8.02 Psychophysiological Bases of Disease PDF

Copyright © 1998 Elsevier Science Ltd. All rights reserved.
8.02
Psychophysiological Bases of
Disease
ANDREW STEPTOE
University of London, UK
8.02.1 INTRODUCTION 40
8.02.2 THE PSYCHOPHYSIOLOGICAL RESEARCH FRAMEWORK 41
8.02.2.1 Stress and Coping 41
8.02.2.2 Research Strategies 42
8.02.2.2.1 Animal studies 42
8.02.2.2.2 Mental stress testing 43
8.02.2.2.3 Field studies 43
8.02.2.2.4 Survey studies 44
8.02.2.2.5 Convergence of methods 44
8.02.3 PSYCHOPHYSIOLOGICAL RESPONSES 45
8.02.3.1 Neuroendocrine Parameters 45
8.02.3.1.1 Adrenal steroid stress response 45
8.02.3.1.2 Catecholamines and the sympathetic nervous system 46
8.02.3.1.3 Endogenous opioids 47
8.02.3.1.4 Other neuroendocrine and hormonal responses 47
8.02.3.2 Cardiovascular and Autonomic Parameters 48
8.02.3.2.1 Blood pressure, heart rate, and regional blood flow 48
8.02.3.2.2 Cardiac function 49
8.02.3.2.3 Platelets and hemostasis 50
8.02.3.2.4 Other physiological systems 50
8.02.3.3 Lipids and Glucose Metabolism 51
8.02.3.3.1 Insulin metabolism and abdominal obesity 51
8.02.3.4 Immune Parameters 52
8.02.3.4.1 Regulation of immune function 53
8.02.3.4.2 Acute stress-induced immune responses 53
8.02.3.4.3 Chronic changes in immune function 53
8.02.3.4.4 Functional significance of stress-induced immune modulation 54
8.02.3.5 Adaptive or Destructive? 55
8.02.4 THE NATURE OF PSYCHOSOCIAL DEMANDS 55
8.02.4.1 Life Events, Chronic Stressors, and Daily Hassles 55
8.02.4.2 Characteristics of Psychosocial Demands 56
8.02.4.2.1 Novelty, familiarity, and predictability 56
8.02.4.2.2 Control and lack of control 57
8.02.4.3 Work Characteristics, Control, and Psychophysiological Responses 57
8.02.4.4 Concurrent Stressors 58
8.02.5 RESISTANCE AND VULNERABILITY FACTORS 58
8.02.5.1 Personality and Behavior Patterns 58
8.02.5.1.1 Disease-prone personality and negative affectivity 59
8.02.5.1.2 Anger and hostility 59
8.02.5.1.3 Depression, pessimism, and optimism 60
8.02.5.1.4 Emotional inhibition 60
39
40 Psychophysiological Bases of Disease
8.02.5.2 Social Isolation and Social Support 61

8.02.5.3 Prior Experience of Stressful Events 62
8.02.6 PATHWAYS TO DISEASEÐPREDISPOSING FACTORS 63
8.02.6.1 Nutrition and Exercise 63
8.02.6.2 Advanced Age 64
8.02.6.3 Gender 64
8.02.6.4 Ethnicity 65
8.02.6.5 Socioeconomic Status and Education 65
8.02.6.6 Genetic Factors 65
8.02.6.7 Individual Patterns of Psychophysiological Responses 66
8.02.7 PSYCHOPHYSIOLOGICAL MODELS OF DISEASE 66
8.02.7.1 Physiological Reactivity as a Causal Factor 67
8.02.7.2 Physiological Reactivity as an Inhibitor of Host Resistance and Defense 68
8.02.7.3 Physiological Reactivity as a Disruptive Factor 69
8.02.7.4 Physiological Reactivity as a Trigger of Acute Clinical Events 70
8.02.8 CONCLUSION 70
8.02.9 REFERENCES 70
8.02.1 INTRODUCTION nervous system psychophysiology. Thus the role

of physiological factors in problems such as
All behavioral states and activities are under- depression, panic, or hypochondriasis will not
pinned by variations in physiological activity, be discussed. This does not imply an endorse-
and are associated with specific patterns of ment of Cartesian dualism, or a belief that
autonomic nervous system, neuroendocrine, psychiatric and nonpsychiatric disorders are
and metabolic response. The relationship be- regulated by different processes. Rather it
tween emotional disturbances and physiological reflects the specific expertise that has developed
function has been recognized since the work of within health psychology and behavioral med-
Sherrington, Cannon and their contemporaries icine over recent years. Many of the important
was carried out nearly 100 years ago. One of the medical conditions that concern health psychol-
fundamental concepts underlying clinical health ogists are detailed in later chapters of this
psychology is that psychosocial factors influ- volume. The present chapter therefore concen-
ence the etiology and maintenance of disease trates on general models rather than specific
through perturbation of physiological func- conditions, and problems such as high blood
tions. This chapter will evaluate the empirical pressure (hypertension), diabetes mellitus, and
evidence supporting this concept, and will bronchial asthma are introduced only for
outline the theoretical framework within which illustrative purposes. The arguments here build
psychophysiological or psychobiological pro- on the models of psychophysiological processes
cesses can best be understood. in disease that have been presented in earlier
The range of experimental and clinical publications (Steptoe, 1980, 1984a, 1991).
research relevant to this topic is large, since it The major theme of this chapter is that there
not only includes work on the regulation of is now abundant evidence that psychophysio-
peripheral bodily functions by the brain, but logical processes have a role in a range of
also the distinctive pathological processes medical conditions. However, the nature of this
implicated in individual medical disorders. role is varied, and depends on the stage of the
The chapter begins with a discussion of the development of the disorder, and in the ways
psychophysiological research framework, basic psychophysiological processes interact with
models of stress and coping, and methods of other factors and pathological mechanisms.
investigation and quantification. The nature Psychophysiological processes are implicated as
and pattern of psychophysiological responses is cofactors in medical conditions, rather than
then described, together with an outline of the exclusive etiological agents. As such, their
psychosocial factors that influence the intensity importance varies across medical problems
and duration of these responses. Later sections and between individuals. The era has passed
of the chapter describe how the physiological in which certain diseases might be regarded as
responses elicited by psychosocial factors actu- ªpsychosomatic,º while others were purely
ally affect disease mechanisms and increase biological. Instead, a more fluid concept needs
health risk. to be understood, in which emotion, behavior,
In keeping with the remit of health psychol- and other psychosocial factors play their parts
ogy, the focus is on nonpsychiatric ªmedicalº to a varying extent right across the disease
conditions and on peripheral rather than central spectrum. Exciting possibilities for management
The Psychophysiological Research Framework 41
and prevention in the new models of psycho- Weiner (1992) has eloquently deconstructed
physiological processes are emerging from the the background to Selye's model, and argues
literature. that it arose from the type of animal experiment
that was carried out in the middle decades of the
century. These studies utilized a variety of
8.02.2 THE PSYCHOPHYSIOLOGICAL intense aversive experiences such as anoxia,
RESEARCH FRAMEWORK limb fracture, extreme cold, and exposure to X
rays. They involved potentially life-threatening
Physiological adjustments are associated with
damage, isolated the organism from its social
the entire range of behavioral states from sleep
context, and the stimuli were typically painful,
to vigorous physical exercise. Patterns of blood
unavoidable, and uncontrollable. These intense
flow, pulmonary function, gastrointestinal ac-
experiences, which lacked ecological relevance,
tivity, and so on are adapted to sustain the
masked variations in biological response pro-
motoric, energetic, and metabolic requirements
duced by different contingencies and patterns of
of the organism. For example, acute exercise is
coping. They also led to the belief that only very
accompanied by an increase in pulmonary
profound and overwhelming experiences were
ventilation, heart rate and blood pressure,
likely to generate damaging physiological
preferential blood flow to skeletal muscle, and
change. The remnants of this concept persist
mobilization of energy supplies stored in the
in today's literature with the emphasis placed on
liver and adipose tissue. These responses
the study of major life events at the expense of
maintain adequate glucose supplies to working
milder everyday aversive experiences that may
muscle, and ensure prompt removal of waste
be cumulatively more significant.
products. In the context of disease, the
It is now recognized that stress is a
physiological responses that are particularly
biopsychosocial construct, and cannot be
relevant are those elicited by potential harm.
defined purely in terms of physiological re-
Responses of this kind are typically described as
sponse. The physiological responses are only
psychophysiological stress responses.
part of the profile that include changes at the
affective, behavioral, and cognitive levels as
8.02.2.1 Stress and Coping well. Nor can stress simply be defined as the
response to aversive environmental stimulation
The definition of psychological stress is an or disturbing events. The same situation may
issue that has generated a great deal of produce quite different responses in two people,
discussion and dispute, reflected in the colorful or in one individual on different occasions.
title of the chapter by Engel (1985) Stress is a Most frameworks of contemporary research
noun! No, a verb!, No, an adjective! It has been and clinical practice therefore recognize that
argued that stress is a term that is so misused stress responses arise through interactions
and abused that it be jettisoned altogether as a between demands on the one hand, and
construct of serious scientific value. Never- psychosocial resources on the other. Cohen,
theless, the term has proved difficult to discard, Kessler, and Gordon (1995a), for example, have
if only as a shorthand to help define a valid area defined stress as a process in which ªenviron-
of human experience and clinical importance. mental demands tax or exceed the adaptive
Many of the problems surrounding the capacity of an organism, resulting in psycho-
concept of stress have stemmed from the logical and biological changes that may place
definition put forward by an early pioneer, persons at risk for diseaseº (p. 3).
Hans Selye. His definition of stress as the This process, and the physiological responses
ªnonspecific response of the body to any that may be elicited, is outlined schematically in
demandº gave rise to two major difficulties. Figure 1. The psychosocial demands (or
First, the conditions eliciting stress responses stressors) can be defined as potential or actual
were defined so widely (as ªany demandº) as to threats or challenges to the integrity, survival,
be virtually meaningless. The second difficulty and reproduction of the organism (Weiner,
is that he introduced the idea of an undiffer- 1992). They may be anticipated, and may be real
entiated biological stress response, character- or imaginary. In the field of health psychology,
ized principally by release of the group of the main categories of psychosocial demand are
steroid hormones known as glucocorticoids acute life events, chronic stressors, and day-to-
from the adrenal glands. He failed to appreciate day hassles and irritations. The characteristics
that the activation of neuroendocrine, auto- of these demands that make them particularly
nomic, and immune pathways is delicately potent elicitors of psychophysiological re-
patterned, depending on the precise demands sponses are described in Section 8.02.4.2.
on the organism and the behavioral and Adaptive capacity is operationalized in terms
cognitive coping responses that are mobilized. of resistance and vulnerability factors, and
Psychosocial demands Resistance and

(stressors) vulnerability factors
Life events Coping responses

Chronic stressors Personality
Daily hassles Social supports
Psychobiological
stress response
Autonomic/
Neuroendocrine Immune
metabolic
Cortisol, ACTH Immunoglobulins

Cardiovascular function
Catecholamines White cell counts
Respiration
Beta-endorphin Lymphocyte
Renal function
Testosterone subpopulations
Gastro-intestinal motility
Insulin Cytokines
Fat metabolism,
Hemostasis
Figure 1 Outline of the major physiological elements of the psychobiological stress response.
aspects of people's psychological makeup and 8.02.2.2 Research Strategies

