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Catecholamines and Environmental Stress

Summary prepared by Ulf Lundberg, Department of Psychology and Centre for Health Equity Studies (CHESS), Stockholm University, for the Allostatic Load notebook. Last revised November, 2008.

Chapter Contents

  1. Background
  2. Catecholamines and Health
  3. Assessment
  4. Methodological Considerations
  5. Gender Differences
  6. Relevance for Allostasis
  7. Conclusion
  8. References

Background

Research on the sympathetic adrenal-medullary (SAM) system has its roots in the work of Walter B. Cannon from the beginning of the 20th century (Cannon, 1914). On the basis of animal experiments, he described the fight-or-flight response, or the emergency function of the adrenal medulla. The SAM system is activated when an individual is challenged in his/her control over the environment (Henry, 1992). Via the hypothalamus and the sympathetic nervous system, psychological stress stimulates the adrenal medulla to secrete the two catecholamines, epinephrine (adrenaline) and norepinephrine (noradrenaline), into the bloodstream. This rapid defence reaction (occurring in less than a minute) prepares the body for battle.

The cardiovascular and neuroendocrine functions activated by the SAM system are aimed at mobilizing energy to the muscles, brain and heart and, at the same time, reducing blood flow to the internal organs, skin and gastro-intestinal system. In response to physical threat, this is an efficient means of survival as it increases the organism's capacity for fight or flight. Today, however, the SAM system is more often challenged by threats of a social or mental nature rather than a physical one. Elevated blood pressure and heart rate and the release of glucose and free fatty acids into the bloodstream in mentally stressful but sedentary work will be harmful to the body, particularly the cardiovascular system. However, short-term activation of this system is often necessary for adequate coping with environmental demands and for the protection of the body, whereas intense, repeated and/or sustained activation of this psychobiological program in response to psychosocial demands may cause stress-related disorders and is relevant for allostasis.

Numerous studies based on laboratory experiments as well as various natural settings illustrate the sensitivity of the SAM system to various psychosocial conditions, such as daily stress at work, home, school, day care centres or hospitals, on commuter trains or buses, etc. (see reviews by Mason, 1968; Levi, 1972; Henry & Stephens, 1977; Ursin et al., 1978; Frankenhaeuser 1971; 1983; Usdin et al., 1980; Lundberg, 1984, 2005).

Catecholamines and Health

The catecholamines and their concomitant effects on other physiological functions, such as blood pressure, heart rate and lipolysis, may serve as objective indicators of the stress an individual is exposed to. However, these bodily effects are also assumed to link psychosocial stress to increased health risks. Long-lasting elevated catecholamine levels are thought to contribute to the development of atherosclerosis and to predispose to myocardial ischemia (Karasek et al., 1982; Krantz & Manuck, 1984; Rozanski et al., 1988; Yusuf et a., 2004). The elevated catecholamine levels also make the blood more prone to clotting, thus reducing the risk of heavy bleeding in case of tissue damage but, at the same time, increasing the risk of arterial obstruction and myocardial infarction.

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Less is known about the role of the catecholamines in other health problems. However, in the study of psychosocial aspects of musculoskeletal disorders (e.g., Moon & Sauter, 1996), it is generally assumed that psychological stress plays an important role by influencing various bodily functions including muscle tension and, thus, forms a link to neck, shoulder and back pain problems (Lundberg & Melin, 2002). For example, Schleifer & Ley (1994) have suggested that stress contributes to hyperventilation, reduced end-tidal PCO2, increased blood pH level and muscle tension and makes the muscles more sensitive to catecholamines. In keeping with this, jobs with a high prevalence of musculoskeletal disorders, such as repetitive assembly-line work, are characterized by elevated sympathetic arousal (cf. Table 3) and slow unwinding after work (Johansson et al., 1978; Melin et al., 1999). In addition, in laboratory experiments (Lundberg et al., 1994; Krantz et al., 2004), positive correlations have been found between blood pressure, norepinephrine and mentally induced EMG activity of the trapezius muscle. A link between high epinephrine levels and low socioeconomic status has recently been demonstrated by Cohen et al. (2005).

