| CATECHOLAMINES
AND ENVIRONMENTAL STRESS
Summary prepared by Ulf Lundberg, Department of Psychology, Stockholm University for
the Allostatic Load notebook. Last revised September, 2003.
Table of Contents
a. Background
b. Catecholamines and health
c. Assessment
d. Methodological considerations
e. Gender differences
f. Relevance for allostasis
g. References
Background
Research on the sympathetic adrenal-medullary (SAM) system
has its roots in the work by Walter B. Cannon in the beginning of this 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
the individual is challenged in its control of the environment (Fig. 1, Henry, 1992). Via
hypothalamus and the sympathetic nervous system, psychological stress stimulates the
adrenal medulla to secrete the two catecholamines, epinephrine (adrenaline) and
norepinephrine (noradrenalin), into the blood stream. This defence reaction prepares the
body for battle.

The cardiovascular and neuroendocrine functions activated by the SAM system are aimed
at mobilizing energy to the muscles and the heart and, at the same time, reducing blood
flow to the internal organs and the gastro-intestinal system. In response to physical
threat, this is an efficient means for survival by increasing the organism's capacity for
fight or flight. Today, however, the SAM system is more often challenged by threats of a
social or mental rather than physical nature. Short term activation of this system is
necessary for adequate coping with environmental demands and for protection of the body,
whereas possible health consequences of intense, repeated and/or sustained activation of
this psychobiological program in response to psychosocial demands is a major objective for
stress research and relevant for allostasis.
Numerous studies from laboratory experiments as well as from various natural settings
illustrate the sensitivity of the SAM system to various psychosocial conditions, such as
daily stress at work, at home, at school, at day-care centers, at hospitals, on commuter
trains, on buses etc. (see reviews by Mason, 1968; Levi, 1972; Henry & Stephens, 1977;
Ursin et al., 1978; Frankenhaeuser 1979; 1983; Usdin et al., 1980; Axelrode and Reisine,
1984; Lundberg, 1984).
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 that an individual is exposed to. However, these bodily
effects are also assumed to link psychosocial stress to increased health risks.
Longlasting elevated catecholamine levels are considered to contribute to the development
of atherosclerosis and predispose to myocardial ischemia (Karasek et al., 1982; Krantz
& Manuck, 1984; Rozanski et al., 1988). 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 infarcfion. The role of the catecholamines in hypertension is also of great
interest (e.g., Nelesen & Dimsdale, 1994).
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, form a link to
neck, shoulder and back pain problems (Lundberg & Melin, 2002). In keeping with this,
jobs with a high prevalence of musculoskeletal disorders, such as repetitive assembly line
work, are characterized by highly elevated sympathetic arousal (cf. Table 3) and slow
unwinding after work (Johansson et al., 1978; Melin et al., 1997). In addition, in a
laboratory experiment (Lundberg et al., 1994), positive correlations were found between
blood pressure, norepinephrine and mentally induced EMG activity of the trapezius muscle.
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 in blood (usually plasma) as well as in 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 indicates a significant positive relationship between changes in urinary
and plasma catecholamines (Akerstedt et al., 1983; Steptoe, 1985).
For obvious reasons, plasma reflects short term stress and acute stress responses more
readily than urinary measurements. 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., 1987). Additional advantages of
urinary measurements in the study of psychosocial stress are that urine samples are
relatively easy to collect, also in field studies, they do not interfere with the
subject's normal habits and environment and they 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 behavior or environment
~Relatively easy to collect
~Integrated measurements are obtained for longer periods of time
Blood measurements
~Measurements can be obtained with 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
+ |
+
-
+
- |
The amount of urinary catecholamines excreted during a
particular period of time can be determined from the concentration in the sample,
multiplied by the 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 are usually determined by high
performance liquid chromatography with electrochemical detection (Lundberg et al., 1988;
Hjemdahl et al., 1990).
Methodological considerations
The catecholamines have a pronounced diurnal pattern which has to be taken into account
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 which remains relatively stable even during
several nights of sleep deprivation (Akerstedt, 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 (betablockers, diuretics) |
Of some importance
~Phase of the 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 10
times greater than the lowest. However, individual catecholamine levels are relatively
stable over time (Forsman & Lundberg, 1982). During mild stress, the epinephrine
output increases about 2-3 times the resting level, whereas during more severe stress,
e.g., during child birth (Alehagen et al., 1999), mean epinephrine levels rise 8-10 times
the resting level, or much more in individual cases. There are no "normal"
catecholamine levels, although pathological levels can be found in association with, e.g.,
adrenal tumours.
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 his/her 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.
Gender differences
In stress research, like in many other research areas, most
studies have been performed on men. However, in the early 1970's, 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
very 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 the male
students did.
A possible explanation for these sex differences is that performance stress is less
challenging to women than to men. Emotional stress has been found to have a more
pronounced effect on catecholamine levels in women (Lundberg, de Châ teau, Winberg &
Frankenhaeuser, 1981) and women in less traditional roles seem to respond to performance
stress with the same epinephrine output as their male colleagues (Collins &
Frankenhaeuser, 1978). More recent studies comparing men and women matched for education
and occupational level show that women may respond by as much epinephrine output at work
and during experimental stress as men do (e.g., Frankenhaeuser et al., 1989).
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.
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.
Relevance for allostasis
Epinephrine levels are significantly elevated by
overstimulation as well as by understimulation compared to more optimal environmental
conditions (Frankenhaeuser et al., 1971; Levi, 1972; Frankenhaeuser & Gardell, 1976).
Work overload, a very high work pace, too much responsibility, and role conflicts as well
as simple, monotonous and repetitive jobs or 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 also during normal work conditions ("tonic"
elevation according to Ursin et al., 1978).
One example of an adequate or economic response to mental stress is presented in Fig. 2
(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.

Another example is shown in Fig. 3, illustrating the epinephrine output of 50 women
giving birth to their first chld (Alehagen et al., 1999). Despite a 500 percent increase
during labor and pushing, the epinephrine levels had returned to the pregnancy levels
after a couple of days.
Fig. 3

Fig. 4

Fig. 4 illustrates the lack of unwinding (norepinephrine) among female managers after a
day at work compared to their male colleagues (Lundberg & Frankenhaeuser, 1999) and,
Fig. 5 shows the correlation between catecholamine levels at work and at home in women and
men (Frankenhaeuser et al., 1989).

Fig. 6 shows how a period of overtime (on Saturdays) at work during several weeks
influenced the epinephrine levels in the evening (measured on Wednesdays) in female white
collar workers (Rissler, 1977). Fig. 7 shows how overtime at work is correlated with
epinephrine output during the weekend at home in full-time employed mothers, but not
fathers, of preschool children (Lundberg & Palm, 1989). It is of interest to note that
Alfredsson et at. (1985) found that overtime at work was associated with elevated risk of
myocardial infarction in women but not in men.


Whereas epinephrine output is mainly influenced 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% |
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. In addition,
workers in repetitive jobs seem to have difficulties to unwind after work, i.e., their
physiological arousal remains elevated at least 1-2 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., 1997). 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).
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 (Rcpetti et al., 1989; Rodin &
Ickovics, 1990; Frankenhaeuser et al., 1991).
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