social world that may render them more or less
susceptible. Personality, behavioral coping Before the physiological systems perturbed by
style, and social resources are among the major stressful transactions are detailed, a note about
resistance and vulnerability factors, and their research strategies is needed. The clinical
role is examined in Section 8.02.5. Of course, it literature contains many sceptical comments
must be recognized that although, for conve- about psychosocial factors in disease, typically
nience, demands and adaptive resources are based on negative results emerging from
viewed as distinct categories, they are difficult to particular studies. It is important to recognize
disentangle in practice. For example, social that evidence for a psychophysiological influ-
isolation can be conceptualized both as the ence on disease does not rest with any one study
absence of a social resource or as a chronic or even with a single research paradigm. Rather,
stressor, while close social contact may be the evidence is assembled from a range of study
supportive or the source of major interpersonal types, each with their strengths and limitations.
conflict.
Psychophysiological responses are elicited
8.02.2.2.1 Animal studies
when the organism's adaptive capacity fails to
match demands. Typically, this will be under Experimental studies with animals can docu-
conditions of over-stimulation, but it is con- ment the ways in which pathological changes
ceivable that lack of stimulation may also lead may emerge following exposure to different
to adverse physiological change. The physiolo- types of behavioral environment. Work with
gical responses themselves include adjustment animals allows precise control over genetic
in a number of biological systems, but the most background, rearing, and physical surround-
important for health risk are neuroendocrine, ings; factors that are difficult to regulate in
immunological and autonomically-mediated human studies. Animals can be randomized to
changes in physiological function. different conditions of behavioral stimulation
The Psychophysiological Research Framework 43
for known periods of time, so true experimental challenge. A wide range of mental stress tests are
designs are feasible. Detailed physiological employed, including cognitive and problem-
assessments are practical, as is concurrent solving tasks, emotionally charged interviews,
measurement of central neurochemistry. public speaking tasks, upsetting movies and
As noted above, early work with animals painful stimuli. Mental stress testing has been a
tended to utilize physical insults; some of these dominant paradigm in cardiovascular research,
methods, such as restraint stress, continue to be and has also been utilized to investigate
used (Glavin, Pare, Sandbak, Bakke, & Mur- immune, musculoskeletal, respiratory and neu-
ison, 1994). Subsequently, experiments in which roendocrine responses. Both reactivity and
the behavioral contingencies surrounding phy- recovery effects may be important (e.g., Seeman
sical insults are manipulated have helped to & Robbins, 1994).
tease out the impact of psychological factors The value of mental stress testing has been the
from the effects of pain or tissue damage. There subject of vigorous dispute. Briefly, the advan-
have, for example, been numerous studies tage of mental stress testing is that responses to
comparing controllable and uncontrollable standardized and uniform sets of stimuli can be
electric shocks matched in intensity and dura- monitored under environmentally controlled
tion, and these have demonstrated pronounced conditions, reducing many of the sources of bias
effects of behavioral control (Steptoe & Appels, and individual difference that are extraneous to
1989). However, stressors such as electric shock the investigation. Experimental designs can be
bear no resemblance to threats that animals used with randomization to different condi-
encounter in their natural environments, so the tions, and sophisticated measurement of phy-
value of studies on social challenges has been siological function is possible in clinical settings.
increasingly recognized. Social disruption and The assertion that responses to mental stress
antagonism have been found to influence a tests show poor reproducibility seems not to be
range of physiological responses of potential true provided that care is taken with procedures,
pathological significance including blood pres- although adaptation to repeated exposure may
sure, coronary atherosclerosis (Kaplan, Man- occur (Kamarck et al., 1992). However, there
uck, Williams, & Strawn, 1993), cell-mediated are other limitations. One is that use of
and humorally-mediated immunity (Lauden- standardized stimuli means that conditions
slager & Fleshner, 1994), visceral fat accumula- may be somewhat divorced from everyday life.
tion (Jayo, Shively, Kaplan, & Manuck, 1993), Few people spend much of their lives carrying
and renal function (Von Holst, 1972). out mental arithmetic under time pressure, or
Animal studies have clearly demonstrated having ice packs placed on their foreheads. The
that behavioral stimuli can elicit physiological monitoring of physiological activity during
responses of pathological significance, and have conversation and speech tasks goes some way
also underlined the importance of coping towards evaluating ecologically more relevant
behaviors and social position. However, caution situations. Second, physiological responses to
is required in their interpretation. Situations standardized conditions may not always be
that promote pathophysiological responses in representative of function outside the labora-
some species do not necessarily transfer to tory or clinic.
others, and there are important strain differ-
ences within the species as well (Gilad & Gilad,
8.02.2.2.3 Field studies
1995). The dominant regulatory mechanisms for
important target responses are not necessarily Field studies are naturalistic investigations in
the same in different species. For example, which physiological measures are obtained
glucocorticoids may play a more prominent role while people go about their lives outside the
in regulating immune function under stress in laboratory or clinic. By taking repeated mea-
rodents than in humans, in whom sympathetic sures, it is possible to monitor the pattern of
pathways are salient (see Section 8.02.3.4). response to real-life stressors, or to assess
Finally, it is important not to be swayed unduly associations with fluctuations in behavioral
by superficial similarities between the types of and emotional state. Three types of field study
challenge that provoke pathological responses are relevant to psychophysiological aspects of
in animal models and the demands to which disease. The first involves recording during
humans are exposed. challenging tasks such as parachuting, learning
to fly aeroplanes, or speaking in public (e.g.,
Biselli, Farrace, Amelio, & Fattorossi, 1993;
8.02.2.2.2 Mental stress testing
Van Doornen & Van Blokland, 1992). These
Mental stress testing involves monitoring investigations are closest to laboratory studies
physiological responses in the laboratory or in that they evaluate responses to acute and
clinic during exposure to acute psychological relatively unusual events. The second type of
study involves repeated assessments of physio- work than nonwork day, and the men also
logical parameters as people go about their reported more frequent stress at work. However,
ordinary lives. For example, repeated samples the blood pressure readings were more likely to
of saliva can been obtained over the day and be associated with high physical activity at work
analyzed to measure the profile of cortisol than during nonwork periods, and this may have
release in people exposed to different levels of accounted in part for differences between the
daily stress (Van Eck, Berkhof, Nicolson, & days. Sophisticated analytic procedures are
Sulon, 1996). The third type of field study required to take account of these factors
involves using automated portable (ambula- (Schwartz, Warren, & Pickering, 1994).
tory) apparatus to measure physiological activ-
ity in a relatively unobtrusive fashion from free
8.02.2.2.4 Survey studies
living individuals. For instance, portable elec-
trocardiograms (EKG) and ambulatory blood The last type of study in which psychophy-
pressure monitoring equipment have proved siological processes are evaluated involves
valuable for assessing psychosocial factors measurement of physiological parameters in
related to cardiovascular disease, while electro- epidemiological surveys or in clinical samples.
myographic (EMG) assessments of muscle Typically, the physiological markers are re-
tension in the neck and forehead are feasible corded on a single occasion rather than
for the investigation of headache (Hatch et al., repeatedly, with efforts being made to standar-
1991 Pickering, 1991). dize recording conditions as far as possible. It is
The main advantage of field studies is that sampling of this type that established high blood
they have ecological validity, in that physiolo- pressure and elevated serum cholesterol con-
gical measures are obtained under naturalistic centration as standard risk factors for coronary
conditions of ongoing behavior and emotion. heart disease, and recent years have witnessed
Studies of blood pressure in patients with extension of the methodology to the study of
hypertension suggest that ambulatory measures psychosocial factors. For instance, the relation-
are even more predictive of pathological ship between blood pressure and psychological
progression than are measures taken in the characteristics such as anger has been assessed
clinic (Pickering, 1991). The limits of field in several surveys (Jorgensen, Johnson, Schreer,
measures are essentially technological, but & Kolodziej, 1996). Immune measures derived
developments of instrumentation mean that from single blood samples have been shown to
even rather complex functions such as the be disturbed in people under the chronic burden
dynamics of the filling and contraction of the of caring for dementing relatives (Kiecolt-
heart can now be monitored. Glaser, Dura, Speicher, Trask, & Glaser,
There are, however, a number of factors that 1991). Concentration of fibrinogen, a substance
need to be borne in mind when interpreting these involved in the process of blood clotting, has
data. The first is that field measures are been related to social class, and may contribute
inevitably somewhat disturbing, since people to the socioeconomic gradient in coronary heart
are aware of the apparatus and may modify their disease (Markowe et al., 1985).
behavioral responses. One study of ambulatory Survey studies are valuable in identifying the
blood pressure demonstrated that in compar- biological parameters relevant to the influence
ison with a control day, people were less of psychosocial disturbances on disease risk.
physically active on the measurement day, and Measures from large representative samples can
rested more (Blanchard, Cornish, Wittrock, & be obtained at relatively low cost, prospective
Jaccard, 1990). Second, there are numerous study designs can be employed, and potential
extrinsic influences on physiological function confounders can be taken into account by
that need to be taken into account, including statistical manipulation. However, survey stu-
cigarette smoking, food and caffeine intake, and dies provide limited information about the
patterns of sleep and activity. Perhaps most dynamics of physiological responses, their
problematic is distinguishing physiological re- origins or consequences, and the causal se-
sponses related to physical activity and exertion quences are often difficult to disentangle.
from those elicited by psychosocial factors. For
example, we have recently studied ambulatory
8.02.2.2.5 Convergence of methods
blood pressure monitored from a group of men
during an eight-hour work shift, and a compar- Efforts are increasingly being made to
able nonwork period (Steptoe, Roy, & Evans, integrate the different methods outlined here.
1996). Blood pressure was recorded every hour This trend has been particularly prominent in
using portable apparatus, and ratings of the cardiovascular area, with work on the
activities were made in diaries. As might be interrelationship between responses to mental
expected, blood pressure was higher over the stress testing and ambulatory cardiovascular
Psychophysiological Responses 45
monitoring. The aim has been to discover hypophyseal portal system to the pituitary
whether acute blood pressure responses during where it initiates the synthesis of adrenocorti-
behavioral tasks correlate with blood pressure cotropin (ACTH) and beta-endorphin. The
levels recorded under naturalistic conditions amygdala is in part responsible for stimulating
(Turner et al., 1994). Another example is the CRF in response to stressors, while the
extension of mental stress testing into the hippocampus plays an inhibitory role (McEwen
epidemiological framework, replacing the small & Sapolsky, 1995). ACTH in turn travels
selected samples typical of laboratory studies by through the circulatory system to the adrenal
large-scale evaluations (Carroll, Smith, Shef- glands, where it stimulates production of steroid
field, Shipley, & Marmot, 1995). Developments hormones such as androgens, estrogens, miner-
in instrumentation technology are likely to alocorticoids and glucocorticoids. The most
promote this important trend, since at present important corticosteroid in the stress response is
the results of investigations carried out with the glucocorticoid cortisol (corticosterone in
different study types are often difficult to rodents).
compare directly. Corticosteroid production is regulated
through negative feedback loops to the hippo-
campus, hypothalamus, and pituitary gland.
8.02.3 PSYCHOPHYSIOLOGICAL Corticosteroid receptors in the hippocampus
RESPONSES mediate a fast feedback loop responding to
The psychophysiological responses relevant increases in plasma corticosteroids by inhibiting
to disease are many and varied. Each system has the HPA, while glucocorticoids inhibit CRF
a complex organization involving the integra- biosynthesis in the hypothalamus and ACTH
tion of autonomic, hormonal, and metabolic release in the pituitary through a delayed
regulatory processes. The brain mechanisms feedback circuit that responds to tonic corti-
responsible are also complicated, and several costeroid levels (Checkley, 1996). The dexa-
neurotransmitters are implicated, including methasone suppression test is a method of
serotonin, gamma-aminobutyric acid and do- assessing the feedback loop by measuring the
pamine (Gray, 1995; Williams, 1994). The aim suppression of HPA function with a synthetic
here is to describe the major psychophysiolo- glucocorticoid. Other important regulators of
gical responses currently thought to be relevant the HPA axis are cytokines, peptides released by
to disease, and briefly to outline their regulation activated immune cells that act on the brain
and effects. More detailed accounts will be cited structures involved in corticosteroid release,
where appropriate. Measurement issues will not and these processes will be described in
be discussed, since there are texts directly Section 8.02.3.4 (Besedovsky & Del Rey,
devoted to these topics (Cohen, Kessler, & 1996). Together, the regulatory mechanisms
Gordon, 1995b). ensure that under normal circumstances, corti-
costeroid production is maintained within a
narrow range.
8.02.3.1 Neuroendocrine Parameters Much of the cortisol secreted by the adrenals
is inactive and bound to carriers. Free corti-
8.02.3.1.1 Adrenal steroid stress response
costeroids have a range of actions including
The adrenal steroids known as corticoster- stimulation of glucose production by the liver,
oids have held center stage in research on the release of free fatty acids from adipose fat
psychophysiological aspects of disease for many stores, the modification of water balance,
decades, largely as a result of Selye's work. alteration in vascular tone and the excretion
There is, however, a growing feeling among of sodium by the kidney, the promotion of anti-
investigators that this emphasis may be mis- inflammatory responses, and immunoregula-
placed, originating as it does in rodent biology. tory effects. Disruption of corticosteroid output
In humans, the sympathetic nervous system and during stress responses may have a variety of
the catecholamines may be more important as adverse effects such as the elevation of lipid
mediators of peripheral physiological dysfunc- concentration in the bloodstream (which may in
tion. Nonetheless, there is no doubt about the turn be incorporated into atherosclerotic pla-
extensive effects of corticosteroid release. que), deposition of fat in abdominal adipose
Corticosteroids are produced by the cortex of tissue, the suppression of some immune func-
the adrenal glands as a result of activity in the tions, decalcification of bone, and impaired
hypothalamic±pituitary±adrenal (HPA) axis. fertility (Sapolsky, 1992; Weiner, 1992). There is
Neurosecretory neurons in the paraventricular evidence that blood pressure increases with
nuclei of the hypothalamus contain a peptide glucocorticoid stimulation, and cardiovascular
called corticotropin releasing factor (CRF), reactivity to sympathetic nervous stimulation is
which is transported through the hypothalamic enhanced (Whitworth, Gordon, Andrews, &
Scoggins, 1989). Within the central nervous 8.02.3.1.2 Catecholamines and the sympathetic
system, sustained elevation of glucocorticoid nervous system
concentration may lead to damage of the
hippocampus, attenuating the hippocampal The autonomic nervous system is the branch
inhibition of CRF production. Increased levels of the nervous system that regulates the function
of glucocorticoids are associated with clinical of visceral organs, and has two divisions, the
depression, and may promote hippocampal sympathetic and the parasympathetic. Many
atrophy in humans (Holsboer & Barden, 1996). tissues are dually innervated, with stimulation
Increased cortisol has been observed under a of the sympathetic and parasympathetic nerves
range of acutely challenging conditions in having opposite effects. For instance, heart rate
humans and animals. Early work in this area accelerates under sympathetic stimulation and
was reviewed by Mason (1968) who did much to slows with parasympathetic (vagal) stimulation.
dispel the notion that corticosteroid production The major neurotransmitter in the sympathetic
bears a simple linear association with the nervous system is norepinephrine (noradrena-
emotional distress. Increased cortisol in the line) while acetylcholine is released from
blood, urine, and saliva is found in response to parasympathetic nerve terminals.
mental arithmetic, speech tasks, simulated The sympathetic nervous system tends to
driving, and other challenges (e.g., Kirschbaum induce activation in many tissues, so the second
et al., 1995; Seeman et al., 1995). Chronic stress major component of the psychophysiological
in animals has been shown to lead to a reduction stress response is the sympathetic-adrenome-
in the number of corticosteroid receptors in the dullary (or sympathoadrenal) system. Norepi-
hippocampus, impairment of central nervous nephrine is stored in granules in the sympathetic
system inhibition of the HPA, and hypertrophy nerve terminals, and is released when these
of the adrenal glands (Herman, Adams, & nerves are stimulated. Much of the neurotrans-
Prewitt, 1995). Results of studies of naturalistic mitter binds to alpha-adrenergic and beta-
stressors in humans have been somewhat adrenergic receptors on effector cells, while
variable, partly because measurement is com- the remainder is released into the bloodstream.
plicated by circadian variations and the influ- Sympathetic pathways also stimulate the synth-
ence of factors such as physical exercise, esis of epinephrine (adrenaline) in the chromaf-
smoking, caffeine, alcohol, and medication. A fin cells of the adrenal medulla. A series of
longitudinal investigation of an elderly popula- enzymes are involved in this process, including
tion showed that plasma cortisol was elevated tyrosine hydroxylase, dopamine beta-hydroxy-
up to three months following severely threaten- lase, and phenylethanolamine N-methyltrans-
ing life events, and cortisol elevations are ferase, that are sometimes measured as indices
particularly marked among depressed people of catecholamine production. The sympathetic
who experience long-term stressors (Willis, nervous system and epinephrine from the
Thomas, Garry, & Goodwin, 1987). High adrenal glands typically operate in concert to
cortisol has also been recorded from people stimulate a wide range of physiological re-
exposed to major threats such as being a hostage sponses that are summarized in Sections
of war (Rahe, Karson, Howard, Rubin, & 8.02.3.2±8.02.3.4.
Poland, 1990). On the other hand, ex-soldiers Catecholamine levels in the bloodstream are
suffering from post-traumatic stress disorder not easy to measure since responses are rapid
show low cortisol levels, and an inverse and transient, and concentrations in venous
relationship with intensity of combat exposure blood may not be representative of the overall
has been described (Boscarino, 1996). level of circulating epinephrine and norepi-
Despite the opinion that many types of work nephrine. Other techniques such as the mea-
are stressful, the results of investigations of surement of norepinephrine spill-over from
corticosteroid levels in people at work have been nerve terminals, electrical recording from
inconsistent, and it appears that only a propor- sympathetic nerves using microneurography,
tion of individuals respond even to very and measures of adrenergic receptor density
challenging occupations such as air traffic provide more direct information. These techni-
control (Rose & Fogg, 1993). Nonetheless, ques indicate that sympathetic activation is not
day-to-day stressors or hassles have been found a generalized phenomenon with mental stress,
to stimulate increased cortisol independently of since the degree of sympathetic response differs
factors such as smoking, food intake, and coffee substantially across tissues (e.g., Anderson,
consumption (Van Eck et al., 1996). There is Wallin, & Mark, 1987). However, most human
sufficient evidence to infer that heightened laboratory and field studies have measured
cortisol secretion may be a mechanism through catecholamines from venous blood samples or
which psychophysiological factors influence from urine. In the laboratory, acute increases in
risk of disease. epinephrine and norepinephrine have been
recorded in response to mental stress tests such anterior lobe of the pituitary gland is regulated
as arithmetic, cold stimulation, and social by CRF, and occurs in response to a wide
conflict (Malarkey, Kiecolt-Glaser, Pearl, & range of painful stimuli and stressors (Madden,
Glaser, 1994). In field studies, elevations of Akil, Patrick, & Barchas, 1977). Inescapable
catecholamines have been shown in diverse electric shock in rats has been shown to
groups including the bereaved and victims of produce stress-induced analgesia or increased
industrial disasters and sexual abuse (De Bellis, pain tolerance. One form of this analgesia is
Lefter, Trickett, & Putnam, 1994; Gatchel, dependent on endogenous opioids, in that it is
Schaeffer, & Baum, 1985). blocked by antagonists such as naloxone, and
A substantial amount of research has been shows cross-tolerance with morphine-induced
carried out into sympathoadrenal responses to analgesia (Terman, Shavit, Lewis, Cannon, &
work. Studies from Sweden have shown that Liebeskind, 1984).
catecholamine excretion is elevated among There is growing evidence that endogenous
people on piece work or those carrying out opioids are involved in the regulation of
highly mechanized work (Johansson, Aronsson, neuroendocrine stress responses (McCubbin,
& Lindstrom, 1978). Differences between sexes 1993). Serum concentration of beta-endorphin
and people at higher and lower work grades increases during mental stress tests, and assess-
have been reported, with some evidence for ments have also been made during naturalistic
sustained elevations of norepinephrine in the challenges such as anticipation of academic
evening among women in managerial positions examinations (Malarkey, Pearl, Demers,
(Frankenhaeuser et al., 1989). Frankenhaeuser, Kiecolt-Glaser, & Glaser 1995; Sheps et al.,
Lundberg, and Forsman (1980) have argued 1995). When the opioid antagonist naloxone is
that behavioral performance efficiency under administered under double-blind conditions, it
challenging conditions is positively associated leads to increases in stress-induced heart rate,
with catecholamine secretion. However, one of epinephrine, ACTH and cortisol responses
the problems interpreting catecholamine re- (Morris et al., 1990). This suggests that beta-
sponses is that excretion is positively correlated endorphin normally operates to dampen ex-
with physical effort and with motor activity; cessive responses, and is part of the organism's
consequently, norepinephrine may increase self-regulatory mechanism, preventing over-
when people are more actively engaged in shoot of stress-induced physiological reactions.
tasks. The pathway may operate less effectively in
The sympathoadrenal system and the HPA young people at elevated risk for high blood
axis are not independent of one another. The pressure, since their cardiovascular responses to
glucocorticoids have a role in regulating cate- mental stressors are unchanged by naloxone
cholamine biosynthesis in the adrenal medulla, (McCubbin, Surwit, Williams, Nemeroff, &
while catecholamines stimulate ACTH release McNeilly, 1989). The increase in beta-endor-
from the pituitary (Axelrod & Reisine, 1984). phin with mental stress has been shown to
Under acute conditions, correlations have been correlate with raised pain thresholds in patients
observed between cortisol and sympathetically with coronary artery disease (Sheps et al., 1995).
mediated responses in some but not all studies This may be one explanation for stress-induced
(Cacioppo, 1994). At the same time, there has episodes of reduced coronary blood flow
been great interest in identifying situations that (ischemia) occurring without concomitant chest
lead to differential release of corticosteroids and pain in so-called ªsilentº ischemia.
catecholamines. Extensive evidence (reviewed
by Steptoe, 1983) suggests that HPA activation
8.02.3.1.4 Other neuroendocrine and hormonal
is associated with passivity in the face of
responses
aversive situations, with behavioral withdrawal,
and with loss of control. Sympathoadrenal A range of other hormones are involved in
responses on the other hand are maximized psychophysiological responses. Dopamine in
under conditions of active efforts to cope and the brain increases in response to experimental
maintain control over the environment. This stressors in animals, and peripheral dopamine
distinction may be significant when examining may be particularly important in modulating
psychophysiological pathways to disease. gastrointestinal injury (Glavin, 1992). Repro-
ductive function is inhibited by various com-
ponents of the HPA system, with suppression
8.02.3.1.3 Endogenous opioids
of luteinizing hormone releasing hormone in
Beta-endorphin and the enkephalins are the hypothalamus, and inhibition of testoster-
endogenous opioid peptides, and are derived one and estrogen by glucocorticoids (Rabin,
from the same precursor molecule as ACTH. Gold, Margioris, & Chrousos, 1988). The
The secretion of beta-endorphin from the classic studies of Christian (1970) showed that
crowding in animals impaired reproductive during acute stress. Power spectrum analysis of
efficiency. Social status has also been shown heart rate and blood pressure signals show
to affect ovarian function in cynomolgus changes in spectral density at different frequen-
monkeys, with more anovulatory cycles and cies indicative of these autonomic adjustments
progesterone-deficient luteal phases in subor- (Pagani et al., 1991). The capacity of the kidneys
dinate animals (Adams, Kaplan, Clarkson, & to excrete sodium and maintain fluid balance
Koritnik, 1985). Hypogonadal function in may also be impaired, and this may have
middle-aged men is associated with psychoso- implications for the development of hyperten-
cial risks such as work-related problems, living sion (Light, Koepke, Obrist, & Willis, 1983).
alone, lower social class, and high levels of Several factors need to be taken into account
physical symptoms (Nilsson, Moller, & Solstad, when evaluating acute stress responses in hu-
1995). Vasopressin and prolactin have also mans. First, response patterns depend critically
been studied as components of psychophysio- on the nature of the demands imposed on the
logical responses, although their significance is individual. Actively demanding situations such
not yet clear (Theorell, 1992). as information processing and problem solving
tend to elicit cardiovascular responses that are
mediated by increases in myocardial contrac-
8.02.3.2 Cardiovascular and Autonomic tility leading to elevated stroke volume and
Parameters cardiac output. In contrast, passive aversive
conditions and situations over which people
Psychophysiological responses are organized have little control elicit increases in peripheral
hierarchically, and a series of physiological resistance rather than cardiac responses (Sher-
adjustments take place as a result of the wood, Dolan, & Light, 1990). Consequently, it
neuroendocrine secretions described in Section is not appropriate to regard the cardiovascular
8.02.3.1 coupled with direct autonomic stimula- response to acute stressors as a uniform
tion. They include changes in cardiovascular phenomenon.
function, sweat gland activity, gastrointestinal Second, individuals show characteristic re-
motility and pulmonary ventilation. Not all of sponse patterns that persist across different
these responses are immediately relevant to situations. Manuck (1994) identified groups of
disease risk. Studies using direct stimulation of ªcardiacº and ªvascularº reactors, according to
brain regions in unanaesthetized animals in- whether they showed increases in cardiac
dicate that emotional behaviors can be elicited activity or total peripheral resistance during
that are associated with a range of damaging tasks. The magnitude of blood pressure response
physiological changes such as cardiac arrhyth- was similar in the two groups despite variation in
mias, gastric erosions, and adrenal hyperplasia the underlying pattern of haemodynamic ad-
(Kojima et al., 1996). Cardiovascular and justment. This means that individual differences
metabolic responses are particularly important as well as situational characteristics need to be
when considering psychophysiological pro- taken into account (see also Section 8.02.6.7).
cesses in disease. Third, there appears to be flexibility across
hemodynamic mechanisms, so that certain
aspects of cardiovascular responses are main-
8.02.3.2.1 Blood pressure, heart rate, and
tained during mental stress through alternative
regional blood flow
pathways when necessary. For example, when
Blood pressure and heart rate generally actively demanding mental stress tests are
increase in response to acute challenges in the carried out during inhibition of sympathetic
laboratory. During performance of tasks such pathways by beta-adrenergic blockade, blood
as mental arithmetic, the increase in blood pressure elevations are maintained through
pressure and heart rate is associated with other autonomic mechanisms (Julius, (1988).
vasodilation in skeletal muscle and reduced Similarly, adrenelectomized subjects show the
blood flow to the kidneys, skin, and viscera same blood pressure response to mental arith-
