The stress hormones epinephrine and cortisol are produced by the pituitary gland.

Neuroendocrine

Cortisol levels and hypothalamic–pituitary axis function have also been extensively studied in various anxiety disorders and anxiety in general. Findings regarding basal cortisol levels in various anxiety disorders have been mixed, with reduced cortisol levels in PTSD representing the only relatively consistent finding [Bandelow et al., 2017]. However, atypical cortisol responses in response to stressors or anticipated stressors have been observed in some studies, particularly with phobias. Nonetheless, a lack of measurable cortisol response differences between control and anxiety disorder subjects has frequently been reported as well [Bandelow et al., 2017]. There is also limited evidence linking anxiety disorders to immune responses and inflammatory medical conditions, including cardiovascular disease.

Abstract

Cortisol is generally acknowledged as “the stress hormone,” and therefore, it plays an important role in human adaptation at different levels. In this chapter, we first instruct you on how to get your dream job by focusing on cortisol research. We then present theories and empirical evidence to support a proposed framework [i.e., cortisol–performance framework] for explaining the role of cortisol in performance under pressure. We review factors at the state [e.g., cognitive appraisal] and trait [e.g., emotional intelligence] levels that account for cortisol changes, and we then present the known effects of cortisol on cognition and motor performance. Finally, we discuss the theoretical foundations of the framework, as well as potential applications. Throughout the chapter, we use the sports domain as a showcase to explain performance in competitive settings.

Cortisol

Cortisol, the most important and abundant glucocorticoid, is essential for proper water, carbohydrate, protein, and fat metabolism, and without this hormone, animals die within a week. In addition to these functions, cortisol is also important for the regulation of vascular reactivity, immune cells and inflammatory mediators, and cellular transcription processes. In addition to having a diurnal rhythm under pleasant relaxed conditions, the hypothalamic anterior pituitary system acts to increase circulating cortisol in response to unpleasant or potentially unpleasant stimuli. Although the reason is not well understood, the ability to withstand noxious stimuli is critically reliant on cortisol. In humans, there is far more cortisol than ACTH measured in the periphery, with a ratio of 7:1. Stimuli which activate ACTH secretion also elevate cortisol, and it is cortisol which is more readily measured in the periphery.

Although ACTH and cortisol are considered to be under strong circadian control, sleep loss and other behaviors do influence portions of the amplitude and shape of the curve. For example, waking causes a surge of ACTH and cortisol. This increase in ACTH is not simply a response to rising, but may also play a role in preparing for rising in that it has been shown that the anticipation of an earlier than normal awakening causes ACTH to rise earlier. Cortisol is also influenced by meals, the first morning exposure to light, stress, and noxious and other stimuli.

During sustained extended wakefulness under controlled laboratory conditions, an increase in the nadir of cortisol during total sleep deprivation has been observed. An afternoon elevation of cortisol has also been described under conditions of sustained reduced sleep. Although the significance of these modifications to the cortisol rhythm under conditions of insufficient sleep is not completely understood, it is known that during aging the nadir of cortisol increases, leading some to consider sleep loss a model of aging.

Cortisol levels are increased in depression and also have been seen to be elevated in individuals suffering from sleep disturbance. Sleep that is disturbed, either by sleep disorders such as sleep apnea or insomnia or disrupted by experimental means that cause fragmentation of the nocturnal sleep period, may lead to blunted GH and an elevated afternoon and early nighttime cortisol secretion.

Cortisol production in health

Cortisol production from the adrenal glands occurs in response to ACTH secretion from the pituitary, which in turn is secreted after stimulation by corticotropin-releasing hormone [CRH] and also by vasopressin [AVP] from the hypothalamus.

There is a clinical spectrum associated with ACTH deficiency. With severe deficiency, patients present with features of marked hypotension, oliguria, and deranged electrolytes. In other circumstances, patients may have adequate HPA axis function for day-to-day health, but lack the reserve to increase cortisol levels in times of stress, such as surgery, trauma, or sepsis. Whilst this latter group of patients may not need long-term replacement of hydrocortisone, they must be aware of the need to introduce “sick-day” hydrocortisone in the case of intercurrent illness or physiologic stress.