Assessment

A small but relatively constant fraction of the circulating levels of epinephrine and norepinephrine in the blood is excreted into the urine (Frankenhaeuser, 1971; Levi, 1972). Consequently, assessment can be made using blood (usually plasma) as well as urine. However, whereas epinephrine is mainly produced by the adrenal medulla, the major part of the circulating norepinephrine is produced by sympathetic nerve endings. Studies comparing urinary levels with corresponding hormone determinations in plasma are scarce, but available data indicate a significant positive relationship between changes in urinary and plasma catecholamines (Åkerstedt et al., 1983; Steptoe, 1985).

For obvious reasons, plasma reflects short-term and acute stress responses more readily than urinary measurements do. Urinary values provide integrated measurements for extended periods of time (usually an hour or more), which is an advantage in the study of long-term (chronic) psychosocial stress (Baum et al., 1985). Additional advantages of urinary measurements in the study of psychosocial stress are that urine samples are relatively easy to collect, and in field studies they do not interfere with the subject's normal habits and environment and cause no harm or pain. The characteristics of plasma and urine measurements are summarized in Table 1.

Table 1. Characteristics of Catecholamine Assessment in Urine and Blood (Plasma)

Urinary measurements
  • Cause no pain or harm
  • Do not influence the individual's normal behaviour or environment
  • Relatively easy to collect
  • Integrated measurements are obtained for longer periods of time
Blood measurements
  • Can be obtained at short intervals
  • Can be experienced as unpleasant and influence catecholamine output
  • May affect the normal work situation
  • A trained nurse is needed
Summary of advantages (+) and disadvantages (-) in different types of studies
  Urine Plasma
Acute stress
Chronic stress
Laboratory experiments
Field studies
-
+
0
+
+
-
+
-

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The amount of urinary catecholamines excreted during a particular period of time can be determined from the concentration in the sample, multiplied by total urine volume, or by relating the concentration to a reference substance such as creatinine excretion. Provided that reliable measurements are obtained and the subject is able to empty his/her bladder completely, the results from the different methods are almost identical. The catecholamines can be determined using high performance liquid chromatography with electrochemical detection (Lundberg et al., 1988; Hjemdahl et al., 1989).

Methodological Considerations

The catecholamines have a pronounced diurnal pattern, which has to be considered in the assessment of the stress response. Under normal sleep/wake conditions, the catecholamines peak in the middle of the day and reach their lowest levels during night sleep. Epinephrine has an endogenous pattern that remains relatively stable, even during several nights of sleep deprivation (Åkerstedt, 1979), whereas norepinephrine is more influenced by physical activity. Consistent changes in the sleep/wake pattern, e.g., habitual night work, will completely reverse the circadian rhythm of the catecholamines in about a week. Other non-psychological factors influencing catecholamine secretion are the intake of caffeine (coffee), alcohol and nicotine (cigarette smoking), medication (beta blockers, diuretics, etc.) and heavy physical exercise (Table 2).

Table 2. Non-psychological Factors Influencing Catecholamine Levels

Of great importance
  • Circadian rhythms (time of day)
  • Nicotine (e.g., cigarette smoking)
  • Caffeine (coffee, tea)
  • Medication (beta blockers, diuretics)
Of some importance
  • Phase of menstrual cycle
  • Gender
  • Body weight
  • Food intake

The increase in catecholamine levels in the blood occurs within minutes in response to an acute stressor and may vary considerably depending on the mental and physical load on the individual. Individual variations in baseline levels are also pronounced. The highest epinephrine level in a random sample of individuals may be ten times greater than the lowest. However, individual catecholamine levels are relatively stable over time (Forsman & Lundberg, 1982). During mild stress, epinephrine output increases to about 2-3 times the resting level, whereas during more severe stress, e.g., childbirth (Alehagen et al., 2005), mean epinephrine levels rise to 8-10 times the corresponding level of a day during pregnancy, or much more in individual cases. There are no "normal" catecholamine levels, although pathological levels can be found in association with adrenal tumours, for example.