(Tidgren & Hjemdahl, 1989). The high heart metic or other stimuli as healthy controls,
rate (tachycardia) is a result of sympathetic despite the lack of epinephrine response and a
stimulation coupled with parasympathetic or reduced heart rate increase (Lenders, Peters,
vagal withdrawal. Blood flow in adipose tissue is Pieters, Willemsen, & Thien, 1988). Julius
increased, and is associated with enhanced (1988) had described this as a ªblood pressure-
lipolysis (Linde, Hjemdahl, Freyschuss, & seeking propertyº of the central nervous system,
Juhlin-Dannfelt, 1989). The sensitivity of the with integrative mechanisms in the brain
cardiac baroreceptor reflex, the mechanism operating to maintain sustained high blood
through which increased blood pressure is offset pressure during challenge through a variety
by slower heart rates and vice versa, is inhibited of physiological mechanisms. If this is true, it
has important implications for interventions Blood flow abnormalities in the coronary
designed to reduce blood pressure stress circulation can provoke ischemia and abnorm-
responses. alities of contractility and left ventricular wall
motion. In classical angina pectoris, cardiac
ischemia due to increased myocardial oxygen
8.02.3.2.2 Cardiac function
demand during exercise is associated with chest
Several aspects of cardiac function may be pain, but episodes of ªsilentº ischemia (without
disturbed as part of the psychophysiological pain) are also common. Mental stress may
stress response in vulnerable individuals (see stimulate cardiac ischemia in a manner similar
Steptoe & Tavazzi, 1996). The two most to exercise, with raised blood pressure and heart
important types of response are changes in rate leading to heightened myocardial oxygen
the rhythm of cardiac contraction and altera- demand. Alternatively, there may be a direct
tions in blood flow in the coronary circulation. influence of the central nervous system on the
Clinical disturbances of the generation and vascular tone of the coronary arteries and
conduction of heart beats include various types arterioles, leading to reductions in coronary
of tachycardia and arrhythmia (Janse & Davies, blood flow.
1996). Arrhythmias affecting the left ventricle of Sustained infusions of norepinephrine have
the heart (ventricular arrhythmias) can be been shown to induce myocardial lesions
provoked by sympathetic nervous stimulation, indicative of ischemia (Schenk & Moss, 1966).
while the parasympathetic system is protective. Several new methods of assessing cardiac
Stimulation of the posterior hypothalamus in function in conscious people have allowed
dogs reduces the threshold for potentially lethal stress-induced silent ischemia to be evaluated
ventricular fibrillation, and similar responses in detail. In an early study, positron tomogra-
have been observed during avoidance condi- phy was used in a study of 16 angina patients
tioning and other types of psychological stress (Deanfield et al., 1984). Twelve patients showed
(Lown, Verrier, & Rabinowitz, 1977). In cardiac abnormalities of perfusion of the heart during
patients, ventricular arrhythmias have been mental arithmetic, but pain was experienced by
associated with high levels of norepinephrine only four. Rozanski et al. (1988) documented a
spill-over indicative of sympathetic activity high incidence of left ventricular wall motion
(Meredith, Broughton, Jennings, & Esler, abnormalities during mental stress in patients
1991). Tavazzi, Zotti, and Rondanelli (1986) with coronary artery disease using radionuclide
evaluated the influence of mental stress on the ventriculography, with public speaking being a
electrophysiology of the heart using programed particularly provocative stress test. Similar
ventricular stimulation in postinfarction pa- results have emerged with other methods
tients. Transient ventricular tachycardia and (Steptoe & Tavazzi, 1996).
fibrillation were induced in patients during Studies of ischemic responses under field
psychological stress, but not under resting conditions have largely been confined to
control conditions. These studies suggest that examining abnormalities of the EKG rather
the disturbances of cardiac rhythm can be than more sensitive measures, although the
induced by activation of psychophysiological introduction of the ambulatory ªnuclear vestº
pathways. may be helpful in the future (Legault, Freeman,
High levels of parasympathetic or vagal tone Langer, & Armstrong, 1995). Gabbay et al.
act in opposition to sympathetic traffic, and (1996) assessed the frequency of ST-segment
reduce vulnerability to certain arrhythmias. depression (an EKG change indicative of
Clinically, it has been observed that high heart myocardial ischemia) in patients during ambu-
rate, which may be a reflection of low vagal latory monitoring. It was found that both
activity, may be an independent risk factor for physical exertion and mental stress (anxiety
coronary heart disease (Dyer et al., 1980). The and anger) were associated with ischemic
minimum heart rate achieved during 24-hour episodes. The presence of ischemic responses
ambulatory monitoring is positively associated to mental stress in the laboratory has recently
with coronary atherosclerosis as determined by been found to predict silent ischemia during
angiography (Perski et al., 1992). Parasympa- ambulatory monitoring in a large sample of
thetic activity is also related to heart rate patients with coronary artery disease (Blu-
variability, with higher variability being indi- menthal et al., 1995). Interestingly, positive
cative of greater parasympathetic tone. Mor- correlations have also been recorded between
tality in postmyocardial infarction patients has the number and duration of ischemic episodes in
been related to low heart rate variability, and daily life, and heart rate responses to mental
this may be another important marker of the stress in the laboratory (Krittayaphong, Light,
psychophysiological response (Klieger, Miller, Biles, Ballenger, & Sheps, 1995). These results
Bigger, & Moss, 1987). indicate that laboratory responses to mental
stress may have genuine significance for cardiac observed, while the depth of breathing (tidal
function in patients with coronary artery volume) is augmented. Changes in the constric-
disease. tion of the airways can also be induced as part of
the psychophysiological stress response. Re-
striction of the airways (or bronchoconstriction)
8.02.3.2.3 Platelets and hemostasis
is stimulated not by the sympathetic but by the
The ability of blood to coagulate rapidly is parasympathetic nervous system, while epi-
one of the primary defense mechanisms redu- nephrine relaxes the smooth muscle of the
cing the impact of injury. One of the early stages bronchial tree. The airways therefore operate in
of the clotting process is the adhesion of blood the opposite fashion to cardiovascular para-
platelets to the lips of a wound and the meters, in that problems are more likely to be
formation of a platelet plug. This is followed induced by parasympathetic than sympathetic
by reinforcement of the platelet plug with fibrin. stimulation. Effects are found most prominently
Later the deposit is removed by fibrinolytic and among people suffering from bronchial asthma,
other mechanisms. This process is also involved for whom challenges such as the suggestion that
in the formation of the thrombi in the vascular an agent which causes wheezing is being inhaled
system that contribute to clinical events such as can stimulate pronounced bronchoconstriction
myocardial infarction and stroke. (Steptoe, 1984b). These responses are blocked
It has been known for many decades that by atropine and other anticholinergic agents,
catecholamines stimulate the activation of confirming that the parasympathetic nervous
platelets and their aggregation (Ardlie, Glew, system is involved. Passive aversive situations in
& Schwartz, 1966). Platelet activation and which the person is not required to respond
aggregation have been shown to increase in actively but rather to endure stressful conditions
healthy subjects carrying out challenging mental are especially provocative (Lehrer et al., 1996).
stress tests (Larsson, Hjemdahl, Olsson, Egberg, There is some evidence that bronchoconstrictive
& Hornstra, 1989). Rapid increases in platelet responses can be elicited in nonasthmatics as
activation and aggregability have also been well as asthmatic individuals, but the findings
recorded in patients with coronary artery are controversial.
disease performing mental arithmetic (Grignani The gastrointestinal tract is innervated by the
et al., 1991). The implication of such findings is autonomic nervous system in such a way that
that vulnerability to the formation of thrombi stimulation of the sympathetic branch decreases
may be enhanced as part of the psychophysio- digestive functions such as saliva production,
logical stress response. Unfortunately, results of bile secretion, and gut motility, while these
naturalistic studies have been rather inconsis- processes are enhanced by ACTH and para-
tent, with both increases and decreases in sympathetic responses. Large individual differ-
platelet activation and aggregation being re- ences have been recorded in studies of gastric
ported under challenging conditions (Haft & acid secretion with mental stress (Holtmann,
Arkel, 1976, Levine et al., 1985). One complica- Kriebel, & Singer, 1990). Thompson, Richelson,
tion is that there are several markers of platelet and Malagelada (1982) have shown how a
function and they may not produce uniform variety of acute stressors, such as the cold
results. pressor test or ear irrigation with cold water,
The later stages of the coagulation cascade delay gastric emptying and perturb duodenal
culminate in the action of the enzyme thrombin, motility. Other measures of gastrointestinal
which converts fibrinogen into fibrin. There has function are disturbed with acute stressors in
been limited study of this process in the people suffering from disorders such as duode-
psychophysiological context, although one nal ulcer and irritable bowel syndrome (Kumar
study showed a decrease in fibrinogen and & Wingate, 1985).
other blood coagulation factors during a Changes in skeletal muscle tension are
prolonged episode of work without sleep important components of the psychobiological
(Palmblad et al., 1977), while work stress has stress response. These reactions are difficult to
been associated with elevated fibrinogen levels quantify without elaborate instrumentation,
(Davis, Matthews, Meilahn, & Kiss, 1995). since no one set of muscles is a reliable indicator
of general tension. Levels of tension in various
tissues are heightened among patients with
8.02.3.2.4 Other physiological systems
anxiety disorders, and acute stressors may also
Respiration is regulated by brain stem affect both level and variability of muscle
mechanisms that are closely integrated with tension (Hoehn-Saric, McLeod, & Zimmerli,
cardiovascular control systems. During chal- 1989). The role of these responses in headache
lenges that involve active efforts to cope, and low back pain is discussed in further detail
increases in respiration rate are typically in Section 8.02.7.3.
8.02.3.3 Lipids and Glucose Metabolism and rodents, while socially subordinate ba-
boons have lower HDL-cholesterol than domi-
The level of blood cholesterol is well nant animals, and this is coupled with a higher
recognized as a risk factor for coronary artery cortisol concentration (Sapolsky & Mott, 1987).
disease, so the influence of psychosocial factors However, it is striking that in the series of
on cholesterol metabolism is of great interest. studies of social stress in cynomolgus monkeys
Cholesterol is a fat-like material synthesized carried out by Kaplan, Manuck and co-work-
mainly in the liver, and is transported through ers, increases in coronary atherosclerosis have
the circulation in the form of lipoprotein been observed that were not due to elevations in
particles. These protein molecules are of several lipid concentration (Kaplan et al., 1993;
types. Low-density lipoproteins (LDL) carry Manuck, Kaplan, Adams, & Clarkson, 1989).
much of the cholesterol, and are the main culprit In this animal model, social stress promotes
in coronary artery disease. High-density lipo- atherosclerosis independently of lipid concen-
proteins (HDL) also carry cholesterol but are tration, through mechanisms such as damage to
protective in that they clear lipid from blood the endothelial surface of arterial walls, which
vessel walls. In addition, triglycerides are fats may permit greater deposition of lipids in vessel
that are not attached to proteins; they may be walls (Strawn et al., 1991).
associated independently with cardiovascular
disease risk, although the importance of this
8.02.3.3.1 Insulin metabolism and abdominal
mechanism remains uncertain.
obesity
Indirect evidence for the involvement of
psychophysiological stress responses in lipid One of the critical mechanisms linking
metabolism comes from experiments showing neuroendocrine activation with lipid metabo-
that blood pressure, heart rate, and catechol- lism is insulin. Insulin is a hormone produced by
amine responses are correlated with the con- the cells of the Islets of Langerhans in the
centration of cholesterol and lipid fractions pancreas, and facilitates the utilization of
(e.g., Fredrikson, Lundberg, & Tuomisto, 1991; glucose by tissues. Destruction of the insulin-
Suarez, Williams, Kuhn, Zimmerman, & Schan- producing cells leads to insulin-dependent (or
berg, 1991). If people prone to large physiolo- Type 1) diabetes mellitus, in which protein and
gical stress responses show higher lipid levels, fat are metabolized instead of glucose, resulting
then a common pathway of sympathetic or in accumulation of toxic substances in the blood
HPA activation may be responsible. Psycholo- and kidney damage. A more common disorder
gical challenges can also lead to acute increases is noninsulin dependent (or Type II) diabetes, in
in total cholesterol and LDL-cholesterol con- which high levels of circulating glucose (hyper-
centration (McCann et al., 1995). However, it glycemia) arise either because of failure to
has been discovered that this response may be produce adequate insulin, or because of defects
secondary to alterations in blood volume. in the ability of tissues to respond to insulin
Plasma volume shows small reductions during (insulin-resistance).
mental stress tests because of shifts between Both the sympathoadrenal and HPA axes
intra-cellular and extra-cellular compartments. influence insulin metabolism, affecting its
This can lead to an increase in blood protein secretion, the conversion of glycogen to glucose
concentration that accounts for the apparent in the liver, and glucose uptake in tissues. A
elevation in blood lipid levels. constellation of metabolic disturbances (some-
The impact on lipids of longer-term stressors times known as syndrome X or the insulin
such as anticipation of academic examinations, resistance syndrome) coexist in people at raised
stressful work, and threat of unemployment has risk for cardiovascular disease. Their problems
also been evaluated (Brindley, McCann, include insulin resistance, hyperinsulinemia,
Niaura, Stoney, & Suarez, 1993). Results have glucose intolerance, low concentrations of
been quite mixed, with increases in total HDL-cholesterol and high blood pressure
cholesterol and LDL-cholesterol in some stu- (Reaven, 1988). Another element of this risk
dies but not others. The problem in under- profile is obesity, due particularly to deposition
standing these responses is that under of fat in the central or abdominal fat stores.
naturalistic conditions, changes may take place Bjorntorp (1990) has argued that a disturbance
in dietary composition, smoking, and other of corticosteroid control over lipid metabolism
factors that influence lipids independently of may underlie the development of abdominal
any psychophysiological processes. Clearer obesity. Cortisol responses to mental stress tests
evidence derives from animal studies in which have been shown to correlate positively with the
diet and other factors can be controlled. degree of abdominal obesity (Moyer et al.,
Infusion of epinephrine has been shown to 1994), while animal studies have demonstrated
increase cholesterol concentration in primates that social stress promotes deposition of
abdominal fat (Jayo et al., 1993). It appears, immunoglobulins. These are proteins that
therefore, that lipid and glucose metabolism derive from B-lymphocytes in the bone marrow,
play important roles in psychophysiological and react with specific antigens. There are five
responses, and may be relevant to the pathogen- major classes of immunoglobulin, IgA, IgM,
esis of coronary heart disease and diabetes. IgG, IgE, and IgD, and each has unique
characteristics. For example, IgE has a primary
8.02.3.4 Immune Parameters role in defense against parasites, and elicits a
range of responses designed to exclude these
One of the most exciting developments in the organisms including bronchoconstriction, vo-
psychophysiological studies of disease over miting, inflammation, itching, and coughing. It
recent decades has been the discovery that also has a key role in allergic responses which
immune function may alter as part of the stress are generally caused by overproduction of IgE
response. Knowledge of these links increases (Sutton & Gould, 1993). IgA is found in
understanding of the mechanisms through secretions such as saliva and tears, and is
which psychosocial factors can influence vul- important in defense against local infections in
nerability to infection, inflammation, autoim- the gut and respiratory system.
mune disease, and certain types of cancer. Cellular immunity involves T-lymphocytes
Sweeping assertions that stress suppresses that arise in the bone marrow and mature in the
immune function are not appropriate, since it thymus before circulating in the blood and
is now recognized that the central nervous lymph. T-cells do not recognize antigens by
system and immune system engage in a complex themselves, so antigens are usually presented to
interplay, and that immune responses can be them by macrophages. T-cells have to be
both up-regulated and down-regulated by activated, but once activated become memory
different behavioral and emotional states. cells, migrating to tissues in which they are most
The immune system is the body's primary likely to re-encounter their specific activating
defense against infection and invading patho- antigen. They are differentiated into various
gens such as viruses, bacteria, and fungi. Some types. Of particular importance to work on
immunity is innate and is present from birth, stress and immune function are cytotoxic T-
acting nonspecifically to protect against foreign lymphocytes that kill invading pathogens and
materials. The skin and mucus membranes are are involved in defense against infections such as
part of this innate immune defence, using influenza and the herpes simplex virus. T-cells
autonomic and chemical methods to prevent are classified by surface cell markers, and
invasion, while cells such as macrophages are cytotoxic T-cells fall into the CD8+ class.
also involved. Local invasion can also trigger a Helper T-cells (CD4+) play a central regulatory
general or systemic ªacute phase response,º in role in immune defense, stimulating B-cells to
which several general bodily processes are produce antibody, activating macrophages to
elicited, including fever and raised body engage in antimicrobial activity, and cytotoxic
temperature. T-cells. Some of these actions are mediated
Although the innate system is highly effective, through immune products called cytokines that
it cannot cope with all pathogens, so there is a have very specific actions on other branches of
second form of immunity which is acquired or the immune system. Another type of lympho-
specific. Acquired immunity involves the re- cyte, the suppressor T-cell, largely falls into the
cognition of substances (antigens) as ªnonself,º CD8+ category, but is less well understood.
and the destruction or elimination of these Suppressor cells are thought to shut off the
materials. The immune system has memory, activity of helper cells, and the helper/cytotoxic-
reflected in the fact that secondary exposure to suppressor ratio is sometimes assessed as a
antigens elicits a more vigorous immune marker of immune health. Natural killer cells
response than the initial reaction, although are a further class of immune cell, and are
the mechanism is poorly understood (Ahmed & involved in immune surveillance, acting non-
Gray, 1996). The main organs of the immune specifically to defend against certain tumor cells
system include the bone marrow, thymus gland, and virus-infected cells.
spleen, and lymphatics, but there are also cells Many different assays of immune function
active in the skin, lungs and gut. have been used in the context of health
There are two major arms of the immune psychology (Kiecolt-Glaser & Glaser, 1995).
system. Humoral immunity is involved in They include enumerative assays or counts of
defense against bacteria and viruses in body various cell types, measures of concentration
fluids, while cell-mediated immunity is relevant of immunoglobulins in the blood and saliva,
to intracellular viruses and fungi, and also to measures of cytokine activity, and functional
cancer cells and transplanted tissue. Humoral assays. Functional assays include testing re-
immunity is mediated by serum antibodies or sponses to mitogens, which are substances that
stimulate replication or proliferation of T and B infection and inflammation. Cytokines also act
cells. Common mitogens include phytohemag- centrally, affecting neural growth and repair,
glutinin (PHA) and concanavalin A (Con A), stimulating sickness behaviors such as reduced
with larger responses indicating more effective social exploration, food intake and weight loss,
function. Natural killer cell activity (or cyto- and in addition disturbing cognitive functioning
toxicity) is assessed by measuring the ability of (Aubert, Vega, Dantzer, & Goodall, 1995).
natural killer cells to lyse target cells from Dantzer and Kelley (1989) have argued that
known tumor cell lines. many of the nonspecific symptoms of sickness
and behavioral responses to infectious illness
are mediated by immune products, helping to
8.02.3.4.1 Regulation of immune function
coordinate the central and peripheral responses
Both the HPA and sympathoadrenal path- to infection.
ways are involved in immune regulation
(Besedovsky & Del Rey, 1996). There are
8.02.3.4.2 Acute stress-induced immune
receptors in the cytoplasm of lymphocytes for
responses
cortisol, and glucocorticoids suppress the
activation of circulating lymphocytes and A number of studies of cellular immune
inhibit production of cytokines (Chrousos, responses to acute challenges such as problem
1995). The HPA plays a major role in the solving and public speaking have been reported.
regulation of inflammation, and corticosteroids Among the most consistent effects are an
have long been used as anti-inflammatory increase in the number of circulating CD8+
agents. In addition, stress-induced production and natural killer cells, and reductions in
of CRF by the hypothalamus has been shown to mitogen-induced lymphocyte proliferation
reduce T-cell proliferation in response to (Herbert et al., 1994). Changes in natural killer
mitogens independently of adrenal mechanisms cell activity have been variable, with increases in
(Jain et al., 1991). The sympathetic nervous cytotocity in some studies and inhibition in
system innervates immune organs such as the others (Bachen et al., 1992; Gerritsen, Heijnen,
spleen and lymph nodes, and there are adre- Weigant, Bermond, & Frijda, 1996). In a
nergic receptors on circulating lymphocytes. particularly striking set of studies, Kiecolt-
Many of the immune responses to acute Glasser et al. (1993) assessed newly-wed couples
stressors are similar to those elicited by injection during a discussion of martial problems, and
of epinephrine. It has been argued that analyzed neuroendocrine and immune functions
sympathetic stimulation may lead to contrac- from blood samples. They showed that those
tion of smooth muscle in the spleen which who manifest critical interpersonal behaviors
results in extrusion of lymphocytes into the produced greater decrements than did other
circulation. Alternatively, the sympathetic ner- couples in natural killer cell activity and
vous system may inhibit production of the mitogen-induced lymphocyte proliferation.
cytokine interleukin-2 by helper T cells. Cate- The evidence that these responses are related
cholamines also modulate natural killer cell to sympathoadrenal pathways is strong. The
activity. magnitude of immune response has been shown
In many studies of the stress process, it is not to correlate with the magnitude of cardiovas-
possible to determine whether HPA or sym- cular reactions (Herbert et al., 1994). Further-
pathoadrenal pathways (or both) are respon- more, many of these responses can be
sible for stress-induced changes in immune attenuated by the blockade of adrenergic path-
function. However, there are striking examples ways with pharmacological agents (Bachen
of chronic increases in corticosteroid activity et al., 1995; Benschop et al., 1994). In contrast
being maintained with behavioral stressors in with work on cell-mediated effects, studies of
the absence of changes in immune activity acute changes in immunoglobulins have been
(Klein et al., 1992). In addition, alterations of very limited, although some investigation of
immune function may occur in acute settings IgA concentration in the saliva have been
before changes in circulating corticosteroid carried out (Herbert & Cohen, 1993b). Im-
concentrations have evolved. In these cases, munoglobulins have long half-lives, and sali-
sympathoadrenal activity is almost certainly vary IgA may be influenced by saliva flow rate,
responsible for regulating immune function. making interpretation difficult.
The brain and immune system engage in a
two-way dialogue, and the flow of information
8.02.3.4.3 Chronic changes in immune function
and control is not simply from the central
nervous system to the periphery. Cytokines such There is an extensive literature in animals
as interleukin-1 are released during immune demonstrating the impact of chronic stressors
activation and mediate the host's response to on immune function such as mitogen-induced
lymphocyte proliferation (Coe, 1993; Line et al., Rather consistent changes in antigen-specific
1996). It appears that these effects are amelio- salivary IgA and serum antibody response have
rated by social affiliation, which may be an also been recorded in studies by Stone et al.,
analogue of social support (Cohen, Kaplan, (1994). Subjects consumed a capsule containing
Cunnick, Manuck, & Rabin, 1992). In humans, a novel oral antigen on a daily basis, so the IgA
some of the changes in immune function antibody response was elicited in a way that
associated with long-term threats are similar might be analogous to invasion by a novel virus.
to those observed with acute challenges. Thus a Over several weeks, desirable daily events were
reduction in mitogen-induced lymphocyte pro- associated with elevated IgA antibody produc-
liferation to PHA has been recorded in care- tion, while undesirable events led to a sup-
givers for demented patients, bereaved people, pressed antibody response.
and in couples experiencing severe disruption of
marital relationships leading to separation or
8.02.3.4.4 Functional significance of stress-
divorce (Herbert & Cohen, 1993b; Kiecolt-
induced immune modulation
Glaser, Malarkey, Cacioppo, & Glaser, 1994).
The effects are rather persistent, with deficits An issue that arises in the investigation of
being recorded over several years, and responses immune responses is whether the changes are of
may be associated with depression (Herbert & clinical significance, or are so small as to be
Cohen, 1993a). Changes in the number of helper solely of academic interest. Many alterations in
T-cells and cytotoxic-suppressor cells have been immune function will only affect health if an
inconsistent, with modifications being recorded invading pathogen is present, so a short-term
in some studies but not others. change in function may have few consequences
One important difference from acute reac- if it does not coincide with exposure. There are
tions is that instead of an increase in natural now studies that have addressed functional
killer cell number, a reduction has generally significance more directly. One of the first
been observed with chronic stressors (Castle, models to be used was the response to latent
Wilkins, Heck, Tanzy, & Fahey, 1995). In viruses that remain within the host undetected
addition, natural killer cell cytotoxicity is unless deficits in immune control allow replica-
suppressed. The reason for these differences tion to increase. Large antibody titers to latent
from the responses to acute stressors is unclear, herpes viruses such as herpes simplex or
but immune parameters are influenced by Epstein-Barr virus indicate poor control by
lifestyle variables such as smoking, exercise, the cellular immune system over these patho-
and intake of dietary fat and vitamins. These gens. Reports by Kiecolt-Glaser, Glaser and
variables are not controlled in naturalistic colleagues have shown that antibody titers are
studies, but may be modified among individuals elevated as part of the stress response (Kiecolt-
enduring chronic threats, so affecting the Glaser et al., 1994).
immune responses that are recorded. In addi- A second approach has been to assess
tion, the pattern of hormonal reaction may alter responses to nonpathogenic antigens, since
with long-term threat, and also has a bearing on studying the immune response to experimental
immune competence. infection is rarely ethical. Vaccination provides
One interesting study of innate immune a useful model, but results to date have been
responses was published by Bosch et al., inconclusive. One study of responses to influ-
(1996), who assessed the aggregation of strep- ence of vaccine showed that psychological
tococcal bacteria in the saliva of students under distress was associated with poor lymphocyte
normal conditions and then prior to an proliferative responses, while a second study
academic examination. Bacterial aggregation showed no significant effects. Poor immune
was reduced in the pre-exam period, suggesting responses to hepatitis B vaccines have been
that the saliva was less effective in preventing elicited by acute or chronic stressors in some
bacterial adhesion to oral surfaces, and defend- investigations but not in others (Glaser et al.,
ing against the early stages of infection. As far as 1992, Jabaaij et al., 1996). Results evidently
immunoglobulins are concerned, studies have depend critically on the timing of measures of
been carried out relating nonspecific salivary the immune response, and on the size of the
IgA to mood fluctuations (Evans, Bristow, vaccination dose.
Hucklebridge, Clow, & Walters, 1993). No A third method that shows considerable
differences in the production of IgM or IgG in promise relates to wound healing. Cellular
adults exposed to severe long-term threat and immunity plays an important role, since
control were recorded by McKinnon, Weisse, cytokines such as interleukin-1 and tumor
Reynolds, Bowles, and Baum (1989), while necrosis factor help to protect against infection
another study recorded associations with daily and repair the damaged tissue. An investigation
hassles (Jabaaij, Benschop, et al., 1993a). of caregivers for Alzheimer victims and matched
The Nature of Psychosocial Demands 55
controls has been published (Kiecolt-Glaser, prevent transmission of pathogens to conspe-