It is important to note that there can be considerable variation in serum cortisol measurements between laboratories, according to the assays utilized and their methodology [Clarke et al., 1998]. Comparison of cortisol responses between different laboratories can therefore be difficult. When measuring a serum cortisol level, this refers to the total cortisol level, the majority of which is bound to cortisol-binding globulin [CBG] in the serum and therefore biologically inactive. Only 5–10% of cortisol is in the free and biologically active form. Serum cortisol measurements are therefore affected by changes in CBG level, and this is increased in pregnancy, or with oral estrogen therapy. Oral estrogen should therefore be discontinued where possible, at least 6 weeks prior to evaluation of the HPA axis, as the induction of CBG will artificially increase the total cortisol level. As well as CBG, around 15% of cortisol is bound to albumin and as such, testing can be more complex in patients with disorders affecting their albumin, such as nephrotic syndrome or hepatic cirrhosis. Salivary cortisol is a surrogate marker for serum free cortisol and is a potential means of minimizing the effect of estrogen therapy on CBG [Laudat et al., 1988].

5.4.2 Cortisol

Cortisol is a hormone that is released by the adrenal cortex, which is found on the perimeter of the adrenal glands, which in turn are located just above the kidneys. The release of cortisol is triggered by physical or psychological stress. The function of cortisol is to prepare the body for action in response to stress, and among its effects are an increase in blood pressure, an increase in blood sugar, and a suppression of the immune system. As with testosterone levels, researchers have been interested in examining whether individual differences in cortisol levels are associated with personality differences. Some research has suggested that lower cortisol levels may be associated with “callous-unemotional” personality traits in boys but not in girls [Loney, Butler, Lima, Counts, & Eckel, 2006]. However, this result remains tentative, as there have not yet been any studies of cortisol/personality links based on large samples and examining the major dimensions of personality.

Cortisol

Cortisol is one of the few hormones essential for life. It is termed as “glucocorticoid” and regulates the activity of the hypothalamus and pituitary by negative feedback effects [Mitrovic cited in Boron & Boulpaep, 2002]. Peripheral cortisol levels have a circadian rhythm peaking in the morning and decreasing in the evening, with the lowest levels during early sleep cycles. Stress of various types causes activation of PVN, resulting in peaks of cortisol levels superimposed on the usual rhythm [Herman, Flak, & Jankord, 2008]. Approximately 75% of the cortisol in the circulation is bound to a plasma protein named transcortin or corticosteroid-binding globulin. Another 15% is bound to albumin, and the remaining 10% is “free.” It is the free cortisol that is biologically active. Transcortin is produced by the liver and stimulated by estrogens.

Plasma transcortin levels increase during pregnancy. As a result, more cortisol is bound, free cortisol concentration decreases, and ACTH secretion increases. Cortisol production then increases until the free cortisol concentration returns to normal. For this reason, pregnant women have elevated blood cortisol levels but do not have symptoms of glucocorticoid excess. The same phenomenon occurs in women taking estrogen-containing oral contraceptives [Mitrovic cited in Boron & Boulpaep, 2002].

Cortisol has many effects including anabolic effects on the liver and catabolic effects [proteolysis and lipolysis] at several sites including muscle, adipose tissue, connective tissue, and lymphoid tissue. Cortisol increases glucose output by the liver, and glucose uptake by muscle, adipose, and other tissues decreases. As a result, blood glucose increases. These actions are mechanisms to mobilize energy sources [amino acids, fatty acids, and glycerol] from some tissues to provide energy, particularly glucose, for the brain and heart. Other hormones, particularly insulin, may counterbalance the metabolic effects of glucocorticoids. Insulin secretion is stimulated by the rise in blood glucose [Herman et al., 2008].