In order to reduce the influence of circadian rhythms and individual differences in baseline levels, it is recommended to express individual responses to stress in relation to a person's corresponding baseline level obtained during relaxation at the same time of the day on another day. Thus, percent change from baseline is usually a more relevant measure than absolute levels.

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Gender Differences

In stress research, like in many other research areas, most studies have been performed on men. However, in the early 1970s, investigators in Marianne Frankenhaeuser's group in Stockholm started to compare stress responses of males and females. In these early studies of sex differences in psychophysiological stress responses, it was consistently found that women were less reactive than men in terms of epinephrine secretion during experimental stress (e.g., Frankenhaeuser, Dunne & Lundberg, 1976; Johansson, 1972). Although women performed as well or usually even better than men on the various stress tests, they did not increase their epinephrine secretion much. However, during more intense stress such as a stressful examination (Frankenhaeuser, Rauste von Wright et al., 1978), female students were found to increase their epinephrine output significantly but, still, to a lesser extent than male students did.

A possible explanation for these sex differences is that performance stress is less challenging to women than to men. Emotional stress, for example induced in parents when accompanying their child to a health check-up at the hospital, has been found to have a more pronounced effect on catecholamine levels in women (mothers) than men (fathers) (Lundberg, de Château, Winberg & Frankenhaeuser, 1981). In addition, women in less traditional roles, for example female students in male-dominated lines of education, seem to respond to performance stress with the same epinephrine output as their male colleagues do (Collins & Frankenhaeuser, 1978). Studies comparing men and women matched for education and occupational level show that women may respond with as much epinephrine output at work and during experimental stress as men do (Lundberg, 2005). However, women's stress levels, but not men's, have been found to remain elevated even after work (Frankenhaeuser et al., 1989; Lundberg & Frankenhaeuser, 1999).

Although the possible influence of biological factors such as steroid sex hormones on catecholamine responses cannot be excluded (Wasilewska, Kobus and Bargiel, 1980; Tersman, Collins and Eneroth, 1991), it seems as if psychological factors and gender role patterns are more important than biological factors for the sex differences in catecholamine responses. For example, oestrogen replacement therapy did not significantly influence catecholamine responses in women during experimental stress (Collins et al., 1982), and women with elevated testosterone levels did not differ in catecholamine responses from women with normal levels (Lundberg et al., 1983).

In men, a significant positive correlation is usually found between perceived stress and physiological responses at work (e.g., Lundberg, Granqvist, Hansson, Magnusson & Wallin, 1989; Frankenhaeuser et al., 1962; Frankenhaeuser et al., 1989). However, in women, physiological stress levels at work seem to spill over into non-work situations (Rissler, 1977; Frankenhaeuser et al., 1989; Lundberg, 1996; Lundberg & Frankenhaeuser, 1999). This interaction between stress from paid employment and unpaid work at home is important to consider in the study of women's stress.

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Relevance for Allostasis

Epinephrine levels are significantly elevated by overstimulation as well as understimulation, compared to more optimal environmental conditions (Frankenhaeuser et al., 1971; Levi, 1972; Frankenhaeuser & Gardell, 1976). Work overload, a very fast work pace, too much responsibility and role conflicts as well as simple, monotonous and repetitive jobs or a lack of meaningful activities (e.g., unemployment) may contribute to elevated epinephrine levels.

The acute response ("phasic" elevation, according to Ursin et al., 1978) to a novel environmental situation diminishes as the individual habituates but, in contrast to cortisol levels which seem to return to baseline (Pollard, 1995), catecholamine levels remain chronically elevated during normal work conditions also ("tonic" elevation, according to Ursin et al., 1978).

One example of an adequate or economic response to mental stress is presented in Fig. 1 (Forsman, 1983), which shows the epinephrine changes of healthy male students during successive periods of experimental stress and rest in the laboratory. The subjects were able to return to their baseline level each time the stress exposure ended.

Fig. 1. Epinephrine output (pmol/min) during successive periods of rest and experimental stress (based on Forsman, 1983).

Another example is shown in Fig. 2, illustrating the epinephrine output of 50 women giving birth to their first child (Alehagen et al., 2001). Despite a more than 500 percent increase during labour and pushing, the epinephrine levels had returned to the pregnancy levels after a couple of days.