Marucha, Malarkey, Mercado, & Glaser, 1995). cifics. This active negative self-selection may
Participants were given a punch biopsy to create sacrifice the individual to ensure survival of
a standard small wound on the forearm, and the other members of the population.
rate of healing was assessed in the two groups. Another view that has gained widespread
Wound healing was delayed among care-givers, acceptance is that the role of the HPA axis is not
and cytokine responses were impaired. This to stimulate defense reactions, but rather to act
approach provides direct evidence for stress- as a regulatory mechanism and a restraint on
induced suppression of immune defense being other defenses. Munck, Guyre, and Holbrook
significant for health, and may be relevant to (1984) have proposed that glucocorticoids play
studies of psychosocial influences over recovery a central role in preventing the overshoot of
from surgery. inflammatory, immune, and metabolic re-
sponses that might otherwise take place when
8.02.3.5 Adaptive or Destructive? the organism is challenged. They suggest, for
example, that in the absence of glucocorticoid
It has been argued since the earliest scientific counter-control, high levels of insulin might
investigations that the physiological activation cause dangerous hypoglycemia, and that the
seen under conditions of behavioral stress is an suppression of vasopressin prevents excessive
adaptive response. Its ªpurposeº is to prepare fluid retention. Chrousos (1995) has extended
the organism for vigorous physical work such as this perspective by pointing out that corticos-
might be called upon with fighting or escaping teroid release may protect against susceptibility
from danger. Thus, stored energy supplies are to autoimmune diseases. These are diseases in
mobilized to feed working muscle, clotting which the body's own antibodies cause inflam-
processes are stimulated to prevent blood loss mation and tissue destruction, and include
from wounds, and vegetative functions that are rheumatoid arthritis, pernicious anemia and
not essential for short-term activity are sup- various types of thyroid dysfunction. In the
pressed. Unfortunately, this phylogenetically absence of sustained control over immune
primitive psychophysiological response is sti- responses by corticosteroids, risk might be
mulated in humans under circumstances that do increased.
not call for vigorous exercise, and may therefore
become destructive. 8.02.4 THE NATURE OF PSYCHOSOCIAL
There are, however, features of psychophy- DEMANDS
siological responses that are puzzling from
this perspective. They include the inhibition It will be apparent from the discussion thus
of inflammatory responses, the suppression far that a wide range of physiological responses
of cell-mediated immunity, and the promotion are mobilized as part of the stress response. The
of fluid loss through inhibition of the anti- question arises of what types of psychosocial
diuretic hormone vasopressin. How can the demand stimulate these responses, and what
hypothesis that the response pattern is adaptive characteristics of stressors are particularly
be reconciled with the evidence that some relevant.
of the body's major defense systems are
disrupted? How could such an organization 8.02.4.1 Life Events, Chronic Stressors, and
of physiological responses survive the pressures Daily Hassles
of evolution?
Various explanations of this apparent anom- Adverse experiences that have an impact on
aly have been put forward. One possibility is psychophysiological responses are conveniently
that suppression of immune responses is divided into acute events that can be pin-
adaptive in directing energy to more pressing pointed in time and cause substantial disruption
needs. Maier, Watkin, and Fleshner (1994) have to life, chronic adverse social factors that may
argued that the production of acute phase continue for months or even years, and less
responses, which include substantial cellular severe day-to-day sources of irritation (daily
proliferation plus increases in body tempera- hassles). All three types of phenomenon have
ture, requires an increment in caloric energy been associated with psychophysiological re-
production of at least 10%. Such responses sponses and subsequent health risk. Among the
might be difficult to sustain in the presence of acute events, earthquakes and other natural
the simultaneous demands of vigorous exercise. disasters may be followed by elevations in
A second possibility developed by Besedovksy health problems and mortality (e.g., Adams &
and Del Rey (1996) is that it may be adaptive for Adams, 1984, Trevisan et al., 1992). Bereave-
a species if on occasion immune systems fail and ment through death of a partner leads to
lead to the death of an individual, since this may responses such as immune down-regulation and
an increase in all-cause mortality risk (Jones, having a child with chronic illness, daily hassles,
1987), while other life events have been and psychological distress. Different links
associated with problems such as premature between hassles and the various types of major
delivery for pregnant women (Nordentoft, Lou, threat were observed. The impact of divorce on
& Hanson, 1996). Chronic stressors, such as psychological distress was mediated almost
living in the presence of loud ambient noise, entirely through daily hassles, while the impact
crowding, unemployment, or caring for dement- of a serious childhood illness was independent
ing relatives, also have effects on psychophy- of daily hassle levels. The associations between
siological processes, and in some cases on bereavement and distress were partly direct, and
mortality (Evans, Hygge, & Bullinger, 1995; partly mediated through an increase in daily
Kiecolt-Glaser et al., 1994; Morris, Cook, & hassle levels.
Shaper, 1994). Daily hassles have been linked These issues have implications for systematic
with fluctuations in salivary cortisol levels, investigations of psychosocial factors in health
blood pressure, and IgA (Steptoe et al., 1996; risk. One of the major problems encountered in
Stone et al., 1994; Van Eck et al., 1996). the study of physical illness is the ªindepen-
The quantification of psychosocial demands denceº of events from the prodromata of clinical
has been discussed and criticized extensively illness. Many cross-sectional or retrospective
elsewhere (Cohen et al., 1995b). One of the studies of psychosocial factors examine life
issues to emerge is that many standard measures events or chronic stressors in case-controlled
of life events may misrepresent the impact of designs, comparing, for example, women who
adverse experiences by failing to be compre- show a recurrence of breast cancer with
hensive (Turner, Wheaton, & Lloyd, 1995). If nonrecurrence (Ramirez et al., 1989), or insulin-
certain types of events are more common in one dependent diabetics and their siblings (Robin-
sector of society than another, then failure to son & Fuller, 1985). Inferences concerning the
include such experiences in the assessment causal sequence depend critically on the timing
instrument would lead to underestimation of of adverse life experiences. But many threaten-
exposure. This may account for the observation ing events such as being sacked from a job, or a
that has repeatedly been made in the literature breakdown in important relationships, may be
that young adults experience more stressful the culmination of a series of hassles, some of
events than older people; this is because many which may have preceded physical pathology,
life event measures target events such as or have even been caused by early symptoms
pregnancy, marriage, and so forth at the and limitations in capacity brought on by the
expense of the infirmities and loss of capacity medical condition itself.
that are more common among the elderly.
Aneshensel (1992) has argued that life event 8.02.4.2 Characteristics of Psychosocial
research may neglect the problems of ordinary Demands
social life and that the latter show strong
gradients with socioeconomic status that may The arguments outlined in earlier sections
not be apparent for acute events. Although it is indicate that psychophysiological responses are
convenient to distinguish acute events from not uniform across situations, but vary with the
chronic stressors, in reality the classification is nature of demands. Some of the broad dimen-
far from clear cut. Many important life events sions that appear relevant are described in this
have long-term ramifications that either precede section.
the actual event (such as discord leading up to a
marital separation), or last well beyond the
8.02.4.2.1 Novelty, familiarity, and
incident itself. Single acute events may show a
predictability
sustained capacity to elicit physiological activa-
tion through repetitive intrusive memories and Psychophysiological responses tend to be
other cognitive transformations. more intense when animals or humans are
Rather little is known about the extent to placed in unfamiliar situations and confronted
which the impact of acute events or chronic with novel demands. This was strikingly illu-
severe stressors is mediated through daily strated by Mason (1975) who found that the
hassles. An event such as the death of a spouse neuroendocrine reactions elicited in primates
is distressing in itself, but may also lead to were as great when animals were placed in the
numerous petty difficulties in financial and legal experimental situation for the first time, as they
matters, the practicalities of living, and in social were to any subsequent ªstressors.º The
life. An interesting analysis of this issue was neuroendocrine and autonomic reactions in
described by Pillow, Zautra, and Sandler (1996), people learning new dangerous skills such as
who investigated the links between major parachuting also typically diminish rapidly with
threats such as death of a spouse, divorce, or repeated exposure.
The Nature of Psychosocial Demands 57
The reduction in psychophysiological re- responses are relatively easy to carry out. When
sponsivity with familiarity may be due to contingencies are more complex or when
several factors. Natelson et al. (1988) have behavioral tasks are difficult, physiological
argued that adaptation in physiological stress responses may be enhanced. This was neatly
responses is similar to the process of sensory demonstrated in the study of gastric lesions in
habituation. Many biological systems show rats administered escapable or yoked inescap-
reduced responsivity over time, with alterations able electric shocks (Tsuda, Tanaka, Nishika-
in biosynthesis, storage, secretion and re-uptake wa, & Hirai, 1983). When the behavioral
capacity, modulation of receptor sensitivity, response was simple, animals in the uncontrol-
and the institution of counter-regulatory feed- lable condition showed greater ulceration than
back mechanisms. Familiar conditions may also those in the controllable group. But with
elicit smaller psychophysiological responses complex contingencies, the situation reversed.
because they become predictable. Psychophy- In humans, it is known that increasing task
siological responses are more pronounced in difficulty is associated with greater blood
unpredictable conditions, even if the duration pressure and sympathetic nervous system
and intensity of stimulation is the same as that in activity (Callister, Suwarno, & Seals, 1992).
predictable conditions (Abbott, Schoen, & When the tasks that must be carried out to
Badia, 1984). To take just a few examples, rat maintain control over aversive stimulation are
studies have shown that corticosteroid re- difficult and require considerable effort, psy-
sponses are enhanced and the proliferative chophysiological responses may be greater than
capacity of lymphocytes is suppressed by in uncontrollable conditions (Bongard, Ho-
unpredictable as opposed to predictable stres- dapp, Frisch, & Lennartz, 1994). Even the
sors (De Boer, Van der Gugten, & Slangen, perception that the person has chosen difficult
1989; Mormede, Dantzer, Michaud, Kelley, & tasks to perform may elicit heightened cardio-
Le Moal, 1988), while in humans, Zakowski, vascular responses (Sherwood, Royal, & Light,
Hall, and Baum (1992) found that lymphocyte 1993). However, it should be emphasized that in
proliferative responses to Con A were impaired humans, the negative consequences of effortful
to a greater extent with unpredictable stressors. control have largely been recorded during acute
laboratory studies. Whether effects are suffi-
cient to offset the benefits of perceived control
8.02.4.2.2 Control and lack of control
in clinical and naturalistic settings remains
Behavioral control over psychosocial de- unknown.
mands can be defined as the possibility of being
able to take actions that prevent, terminate, or 8.02.4.3 Work Characteristics, Control, and
modify aversive stimulation. Lack of control Psychophysiological Responses
implies that such actions are not available to the
individual because of the prevailing circum- For people in employment, work occupies a
stances, or because the actions are not in the considerable portion of waking life. It is scarcely
behavioral repertoire. In the context of psycho- surprising therefore that the work character-
physiological stress responses, perceived con- istics associated with ill-health have been
trol, or the perception that actions can be taken, extensively studied. Various types of pathology
may be as important as actual control. such as hypertension and peptic ulcer are more
There is ample evidence from acute studies in prevalent in people in certain demanding
animals that simple forms of behavioral control occupations, although it is often difficult to
such as pressing a lever to avoid or escape shock disentangle psychophysiological processes from
are associated with smaller psychophysiological variations in lifestyle and health behavior (Cobb
responses than equivalent uncontrollable sti- & Rose, 1973). Work may also lead to increases
mulation. Uncontrollable conditions elicit in catecholamines and blood pressure, notwith-
greater corticosterone and catecholamine re- standing the points made in Section 8.02.2.2.3
sponses, an increased tendency to gastric about the role of physical activity that remain
lesions, a decrease in natural killer cell cytotoxic pertinent to these investigations.
activity and mitogen-induced lymphocyte pro- Much research on the health risks of work has
liferation, and greater weight loss (Steptoe & been oriented around the demand-control
Appels, 1989). In humans, diminution in blood model of job strain put forward by Karasek
pressure, heart rate, and cortisol responses have (1979). This proposes that risks to health are
been recorded with controllable demands as particularly great when work is characterized by
opposed to equivalent demands that are not high demands or work load coupled with low
controllable. control or autonomy. The model therefore
However, the beneficial effects of control are points to control as being an important element
limited to circumstances in which the behavioral of psychosocial demand. A substantial literature
has accumulated suggesting that high demand/ 1993b). It is not certain what factors determine
low control jobs are associated with increased whether concurrent stressors enhance or inhibit
risk of coronary artery disease and high blood psychophysiological responsivity.
pressure (Schnall, Landsbergis, & Baker, 1994).
The data are not all consistent, and other factors 8.02.5 RESISTANCE AND
such as social support at work and psychological VULNERABILITY FACTORS
traits also need to be taken into account. A study
from the author's laboratory suggested that The other side of the model outlined in
perceptions of job strain and a disposition to Figure 1 concerns the personal characteristics,
high physiological stress reactivity interact in social resources, and experiential and biological
determining elevated blood pressure at work factors that serve to increase or decrease the
(Steptoe, Roy, Evans, & Snashall, 1995). A ability of people to adapt effectively to psycho-
group of healthy young men working as fire- social demands. These factors will be outlined in
fighters were classified on the basis of job strain this section, focusing particularly on the evi-
and their blood pressure reactivity to standar- dence for influence over psychophysiological
dized mental stress tests. Eighteen months later, processes. The inclusion of both resistance and
blood pressure was monitored during a work vulnerability factors reflects the presumption
shift and an equivalent period of leisure using that some characteristics are protective, while
automated ambulatory apparatus. Neither high others are potentially damaging.
job strain nor physiological reactivity in isola- Perhaps the ideal type of evidence is from
tion predicted blood pressure at work, but men studies in which individuals or groups who
who displayed both characteristics had elevated differ on a putative resistance or vulnerability
blood pressure during the later hours of their factor are exposed to identical demands. Any
work shifts. difference in psychophysiological response or
health risk would indicate that the factor in
8.02.4.4 Concurrent Stressors question was indeed operative. Within this
framework, the resistance or vulnerability
Adverse life experiences do not occur in factors might exert a ªbufferingº effect, being
isolation, but are superimposed on a back- operative at high but not low levels of
ground of hassles or chronic stressors. An issue psychosocial demand. Alternatively, they might
that is poorly understood is the role of exert ªdirectº effects, influencing responses
concurrent stressors in determining levels of irrespective of the level of demand. Many
psychophysiological activity. It might be as- resistance and vulnerability factors may influ-
sumed that if people are already under pressure ence psychophysiological variables through
because of other problems in their lives, then the their associations with different types of
reactions to fresh threats would be heightened. behavioral and cognitive coping response.
Alternatively, it is possible that new demands The vulnerability factors discussed in this
might act as distractors from concurrent diffi- section are those related to psychophysiological
culties, dampening the intensity of responses. responses in general. The factors that may
Cardiovascular responses to mental stress predispose people to particular types of health
were inversely related to recent life events in a problem are considered in Section 8.02.6.
study of adolescents (Boyce & Chesterman,
1990), and beta-adrenergic receptor density was 8.02.5.1 Personality and Behavior Patterns
lower among homeless people who had experi-
enced severe life events over the past six months A number of personality factors have been
(Dimsdale, Mills, Paterson, Ziegler, & Dillon, postulated as relevant to stress vulnerability
1994). Other studies have shown that high and resistance. Some have been linked to risk
occupational demands are associated with for specific disorders (the best known case
reduced blood pressure responses to acute being Type A coronary-prone behavior), while
mental stress tests (Schaubroeck & Ganster, others are thought to affect general vulner-
1993). These reports are consistent with the ability to psychosocial demands. There are
notion that concurrent stressors dampen phy- several processes through which personality
siological responses to fresh challenges. But might influence psychophysiological responses,
other work points to the opposite conclusion, and these have been described by Bolger and
with the chronic stress of crowding and high Zuckerman (1995). First, personality factors or
levels of recent hassles being associated with habitual ways of behaving might affect exposure
elevated cardiovascular reactions and reduced to demands, increasing or decreasing the
antibody formation to hepatitis B vaccination experience of potential threats by influencing
(Fleming, Baum, Davidson, Rectanus, & social, vocational, and recreational activities.
McArdle, 1987; Jabaaij, Grosheide et al., For instance, a person high in extroversion may
Resistance and Vulnerability Factors 59
have a very different experience of life than one Kewley lead to functional limitations, pain, and
who is introverted. Second, personality factors impaired quality of life. It is not surprising that
may affect the appraisal of situations, and individuals with these problems score higher on
whether or not they are perceived as threaten- measures of anxiety, depression, and anger or
ing, challenging, irrelevant, exciting, controlla- irritation than healthy people. In some cases
ble, and so on. Neuroticism and hostility come such as hypertension, it is known that diagnosed
to mind as exemplars of this process. Third, cases and awareness of the problem are
personality can influence the individual's choice associated with increased psychological distress
of coping responses. For example, an individual and neuroendocrine activation independently
with high internal locus of control may launch of blood pressure levels (Rostrup, Mundal,
into efforts at active problem-solving more Westheim, & Eide, 1991).
readily than someone with external beliefs. Second, the constellation of factors thought
Finally, personality may have an impact on to reflect disease-prone personality overlaps
the effectiveness of coping responses. A person strikingly with negative affectivity. Negative
with high hostility scores may mobilize social affectivity is a tendency to pervasive dysphoria
support in an effort to cope, but alienate his or and low mood, and has been found to influence
her social contacts with abrasive behavior. Thus reports of social support, life events, and
far, there are rather few studies that have been symptoms, and to affect health service utiliza-
able to tease out these different modes of action. tion (Watson & Pennebaker, 1989). It is
Intriguing findings have been described for a frequently indexed by measures such as neuroti-
number of personality and behavioral patterns cism, so is difficult to distinguish operationally
including locus of control (Parkes, 1984), sense from a personality trait in cross-sectional
of coherence and conscientiousness (Friedman studies. Negative affectivity is a mediator of
et al., 1995). The concept of the hardy associations between stressors and affective
personality developed by Kobasa has attracted responses, and may consequently contribute
considerable attention, but has also been to the correlation between disease and person-
criticized on conceptual and empirical grounds ality as well.
(Funk, 1992; Kobasa, Maddi, Puccetti, & Zola, The third reason for reservations about the
1985). This review is therefore confined to four disease-prone personality is that it agglomerates
areas of research into personality and behavior- a range of characteristics, each of which may
al patterns that appear especially relevant to have distinct associations with health risk and
psychophysiological processes. psychophysiological responses. To group fac-
tors such as depression, anxiety, and hostility
together loses the potential for refining the role
8.02.5.1.1 Disease-prone personality and
of psychosocial factors.
negative affectivity
The notion that a constellation of personality
8.02.5.1.2 Anger and hostility
characteristics may put people at higher risk for
all manner of diseases was proposed by Fried- The constructs of anger and hostility illus-
man and Booth-Kewley (1987). They described trate this point very well. There has been great
meta-analyses in which high levels of anxiety, interest in the role of these factors in physical
neuroticism, depression, anger, and hostility health. However, there are many different types
emerged as features linked with a range of of measure and experience that fall within this
pathologies including coronary heart disease, area, and not all may be relevant to health risk.
bronchial asthma, peptic ulcer, rheumatoid Thus anger as an emotional state or trait can be
arthritis, and headache. It was postulated that separated from hostility, which is generally
a person with these characteristics was predis- regarded as a broader construct involving
posed to developing physical illness, but that the cognitive and behavioral factors. Cynical
nature of the illness would depend on biological hostility, for example, is centered on beliefs
factors such as genetic risk. that others are motivated by selfish concerns,
This position can be criticized on three main and is a dimension tapped by the Cook and
grounds. First, many of the studies used to Medley Hostility Scale. These characteristics
support this proposition are cross-sectional or can in turn be distinguished from the expression
retrospective in nature. It cannot be assumed of anger (a behavioral response) and from overt
that the psychological characteristics displayed aggression.
by someone with manifest disease were present Space prevents more than a brief summary of
prior to diagnosis, or are present among people the literature relating anger and hostility to
with similar medical conditions who have not physical health and psychophysiological pro-
been diagnosed (the ªclinical icebergº). Many of cesses. Interest has chiefly focused on cardio-
the illnesses discussed by Friedman and Booth- vascular disorders. Although the literature is
not all consistent, meta-analyses indicate that nature increases risk of physical illness. There
coronary heart disease and its manifestations has been speculation on this topic for many
such as myocardial infarction are positively decades, and recent years have seen the
associated with overt hostility (Miller, Smith, publication of several convincing systematic
Turner, Guijarro, & Hallett, 1996). There is studies. For example, Huppert and Whittington
limited evidence that hostility also predicts all- (1995) used data from the Health and Lifestyle
cause mortality and by implication health in Survey to show that elevated scores on the
general. A different pattern is found for high General Health Questionnaire predicted mor-
blood pressure, which is associated with low tality over a seven-year follow-up period
levels of anger expression, particularly among independently of age, diagnosed physical dis-
people who are not aware of their blood order at the start, social class, and smoking. A
pressure level (Jorgensen et al., 1996). more rigorous interview-based measure of
These effects are not of course necessarily depression was used in a study of first-degree
mediated through psychophysiological path- relatives of depressed patients and controls
ways, since hostility has also been associated (Moldin, et al., 1993). People classified as
with poor health habits such as lack of exercise having experienced clinical depression at some
and drinking and driving (Leiker & Harley, time in their lives were at increased risk for
1988). However, a number of investigators have headache, skin infection, respiratory illness,
shown that hostility is positively related to diabetes, and low blood pressure, after control-
cardiovascular reactions to mental stress, ling for age, sex, and alcohol use.
particularly under conditions of harassment In a larger study of people with diagnosed
and provocation (Suls & Wan, 1993). Hostility anxiety and depressive disorder in Sweden, risk
is also positively correlated with cortisol excre- of death from coronary heart disease was
tion during the day, and with blood platelet increased among men but not women (Allgu-
activation, an early marker of thrombotic lander, 1994). Unfortunately, interpretation of
processes (Markovitz, Matthews, Kriss, & studies of this kind is problematic, since
Smitherman, 1996; Pope & Smith, 1991). It is utilization of healthcare services may be
reasonable to assume, therefore, that anger and different among people who are distressed or
hostility are vulnerability factors in psychophy- depressed, leading in some circumstances to an
siological processes and disease. increased likelihood of diagnosis of conditions
that might otherwise go unnoticed. Psycholo-
gical disturbance may be a product of early
8.02.5.1.3 Depression, pessimism, and optimism
subclinical physical illness, and not predate
People with serious illnesses frequently health problems. Patterns of health behavior
experience depression. Clinically, it is com- such as exercise and food choice also vary with
monly observed that people suffering from mental health, and may contribute to increased
painful conditions such as chronic back pain or risk of disease.
rheumatoid arthritis are at least mildly de- The other side of the coin is optimism, which
pressed for a great deal of the time. Depression has been defined by Scheler and Carver (1992)
is also associated with nonpainful but restric- as a set of global expectancies in which people
tive conditions such as bronchial asthma and generally experience good as opposed to bad
various cardiomyopathies. Herbert and Cohen outcomes in life. Optimism as measured, for
(1993a) have reported a meta-analysis of example, by the Life Orientation Test, has been
studies linking depression with immune func- associated with favorable adaptation to cardiac
tion, and conclude that depressed people surgery, lower distress among women with
generally exhibit lower mitogen-induced lym- breast cancer and HIV positive men, and fewer
phocyte proliferation, natural killer cell activ- psychological problems following unsuccessful
ity, and smaller numbers of circulating helper medical interventions (e.g., Carver et al., 1993;
T-cells than do comparison groups. Studies of Taylor et al., 1992). An optimistic disposition
patients following myocardial infarction in- appears to be associated with the use of adaptive
dicate that depressed individuals are at high coping strategies in the face of threat, such as
risk for future complications and early mor- planning and positive reinterpretation, with low
tality independent of cardiological variables levels of cognitive avoidance. In this respect,
(Frasure-Smith, LespeÂrance, & Talajic, 1993), optimism would appear to fulfill the criteria for
and pessimism as a trait has been shown to a general resistance factor.
predict future mortality in at least one long-
itudinal study (Peterson, Seligman, & Vaillant,
8.02.5.1.4 Emotional inhibition
1988).
These associations raise the question of One of the key concepts underlying the
whether psychiatric disorder of an affective psychodynamic tradition of psychosomatics is
Resistance and Vulnerability Factors 61
that physical disorders might emerge through some evidence for a reduction in episodes of
repression of neurotic conflicts. From this, the minor illness over subsequent weeks. There are
idea developed that people suffering from other intriguing preliminary findings suggesting
various physical complaints might be emotion- that lack of disclosure may have important
ally repressed or inhibited. A more modern health consequences. Cole, Kemeny, Taylor,
development of this theme is the construct of and Visscher (1996) followed a cohort of HIV-
alexithymia, a difficulty in accessing feelings negative homosexual men with regular health
and bodily sensations and in relating to checks over a five-year period. They found that
emotional experiences (Sifneos, 1973). The men who concealed their homosexual identity
hypothesis that the inhibition of emotion is experienced a high incidence of infectious
potentially damaging can be supported without illnesses such as sinusitis and bronchitis,
accepting all the intellectual penumbra of independent of common health behaviors,
psychodynamic thought. Openly discussing negative affect, age, and education. Risk for
emotionally-charged events may facilitate emo- these types of disorder might be mediated
tional processing, may help give meaning to through suppression of immune defense.
distressing experiences, and may allow for social
comparison and input of information and
advice from others. 8.02.5.2 Social Isolation and Social Support
Several different methods of operationalizing
the inhibition of emotion have been developed The influence of social isolation, social
in the research literature (Pennebaker, 1995). integration, and social support on health risk
The method developed by Weinberger and co- is now well established. A substantial literature
workers involves measuring anxiety and social on social support and physiological processes
desirability so as to identify people who report has also emerged, and this has been amply
low anxiety together with high social desir- reviewed by Uchino, Cacioppo, and Kiecolt-
ability scores (Weinberger, Schwartz, & Da- Glaser (1996). Social network refers to the
vidson, 1979). The rationale is that people with a person's web of social relationships and ties,
ªrepressive coping styleº fail to acknowledge and is typically assessed by measures such as
emotional distress (hence having low anxiety) marital status, number of people in the house-
but also desire social approval. Weinberger et hold, number of close friends and relatives,
al., found that students with repressive coping church attendance, and participation in group
styles showed greater autonomic responses to a activities. Composite measures of social net-
task than did genuinely low anxious individuals. works have been shown to predict mortality in
This finding has been replicated in other studies, the Alameda County study, Tecumseh, Scandi-
although not entirely consistently. For example, navian cohorts, and elsewhere (House, Landis,
antibody titers to Epstein-Barr virus antigen & Umberson, 1988). It is apparent that network
were found to be raised among students with measures may include a number of quantita-
high anxiety plus high social desirability scores tively different types of social contact, and it is
by Esterling, Antoni, Kumar, and Schneider- unlikely that all are equally important. Church
man (1993), and not among repressors. attendance may bring with it particular atti-
Simpler measures of emotional expression are tudes to problems and styles of coping that have
also negatively associated with physiological little to do with group involvement per se, while
responses to challenge, a pattern that has been marriage is much more than having someone
identified even in children of three and four close in the social network.
years old (Cole, Zahn-Waxler, Fox, Usher, & The function of social networks is thought to
Welsh, 1996). Anger inhibition may be parti- be to provide social resources and support, and
cularly relevant to the development of hyper- several types of support can be distinguished.
tension, and has been shown to predict They include material or tangible support, such
heightened cardiovascular reactions to mental as the provision of assistance with tasks;
stress tests in people with a family history of emotional support, or the availability of some-
high blood pressure (VoÈgele & Steptoe, 1993). one with whom to share personal problems and
Another approach has been to assess the from whom to receive comfort and concern;
psychophysiological and health consequences informational support which involves the
of disclosure of emotionally distressing infor- provision of advice and suggestions about plans
mation. In one study of this kind, students were of action; and belongingness, or a sense that one
randomized into writing about very traumatic is part of a group with similar interests and
episodes in their pasts, or essays on neutral concerns. Again, not all these elements are
topics (Pennebaker, Kiecolt-Glaser, & Glaser, equally important across situations. The mother
1988). Cellular immune function appeared to be with young children who has recently been left
favorably affected by confronting traumas, with by an errant spouse might benefit particularly