Cortisol inhibits ACTH secretion both at the hypothalamus and at the pituitary levels. It is the free cortisol that is responsible for the inhibition. In addition to its effects on the organs and tissues directly involved in metabolic homeostasis, cortisol influences a number of other organs and systems. Cortisol maintains the responsiveness of vascular smooth muscle to catecholamines and, therefore, participates in blood pressure regulation. Glucocortoicoids inhibit the inflammatory response to tissue injury. For example, cortisol [and all known glucocorticoids] suppresses synthesis and decreases the release of arachnidonic acid, the key precursor for a number of mediators of inflammation [e.g., prostaglandins and leucotrienes]. It also decreases circulating T4 lymphocytes, proliferation of local mast cells, stabilizes lysosomes, and decreases production of platelet-activating factor and nitric oxide. All of these effects suppress local inflammatory response [Spiga, Walker, Terry, & Lightman, 2011].

Comparison with Cortisol Levels in Blood

Because cortisol is a small [molecular weight, MW, 362] and highly lipid-soluble molecule, the unbound hormone can pass easily through the lipid-bilayer membranes of nucleated cells. This allows free cortisol to appear in all bodily fluids, including blood, cerebral spinal fluid, urine, sweat, semen, and saliva. Cortisol bound to carriers is usually excluded from these body compartments.

Most important for stress research, cortisol levels measured in saliva agree very well with the amount of free cortisol in blood. Correlations between salivary and unbound blood cortisol levels usually explain more than 80% of the total variance observed [r ≥ 0.90]. This high agreement is due to the fact that cortisol enters the cell and the oral cavity mainly by passive diffusion. It is therefore independent of transport mechanisms and saliva flow rate, in contrast to other components also found in saliva [e.g., immunoglobulin A and catecholamines]. Absolute levels of free cortisol are lower in saliva due to a relative abundance of the cortisol-metabolizing enzyme 11-β hydroxysteroid dehydrogenase.

The Moderating Role of Cortisol

Cortisol, like testosterone, is a steroid hormone. Cortisol is known primarily for its role in the physiological stress response via activation of the hypothalamic–pituitary–adrenal axis [HPA-axis]. The HPA-axis consists of the series of communications between the hypothalamus and the pituitary and adrenal glands. When the hypothalamus receives information that there is a threat in the environment, it relays a signal via the pituitary gland to the adrenal gland, which releases cortisol, as well as other hormones such as epinephrine and norepinephrine. The resulting stress response causes physiological changes which include increased respiration, heart rate, blood pressure, and blood glucose levels. These changes are all intended to prime the organism to physically respond to the threat by facilitating fight or flight behaviors. Unlike the catecholamines [i.e., epinephrine and norepinephrine], cortisol is able to pass through the blood–brain barrier, making it the primary behavioral influence during active stress responses. As such, cortisol has been shown to have not only physiological effects, but psychological and behavioral effects as well.

Not only is cortisol linked to the experience of stress, but it has been linked to approach and avoidance behaviors as well. Approach motivation is conceptualized as a broad system motivating behavior toward desirable and rewarding outcomes. Avoidance motivation, on the other hand, is a parallel system that motivates an individual to behave in ways that facilitate moving away from undesirable outcomes. Essentially, high approach motivation is characterized by appetitive behaviors and sensitivity to reward, whereas avoidance motivation is characterized by avoidant behaviors and sensitivity to punishment. High levels of cortisol have been found to correspond to behavioral inhibition, shyness, and introverted behavior, all avoidance motivation behaviors. Low levels of cortisol, on the other hand, have been found to correspond to extraverted and disinhibited behaviors, more approach-motivated behaviors.

Cortisol has been shown to play a moderating role between testosterone and behavior. Namely, high cortisol levels can suppress the action of testosterone. Given what we know about the relationship between testosterone and dominance behaviors, combined with the moderating role of status-relevant situational cues, the impact of cortisol provides yet another important factor underlying the manifestation of social competition. Testosterone is the underlying force driving social competition, but certain psychological [e.g., need for power] and situational [e.g., status threat] conditions must be met for testosterone to be manifested behaviorally. In addition to these conditions, testosterone's behavioral manifestation also depends on low levels of basal cortisol.

