Cortisol awakening response
Encyclopedia
The cortisol awakening response (CAR) is an increase of about 50% in cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

 levels occurring 20–30 minutes after awakening in the morning in some people. This rise is superimposed upon the late-night rise in cortisol which occurs before awakening. It is thought to be linked to the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

' preparation of the hypothalamic-pituitary-adrenal axis
Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...

 (HPA) to face anticipated stress.

Description

Shortly after awakening, a sharp 38–75% (average 50%) increase occurs in the blood level of cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

 in about 77% of healthy adults, and it occurs in people of all ages. The average level of 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.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. PMID 17408865

Cortisol awakening response provides an easy measure of the reactivity capacity of the HPA axis.

Sleep factors

  • Waking up
    Waking Up
    Waking Up is a solo album by Topper Headon best known as the drummer of The Clash. The album was released by Mercury in 1986 with a cover photograph taken by Tim White. "Leave It to Luck" was released as a single and as part of an EP...

     earlier in the morning increases the response.
  • Shift work
    Shift work
    Shift work is an employment practice designed to make use of the 24 hours of the clock. The term "shift work" includes both long-term night shifts and work schedules in which employees change or rotate shifts....

    : 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 this attributed this greater respose to increased stress and impaired sleep quality before an early work shift
    Shift work sleep disorder
    Shift work sleep disorder is a circadian rhythm sleep disorder characterized by insomnia and excessive sleepiness affecting people whose work hours are scheduled during the typical sleep period...

    .
  • Nap
    Nap
    A nap is a short period of sleep.Nap may also refer to:-Politics:* National Action Party , a political movement* National Action Plan on the Elimination of Child Labour...

    s: 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
    Noise pollution
    Noise pollution is excessive, displeasing human, animal or machine-created environmental noise that disrupts the activity or balance of human or animal life...

    : there is no cortisol rise after nights with traffic-like low-frequency noise.
  • Alarm clock
    Alarm clock
    An alarm clock is a clock that is designed to make a loud sound at a specific time. The primary use of these clocks is to awaken people from their night's sleep or short naps; they are sometimes used for other reminders as well. To stop the sound, a button or handle on the clock is pressed; but...

     vs. spontaneous waking: there is no difference on days when people woke up spontaneously or used the alarm clock.
  • Aspirin
    Aspirin
    Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

     has been found to reduce the response probably through an action upon ACTH.

Individual factors

  • Morning types
    Lark (person)
    Lark is a term used to describe a person who usually gets up early in the morning and goes to bed early in the evening. Other terms are "morning person" and "early bird"....

     show a larger cortisol awakening response than evening types
    Night owl (person)
    Night owl is a term used to describe a person who tends to stay up until late at night. Another name for a night owl is evening person.The opposite of a night owl is an early bird, a lark as opposed to owl, someone who tends to begin sleeping at a time that is considered early and also wakes early...

    .
  • Those suffering fatigue show a low rise and flat plateau.
  • Those in pain
    Pain
    Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

    : the response is reduced the more people are in pain.
  • The lower a person's socioeconomic status
    Socioeconomic status
    Socioeconomic status is an economic and sociological combined total measure of a person's work experience and of an individual's or family’s economic and social position in relation to others, based on income, education, and occupation...

    , the higher their response. This might link to the material hardship that occurs with low socioeconomic status.

Stress

Cortisol awakening response is larger for those:
  • waking up to a working day
    Workweek
    The workweek and weekend are those complementary parts of the week devoted to labour and rest respectively. The legal working week , or workweek , is the part of the seven-day week devoted to labor. In most Western countries it is Monday to Friday. The weekend comprises the two traditionally...

     compared to work-free weekend day.
  • experiencing chronic stress and worry
    Worry
    Worry is thoughts, images and emotions of a negative nature in whichmental attempts are made to avoid anticipated potential threats. As an emotion it is experienced as anxiety or concern about a real or imagined issue, usually personal issues such as health or finances or broader ones such as...

  • 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
    Burnout (psychology)
    Burnout is a psychological term for the experience of long-term exhaustion and diminished interest. Research indicates general practitioners have the highest proportion of burnout cases; according to a recent Dutch study in Psychological Reports, no less than 40% of these experienced high levels of...

    : some studies find an increased though other researchers find a decreased or normal response.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. PMID 16150550

Neurology

Cortisol is released from the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

s 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
Dexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

. This is a synthetic glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

 and this inhibition allows the detection of the presence of negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...

 from circulating cortisol that controls to ACTH-secreting cells of the pituitary.

In the hypothalamic-pituitary-adrenal axis
Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...

 the pituitary release of ACTH is regulated by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

. In the cortisol awakening response, the hypothalamic-pituitary-adrenal axis is controlled by the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

. For example, cortisol awakening response is absent in those with bilateral and unilateral hippocampus damage and hippocampal atrophy
Cerebral atrophy
Cerebral atrophy is a common feature of many of the diseases that affect the brain. Atrophy of any tissue means loss of cells. In brain tissue, atrophy describes a loss of neurons and the connections between them...

. Those with severe amnesia
Amnesia
Amnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause amnesia...

, and thus with presumed damage to the temporal lobe
Temporal lobe
The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....

, also do not have it. Those with a larger hippocampus have a greater response.

It plausible also that the suprachiasmatic nucleus
Suprachiasmatic nucleus
The suprachiasmatic nucleus or nuclei, abbreviated SCN, is a tiny region on the brain's midline, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms...

, the light-sensitive biological clock, plays a role in cortisol awakening response regulation.

Function

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."
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