Fig. 2. Epinephrine output of 50 women giving birth to their first child (Alehagen et al., 2001).

Epinephrine output of 50 women giving birth to their first child

Lack of unwinding (norepinephrine) among female managers after a day at work compared to their male colleagues, has been found in two studies (Frankenhaeuser et al., 1989; Lundberg & Frankenhaeuser, 1999). This gender difference was found mainly in women with children at home, whereas in men the presence of children at home did not influence their stress hormone levels. Fig. 3 shows positive correlations between catecholamine levels at work and at home in women but not in men (Frankenhaeuser et al., 1989).

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Fig. 3. Correlation between catecholamine levels at work and in the evening at home in women and men (based on Frankenhaeuser et al., 1989).

Correlation between catecholamine levels at work and in the evening at home in women and men

Rissler (1977) found that a period of overtime (on Saturdays) at work during a period of several weeks influenced the epinephrine levels in the evening (measured on Wednesdays) in female white-collar workers. Lundberg and Palm (1989) found that overtime at work was correlated with epinephrine output during the weekend at home in full-time employed mothers, but not fathers, of preschool children. It is of interest to note that Alfredsson et al. (1985) found that overtime at work was associated with an elevated risk of myocardial infarction in women but not in men.

Whereas epinephrine output is influenced mainly by mental stress, norepinephrine is more sensitive to physical activity and body posture. Comparisons of work stress in blue and white-collar workers are consistent with experimental findings as shown in Table 3, where data from a series of real-life studies are summarized. It is shown that male and female managers, and male and female clerical workers, increase their epinephrine but not their norepinephrine levels at work, whereas assembly workers and supermarket cashiers increase both their epinephrine and norepinephrine levels compared to their normal resting levels (=100). The physical activity of the white-collar workers is probably too low to influence norepinephrine output.

Table 3. Catecholamine Responses in Different Occupations (Increase from Non-work Level)

    Epinephrine Norepinephrine
Managers men
women
++
+
+
0
Clerical workers men
women
+
++
0
0
Assembly workers men
women
++++
++
++
++
Assembly-line workers men +++ ++++
Cashiers women +++ +++
+ < 25%, ++25<50%, +++50<75%, ++++75<100%

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Considering the various cardiovascular and metabolic functions influenced by the catecholamines, this means that blue-collar workers in general are exposed to a greater total physiological load than white-collar workers are. In addition, workers in repetitive jobs seem to have difficulties unwinding after work, i.e., their physiological arousal remains elevated at least one to two hours after work compared to the rapid unwinding of workers in more flexible jobs (Johansson et al., 1978; Lundberg et al., 1993; Melin et al., 1999). This means that workers in simple, monotonous and repetitive jobs not only have to pay a greater physiological toll at work but also have less chance for relaxation and recovery off the job (Melin & Lundberg, 1997). Physical stressors at work such as noise may further contribute to the total load on blue-collar workers (Glass & Singer, 1972). This pattern of catecholamine responses is also consistent with the association between low SES and high catecholamine levels reported by Cohen et al. (2005).

In view of traditional gender differences in responsibility for unpaid work at home (Hall, 1990; Kahn, 1991; Lundberg et al., 1994), the long-term health risks for women in repetitive work seem to be of particular importance (Repetti et al., 1989; Rodin & Ickovics, 1990; Frankenhaeuser et al., 1991; Lundberg 2005).

Conclusion

Catecholamine responses are strongly related to the intensity of mental stress regardless of its emotional valence. This was demonstrated in early experiments by Levi (1965), in which participants were exposed to films with contrasting emotional content, and by Lundberg et al. (1991/92) who found elevated epinephrine levels in five-year-old preschool children watching funny movies at their day care centre. Thus, elevated catecholamine levels reflect negative stress as well as strong positive emotions.

Urinary catecholamines are particularly useful in the study of occupational psychosocial stress as they reflect the mean stress levels for longer periods of time and do not cause pain or discomfort to the participants. In addition, catecholamines are linked to certain health problems such as cardiovascular disorders.

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