from practical support in terms of help with Physiological variables have also been as-
child-care and shopping, and informational sessed in a series of acute laboratory studies of
support such as legal advice. By contrast, a responses to standardized tasks carried out in
person worried about being dismissed from the presence of supportive friends. Effects have
their job might especially value emotional been somewhat mixed, although there is some
support and a feeling that they still belong to evidence that cardiovascular reactions are
their social group. reduced in the presence of friends (Kamarck,
Social support and strong social networks are Annunziato, & Amateau, 1995). Evidence
not uniformly distributed through the popula- concerning neuroendocrine function and social
tion. Perceived social support from spouses, support is less consistent, with several studies
friends, relatives, and co-workers is greater showing little effect. Immune data are more
among people of higher socioeconomic status compelling in showing that the down-regulation
(Turner & Marino, 1994). In the Whitehall II of function elicited by chronic stressors may be
epidemiological study of British civil servants, ameliorated by support (Baron, Cutrona,
satisfaction with practical support was greater Hicklin, Russell, & Lubaroff, 1990; Kiecolt-
in men of higher than lower employment grade Glaser et al., 1991).
(Marmot et al., 1991). Women tend to report The results of studies that have attempted to
higher social support than men from most bolster social support but have been rather
sources, although ratings of relationships with disappointing to date. For example, Arnetz et
spouses are frequently less positive. In their al. (1987) randomized unemployed women to
studies of the social origins of depression, control or intervention groups that provided
Brown and Harris (1978) showed that poor information and engaged in alternative activ-
spouse/partner support was more frequent ities. No effect on immune or endocrine
among women of low social class with young function was observed. A very substantial study
children at home than it was in other groups. It providing social support to deprived young
should of course be recognized that in general, pregnant women in Latin America failed to find
social ties may have many negative conse- any protective effects on birth outcomes (Villar
quences, and some of the most potent sources of et. al., 1992). Helgeson and Cohen (1996) have
chronic distress arise from relationships in the argued that although emotional support groups
family (Burg & Seeman, 1994). are desired by patients with cancer, there is little
The literature is rather consistent in showing evidence that they are of benefit in terms of
that social networks and social support are psychological well-being or other aspects of
associated with favorable cardiovascular func- adjustment. It is not yet clear that support
tion (Uchino et al., 1996). For example, a study provided externally will necessarily have com-
of elderly Swedish men found that blood parable effects to support that emerges more
pressure was negatively correlated with degree naturally from the individual's evolving social
of anchorage in formal and informal social world.
groups after controlling for social class, marital
status, alcohol, smoking, body weight, and
physical activity (Hanson, Isacsson, Janzon, 8.02.5.3 Prior Experience of Stressful Events
Lindell, & Rastam, 1988). A frequently cited
follow-up study of Italian nuns from a secluded There are distinct schools of thought about
and close-knit religious order showed that their whether prior adverse experience helps to
rise in blood pressure with age was less marked strengthen the individual's resistance to later
than in the general population, although being a threats, or whether it increases vulnerability.
nun has more to it than social integration (Timio On one side, there is evidence that earlier
et al., 1988). Dressler (1991a, 1991b) has stressful experiences increase vulnerability to
performed an interesting set of studies showing later adverse events. Thus experiences such as
an interaction between chronic life stress and disruption of family relationships early in life
support among black men in southern USA. A increase risk for later emotional and behavioral
subgroup were characterized by ªlifestyle problems (Wadsworth, Maclean, Kuh, &
incongruity,º in that their lifestyle in terms of Rogers, 1990). In work on life events and
material goods and status displays exceeded depression, Brown and Harris (1978) found
their occupational position. Dressler argued that women who had as children experienced
that efforts to maintain such an ostentatious the loss of their own mothers through death,
lifestyle in the absence of sufficient funds ran a high risk of developing depression in
constituted a source of chronic life stress. He adult life in the face of negative life events.
found that blood pressures were indeed higher Adverse effects are by no means inevitable,
among men with lifestyle incongruity, but only since the impact of early stressful experiences is
when they had low levels of social support. ameliorated by temperamental factors and
Pathways to Disease±Predisposing Factors 63
coping style (Garbarino, Kostelny, & Dubrow, credible biological pathways, models of psy-
1991). Cortisol responses to stressful situations chophysiological processes in disease must
are smaller among infants with more secure account for individual differences. Why is it
attachments (Nachmias, Gunnar, Mangels- that groups who suffer from ªstress-relatedº
dorf, Parritz, & Buss, 1996). Animal studies pathology often do not appear to have more
have shown that early social isolation leads to stressful lives than those who remain healthy?
increased HPA output, reduced lymphocyte How is it that two people may have similar life
activation by mitogens, and an elevation of experiences, yet one becomes ill while the other
central norepinephrine turnover (Suomi, 1991). remains healthy? Why, in the face of chronic
The enhancement of psychophysiological re- stressors, do some people succumb to infectious
sponses arising from disruption of early illness while others show increases in blood
development may increase vulnerability to later pressure and the development of hypertension?
disease. Prenatal factors may also be signifi- Faced with these issues, it has been traditional
cant. For example, the exposure of pregnant in psychophysiological models to invoke ªbio-
rats to behavioral stress has been shown to logical vulnerabilityº as an explanation. People
influence the immune function of their off- will succumb to the pathologies to which they
spring (Klein & Rager, 1995), and influences on are most vulnerable, depending on their locus
later neuroendocrine function have been de- minoris resistentiae. Thus an individual prone to
scribed as well. coronary artery disease will show accelerated
On the other side, prior experience may atherogenesis with adverse life experience, while
mitigate the effects of later aversive stimulation. another susceptible through biological factors
Thus early handling in laboratory animals to muscular contraction will be at increased risk
produces more rapid adaptation to avoidance for headache or muscular skeletal pain. Still
conditioning, smaller adrenal responses to another person may be physically robust, but
chronic stress, and enhanced antibody re- prone to anxiety disorders.
sponses to experimental infections (Solomon, This model may account superficially for
Levine, & Kraft, 1968). Dienstbier (1989) has individual differences, but unless it is properly
argued that prior stressful experiences lead to characterized it has little explanatory power.
ªphysiological toughening,º and more effective The problem is that unless biological vulner-
adaptation to later challenges. A direct test of ability is defined a priori with clear measurable
this model was described by Norris and Murrell markers, then there is the danger that vulner-
(1988) who examined the impact of a natural abilities are identified after the event, and that
disaster (serious flooding) on anxiety symp- reasoning becomes circular. Fortunately, there
toms. It was found that older adults who had has been progress over recent years in delineat-
experienced similar disasters earlier in their lives ing predisposing factors. Some of these help
showed better adaptation than did those who account for why one person becomes ill and
lacked prior experience. another does not, while others explain why
These discrepant findings can probably be individuals succumb to particular forms of ill-
reconciled through consideration of the specific health.
adverse events experienced in the past and
current demands on the individual. Previous
exposure to a particular threat (such as a natural 8.02.6.1 Nutrition and Exercise
disaster) might indeed improve adaptation,
since the sequence of events will be more Nutritional deficits in early life affect later
familiar and less unpredictable than before, and functioning of the immune system even after
strategies for coping may already have evolved. proper nutrition has been reinstated. A persis-
Other types of threatening experience may tent alteration in phagocytosis and an acceler-
disrupt developmental trajectories, impair self- ated decline in cell-mediated immunity have
esteem and reduce the individual's social been described (Dutz, Kohout, Rossipal, &
resources, leading to heightened responsivity Vessal, 1976). Serum immunoglobulins appear
to later events. relatively unaffected by malnutrition through
protein and energy deficits, but secretory IgA
responses are reduced and may enhance the risk
8.02.6 PATHWAYS TO DISEASEÐ of succumbing to viral infection. Among elderly
PREDISPOSING FACTORS people, subtle and often undetected micronu-
trient deficiencies lead to reductions in lym-
Thus far, factors have been described that phocyte function and natural killer cell activity
influence the magnitude and duration of (Chandra, 1989). Other aspects of nutrition
psychophysiological responses in a general such as the consumption of saturated fats, salt,
fashion. However, as well as establishing and fruit and vegetables are of clear importance
as risk factors in disease. Thus nutritional networks due to death and changing roles.
profiles may have a profound influence on the People who appear to age more successfully may
extent to which psychophysiological responses adapt by lowering their evaluation of the
will have clinical consequences in terms of importance of areas of life over which they lose
disease risk. control (Brandtstadter & Rothermund, 1994).
Regular physical activity and physical fitness However, flexibility and adaptation may be
may potentially be protective. A substantial reduced at both the psychological and biological
number of studies have assessed associations levels, contributing to increased disease risk.
between fitness or regular activity and psycho- The profile of biological stress responses
physiological stress responsivity. Although by changes with age. Older age is characterized by
no means consistent, investigators have shown higher levels of circulating catecholamines but
that blood pressure and catecholamine stress reduced responsiveness to sympathetic stimula-
responses are smaller among fit or more active tion (Lakatta, 1993). Thus, heart rate responses
individuals (Seraganian, 1993). However, cross- to challenging tasks are reduced, while a
sectional differences may be due to selection decrease in the dilation of blood vessels
factors or other aspects of the lifestyle of supplying working muscle results in increased
sedentary and active people. Efforts have blood pressure responsivity. Animal studies
therefore been made to assess psychophysiolo- suggest that the magnitude of acute responses in
gical responsivity to mental stress before and the HPA system is unchanged with age, but that
after exercise training. Again the results have cortisol elevations are more prolonged in older
been very mixed, with reductions in stress animals, suggesting disruption to regulatory
responsivity with physical training emerging feedback mechanisms (Seeman & Robbins,
in some studies but not others (De Geus, Van 1994). A limited amount of evidence suggests
Doornen, & Orlebeke, 1993; Rogers, Probst, similar processes are at work in humans,
Gruber, Berger, & Boone, 1996). The explana- although increased cortisol responses to chal-
tion of these discrepancies is not clear, so the lenging tasks with age have also been described
extent to which psychophysiological mechan- (Gotthardt et al., 1995). The magnitude of
isms are moderated by regular physical activity ACTH and cortisol responses to a simulated
and fitness is uncertain. Field studies certainly real-life challenge (a driving test) were shown to
suggest that fitness is protective. For example, be inversely associated with self-esteem in an
Brown (1991) found that in a sample of elderly cohort, suggesting that maintenance of
students, adverse life events over the past year psychological well-being in old age may help
were associated with psychological distress and reduce adverse psychophysiological response
self-reported illness level. However, both illness patterns (Seeman et al., 1995).
rates and healthcare utilization were lower in
those who had experienced life events but were
also physically fit, as opposed to the unfit. 8.02.6.3 Gender
Results of this kind indicate that further
investigation of the influence of regular activity Many of the medical disorders discussed in
and fitness on psychophysiological processes other chapters of this volume have different
and disease is warranted. rates of occurrence in men and women. There
are also consistently higher reports of psycho-
logical distress on measures such as anxiety and
8.02.6.2 Advanced Age depression among women than men, and these
differences do not appear to be accounted for by
Many of the medical disorders investigated in disclosure or response biases (Mirowksy &
health psychology are more common in older Ross, 1995). The question therefore arises of
than younger adults, including coronary artery whether psychophysiological processes contri-
disease, rheumatoid arthritis, high blood pres- bute to differences in disease and distress
sure, and various cancers. The issue of aging is between the sexes.
becoming increasingly important to an under- Faced with identical challenges, young men
standing of psychosocial contributions to dis- tend to show more sustained cortisol reactions
ease risk (Schaie, Blazer, & House, 1992). The than young women (Kirschbaum, Wust, &
nature of psychosocial demands changes with Hellhammer, 1992), together with higher epi-
age. Heckhausen and Schulz (1995) have argued nephrine responses (Frankenhaeuser, Dunne, &
that later years are characterized by increasing Lundberg, 1976). Men also manifest greater
exposure to events over which the individual has blood pressure responses than women, and this
little control, including bereavement, health pattern can be seen even in childhood (Allen,
problems, the reduced economic power asso- Stoney, Owens, & Matthews, 1993; Murphy,
ciated with retirement, and diminution in social Stoney, Alpert, & Walker, 1995). By contrast,
Pathways to Disease±Predisposing Factors 65
heart rate responses are typically greater in among people of lower socioeconomic status
women. Studies comparing women at different (Blane, Brunner, & Wilkinson, 1996; Kaplan &
phases of the menstrual cycle have not reached a Keil, 1993). Socioeconomic status may be
consensus about effects on stress responsivity assessed by a variety of indices including
(Stoney, Owens, Matthews, Davis, & Caggiula, occupation, income, type of housing and
1990). However, it is probable that the low education. Differences are present not only in
responsivity of young women is mediated at manifest disease but in subclinical pathology,
least in part by circulating estrogen, and after and are present throughout the life course. As
menopause the blood pressure stress responsiv- noted earlier, psychosocial demands are greater
ity and ambulatory blood pressure of women among people of the lower socioeconomic
approach that of men (Owens, Stoney, & status, while perceived social support is poorer
Matthews, 1993). (Turner & Marino, 1994; Turner et al., 1995).
Low socioeconomic status is associated with
chronic stressors such as excessive work
8.02.6.4 Ethnicity demands, inadequate rewards, economic hard-
ship and uncertainty, increased exposure to
There are pronounced ethnic differences in
crime and noise in everyday life, frustration in
the prevalence of a variety of diseases (Murray
expectations associated with social roles, and
& Lopez, 1996). The contribution of psycho-
greater barriers to achieving life goals (Ane-
social factors has been investigated extensively
shensel, 1992). A combination of biological
in relation to cardiovascular disorders and
factors, health behaviors and psychosocial
diabetes. Noninsulin dependent diabetes is
influences such as poorer support appears to
particularly common among Micronesians,
account for much of the socioeconomic gradient
native Americans, Hispanic Americans, and
in mortality and cardiovascular disease risk
in migrants from South Asia to the UK. It is
factors (Lynch, Kaplan, Cohen, Tuomilehto, &
accompanied by a high prevalence of insulin
Salonen, 1996). However, some social varia-
resistance, low concentrations of HDL-choles-
tions require further explanation. For example,
terol and high levels of abdominal obesity.
Nordentoft et al. (1996) found that life stress
Although there have as yet been few studies of
and education were independent predictors of
psychophysiological processes, it is plausible
premature delivery in a large sample of pregnant
that these ethnic differences may relate to the
women. There is limited evidence that psycho-
stress-related pathways described in Section
physiological responsivity is associated with
8.02.3.3.1.
socioeconomic markers such as education and
Hypertension is more prevalent among black
work status, but further study of these issues is
than white people in urbanized societies, and
essential (Carroll, Smith, Sheffield, Shipley, &
research indicates that factors such as repressed
Marmot, 1997; Owens et al., 1993)
hostility, socioeconomic status, and social
integration may all contribute (Anderson,
Myers, Pickering, & Jackson, 1989). There
have been many studies of differences in the 8.02.6.6 Genetic Factors
responses of black and white volunteers to
Genetic factors are probably responsible for
laboratory mental stress tests. The data suggest
many of the differences between people who are
that black people show greater increases in
at risk of psychophysiological disease. They
peripheral vascular resistance than whites,
may operate in several different ways. First,
particularly when confronted by passive aver-
twin adoption studies indicate that a substantial
sive tasks such as the cold pressor test (Saab
proportion of the variance in the experience of
et al., 1992). White people by contrast show
adult life events and in social support is
increases in heart rate and myocardial contrac-
accounted for by genetic influences (Bergeman,
tility, indicative of greater sensitivity to beta-
Plomin, Pedersen, McClearn, & Nesselroade,
adrenergic sympathetic nervous stimulation.
1990; Plomin, Lichtenstein, Pedersen,
These findings indicate that when faced with
McClearn, & Nesselroade, 1990). Psychological
the same psychosocial demands, ethnic differ-
factors such as optimism, hostility, and Type A
ences in responsivity may contribute to differ-
behavior are also heritable. Consequently, the
ential disease risks.
likelihood that a person will manifest intense
psychophysiological responses is determined
8.02.6.5 Socioeconomic Status and Education not only by his or her experience, but by genetic
makeup. Second, the magnitude of psychophy-
The major sources of morbidity and mortality siological stress responses to standardized tasks
in developed countries show strong socio- in the laboratory shows significant heritability
economic gradients, with higher prevalence (Hewitt & Turner, 1995). Third, genetics
contribute to other predisposing factors like actual mechanisms through which disease is
obesity, and to activities such as alcohol initiated and exacerbated. However, before
consumption, thereby increasing risk of disease these psychophysiological processes are de-
through behavioral pathways. Overall, there is a scribed, it must be emphasized that they are
sizeable genetic contribution to risk of illnesses not the only pathways through which psycho-
such as coronary heart disease, hypertension, social factors affect disease and physical health.
rheumatoid arthritis, diabetes, and certain types Psychosocial factors may influence disease not
of cancer, so it is likely that psychophysiological only through psychophysiological processes,
processes will have a greater impact on an but also through behavioral, affective, and
individual who is genetically predisposed to a social-cognitive pathways. These latter will not
particular condition. be discussed here, since they have been
extensively described previously (Cohen &
Rodriguez, 1995; Steptoe, 1991).
8.02.6.7 Individual Patterns of Cognitive processes such as the identification
Psychophysiological Responses of symptoms or decisions to seek help from
health professionals, and behaviors such as
The final predisposing factor that needs to be
alcohol consumption, adherence to medical
considered is each person's tendency to show a
advice, and risky sexual practices, may all be
particular pattern of physiological responsivity
affected by the psychosocial factors described in
to psychosocial demands. As noted earlier,
this chapter. They may in turn impact on
physiological responsivity is a relatively stable
diagnosis and disease. It is frequently difficult
characteristic for each individual, and it is one
fully to apportion accountability to psychophy-
that emerges early in life in animals and humans
siological and behavioral mediators. For ex-
(Brown-Borg, Klemcke, & Blecha, 1993). Lewis,
ample, both poor social support and depressed
Thomas, and Worobey (1990) showed that
mood have been shown to predict early
infants who were emotionally reactive to a
mortality following myocardial infarction
painful stimulus (inoculation) at two months
(Berkman, Leo-Summers, & Horwitz, 1992;
old were more prone to infection over the
Frasure-Smith et al., 1993). The known effects of
subsequent year, probably because of a ten-
these factors on physiological systems relevant
dency towards stress-induced immunosuppres-
to coronary disease may be responsible, but so
sion. In adult life, many people show individual-
might behavioral factors. For instance, there
response specificity, which is the tendency to
may be differences in adherence to medication,
respond maximally and consistently in a
or small variations in the speed with which help
particularly physiological pathway. It has
is sought following the onset of symptoms, that
typically been evaluated by measuring a range
might occur between the socially isolated or
of autonomic responses to a series of different
depressed patients and others. These might
tasks. A person manifests individual-response
determine whether or not the patient survives a
specificity if they are maximally reactive in one
fresh cardiac event irrespective of psychophy-
measure across situations. Individuals differ in
siological disturbances.
the measures in which they are most responsive,
Notwithstanding these considerations, there
so some may be blood pressure responders,
is ample evidence for psychophysiological
while others are most sensitive in terms of the
involvement in disease pathology. In fact,
electrodermal system or cortisol (Steptoe,
several types of mechanism have now been
1984a). Multivariate analyses suggest that
identified, and these are summarized below. It is
about one-third of people show consistent
important to recognize the differences between
individual-response specificity. It is appealing
them, since the role played by psychophysiolo-
to speculate that these people may be prone to
gical factors in disease pathology is somewhat
developing disorders associated with the psy-
varied. Moreover, the types of research design
chophysiological parameter in which they are
needed to evaluate the various mechanisms are
most responsive.
also quite distinct.
(i) Psychosocially induced physiological re-
8.02.7 PSYCHOPHYSIOLOGICAL activity as a causal factor.
MODELS OF DISEASE (ii) Psychosocially induced physiological re-
activity as an inhibitor of host resistance and
The previous sections have described the host defenses.
physiological responses that are activated when (iii) Psychosocially induced physiological re-
psychosocial demands outweigh the resources activity as a disruptive factor on existing
available to the individual, and have outlined pathology.
the factors that increase vulnerability and (iv) Psychosocially induced physiological re-
predisposition to disease. There remain the activity as a trigger of acute clinical events.
Psychophysiological Models of Disease 67
8.02.7.1 Physiological Reactivity as a Causal may be an effect rather than cause of the medical
Factor condition.
A way of circumventing this cause±effect
The first possibility is that psychophysiolo- problem is to identify people who are at
gical reactivity is directly responsible for enhanced risk for a particular disorder prior
disease. Particular individuals show heightened to the onset of pathology. If aberrant reactivity is
reactivity in specific physiological parameters present among these individuals, then the
such as blood pressure, gastrointestinal moti- psychophysiological disturbance clearly pre-
lity, or muscle tension in the head and neck. cedes the development of the disorder. Unfortu-
Through regular or sustained exposure to nately, markers of enhanced risk are rare for
psychosocial demands that over-tax resources, many medical disorders, making this approach
these physiological responses may be repeatedly difficult to implement. The field in which this
elicited and in due course may gravitate from strategy has been developed most vigorously is
acute reactions to sustained pathology. Of hypertension, since there is a moderate but
course, physiological reactivity does not act consistent hereditary contribution to blood
alone, but against the substrate of predisposi- pressure level. This means that young people
tions outlined in Section 8.02.6. whose parents have hypertension are at in-
The type of study needed to evaluate this creased risk themselves. The blood pressure and
mechanism is a longitudinal investigation in other cardiovascular responses to mental stress
which psychobiological predispositions and of normotensive people with and without a
reactivity patterns are measured at the outset, family history of hypertension have therefore
and exposure to the stressors that trigger been examined. It is frustrating that despite a
appropriate physiological responses is tracked. large number of studies, findings have been
It would then be predicted that people with inconclusive, with heightened reactivity being
heightened reactivity in a particular physiolo- recorded from high risk people in some studies
gical response system, and who also experience but not in others (Steptoe, 1997). The explana-
psychosocial demands that elicit these reactions tion for the variability in results is not clear,
over a sustained period, will be at increased risk although the nature of psychological demands
for developing the disease. and the co-existence of vulnerability factors such
This type of study is difficult to carry out in as emotional inhibition may be relevant. Perhaps
humans, although it forms the basis of some more importantly, even this research strategy
animal models of pathology (Manuck et al., does not completely overcome the cause±effect
1989). More readily available in humans is problem in interpretation. A variety of patho-
evidence that people with a variety of disorders physiological processes are disturbed in young
tend to react to cognitive and emotional chal- normotensives with a family history of hyper-
lenges with heightened responses in the phy- tension, including sodium transport, vascular
siological systems relevant to their disorder. distensibility and left ventricular structure.
Thus people with hypertension typically show Consequently, the possibility cannot be ruled
larger blood pressure responses to mental stress out that heightened psychophysiological reac-
tests than do those with normal blood pressure. tivity is secondary in these groups, just as it may
Asthmatics react to challenges with greater be in established hypertensives.
increases in bronchoconstriction, people with Longitudinal studies have also been con-
irritable bowel or irritable colon show greater ducted, testing the hypothesis that normoten-
disturbances in motility of the gut, patients sive people with heightened reactivity will be at
suffering from tension headache or chronic low increased risk of developing hypertension in the
back pain show heightened reactivity in future. Here the evidence is rather more
muscles in appropriate tissues, and so on (Flor compelling, with an increasing number of
& Turk, 1989; Kumar & Wingate, 1985; studies showing that high reactivity does predict
Steptoe, 1997). future hypertension (Light, Dolan, Davis, &
These studies are consistent with psychophy- Sherwood, 1992; Treiber et al., 1996). Blood
siological reactivity being involved in disease pressure reactivity to mental stress is also
etiology, but do not provide strong evidence. associated with the pathological consequences
The reason is that disturbances in reactivity to of hypertension such as hypertrophy of the left
behavioral challenges may be secondary to the cardiac ventricle (Hinderliter, Light, Girdler,
pathological changes characteristic of the dis- Willis, & Sherwood, 1996). Yet it is also the case
ease itself. Thus bronchial hyper-reactivity is a that some longitudinal studies have failed to
general process in asthma that triggers reactions show any prediction of future cardiovascular
to exercise, cold, housedust mite and other problems (Carroll et al., 1995). Two issues are
factors apart from emotional challenges. In relevant. The first is that heightened psycho-
other conditions as well, exaggerated reactivity physiological reactivity may only be significant
in the presence of co-factors such as obesity or account of all these alternatives probably goes
salt sensitivity. Second, it is necessary in beyond the scope of any study in humans that
longitudinal studies to include measures of the has been conducted thus far.
life experience of the cohort over the follow-up Some of the most convincing evidence for
period. Unless this is done, one important psychosocially induced impairment of host
element of the psychophysiological causal defenses comes from studies in which infectious
hypothesis is missing. agents were administered experimentally. Co-
hen, Tyrrell, and Smith (1991) demonstrated
8.02.7.2 Physiological Reactivity as an Inhibitor that the acquisition of infection following
of Host Resistance and Defense administration of known doses of common
cold viruses was related to a composite measure
The second mechanism through which of psychological stress; subsequent analyses
psychosocially-induced physiological reactions suggested that infection rate was predicted by
may influence disease is by altering physical negative affect and subjectively-rated stress,
vulnerability in ways that render the person while illness was predicted by negative life
more susceptible to invasive organisms. The events. These findings have been replicated in
mechanism is presented diagrammatically in broad outline, albeit without assessment of the
Figure 2, which shows four possible scenarios immune parameters that might have mediated
linking exposure to pathogens and bodily clinical effects (Cohen, Boyle et al., 1995, Stone
defenses. The mechanism is illustrated through et al., 1992).
the case of infectious agents and immune Psychosocial factors are associated with
defense, although it is equally applicable to infectious illness in naturalistic settings as well
other pathogens and defense systems. Panel A (Cohen & Williamson, 1991). For example, the
represents the situation when the organism herpes virus responsible for cold sores and
mounts an adequate immune response that genital lesions may remain latent in the body
tackles the infection effectively and prevents after the first exposure, but can be reactivated to
disease. In panel B, exposure takes place in the produce new episodes of illness. Several retro-
presence of a stress-induced impairment of spective studies have shown that recurrence is
immune response, allowing the infection to be more likely during episodes of psychosocial
acquired and illness to develop. This is the stress. One prospective investigation with daily
situation that pertains when physiological ratings of mood indicated that the ten days prior
reactivity alters host resistance. to a recurrence of genital herpes were char-
This psychophysiological mechanism is dif- acterized by elevations in ratings of nervousness
ferent from the process described in Section (Dalkvist, Wuahlin, Bartsch, & Forsbeck,
8.02.7.1 in two important ways. First, the 1995). Interestingly, Turner-Cobb and Steptoe
psychophysiological response is not presumed (1996) found in another longitudinal experi-
to cause illness, but rather to influence vulner- ment that symptoms of upper respiratory tract
ability. Second, it is not necessary to postulate illness were preceded by high levels of perceived
that people are exposed to intense, repeated stress for two to three weeks. In the study of
stressors in order for disease risk to be immune function in care-givers for dementing
enhanced. Rather, heightened vulnerability patients alluded to in Section 8.02.3.4.3,
for a single short time period may be sufficient, Kiecolt-Glaser et al., 1991) reported that care-
if it is contiguous with a critical state of invasion. givers experienced longer episodes of illness
The ideal type of study of this mechanism is a over a 12-month follow-up than did controls.
longitudinal investigation in which psychosocial This suggests that the immune suppression
factors are monitored together with measures of recorded among care-givers may have led to
bodily defenses, exposure to infectious agents, prolongation of illness.
and illness. Such studies are difficult to carry out Evidence for psychosocially-induced impair-
at a technical level and also require high levels of ment of host resistance having a clinical role is
cooperation from participants. Interpretation therefore becoming increasingly convincing. In
of results is also complicated by the two studies of pathophysiology, there is a new
additional scenarios shown in panels C and D understanding that infectious processes are not
of Figure 2. Panel C describes a situation when confined to traditional self-limiting disorders,
the infectious agent to which the individual is but may contribute to conditions such as peptic
exposed is particularly virulent. Under these ulcer, gastric cancer, dementia, vasculitis, and
circumstances, illness may occur even though insulin-dependent diabetes (Lorber, 1996;
immune responses are intact. Another possibi- O'Connor, Buckley, & O'Morain, 1996). As
lity is that bodily defenses are disrupted, but these mechanisms are uncovered, the role of
since there is no simultaneous exposure to a psychophysiological processes in reducing re-
pathogen, no illness results (Panel D). Taking sistance may assume even greater importance.
Psychophysiological Models of Disease 69
Stress, immune responses and infection

