic position, gender and cortisol responses to waking in an elderly population". Psychoneuroendocrinology. 30 (6): 582–90. doi:10.1016/j.psyneuen.2005.01.007. PMID 15808928. S2CID 36466495.
- Ranjit N, Young EA, Kaplan GA (2005). "Material hardship alters the diurnal rhythm of salivary cortisol". Int J Epidemiol. 34 (5): 1138–43. doi:10.1093/ije/dyi120. PMID 15951357.CS1 maint: multiple names: authors list (link)
- Thorn L, Hucklebridge F, Evans P, Clow A (2006). "Suspected non-adherence and weekend versus week day differences in the awakening cortisol response". Psychoneuroendocrinology. 31 (8): 1009–18. doi:10.1016/j.psyneuen.2006.05.012. PMID 16876958. S2CID 42619910.CS1 maint: multiple names: authors list (link)
- Schlotz W, Hellhammer J, Schulz P, Stone AA (2004). "Perceived work overload and chronic worrying predict weekend-weekday differences in the cortisol awakening response". Psychosom Med. 66 (2): 207–14. doi:10.1097/01.psy.0000116715.78238.56. PMID 15039505. S2CID 21210648.CS1 maint: multiple names: authors list (link)
- Steptoe A, Cropley M, Griffith J, Kirschbaum C (2000). "Job strain and anger expression predict early morning elevations in salivary cortisol". Psychosom Med. 62 (2): 286–92. doi:10.1097/00006842-200003000-00022. PMID 10772410. S2CID 1182409.CS1 maint: multiple names: authors list (link)
- Rohleder N, Beulen SE, Chen E, Wolf JM, Kirschbaum C (2007). "Stress on the dance floor: the cortisol stress response to social-evaluative threat in competitive ballroom dancers". Pers Soc Psychol Bull. 33 (1): 69–84. doi:10.1177/0146167206293986. PMID 17178931. S2CID 1430950.CS1 maint: multiple names: authors list (link)
- Grossi G, Perski A, Ekstedt M, Johansson T, Lindström M, Holm K (2005). "The morning salivary cortisol response in burnout". J Psychosom Res. 59 (2): 103–11. doi:10.1016/j.jpsychores.2005.02.009. PMID 16186006.CS1 maint: multiple names: authors list (link)
- De Vente W, Olff M, Van Amsterdam JG, Kamphuis JH, Emmelkamp PM (June 2003). "Physiological differences between burnout patients and healthy controls: blood pressure, heart rate, and cortisol responses". Occup Environ Med. 60 Suppl 1: i54–61. doi:10.1136/oem.60.suppl_1.i54. PMC 1765727. PMID 12782748.CS1 maint: multiple names: authors list (link)
- Pruessner JC, Hellhammer DH, Kirschbaum C (1999). "Burnout, perceived stress, and cortisol responses to awakening". Psychosom Med. 61 (2): 197–204. doi:10.1097/00006842-199903000-00012. PMID 10204973.CS1 maint: multiple names: authors list (link)
- Mommersteeg PM, Heijnen CJ, Verbraak MJ, van Doornen LJ (2006). "Clinical burnout is not reflected in the cortisol awakening response, the day-curve or the response to a low-dose dexamethasone suppression test". Psychoneuroendocrinology. 31 (2): 216–25. doi:10.1016/j.psyneuen.2005.07.003. PMID 16150550. S2CID 8444094.CS1 maint: multiple names: authors list (link)
- Ehrhart-Bornstein M, Bornstein SR, Scherbaum WA (1996). "Sympathoadrenal system and immune system in the regulation of adrenocortical function". Eur J Endocrinol. 135 (1): 19–26. doi:10.1530/eje.0.1350019. PMID 8765968.CS1 maint: multiple names: authors list (link)
- Widmarier, Eric P.; Raff, Hershel; Strang, Kevin T. (2016). Vander's Human Physiology: The Mechanisms of Body Function (14th ed.). New York, NY: McGraw Hill. p. 335.
- Buchanan TW, Kern S, Allen JS, Tranel D, Kirschbaum C (2004). "Circadian regulation of cortisol after hippocampal damage in humans". Biol Psychiatry. 56 (9): 651–6. doi:10.1016/j.biopsych.2004.08.014. PMID 15522248. S2CID 7401473.CS1 maint: multiple names: authors list (link)
- Bruehl H, Wolf OT, Convit A (2009). "A blunted cortisol awakening response and hippocampal atrophy in type 2 diabetes mellitus". Psychoneuroendocrinology. 34 (6): 815–21. doi:10.1016/j.psyneuen.2008.12.010. PMC 2774914. PMID 19167831.CS1 maint: multiple names: authors list (link)
- Wolf OT, Fujiwara E, Luwinski G, Kirschbaum C, Markowitsch HJ (2005). "No morning cortisol response in patients with severe global amnesia". Psychoneuroendocrinology. 30 (1): 101–5. doi:10.1016/j.psyneuen.2004.05.001. PMID 15358447. S2CID 19739260.CS1 maint: multiple names: authors list (link)
- Pruessner M, Pruessner JC, Hellhammer DH, Bruce Pike G, Lupien SJ (2007). "The associations among hippocampal volume, cortisol reactivity, and memory performance in healthy young men". Psychiatry Res. 155 (1): 1–10. doi:10.1016/j.pscychresns.2006.12.007. PMID 17395434. S2CID 31707798.CS1 maint: multiple names: authors list (link)
- Law, Robin; Evans, Phil; Thorn, Lisa; Clow, Angela; Hucklebridge, Frank (2015). "The cortisol awakening response predicts same morning executive function: results from a 50-day case study". Stress. 18 (6): 616–621. doi:10.3109/10253890.2015.1076789. ISSN 1025-3890. PMID 26382884. S2CID 22921488.