For instance, research shows that basal cortisol and basal testosterone interact to significantly predict individual differences in overt aggression among adolescent males, such that testosterone and aggression are related only when the individual also has low levels of cortisol. When cortisol is high, testosterone and aggression are unrelated. Furthermore, the effects of testosterone on competition and leadership behaviors are also only expressed when basal cortisol is low. For instance, when cortisol is low, basal testosterone predicts whether or not an individual will continue competing or will withdraw from competition after having been defeated once. Specifically, high basal testosterone motivates an individual to recompete after a loss, while low basal testosterone motivates withdrawal to avoid further losses, but this effect is only observed if basal cortisol is low. When cortisol is high the effects of testosterone following a defeat are suppressed. This cortisol–testosterone interaction effect can even be extended to other dominance-relevant situations, such as leadership. Once again, basal cortisol moderates the effect of testosterone on behavior, such that when cortisol is low, the higher an individual's basal testosterone, the more dominant their behavior will appear to others. This behavioral effect of testosterone completely disappears among those leaders who have high levels of basal cortisol.

This moderation suggests that the biological underpinnings of social competition are more complex than a univariate relationship between testosterone and competition. It is not enough to have a testosterone-fueled desire to attain and maintain high status, but one also needs to have an approach motivated social style to act on that desire. Or at the very least, to not have a socially fearful, avoidance motivated behavioral style.

Research on the physiological interaction of testosterone and cortisol suggests a number of possible mechanisms for how cortisol is able to moderate the relationship between testosterone and behavior. Just as cortisol is tied to the HPA-axis, testosterone is tied to the hypothalamic–pituitary–gonadal axis [HPG-axis]. The HPG-axis cues the release of testosterone in preparation for reproductive behaviors. These two axes have an antagonistic relationship, that is, when one axis is activated, the other is suppressed. Thus, when the stress response is activated, reproductive behaviors will be suppressed until an organism's physiology has returned to baseline. Cortisol, as well as other glucocorticoids, can also have an impact on the expression of androgen receptors. High levels of glucocorticoids downregulate the expression of androgen receptors. Thus, high levels of cortisol might not affect testosterone levels, but rather affect the degree to which testosterone could influence behavior by regulating the number of available receptor sites for testosterone to bind to.

Cortisol Levels in Response to Stress

Although cortisol levels may be lower at baseline, they may actually be elevated in PTSD relative to comparison subjects when challenged by physiological or psychological stressors. In particular, subjects with PTSD appear to show more anticipatory anxiety to laboratory stressors, which is reflected by increased cortisol levels. These studies provide at least some evidence that the adrenal is capable of producing ample cortisol levels at baseline and in response to stress. In fact, transient increases in cortisol levels are consistent with the notion of a more generalized HPA axis reactivity in PTSD, as reflected by enhanced negative feedback inhibition.

Cortisol – How do Stress Hormones Respond to Dopamine Blockade?

Cortisol is a hormone that is typically associated as a biomarker for stress that has also been shown to be elevated in depression and anxiety. It is also been shown to be elevated overall in schizophrenia. A correlation has been seen between increased negative symptoms, measured by the Scale for the Assessment of Negative Symptoms [SANS], and elevations in cortisol, though overall psychopathology scores, medication dosage, and type of medication needed do not necessarily correlate with cortisol levels. Cognitive symptoms, often considered to be most predictive of future prognosis in schizophrenia, are also correlate severity with increased cortisol levels.

The worsened cognitive symptoms with hypercortisolemia may be related to long-term damage to the hippocampus that is seen with chronic elevations in cortisol. In the primate brain, high concentrations of glucocorticoid receptors are seen in the hippocampus and in the primates given chronic dexamethasone treatment, there is an approximately 30% reduction in size and segmental volumes of the hippocampus over time. Similar effects on the hippocampus are seen in primates exposed to animal paradigms of chronic stress. Schizophrenia patients, even at initial presentation, are known to have structural deficits of the hippocampus.

In a double-blind, randomized, cross-over trial, olanzapine and quetiapine showed decreased cortisol levels compared to haloperidol and placebo. The mechanism behind such a direct action on cortisol is not fully understood, but may be most prominently related to the action on serotonergic receptors, with some contribution from histaminergic or adrenergic blockade. The decreased level of cortisol may relate to the antidepressant and anxiolytic action seen with these agents over the first-generation antipsychotic drugs.