A B
Infectious Adequate Infectious Impaired

agent immune response agent immune response
No
illness Illness
C D
No
Powerful Adequate Impaired
infectious
infection immune response immune response
agent
Illness No
illness
Figure 2 Schematic outline of associations between immune defenses and infection.
8.02.7.3 Physiological Reactivity as a Disruptive turbances of bronchoconstriction in asthma) or

Factor may disrupt host resistance, as in the case of
autoimmune conditions. There may be some
If psychosocially induced physiological reac- problems such as insulin-dependent diabetes
tions do not act as causal factors, how do they where effects could be mediated either directly
contribute to the disease process? An important through disturbances of insulin metabolism or
possibility is that psychophysiological reactions indirectly through failures in resistance to
act on existing pathology to disrupt regulatory enteroviruses.
mechanisms. The result may be exacerbation of There is a substantial amount of data
the patient's clinical state, possibly leading to showing that symptoms and other indicators
symptomatic episodes, or to more rapid of medical conditions covary with psychosocial
degeneration in progressive conditions than factors, and the mechanism outlined here may
would otherwise be the case. be responsible for these associations. By way of
The role of physiological reactivity as a illustration, factors such as negative mood and
disruptive factor differs from its involvement in daily stressors have been shown to covary with
the processes outlined in Section 8.02.7.1 disability and symptoms in rheumatoid arthritis
and 8.02.7.2 in several ways. First, this (Affleck, Tennen, Urrows, & Higgins, 1994),
mechanism is operative in people already irritable bowel syndrome (Suls, Wan, & Blan-
suffering from disease, although the pathology chard, 1994), the chronic inflammatory condi-
may not necessarily have reached the stage of tion systemic lupus erythematosus (Adams,
clinical diagnosis. It is particularly likely to be Dammers, Saia, Brantley, & Gaydos, 1994),
active in chronic or episodic conditions such as headache, Crohn's disease (Brantley & Jones,
pain syndromes, bronchial asthma, and dia- 1993), insulin-dependent diabetes (Goldston,
betes. Second, the influence of psychophysio- Kovacs, Obrosky, & Iyengar, 1995), and
logical responses may be manifest at the level of phantom limb pain (Arena, Sherman, Bruno,
day-to-day clinical status, and consequently & Smith, 1990). However, the problem arises of
relatively minor daily hassles may be influential. whether these associations reflect genuine
Third, the physiological reactions may either be influences on pathology, or effects on symptom
directly involved in pathology (such as dis- reporting and complaints. In order to show that
psychophysiological processes are operative at clinical events in susceptible individuals. One

the biological level, it is necessary to measure study assessed anger during the hours prior to
covariation of psychosocial factors with phy- acute infarction in comparison with other time
siological regulatory parameters as well as periods (Mittleman et al., 1995). A high
symptoms. Here findings are more sparse, but incidence of severe anger was recorded in the
nevertheless suggestive. Thus several studies of two hours before symptom onset. The effect was
insulin-dependent diabetes have shown that not present among patients taking beta-block-
stressors influence blood glucose levels and ers, suggesting that stimulation of coronary
metabolic control independently of variations in vasospasm or thrombotic processes by sym-
diet, exercise, or compliance with medical advice pathoadrenal activation may have been in-
(Goldston et al., 1995; Halford, Cuddihy, & volved. Emotional triggers of acute cardiac
Mortimer, 1990). In patients with rheumatoid events have been reported in other studies as
arthritis, the experience of minor life events was well (Tofler et al., 1990). Jain, Burg, Soufer, &
associated with fluctuations in T and B Zaret (1995) showed that cardiac patients who
lymphocyte counts (Zautra et al., 1989). As responded to laboratory mental stress with
methods of physiological monitoring become disturbances of myocardial function were more
more sophisticated and less obtrusive, it is likely likely over the next two years to have acute
that more influences of this kind will become infarctions or develop unstable angina pectoris
apparent. than were nonresponders to stress. Taken
The role of psychosocial factors in the together, these findings suggest a plausible link
development of cancer and progression of between psychosocially-induced physiological
HIV infection are controversial issues that are reactions and acute episodes of clinical disease.
discussed in other chapters of this volume. It is
probable that if psychophysiological processes
are involved, they act through the dysregulation 8.02.8 CONCLUSION
of immune surveillance in a fashion similar to The psychophysiology of disease is a vigorous
the mechanisms outlined in this section. and exciting area of research. It involves the
integration of several disciplines including
neuroscience, pathophysiology, and health
8.02.7.4 Physiological Reactivity as a Trigger of psychology, and in each of these areas new
Acute Clinical Events discoveries are constantly changing our levels of
understanding. The complexity of links between
The fourth distinct psychophysiological me- the brain, peripheral physiological function,
chanism in disease concerns the elicitation of and disease risk is formidable, and linear models
acute clinical events. It is possible that psycho- are of limited value. The broad processes linking
physiological responses can be so intense as to psychophysiological factors with disease risk
trigger episodes of serious illness, and possibly are now understood, although many of the
even death. Such an effect is unlikely in the biological mediators remain tantalizingly illu-
absence of severe underlying disease rendering sive. Important challenges for future research
the victim especially vulnerable. The mechanism include delineation of the processes through
is distinctive in that a single occurrence may which psychosocial factors such as social
have serious clinical consequences. inequality and social isolation affect disease,
It has been proposed that such a process may understanding how emotional and behavioral
be involved in the precipitation of epileptic coping responses can modify physiological
seizures (Webster & Mawer, 1989). One study of reaction patterns and contribute to resistance
civilians under threat of missile attack showed and vulnerability, and defining the ways in
seizures to be triggered by raid alarms in a small which psychophysiological knowledge can be
group of patients (Neufeld, Sadeh, Cohn, & harnessed for prevention and disease manage-
Korczyn, 1994). It is conceivable that the ment. Psychophysiology is one of the corner-
process is also relevant to the occurrence of stones of clinical health psychology, and is of
stroke, although evidence is sparse (House, prime importance in understanding how psy-
Dennis, Mogridge, Hawton, & Warlow, 1990). chological and social experience can influence
Probably the best illustration of the impact of health and disease.
psychophysiological processes on acute clinical
events is in the cardiovascular field, with the
triggering of myocardial infarction and sudden 8.02.9 REFERENCES
cardiac death. Recent studies of myocardial
Abbott, B. B., Schoen, L. S., & Badia, P. (1984).
infarction victims suggest that the disturbances Predictable and unpredictable shock: Behavioral mea-
of cardiac rhythm and coronary blood flow sures of aversion and physiological measures of stress.
described in Section 8.02.3.2.2 may precipitate Psychological Bulletin, 96, 45±71.
References 71
Adams, M. R., Kaplan, J. R., Clarkson, T. B., & Koritnik, (1994). Effects of beta-adrenergic blockade on immuno-
D. R. (1985). Ovariectomy, social status, and athero- logic and cardiovascular changes induced by mental
sclerosis in cynomolgus monkeys. Arteriosclerosis, 5, stress. Circulation, 89, 762±769.
192±200. Bergeman, C. S., Plomin, R., Pedersen, N. L., McClearn,
Adams, P. R., & Adams, G. R. (1984). Mount Saint G. E., & Nesselroade, J. R. (1990). Genetic and
Helen's ashfall: Evidence for a disaster stress reaction. environmental influences on social support: The Swedish
American Psychologist, 39, 252±260. Adoption/Twin Study of Aging. Journal of Gerontology,
Adams, S. G., Dammers, P. M., Saia, T. L., Brantley, P. J., 45, 101±106.
& Gaydos, G. R. (1994). Stress, depression and anxiety Berkman, L. F., Leo-Summers, L., & Horwitz, R. I. (1992).
predict average symptom severity and daily symptom Emotional support and survival after myocardial infarc-
fluctuation in systemic lupus erythematosus. Journal of tion. Annals of Internal Medicine, 117, 1003±1009.
Behavioral Medicine, 17, 459±477. Besedovsky, H. O., & Del Rey, A. (1996). Immune-neuro-
Affleck, G., Tennen, H., Urrows, S., & Higgins, P. (1994). endocrine interactions: Facts and hypotheses. Endocrine
Person and contextual features of daily stress reactivity: Reviews, 17, 64±102.
Individual differences in relation to undesirable daily Biselli, R., Farrace, S. D., Amelio, R., & Fattorossi, A.
events with mood disturbance and chronic pain intensity. (1993). Influence of stress on lymphocyte subset
Journal of Personality and Social Psychology, 66, distributionÐa flow cytometric study in young student
329±340. pilots. Aviation Space and Environmental Medicine, 64,
Ahmed, R., & Gray, D. (1996). Immunological memory 116±120.
and protective immunity: Understanding their relation. Bjorntorp, P. (1990). ªPortalº adipose tissue as a generator
Science, 272, 54±60. of risk factors for cardiovascular disease and diabetes.
Allen, M. T., Stoney, C. M., Owens, J. F., & Matthews, K. Arteriosclerosis, 10, 493±496.
A. (1993). Hemodynamic adjustments to laboratory Blanchard, E. B., Cornish, P. J., Wittrock, D. A., &
stress: The influence of gender and personality. Psycho- Jaccard, J. (1990). Effects of 24-hour ambulatory blood
somatic Medicine, 55, 505±517. pressure monitoring on daily activities. Health Psychol-
Allgulander, C. (1994). Suicide and mortality patterns in ogy, 9, 647±652.
anxiety neurosis and depressive disorder. Archives of Blane, D., Brunner, E., & Wilkinson, R. G. (Eds.) (1996).
General Psychiatry, 51, 708±712. Health and social organization. London: Routledge.
Anderson, E. A., Wallin, B. G., & Mark, A. L. (1987). Blumenthal, J. A., Jiang, W., Waugh, R. A., Frid, D. J.,
Dissociation of sympathetic nerve activity in arm and leg Morris, J. J., Coleman, R. E., Hanson, M., Babyak, M.,
muscle during mental stress. Hypertension, 9, III- Thyrum, E. T., Krantz, D. S., & O'Connor, C. (1995).
114±III-119. Mental stress-induced ischemia in the laboratory and
Anderson, N. B., Myers, H. F., Pickering, T., & Jackson, J. ambulatory ischemia during daily life. Circulation, 92,
S. (1989). Hypertension in blacks: Psychosocial and 2102±2108.
biological perspectives. Journal of Hypertension, 7, Bolger, N., & Zuckerman, A. (1995). A framework for
161±172. studying personality in the stress process. Journal of
Aneshensel, C. S. (1992). Social stress: Theory and Personality and Social Psychology, 69, 890±902.
research. Annual Review of Sociology, 18, 15±38. Bongard, S., Hodapp, V., Frisch, M., & Lennartz, K.
Ardlie, N. G., Glew, G., & Schwartz, C. J. (1966). (1994). Effects of active and passive coping on task
Influence of catecholamines on nucleotide-induced performance and cardiovascular reactivity. Journal of
platelet aggregation. Nature, 212, 415±417. Psychophysiology, 8, 219±230.
Arena, J. G., Sherman, R. A., Bruno, G. M., & Smith, J. Boscarino, J. A. (1996). Post-traumatic stress disorder,
D. (1990). The relationship between situational stress exposure to combat, and lower plasma cortisol among
and phantom limb pain: Cross-lagged correlational data Vietnam veterans: Findings and clinical implications.
from 6 month pain logs. Journal of Psychosomatic Journal of Consulting and Clinical Psychology, 64,
Research, 34, 71±77. 191±201.
Arnetz, B. B., Wasserman, J., Petrini, B., Brenner, S. O., Bosch, J. A., Brand, H. S., Ligtenberg, T. J. M., Bermond,
Levi, L., Eneroth, P., Salovaara, H., Hjelm, R., B., Hoogstraten, J., & Nieuw-Amerongen, A. V. (1996).
Salovaara, L., Theorell, T., & Petterson, I-L. (1987). Psychological stress as a determinant of protein levels
Immune function in unemployed women. Psychosomatic and salivary-induced aggregation of streptococcus gor-
Medicine, 49, 3±12. donii in human whole saliva. Psychosomatic Medicine,
Aubert, A., Vega, C., Dantzer, R., & Goodall, G. (1995). 58, 374±382.
Pyrogens specifically disrupt the acquisition of a task Boyce, W. T., & Chesterman, E. (1990). Life events, social
involving cognitive processing in the rat. Brain, Behavior, support, and cardiovascular reactivity in adolescence.
and Immunity, 9, 129±148. Developmental and Behavioral Pediatrics, 11, 105±111.
Axelrod, J., & Reisine, T. D. (1984). Stress hormones: Brandtstadter, J., & Rothermund, K. (1994). Self-percepts
Their interaction and regulation. Science, 224, 452±459. of control in middle and later adulthood: Buffering
Bachen, E. A., Manuck, S. B., Cohen, S., Muldoon, M. F., losses by rescaling goals. Psychology and Aging, 9,
Raible, R., Herbert, T. B., & Rabin, B. S. (1995). 265±273.
Adrenergic blockade ameliorates cellular immune re- Brantley, P. J., & Jones, G. N. (1993). Daily stress and
sponses to mental stress in humans. Psychosomatic stress-related disorders. Annals of Behavioral Medicine,
Medicine, 57, 366±372. 15, 17±25.
Bachen, E. A., Manuck, S. B., Marsland, A. L., Cohen, S., Brindley, D. N., McCann, B. S., Niaura, R., Stoney, C. M.,
Malkoff, S. B., Muldoon, M. F., & Rabin, B. S. (1992). & Suarez, E. C. (1993). Stress and lipoprotein metabo-
Lymphocyte subset and cellular immune responses to a lism: modulators and mechanisms. Metabolism: Clinical
brief experimental stressor. Psychosomatic Medicine, 54, and Experimental, 42 (9 Suppl. 1), 3±15.
673±679. Brown, J. D. (1991). Staying fit and staying well: Physical
Baron, R. S., Cutrona, C. E., Hicklin, D., Russell, D. W., fitness as a moderator of life stress. Journal of
& Lubaroff, D. M. (1990). Social support and immune Personality and Social Psychology, 60, 555±561.
function among spouses of cancer patients. Journal of Brown, G. W., & Harris, T. (1978). Social origins of
Personality and Social Psychology, 59, 344±352. depression. London: Tavistock.
Benschop, R. J., Nieuwenhuis, E. E., Tromp, E. A., Brown-Borg, H. M., Klemcke, H. G., & Blecha, F. (1993).
Godaert, G. L., Ballieux, R. E., & van Doornen, L. J. Lymphocyte proliferative responses in neonatal pigs with
high or low plasma cortisol concentration after stress cold. New England Journal of Medicine, 325, 606±612.
induced by restraint. American Journal of Veterinary Cohen, S., & Williamson, G. M. (1991). Stress and
Research, 54, 2015±2020. infectious disease in humans. Psychological Bulletin,
Burg, M. M., & Seeman, T. E. (1994). Families and health: 109, 5±24.
The negative side of social ties. Annals of Behavioral Cole, P. M., Zahn-Waxler, C., Fox, N. A., Usher, B. A., &
Medicine, 16, 109±115. Welsh, J. D. (1996). Individual differences in emotion
Cacioppo, J. T. (1994). Social neuroscience: Autonomic, regulation and behavior problems in preschool children.
neuroendocrine, and immune responses to stress. Psy- Journal of Abnormal Psychology, 103, 518±529.
chophysiology, 31, 113±128. Cole, S. W., Kemeny, M. E., Taylor, S. E., & Visscher, B.
Callister, R., Suwarno, N. O., & Seals, D. R. (1992). R. (1996). Elevated physical health risk among gay men
Sympathetic activity is influenced by task difficulty and who conceal their homosexual identity. Health Psychol-
stress perception during mental challenge in humans. ogy, 15, 243±251.
Journal of Physiology, 454, 373±387. Dalkvist, J. Wahlin, T.-B. R., Bartsch, E., & Forsbeck, M.
Carroll, D., Smith, G., Sheffield, D., Shipley, M. J., & (1995). Herpes simplex and mood: A prospective study.
Marmot, M. G. (1995). Pressor reactions to psychologi- Psychosomatic Medicine, 57, 127±137.
cal stress and prediction of future blood pressure: Data Dantzer, R., & Kelley, K. W. (1989). Stress and immunity:
from the Whitehall II study. British Medical Journal, An integrated view of relationships between the brain
310, 771±776. and the immune system. Life Sciences, 44, 1995±2008.
Carroll, D., Smith, G., Sheffield, D., Shipley, M. J., & Davis, M. C., Matthews, K. A., Meilahn, E. N., & Kiss, J.
Marmot, M. G. (1997). The relationship between socio- E. (1995). Are job characteristics related to fibrinogen
economic status, hostility, and blood pressure reactions levels in middle-aged women? Health Psychology, 14,
to mental stress in men: Data from the Whitehall II 310±318.
study. Health Psychology, 16, 131±136. De Bellis, M. D., Lefter, L., Trickett, P. K., & Putnam, F.
Carver, C. S., Pozo, C., Harris, S. D., Noriega, V., Scheier, W., Jr. (1994). Urinary catecholamine excretion in
M. F., Robinson, D. S., Ketcham, A. S., Moffat, F. L., sexually abused girls. Journal of the American Academy
Jr., & Clark, K. C. (1993). How coping mediates the of Child and Adolescent Psychiatry, 33, 320±327.
effect of optimism on distress: A study of women with De Boer, S. F., Van der Gugten, J., & Slangen, J. L. (1989).
early stage breast cancer. Journal of Personality and Plasma catecholamine and corticosteroid responses to
Social Psychology, 65, 375±390. predictable and unpredictable noise stress in rats.
Castle, S., Wilkins, S., Heck, E., Tanzy, K., & Fahey, J. Physiology and Behavior, 45, 789±795.
(1995). Depression in caregivers of demented patients is De Geus, E. J. C., Van Doornen, L. J. P., & Orlebeke, J. F.
associated with altered immunity. Clinical and Experi- (1993). Regular exercise and aerobic fitness in relation to
mental Immunology, 101, 487±493. psychological make-up and physiological stress reactiv-
Chandra, R. K. (1989). Nutritional regulation of immunity ity. Psychosomatic Medicine, 55, 347±363.
and risk of infection in old age. Immunology, 67, Deanfield, J. E., Shea, M, Kensett, M., Horlock, P.,
141±147. Wilson, R. A., De Landsheere, C. M., & Selwyn, A. P.
Checkley, S. (1996). The neuroendocrinology of depression (1984). Silent myocardial infarction due to mental stress.
and chronic stress. British Medical Bulletin, 52, 597±617. Lancet, ii, 1001±1005.
Christian, J. J. (1970). Social subordination, population Dienstbier, R. A. (1989). Arousal and physiological
density, and mammalian evolution. Science, 168, 84±90. toughness: implications for mental and physical health.
Chrousos, G. P. (1995). The hypothalamic±pituitary± Psychological Review, 96, 84±100.
adrenal axis and immune-mediated inflammation. New Dimsdale, J. E., Mills, P., Patterson, T., Ziegler, M., &
England Journal of Medicine, 332, 1351±1362. Dillon, E. (1994). Effects of chronic stress on beta-
Cobb, S., & Rose, R. M. (1973). Hypertension, peptic ulcer adrenergic receptors in the homeless. Psychosomatic
and diabetes in air traffic controllers. Journal of the Medicine, 56, 290±295.
American Medical Association, 224, 489±492. Dressler, W. W. (1991a). Social support, lifestyle incon-
Coe, C. L. (1993). Psychosocial factors and immunity in gruity, and arterial blood pressure in a southern black
nonhuman primates: a review. Psychosomatic Medicine, community. Psychosomatic Medicine, 53, 608±620.
55, 298±308. Dressler, W. W. (1991b). Stress and Adaptation in the
Cohen, S., Boyle, W. J., Skoner, D. P., Fireman, P., Context of Culture: Depression in a southern black
Gwaltney, J. M., Jr., & Newsom, J. T. (1995). State and community. Albany, NY: SUNY Press.
trait negative affect as predictors of objective and Dutz, W., Kohout, E., Rossipal, E., & Vessal, K. (1976).
subjective symptoms of respiratory viral infections. Infantile stress, immune modulations, and disease
Journal of Personality and Social Psychology, 68, patterns. Pathology Annual, 11, 415±454.
159±169. Dyer, A. R., Persky, V., Stamler, J., Paul, O., Shekelle, R.
Cohen, S., Kaplan, J. R., Cunnick, J. E., Manuck, S. B., & B., Berkson, D. M., Lepper, M., Schoenberger, J. A., &
Rabin, B. S. (1992). Chronic social stress, affiliation, and Lindberg, H. A. (1980). Heart rate as a prognostic factor
cellular immune response in nonhuman primates. Psy- for coronary heart disease and mortality: Findings in
chological Science, 3, 301±304. three Chicago epidemiologic studies. American Journal of
Cohen, S., Kessler, R. C., & Gordon, L. U. (1995a). Epidemiology, 112, 736±749.
Strategies for measuring stress in studies of psychiatric Engel, B. T. (1985). Stress is a noun! No, a verb! No, an
and physical disorders. In S. Cohen, R. C. Kessler, & L. adjective! In T. Field, P. M. McCabe, & N. Schneider-
U. Gordon (Eds.), Measuring stress: A guide for health man (Eds.), Stress and coping (pp. 3±14). Hillsdale, NJ:
and social scientists (pp. 3±26). New York: Oxford Erlbaum.
University Press. Esterling, B. A., Antoni, M. H., Kumar, M., & Schneider-
Cohen, S., Kessler, R. O., & Gordon, L. U. (Eds.) (1995b). man, N. (1993). Defensiveness, trait anxiety and Epstein-
Measuring stress: A guide for health and social scientists. Barr viral capsid antigen antibody titers in healthy
New York: Oxford University Press. college students. Health Psychology, 12, 132±139.
Cohen, S., & Rodriquez, M. S. (1995). Pathways linking Evans, G. W., Hygge, S., & Bullinger, M. (1995). Chronic
affective disturbances and physical disorders. Health noise and psychological stress. Psychological Science, 6,
Psychology, 14, 374±380. 334±338.
Cohen, S., Tyrrell, D. A. J., & Smith, A. P. (1991). Evans, P., Bristow, M., Hucklebridge, F., Clow, A., &
Psychosocial stress and susceptibility to the common Walters, N. (1993). The relationship between secretory
References 73
immunity, mood and life events. British Journal of S. (1995). A longitudinal study of life events and
Clinical Psychology, 32, 227±236. metabolic control among youths with insulin-dependent
Fleming, I., Baum, A., Davidson, L. M., Rectanus, E., & diabetes mellitus. Health Psychology, 14, 409±414
McArdle, S. (1987). Chronic stress as a factor in Gotthardt, U., Schweiger, U., Fahrenberg, J., Lauer, C. J.,
physiologic reactivity to challenge. Health Psychology, Holsboer, F., & Heuser, I. (1995). Cortisol, ACTH, and
6, 221±237. cardiovascular response to a cognitive challenge para-
Flor, H., & Turk, D. C. (1989). Psychophysiology of digm in aging and depression. American Journal of
chronic pain: Do chronic pain patients exhibit symptom- Physiology, 268, R865±R873.
specific psychophysiological responses? Psychological Gray, J. A. (1995). A model of the limbic system and basal
Bulletin, 105, 215±259. ganglia: Applications to anxiety and schizophrenia. In
Frankenhaeuser, M., Dunne, E., & Lundberg, U. (1976). M. S. Gazzaniga (Ed.), The cognitive neurosciences
Sex differences in sympathetic-adrenal medullary re- (pp. 1165±1176). Cambridge, MA: MIT Press.
sponses induced by different stressors. Psychopharma- Grignani, G., Soffiantino, F., Zucchella, M., Pacchiarini,
cology, 47, 1±5. L., Taccone, F., Bonomi, E., Pastoris, A., Sbaffi, A.,
Frankenhaeuser, M., Lundberg, U., & Forsman, L. (1980). Fratino, P., & Tavazzi, L. (1991). Platelet activation by
Dissociation between sympatho-adrenal and pituitary- emotional stress in patients with coronary artery disease.
adrenal responses to an achievement situation charac- Circulation, 83(Suppl. 11), 128±136.
terised by high controllability: Comparison between Haft, J. I., & Arkel, Y. S. (1976). Effect of emotional stress
Type A and Type B males and females. Biological on platelet aggregation in humans. Chest, 70, 501±505.
Psychology, 10, 79±91. Halford, W. K., Cuddihy, S., & Mortimer, R. H. (1990).
Frankenhaeuser, M., Lundberg, U., Fredrikson, M., Psychological stress and blood glucose regulation in
Melin, B., Tuomisto, M., & Myrsten, A.-L. (1989). Type 1 diabetic patients. Health Psychology, 9, 516±528.
Stress on and off the job as related to sex and Hanson, B. S., Isacsson, S.-O., Janzon, L., Lindell, S.-E., &
occupational stress in white-collar workers. Journal of Rastam, L. (1988). Social anchorage and blood pressure
Organizational Behavior, 10, 321±346. in elderly menÐa population study. Journal of Hyper-
Frasure-Smith, N., LespeÂrance, F., & Talajic, M. (1993). tension, 6, 503±510.
Depression following myocardial infarction: impact on 6 Hatch, J. P., Prihoda, T. J., Moore, P. J., Cyr-Provost, M.,
month survival. Journal of the American Medical Borcherding, S., Boutros, N. N., & Seleshi, E. (1991). A
Association, 270, 1819±1825. naturalistic study of the relationships among electro-
Fredrikson, M., Lundberg, U., & Tuomisto, M. (1991). myographic activity, psychological stress, and pain in
Serum lipid levels and cardiovascular reactivity. Journal ambulatory tension-type headache patients and
of Psychophysiology, 5, 89±95. headache-free controls. Psychosomatic Medicine, 53,
Friedman, H. S., & Booth-Kewley, S. (1987). The ªdisease- 576±584.
prone personalityº: A meta-analytic view of the con- Heckhausen, J., & Schulz, R. (1995). A life-span theory of
struct. American Psychologist, 42, 539±555. control. Psychological Review, 102, 284±304.
Friedman, H. S., Tucker, J. S., Schwartz, J. E., Martin, L. Helgeson, V. S., & Cohen, S. (1996). Social support and
R., Tomlinson-Keasey, C., Wingard, D. L., & Criqui, M. adjustment to cancer: Reconciling descriptive, correla-
H. (1995). Childhood conscientiousness and longevity: tional and intervention research. Health Psychology, 15,
Health behaviors and cause of death. Journal of 135±148.
Personality and Social Psychology, 68, 696±703. Herbert, T. B., & Cohen, S. (1993a). Depression and
Funk, S. C. (1992). Hardiness: A review of theory and immunity: A meta-analytic review. Psychological Bulle-
research. Health Psychology, 11, 335±345. tin, 113, 472±486.
Gabbay, F. H., Krantz, D. S., Kop, W. J., Hedges, S. M., Herbert, T. B., & Cohen, S. (1993b). Stress and immunity
Klein, J., Gottdiener, J. S., & Rozanski, A. (1996). in humans: A meta-analytic review. Psychosomatic
Triggers of myocardial ischemia during daily life in Medicine, 55, 364±379.
patients with coronary artery disease: physical and Herbert, T. B., Cohen, S., Marsland, A. L., Bachen, E. A.,
mental activities, anger and smoking. Journal of the Rabin, B. S., Muldoon, M. F., & Manuck, S. B. (1994).
American College of Cardiology, 27, 585±592. Cardiovascular reactivity and the course of immune
Garbarino, J., Kostelny, K., & Dubrow, N. (1991). What response to an acute psychological stressor. Psychoso-
children can tell us about living in danger. American matic Medicine, 56, 337±344.
Psychologist, 46, 376±383. Herman, J. P., Adams, D., & Prewitt, C. (1995).
Gatchel, R. J., Schaeffer, M. A., & Baum, A. (1985). A Regulatory changes in neuroendocrine stress-integrative
psychophysiological field study of stress at Three Mile circuitry produced by a variable stress paradigm.
Island. Psychophysiology, 22, 175±181. Neuroendocrinology, 61, 180±190.
Gerritsen, W., Heijnen, C. J., Weigant, V. M., Bermond, Hewitt, J. K., & Turner, J. R. (1995). Behavior genetic
B., & Frijda, N. H. (1996). Experimental social fear: studies of cardiovascular responses to stress. In J. R.
Immunological, hormonal, and autonomic concomi- Turner, L. R. Cardon, & J. K. Hewitt (Eds.), Behavior
tants. Psychosomatic Medicine, 58, 273±286. genetic approaches in behavioral medicine (pp. 87±103).
Gilad, G. M., & Gilad, V. H. (1995). Strain, stress, New York: Plenum.
neurodegeneration and longevity. Mechanisms of Ageing Hinderliter, A. L., Light, K. C., Girdler, S. S., Willis, P.
and Development, 78, 75±83. W., & Sherwood, A. (1996). Blood pressure responses to
Glaser, R., Kiecolt-Glaser, J. K., Bonneau, R. H., stress: Relation to left ventricular structure and function.
Malarkey, W., Kennedy, S., & Hughes, J. (1992). Annals of Behavioral Medicine, 18, 61±66.
Stress-induced modulation of the immune response to Hoehn-Saric, R., McLeod, D. R., & Zimmerli, W. D.
recombinant hepatitis B vaccine. Psychosomatic Medi- (1989). Somatic manifestations in women with general-
cine, 54, 22±29. ized anxiety disorder: Psychophysiological responses to
Glavin, G. B. (1992). Dopamine: A stress modulator in the psychological stress. Archives of General Psychiatry, 46,
brain and gut. General Pharmacology, 23, 1023±1026. 1113±1119.
Glavin, G. B., Pare, W. P., Sandbak, T., Bakke, H. K., & Holsboer, F., & Barden, N. (1996). Antidepressants and
Murison, R. (1994). Restraint stress in biomedical hypothalamic±pituitary±adrenocortical regulation. En-
research: An update. Neuroscience and Biobehavioral docrine Reviews, 17, 187±205.
Reviews, 18, 223±249. Holtmann, G., Kriebel, R., & Singer, M. V. (1990). Mental
Goldston, D. B., Kovacs, M., Obrosky, D. S., & Iyengar, stress and gastric acid secretion: Do personality traits
influence the response? Digestive Disease and Science, 35, Kaplan, J. R., Manuck, S. B., Williams, J. K., & Strawn,
998±1007. W. (1993). Psychosocial influences on atherosclerosis:
House, A., Dennis, M., Mogridge, L., Hawton, K., & Evidence for effects and mechanisms in nonhuman
Warlow, C. (1990). Life events and difficulties preceding primates. In J. Blascovich & E. S. Katkin (Eds.),
stroke. Journal of Neurology, Neurosurgery and Psychia- Cardiovascular reactivity to psychological stress and
try, 53, 1024±1028. disease (pp. 3±26). Washington, DC: American Psycho-
House, J. S., Landis, A. R., & Umberson, D. (1988). Social logical Association.
relationships and health. Science, 241, 540±545. Karasek, R. A. (1979). Job demands, job decision latitude,
Huppert, F. A., & Whittington, J. E. (1995). Symptoms of and mental strain: Implications for job redesign. Admin-
psychological distress predict 7-year mortality. Psycho- istrative Sciences Quarterly, 24, 285±307.
logical Medicine, 25, 1073±1086. Kiecolt-Glaser, J. K., Dura, J. R., Speicher, C. E., Trask,
Jabaaij, L., Benschop, R. J., Oostveen, F. G., Duivenvoor- O. J., & Glaser, R. (1991). Spousal caregivers of
den, H. J., Ballieux, R. E., & Vingerhoets, A. J. J. M. dementia victims: Longitudinal changes in immunity
(1993a). Immunologic, endocrine and psychological and health. Psychosomatic Medicine, 53, 345±362.
influences on cortisol-induced immunoglobulin synthesis Kiecolt-Glaser, J. K., & Glaser, R. (1995). Measurement of
in vitro. Psychoneuroendocrinology, 18, 591±605. immune response. In S. Cohen, R. C. Kessler, & L.
Jabaaij, L., Grosheide, P. M., Heijtink, R. A., Duiven- Underwood Gordon (Eds.), Measuring stress: A guide
voorden, H. J., Ballieux, R. E., & Vingerhoets, A. J. J. for health and social scientists (pp. 213±219). New York:
M. (1993b). Influence of perceived psychological stress Oxford University Press.
and distress on antibody response to low dose rDNA Kiecolt-Glaser, J. K., Malarkey, W. B., Cacioppo, J. T., &
hepatitis B vaccine. Journal of Psychosomatic Research, Glaser, R. (1994). Stressful personal relationships:
37, 361±369. Immune and endocrine function. In R. Glaser & J. K.
Jabaaij, L., van Hattum, J., Vingerhoets, A. J. J. M., Kiecolt-Glaser (Eds.), Handbook of human stress and
Oostveen, F. G., Duivenvoorden, H. J., & Ballieux, R. E. immunity (pp. 321±339). San Diego, CA: Academic
(1996). Modulation of immune response to rDNA Press.
hepatitis B vaccination by psychological stress. Journal Kiecolt-Glaser, J. K., Malarkey, W. B., Chee, M., Newton,
of Psychosomatic Research, 41, 129±137. T., Cacioppo, J. T., Mao, H.-Y., & Glaser, R. (1993).
Jain, D., Burg, M., Soufer, A., & Zaret, B. L. (1995). Negative behavior during marital conflict is associated
Prognostic implications of mental stress-induced silent with immunological down-regulation. Psychosomatic
left ventricular dysfunction in patients with stable angina Medicine, 55, 395±409.
pectoris. American Journal of Cardiology, 76, 31±35. Kiecolt-Glaser, J. K., Marucha, P. T., Malarkey, W. B.,
Jain, R., Zwickler, D., Hollander, C., Brand, H., Saper- Mercado, A. M., & Glaser, R. (1995). Slowing of wound
stein, A., Hutchinson, B., Brown, C., & Audhya, T. healing by psychological stress. Lancet, 346, 1194±1196.
(1991). Corticotropin-releasing factor modulates the Kirschbaum, C., Prussner, J. C., Stone, A. A., Federenko,
immune response to stress in the rat. Endocrinology, I., Gaab, J., Lintz, D., Schommer, N., & Hellhammer, D.
128, 1329±1336. H. (1995). Persistent high cortisol responses to repeated
Janse, M. J., & Davies, M. J. (1996). Generation and psychological stress in a subpopulation of healthy men.
conduction of the heartbeat and their disturbances. In D. Psychosomatic Medicine, 57, 468±474.
G. Julian, A. J. Camm, K. M. Fox, R. J. C. Hall, & P. A. Kirschbaum, C., Wust, S., & Hellhammer, D. (1992).
Poole-Wilson (Eds.), Diseases of the heart (pp. 88±114). Consistent sex differences in cortisol responses to
London: Saunders. psychological stress. Psychosomatic Medicine, 54,
Jayo, J. M., Shively, C. A., Kaplan, J. R., & Manuck, S. B. 648±657.
(1993). Effects of exercise and stress on body fat Klein, F., Lemaire, V., Sandi, C., Vitiello, S., Van der Logt,
distribution in male cynomolgus monkeys. International J., Laurent, P. E., Neveu, P., Le Moal, M., & Mormede,
Journal of Obesity and Related Metabolic Disorders, 17, P. (1992). Prolonged increase of corticosterone secretion
597±604. by chronic social stress does not necessarily impair
Johansson, G., Aronsson, G., & Lindstrom, B. O. (1978). immune functions. Life Sciences, 50, 723±731.
Social psychological and neuroendocrine stress reactions Klein, S. L., & Rager, D. R. (1995). Prenatal stress alters
to highly mechanised work. Ergonomics, 21, 583±599. immune function in the offspring of rats. Developmental
Jones, D. R. (1987). Heart disease mortality following Psychobiology, 28, 321±336.
widowhood: Some results from the OPCS Longitudinal Klieger, R. E., Miller, P., Bigger, J. T., Jr., & Moss, A. J.
Study. Journal of Psychosomatic Research, 31, 325±333. (1987). Decreased heart rate variability and its associa-
Jorgensen, R. S., Johnson, B. T., Schreer, G. E., & tion with increased mortality after acute myocardial
Kolodziej, M. E. (1996). Elevated blood pressure and infarction. American Journal of Cardiology, 59, 256±262.
personality: A meta-analytic review. Psychological Bulle- Kobasa, S. C., Maddi, S. R., Puccetti, M. C., & Zola, M.
tin, 120, 293±320. A. (1985). Effectiveness of hardiness, exercise and social
Julius, S. (1988). The blood pressure seeking properties of support as resources against illness. Journal of Psychoso-
the central nervous system. Journal of Hypertension, 6, matic Research, 29, 525±533.
177±185. Kojima, K., Ogomori, K., Mori, Y., Hirata, K., Kinukawa,
Kamarck, T. W., Annunziato, B., & Amateau, L. M. N., & Tashiro, N. (1996). Relationship of emotional
(1995). Affiliation moderates the effects of social threat behaviors induced by electrical stimulation of the
on stress-related cardiovascular responses: Boundary hypothalamus to changes in EKG, heart, stomach,
conditions for a laboratory model of social support. adrenal glands and thymus. Psychosomatic Medicine,
Psychosomatic Medicine, 57, 183±194. 58, 383±391.
Kamarck, T. W., Jennings, J. R., Debski, T. T., Glickman- Krittayaphong, R., Light, K. C., Biles, P. L., Ballenger, M.
Weiss, E., Johnson, P. S., Eddy, M. J., & Manuck, S. B. N., & Sheps, D. S. (1995). Increased heart rate response
(1992). Reliable measures of behaviorally-evoked cardi- to laboratory-induced mental stress predicts frequency
ovascular reactivity from a PC-based test battery: and duration of daily life ambulatory myocardial
Results from student and community samples. Psycho- ischemia in patients with coronary artery disease.
physiology, 29, 17±28. American Journal of Cardiology, 76, 657±660.
Kaplan, G. A., & Keil, J. E. (1993). Socioeconomic factors Kumar, D., & Wingate, D. L. (1985). The irritable bowel
and cardiovascular disease: A review of the literature. syndrome: A paroxysmal motor disorder. Lancet, 2,
Circulation, 88, 1973±1998. 973±977.
References 75
Lakatta, E. G. (1993). Deficient neuroendocrine regulation Psychoneuroimmunology: The interface between beha-
of the cardiovascular system with advancing age in vior, brain, and immunity. American Psychologist, 49,
healthy humans. Circulation, 87, 631±636. 1004±1017.
Larsson, P. T., Hjemdahl, P., Olsson, G., Egberg, N., & Malarkey, W. B., Kiecolt-Glaser, J. K., Pearl, D., &
Hornstra, G. (1989). Altered platelet function during Glaser, R. (1994). Hostile behavior during marital
mental stress and adrenaline infusion in humans: conflict alters pituitary and adrenal hormones. Psycho-
Evidence for an increased aggregability in vivo as somatic Medicine, 56, 41±51.
measured by filtragometry. Clinical Science, 76, 369±376. Malarkey, W. B., Pearl, D. K., Demers, L. M., Kiecolt-
Laudenslager, M. L., & Fleshner, M. (1994). Stress and Glaser, J. K., & Glaser R. (1995). Influence of academic
immunity: Of mice, monkeys, models and mechanisms. stress and season on 24-hour mean concentrations of
In R. Glaser, & J. Kiecolt-Glaser (Eds.), Handbook of ACTH, cortisol, and beta endorphin. Psychoeneuroen-
human stress and immunity (pp. 161±181). San Diego, docrinology, 20, 499±508.
CA: Academic Press. Manuck, S. B. (1994). Cardiovascular reactivity in cardio-
Legault, S. E., Freeman, M. R., Langer, A., & Armstrong, vascular disease: ªOnce more unto the breach.º Interna-
P. W. (1995). Pathophysiology and time course of silent tional Journal of Behavioral Medicine, 1, 4±31.
myocardial ischaemia during mental stress: Clinical, Manuck, S. B., Kaplan, J. R., Adams, M. R., & Clarkson,
anatomical, and physiological correlates. British Heart T. B. (1989). Behaviorally elicited heart rate reactivity
Journal, 73, 242±249. and atherosclerosis in female cynomolgus monkeys
Lehrer, P. M., Hochron, S., Carr, R., Edelberg, R., Hamer, (Macaca fascicularis). Psychosomatic Medicine, 51,
R., Jackson, A., & Porges, S. (1996). Behavioral task- 306±318.
induced bronchodilation in asthma during active and Markovitz, J. H., Matthews, K. A., Kriss, J., & Smither-
passive tasks: A possible cholinergic link to psychologi- man, T. C. (1996). Effects of hostility on platelet
cally induced airway changes. Psychosomatic Medicine, reactivity to psychological stress in coronary heart
58, 413±422. disease patients and in healthy controls. Psychosomatic
Leiker, M., & Harley, B. J. (1988). A link between hostility Medicine, 58, 143±149.
and disease: Poor health habits? Behavioral Medicine, 14, Markowe, H. L., Marmot, M. G., Shipley, M. J., Bulpitt,
129±133. C. J., Meade, T. W., Stirling, Y., Vickers, M. V., &
Lenders, J. W., Peters, J. H., Pieters, G. F., Willemsen, J. Semmence, A. (1985). Fibrinogen: A possible link
J., & Thien, T. (1988). Hemodynamic reactivity to between social class and coronary heart disease. British
sympathoadrenal stimulation in adrenalectomized wo- Medical Journal, 291, 1312±1314.
men. Journal of clinical Endocrinology and Metabolism, Marmot, M. G., Davey Smith, G., Stansfeld, S., Patel, C.,
67, 139±143. North, F., Head, J., White, I., Brunner, E., & Feeney, A.
Levine, S. P., Towell, B. L., Suarez, A. M., Knieriem, L. (1991). Health inequalities among British civil servants:
K., Harris, M. M., & George, J. N. (1985). Platelet The Whitehall II study. Lancet, 337, 1387±1393.
activation and secretion associated with emotional stress. Mason, J. W. (1968). A review of psychoendocrine research
Circulation, 71, 1129±1134. on the pituitary-adrenal cortical system. Psychosomatic
Lewis, M., Thomas, D. A., & Worobey, J. (1990). Medicine, 30, 576±607.
Developmental organization, stress and illness. Psycho- Mason, J. W. (1975). Emotion as reflected in patterns of
logical Science, 1, 316±318. endocrine integration. In L. Levi (Ed.), EmotionsÐtheir
Light, K. C., Dolan, C. A., Davis, M. R., & Sherwood, A. parameters and measurement (pp. 143±181). New York:
(1992). Cardiovascular responses to an active coping Raven Press.
challenge as predictors of blood pressure patterns 10 to McCann, B. S., Magee, M. S., Broyles, F. C., Vaughan,
15 years later. Psychosomatic Medicine, 54, 217±230. M., Albers, J. J., & Knopp, R. H. (1995). Acute
Light, K. C., Koepke, J. P., Obrist, P. A., & Willis, P. W. psychological stress and epinephrine infusion in normo-
(1983). Psychological stress induces sodium and fluid lipidemic and hyperlipidemic men: Effects on plasma
retention in men at high risk for hypertension. Science, lipid and apoprotein concentrations. Psychosomatic
220, 429±431. Medicine, 57, 165±176.
Linde, B., Hjemdahl, P., Freyschuss, U., & Juhlin- McCubbin, J. A. (1993). Stress and endogenous opioids:
Dannfelt, A. (1989). Adipose tissue and skeletal muscle Behavioral and circulatory interactions. Biological Psy-
blood flow during mental stress. American Journal of chology, 35, 91±22.
Physiology, 256, E12±E18. McCubbin, J. A., Surwit, R. S., Williams, R. B., Nemeroff,
Line, S. W., Kaplan, J. R., Heise, E. R., Hilliard, J. K., C. B., & McNeilly, M. (1989). Altered pituitary hormone
Cohen, S., Rabin, B. S., & Manuck, S. B. (1996). Effects response to naloxone in hypertension development.
of social reorganization on cellular immunity in male Hypertension, 14, 633±644.
cynomolgus monkeys. American Journal of Primatology, McEwen, B. S., & Sapolsky, R. M. (1995). Stress and
39, 235±249. cognitive function. Current Opinion in Neurobiology, 5,
Lorber, B. (1996). Are all diseases infectious? Annals of 205±216.
Internal Medicine, 125, 844±851. McKinnon, A., Weisse, C. S., Reynolds, C. P., Bowles, C.
Lown, B., Verrier, R. L., & Rabinowitz, S. H. (1977). A., & Baum, A. (1989). Chronic stress, leukocyte
Neural and psychologic mechanisms and the problem of subpopulations, and humoral response to latent viruses.
sudden cardiac death. American Journal of Cardiology, Health Psychology, 8, 389±402.
39, 890±902. Meredith, I. T., Broughton, A., Jennings, G. L., & Esler,
Lynch, J. W., Kaplan, G. A., Cohen, R. D., Tuomilehto, J., M. D. (1991). Evidence of selective increase in cardiac
& Salonen, J. (1996). Do cardiovascular risk factors sympathetic activity in patients with sustained ventricu-
explain the relation between socio-economic status, risk lar arrhythmias. New England Journal of Medicine, 325,
of all-cause mortality, cardiovascular mortality, and 618±624.
acute myocardial infarction? American Journal of Epide- Miller, T. Q., Smith, T. W., Turner, C. W., Guijarro, M.
miology, 144, 934±942. L., & Hallet, A. J. (1996). A meta-analytic review of
Madden, J., Akil, H., Patrick, R. L., & Barchas, J. D. research on hostility and physical health. Psychological
(1977). Stress-induced parallel changes in central opioid Bulletin, 119, 322±348.
levels and pain responsiveness in the rat. Nature, 265, Mirowksy, J., & Ross, C. E. (1995). Sex differences in
358±360. distress: Real or artefact? American Sociological Review,
Maier, S. F., Watkins, L. R., & Fleshner, M. (1994). 60, 449±468.
Mittleman, M. A., Maclure, M., Sherwood, J. B., Mulry, induced stress in man: Effects on blood coagulation
R. P., Tofler, G. H., Jacobs, S. C. Friedman, R., Benson, and fibrinolysis. Journal of Psychosomatic Research, 21,
H., & Muller, J. E. (1995). Triggering of acute 87±92.
myocardial infarction onset by episodes of anger. Parkes, K. R. (1984). Locus of control, cognitive appraisal,
Circulation, 92, 1720±1725. and coping in stressful episodes. Journal of Personality
Moldin, S. O., Scheftner, W. A., Rice, J. P., Nelson, E., and Social Psychology, 46, 655±668.
Knesevich, M. A., & Akiskal, H. (1993). Association Pennebaker, J. W. (Ed.) (1995). Emotion, disclosure, and
between major depressive disorder and physical illness. health. Washington, DC: American Psychological Asso-
Psychological Medicine, 23, 755±761. ciation.
Mormede, P., Dantzer, R., Michaud, B., Kelley, K. W., & Pennebaker, J. W., Kiecolt-Glaser, J. K., & Glaser, R.
Le Moal, M. (1988). Influence of stressor predictability (1988). Disclosure of traumas and immune function:
and behavioral control on lymphocyte reactivity, anti- Health implications for psychotherapy. Journal of
body responses and neuroendocrine activation in rats. Consulting and Clinical Psychology, 56, 239±245.
Physiology and Behavior, 43, 577±583. Perski, A., Olsson, G., Landou, C., de Faire, U., Theorell,
Morris, J. K., Cook, D. G., & Shaper, A. G. (1994). Loss of T., & Hamsten, A. (1992). Minimum heart rate and
employment and mortality. British Medical Journal, 308, coronary atherosclerosis: Independent relations to global
1135±1139. severity and rate of progression of angiographic lesions
Morris, M., Salmon, P., Steinberg, H, Sykes, E. A., in men with myocardial infarction at a young age.
Bouloux, P., Newbould, E., McLoughlin, L., Besser, G. American Heart Journal, 123, 609±616.
M., & Grossman, A. (1990). Endogenous opioids Peterson, C., Seligman, M. E., & Vaillant, G. E. (1988).
modulate the cardiovascular response to mental stress. Pessimistic explanatory style is a risk factor for physical
Psychoneuroendocrinology, 15, 185±192. illness: A thirty-five year longitudinal study. Journal of
Moyer, A. E., Rodin, J., Grilo, C. M., Cummings, N., Personality and Social Psychology, 55, 23±27.
Larson, L. M., & RebuffeÂ-Scrive, M. (1994). Stress- Pickering, T. G. (1991). Ambulatory monitoring and blood
induced cortisol response: A fat distribution in women. pressure variability. London: Science Press.
Obesity Research, 2, 255±261. Pillow, D. R., Zautra, A. J., & Sandler, I. (1996). Major life
Munck, A. Guyre, P. M., & Holbrook, N. J. (1984). events and minor stressors: Identifying mediational links
Physiological functions of glucocorticoids in stress and in the stress process. Journal of Personality and Social
their relation to pharmacological actions. Endocrine Psychology, 70, 381±394.
Reviews, 5, 25±44. Plomin, R., Lichtenstein, P., Pedersen, N. L., McClearn, G.
Murphy, J. K., Stoney, C. M., Alpert, B. S., & Walker, S. E., & Nesselroade, J. R. (1990) Genetic influence on life
S. (1995). Gender and ethnicity in children's reactivity: 7 events during the last half of the life span. Psychology
years of study. Health Psychology, 14, 48±55. and Aging, 5, 25±30.
Murray, C. J. L., & Lopez, A. D. (Eds.) (1996). The global Pope, M. K., & Smith, T. W. (1991). Cortisol excretion in
burden of disease. Cambridge, MA: Harvard University high and low cynically hostile men. Psychosomatic
Press. Medicine, 53, 386±392.
Nachmias, M., Gunnar, M., Mangelsdorf, S., Parritz, R. Rabin, D., Gold, P. W., Margioris, A., & Chrousos, G. P.
H., & Buss, K. (1996). Behavioral inhibition and stress (1988). Stress and reproduction: interactions between the
reactivity: The moderating role of attachment security. stress and reproductive axes. In G. P. Chrousos,
Child Development, 67, 508±522. D. L. Loriaux, & P. W. Gold (Eds), Mechanisms of
Natelson, B. H., Ottenweller, J. E., Cook, J. A., Pitman, physical and emotional stress (pp. 377±387). New York:
D., McCartey, R., & Tapp, W. N. (1988). Effect of Plenum.
stressor intensity on habituation of the adrenocortical Rahe, R. H., Karson, S., Howard, N. S., Rubin, R. T., &
stress response. Physiology and Behavior, 43, 41±46. Poland, R. E. (1990). Psychological and physiological
Neufeld, M. Y., Sadeh, M., Cohn, D. F., & Korczyn, A. D. assessments on American hostages freed from captivity
(1994). Stress and epilepsy: The Gulf War experience. in Iran. Psychosomatic Medicine, 52, 1±16.
Seizure, 3, 135±139. Ramirez, A. J., Craig, T. K., Watson, J. P., Fentiman, I. S.,
Nilsson, P. M., Moller, L., & Solstad, K. (1995). Adverse North, W. R., & Rubens, R. D. (1989). Stress and
effects of psychosocial stress on gonadal function and relapse of breast cancer. British Medical Journal, 298,
insulin levels in middle-aged males. Journal of Internal 291±293.
Medicine, 237, 479±486. Reaven, G. M. (1988). Role of insulin resistance in human
Nordentoft, M., Lou, H. C., & Hanson, D. E. (1996). disease. Diabetes, 37, 1595±1607.
Intrauterine growth retardation and premature delivery: Robinson, N., & Fuller, J. H. (1985). Role of life events and
The influence of maternal smoking and psychosocial difficulties in the onset of diabetes mellitus. Journal of
factors. American Journal of Public Health, 86, 347±354. Psychosomatic Research, 29, 583±591.
Norris, F. H., & Murrell, S. A. (1988). Prior experience as a Rogers, M. W., Probst, M. M., Gruber, J. J., Berger, R., &
moderator of disaster impact on anxiety symptoms in Boone, J. B. (1996). Differential effects of exercise
older adults. American Journal of Community Psychol- training intensity on blood pressure and cardiovascular
ogy, 16, 665±683. responses to stress in borderline hypertensive humans.
O'Connor, F., Buckley, M., & O'Morain, C. (1996). Journal of Hypertension, 14, 1369±1375.
Helicobacter pylori: The cancer link. Journal of the Rose, R. M., & Fogg, L. F. (1993). Definition of a
Royal Society of Medicine, 89, 674±678. responder: Analysis of behavior, cardiovascular and
Owens, J. F., Stoney, C. M., & Matthews, K. A. (1993). endocrine responses to varied workload in air traffic
Menopausal status influences ambulatory blood pressure controllers. Psychosomatic Medicine, 55, 325±338.
levels and blood pressure changes during mental stress. Rostrup, M., Mundal, H. H., Westheim, A., & Eide, I.
Circulation, 88, 2794±2802. (1991). Awareness of high blood pressure increases
Pagani, M., Rimoldi, O., Pizzinelli, P. Furlan, R., arterial plasma catecholamines, platelet noradrenaline
Crivellaro, W., Liberati, D., Cerutti, S., & Malliani, A. and adrenergic responses to mental stress. Journal of
(1991). Assessment of the neural control of the circula- Hypertension, 9, 159±166.
tion during psychological stress. Journal of the Auto- Rozanski, A., Bairey, C. N., Krantz, D. S., Friedman, J.,
nomic Nervous System, 35, 33±42. Resser, K. J., Morell, M., Hilton-Chalfen, S., Hestrin,
Palmblad, J., Blomback, M., Egberg, N., Froberg, J., L., Bietendorf, J., & Berman, D. S. (1988). Mental stress
Karlsson, C.-G., & Levi, L. (1977). Experimentally and the induction of silent myocardial ischemia in
References 77
patients with coronary artery disease. New England implications of laboratory studies. Journal of Psychoso-
Journal of Medicine, 318, 1005±1012. matic Research, 27, 361±367.
Saab, P. G., Llabre, M. M., Hurwitz, B. E., Frame, C. A., Steptoe, A. (1984a). Psychophysiological processes in
Reineke, L. J., Fins, A. I., McCalla, J., Cieply, L. K., & disease. In A. Steptoe & A. Mathews (Eds.), Health care
Schneiderman, N. (1992). Myocardial and peripheral and human behaviour (pp. 77±112). London: Academic
vascular responses to behavioral challenges and their Press.
stability in black and white Americans. Psychophysiol- Steptoe, A. (1984b). Psychological aspects of bronchial
ogy, 29, 384±397. asthma. In S. J. Rachman (Ed.), Contributions to medical
Sapolsky, R. M. (1992). Stress, the aging brain, and the psychology (Vol. 3, pp. 7±30). Oxford, UK: Pergamon.
mechanisms of neuron death. Cambridge, MA: MIT Steptoe, A. (1991). Psychobiological processes in the
Press. etiology of disease. In P. R. Martin (Ed.), Handbook of
Sapolsky, R. M., & Mott, G. E. (1987). Social subordi- behavior therapy and psychological science (pp. 325±347).
nance in wild baboons is associated with suppressed high New York: Pergamon.
density lipoprotein-cholesterol concentrations: The pos- Steptoe, A. (1997). Behavior and blood pressure: Implica-
sible role of chronic social stress. Endocrinology, 121, tions for hypertension. In A. Zanchetti & G. Mancia
1605±1610. (Eds.), Pathophysiology of hypertension (pp. 674±708).
Schaie, K. W., Blazer, D. G. & House, J. S. (Eds) (1992). Amsterdam: Elsevier.
Aging, health behaviors and health outcomes. Hillsdale, Steptoe, A., & Appels, A. (Eds.) (1989). Stress, personal
NJ: Erlbaum. control and health. Chichester, UK. Wiley.
Schaubroeck, J., & Ganster, D. C. (1993). Chronic Steptoe, A., Roy, M. P., & Evans, O. (1996). Psychosocial
demands and responsivity to challenge. Journal of influences on ambulatory blood pressure over working
Applied Psychology, 78, 73±85. and non-working days. Journal of Psychophysiology, 10,
Scheier, M. F., & Carver, C. S. (1992). Effects of optimism 218±227.
on psychological and physical well-being: Theoretical Steptoe, A., Roy, M. P., Evans, O., & Snashall, D. (1995).
overview and empirical update. Cognitive Therapy and Cardiovascular stress reactivity and job strain as
Research, 16, 201±228. determinants of ambulatory blood pressure at work.
Schenk, E. A., & Moss, A. J. (1966). Cardiovascular effects Journal of Hypertension, 13, 201±210.
of sustained norepinephrine infusions. 2: Morphology. Steptoe, A., & Tavazzi, L. (1996). The mind and the heart.
Circulation Research, 18, 605±615. In D. G. Julian, A. J. Camm, K. M. Fox, R. J. C. Hall, &
Schnall, P. L., Landsbergis, P. A., & Baker, D. (1994). Job P. A. Poole-Wilson (Eds.), Diseases of the heart
strain and cardiovascular disease. Annual Review of (pp. 1430±1441). London: Saunders.
Public Health, 15, 381±411. Stone, A. A., Bovbjerg, D. N., Neale, J. M., Napoli, A.,
Schwartz, J. E., Warren, K., & Pickering, T. G. (1994). Valdimarsdottir, H., Cox, D., Hayden, F. G., &
Mood, location and physical position as predictors of Gwaltney, J. M. (1992). Development of common cold
ambulatory blood pressure and heart rate: Application symptoms following experimental rhinovirus infection is
of a multi-level random effects model. Annals of related to prior stressful life events. Behavioral Medicine,
Behavioral Medicine, 16, 210±220. 18, 115±120.
Seeman, T. E., Berkman, L. F., Gulanski, B. I., Robbins, Stone, A. A., Neale, J. M., Cox, D. S., Napoli, A.,
R. J., Greenspan, S. L., Charpentier, P. A., & Rowe, J. Valdimarsdottir, H., & Kennedy-Moore, E. (1994).
W. (1995). Self-esteem and neuroendocrine response to Daily events are associated with a secretory immune
challenge: MacArthur studies of successful aging. response to an oral antigen in men. Health Psychology,
Journal of Psychosomatic Research, 39, 69±84. 13, 440±446.
Seeman, T. E., & Robbins, R. J. (1994). Aging and Stoney, C. M., Owens, J. F., Matthews, K. A., Davis, M.
hypothalamic-pituitary-adrenal response to challenge in C., & Caggiula, A. (1990). Influences of the normal
humans. Endocrine Reviews, 15, 233±260. menstrual cycle on physiologic functioning during
Seraganian, P. (Ed.) (1993). Exercise Psychology. New behavioral stress. Psychophysiology, 27, 125±135.
York: Wiley. Strawn, W. B., Bondjers, G., Kaplan, J. R., Manuck, S. B.,
Sheps, D. S., Ballenger, M. N., De Gent, G. E., Schwenke, D. C., Hansson, G. K., Shively, C., A &
Krittayaphong, R., Dittman, E., Maixner, W., McCart- Clarkson, T. B. (1991). Endothelial dysfunction in
ney, W., Golden, R. N., Koch, G., & Light, K. C. (1995). response to psychosocial stress in monkeys. Circulation
Psychophysical responses to a speech stressor: Correla- Research, 68, 1270±1279.
tion of plasma beta-endorphin levels at rest and after Suarez, E. C., Williams, R. B., Jr., Kuhn, C. M.,
psychological stress with thermally measured pain Zimmerman, E. H., & Schanberg, S. M. (1991).
threshold in patients with coronary artery disease. Biobehavioral basis of coronary-prone behavior in
Journal of the American College of Cardiology, 25, middle-aged men: II. Serum cholesterol, the Type A
1499±1503. behavior pattern, and hostility as interactive modulators
Sherwood, A., Dolan, C. A., & Light, K. C. (1990). of physiological reactivity. Psychosomatic Medicine, 53,
Hemodynamics of blood pressure responses during 528±537.
active and passive coping. Psychophysiology, 27, Suls, J., & Wan, C. K. (1993). The relationship between
656±668. trait hostility and cardiovascular reactivity: A quantita-
Sherwood, A., Royal, S. A., & Light, K. C. (1993). tive review and analysis. Psychophysiology, 30, 615±626.
Laboratory reactivity assessment: Effects of casual blood Suls, J., Wan, C. K., & Blanchard, E. B. (1994). A
pressure status and choice of task difficulty. International multilevel data-analytic approach for evaluation of
Journal of Psychophysiology, 14, 81±95. relationships between daily life stressors and symptoma-
Sifneos, P. E. (1973). The prevalence of ªalexithymicº tology: Patients with irritable bowel syndrome. Health
characteristics in psychosomatic patients. Psychotherapy Psychology, 13, 103±113.
and Psychosomatics, 22, 55±62. Suomi, S. J. (1991). Early stress and adult emotional
Solomon, G. F., Levine, S., & Kraft, J. K. (1968). Early reactivity in rhesus monkeys. In The childhood environ-
experience and immunity. Nature, 220, 821±822. ment and adult disease (pp. 171±188). Ciba Foundation
Steptoe, A. (1980). Stress and medical disorders. In S. J. Symposium 156. Chichester, UK: Wiley.
Rachman (Ed.), Contributions to medical psychology Sutton, B. J., & Gould, H. J. (1993). The human IgE
(Vol. 2, pp. 55±77) Oxford, UK: Pergamon. network. Nature, 366, 421±428.
Steptoe, A. (1983). Stress, helplessness and control: The Tavazzi, L., Zotti, A. M., & Rondanelli, R. (1986). The role
of psychologic stress in the genesis of lethal arrhythmias Uchino, B. N., Cacioppo, J. T., & Kiecolt-Glaser, J. K.
in patients with coronary artery disease. European Heart (1996). The relationship between social support and
Journal, 7(Suppl. A). 99±106. physiological processes: A review with emphasis on
Taylor, S. E., Kemeny, M. E., Aspinwall, L. E., Schneider, underlying mechanisms and implications for health.
S. G., Rodriguez, R., & Herbert, M. (1992). Optimism, Psychological Bulletin, 119, 488±531.
coping, psychological distress, and high-risk sexual Van Doornen, L. J. P., & Van Blokland, R. W. (1992). The
behavior among men at risk for Acquired Immunodefi- relationship between cardiovascular and catecholamine
ciency Syndrome (AIDS). Journal of Personality and reactions to laboratory and real-life stress. Psychophy-
Social Psychology, 63, 460±473. siology, 29, 173±181.
Terman, G., Shavit, Y., Lewis, J. W., Cannon, J. T., & Van Eck, M., Berkhof, H., Nicolson, N., & Sulon, J.
Liebeskind, J. C. (1984). Intrinsic mechanism of pain (1996). The effects of perceived stress, traits, mood
inhibition: activation by stress. Science, 226, 1270±1277. states, and stressful daily events on salivary cortisol.
Theorell, T. (1992). Prolactin: A hormone that mirrors Psychosomatic Medicine, 58, 447±458.
passiveness in crisis situations. Integrative Physiological Villar, J., Farnot, U., Barros, F., Victora, C., Langer, A., &
and Behavioral Science, 27, 32±38. Belizan, J. M. (1992). A randomized trial of psychosocial
Thompson, D. G., Richelson, E., & Malagelada, J.-R. support during high-risk pregnancies. New England
(1982). Perturbation of gastric emptying and duodenal Journal of Medicine, 327, 1266±1271.
motility through the central nervous system. Gastro- Vogele, C., & Steptoe, A. (1993). Anger inhibition and
enterology, 83, 1200±1206. family history as modulators of cardiovascular responses
Tidgren, B., & Hjemdahl, P. (1989). Renal responses to to mental stress in adolescent boys. Journal of Psychoso-
mental stress and epinephrine in humans. American matic Research, 37, 503±514
Journal of Physiology, 257, F682±F689. Von Holst, D. (1972). Renal failure as the cause of death in
Timio, M., Verdecchia, P., Venanzi, S., Gentili, S., Tupaia belangeri exposed to persistent social stress.
Ronconi, M., Francucci, B., Monanari, M., & Bichisao, Journal of Comparative Physiology, 78, 236±273.
E. (1988). Age and blood pressure changes: A 20-year Wadsworth, M., Maclean, M., Kuh, D., & Rogers, B.
follow-up study in nuns in a secluded order. Hyperten- (1990). Children of divorced and separated parents:
sion, 12, 457±461. Summary and review of findings from a long-term
Tofler, G. H., Stone, P. H., Maclure, M., Edelman, E., follow-up study in the UK. Family Practice, 7, 104±109.
Davis, V. G., Robertson, T., Antman, E. M., & Muller,
Watson, D., & Pennebaker, J. W. (1989). Health com-
J. E. (1990). Analysis of possible triggers of acute
plaints, stress, and distress: Exploring the central role of
myocardial infarction (the MILIS study). American
negative affectivity. Psychological Review, 96, 234±254.
Journal of Cardiology, 66, 22±27.
Webster, A., & Mawer, G. (1989). Seizure frequency and
Treiber, F. A., Turner, J. R., Davis, S., Thompson, W.,
major life events in epilepsy. Epilepsia, 30, 162±167.
Levy, W., & Strong, W. B. (1996). Young children's
cardiovascular stress responses predict resting cardiovas- Weinberger, D., A., Schwartz, G. E., & Davidson, R. J.
cular functioning two and a half years later. Journal of (1979). Low-anxious, high-anxious, and repressive cop-
Cardiovascular Risk, 3, 95±100. ing styles: Psychometric patterns and behavioral and
Trevisan, M., Jossa, F., Farinaro, E., Krogh, V., Panico, physiological responses to stress. Journal of Abnormal
S., Giumetti, D., & Mancini, M. (1992). Earthquake and Psychology, 65, 375±390.
coronary heart disease risk factors: A longitudinal study. Weiner, H. (1992). Perturbing the organism: The biology of
American Journal of Epidemiology, 135, 632±637. stressful experience. Chicago: University of Chicago
Tsuda, A., Tanaka, M., Nishikawa, T., & Hirai, H. (1983). Press.
Effects of coping behavior on gastric lesions in rats as a Whitworth, J. A., Gordon, D., Andrews, J., & Scoggins, B.
function of the complexity of coping tasks. Physiology A. (1989). The hypertensive effect of synthetic glucocor-
and Behavior, 30, 805±808. ticoids in man: Role of sodium and volume. Journal of
Turner-Cobb, J. M., & Steptoe, A. (1996). Psychosocial Hypertension, 7, 537±549.
stress and susceptibility to upper respiratory tract illness Williams, R. B. (1994). Neurobiology, cellular and
in an adult population sample. Psychosomatic Medicine, molecular biology, and psychosomatic medicine. Psy-
58, 404±412. chosomatic Medicine, 56, 308±315.
Turner, J., Ward, M., Gellman, M., Johnston, D., Light, Willis, L., Thomas, P., Garry, P. J., & Goodwin, J. S.
K., & van Doornen, L. (1994). The relationship between (1987). A prospective study of response to stressful life
laboratory and ambulatory cardiovascular activity: events in initially healthy elders. Journal of Gerontology,
Current evidence and future directions. Annals of 42, 627±630.
Behavioral Medicine, 16, 12±23. Zakowski, S., Hall, M. H., & Baum, A. (1992). Stress,
Turner, R. J., & Marino, F. (1994). Social support and stress management, and the immune system. Applied and
social structure: A descriptive epidemiology. Journal of Preventive Psychology, 1, 1±3.
Health and Social Behavior, 35, 193±212. Zautra, A. J., Okun, M. A., Robinson, S. E., Lee, D., Roth,
Turner, R. J., Wheaton, B., & Lloyd, D. A. (1995). The S. H., & Emmanual, J. (1989). Life stress and lympho-
epidemiology of social stress. American Sociological cyte alterations among patients with rheumatoid arthri-
Review, 60, 104±125. tis. Health Psychology, 8, 1±14.

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8.02.5.2 Social Isolation and Social Support 61

8.02.1 INTRODUCTION nervous system psychophysiology. Thus the role

Psychosocial demands Resistance and

Life events Coping responses

Cortisol, ACTH Immunoglobulins

aspects of people's psychological makeup and 8.02.2.2 Research Strategies

controls has been published (Kiecolt-Glaser, prevent transmission of pathogens to conspe-

Stress, immune responses and infection

Infectious Adequate Infectious Impaired

Figure 2 Schematic outline of associations between immune defenses and infection.

8.02.7.3 Physiological Reactivity as a Disruptive turbances of bronchoconstriction in asthma) or

psychophysiological processes are operative at clinical events in susceptible individuals. One

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