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Hormones and Behavior 43 (2003) 2–15
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The concept of allostasis in biology and biomedicine
Bruce S. McEwena,* and John C. Wingfieldb
a
Laboratory of Neuroendocrinology, The Rockefeller University, Box 165, 1230 York Avenue, New York, NY 10021, USA
b
Department of Zoology, Box 351800, University of Washington, Seattle, WA 98195, USA
Received 28 February 2002; accepted 8 September 2002
Abstract
Living organisms have regular patterns and routines that involve obtaining food and carrying out life history stages such as breeding,
migrating, molting, and hibernating. The acquisition, utilization, and storage of energy reserves (and other resources) are critical to lifetime
reproductive success. There are also responses to predictable changes, e.g., seasonal, and unpredictable challenges, i.e., storms and natural
disasters. Social organization in many populations provides advantages through cooperation in providing basic necessities and beneficial
social support. But there are disadvantages owing to conflict in social hierarchies and competition for resources. Here we discuss the concept
of allostasis, maintaining stability through change, as a fundamental process through which organisms actively adjust to both predictable
and unpredictable events. Allostatic load refers to the cumulative cost to the body of allostasis, with allostatic overload being a state in which
serious pathophysiology can occur. Using the balance between energy input and expenditure as the basis for applying the concept of
allostasis, we propose two types of allostatic overload. Type 1 allostatic overload occurs when energy demand exceeds supply, resulting in
activation of the emergency life history stage. This serves to direct the animal away from normal life history stages into a survival mode
that decreases allostatic load and regains positive energy balance. The normal life cycle can be resumed when the perturbation passes. Type
2 allostatic overload begins when there is sufficient or even excess energy consumption accompanied by social conflict and other types of
social dysfunction. The latter is the case in human society and certain situations affecting animals in captivity. In all cases, secretion of
glucocorticosteroids and activity of other mediators of allostasis such as the autonomic nervous system, CNS neurotransmitters, and
inflammatory cytokines wax and wane with allostatic load. If allostatic load is chronically high, then pathologies develop. Type 2 allostatic
overload does not trigger an escape response, and can only be counteracted through learning and changes in the social structure.
© 2003 Elsevier Science (USA). All rights reserved.
Introduction
Modern biology provides a framework not only for understanding how the interplay of genes and environment
produces individual characteristics, and how these individuals interact in social groups and with other species, but also
for understanding how these interactions lead to pathophysiology and disease. For example, knowledge of how the life
cycles of organisms are integrated and controlled in the
natural world will allow us to assess the effects upon ecosystems of global climate change, disturbance by humans,
and endocrine disrupters. Of equal importance is a need to
use basic biological frameworks in human society to conceptualize and measure the cumulative impact of social
* Corresponding author. Fax: ⫹1-212-327-8634.
E-mail address: [email protected] (B.S. McEwen).
status, income, education, working and living environments,
lifestyle, health-related behaviors, and stressful life experiences on physical and mental health.
The daily routines of animals and humans alike include
nutritional inputs to maintain normal activities and to anticipate additional requirements (e.g., breeding, migrating,
acclimating to cold and heat, etc.) during the day–night
cycle and the seasons. These homeostatic mechanisms, including functional and structural changes in brain and body,
allow the individual to maintain physiological and behavioral stability despite fluctuating environmental conditions.
Superimposed on this “predictable” life cycle are facultative
physiological and behavioral responses to unpredictable
events that have the potential to be stressors. These responses require extra energy procured from the environment
and/or from endogenous stores of fat, glycogen, and protein.
Moreover, the ability of an individual to maintain such
0018-506X/03/$ – see front matter © 2003 Elsevier Science (USA). All rights reserved.
doi:10.1016/S0018-506X(02)00024-7
B.S. McEwen, J.C. Wingfield / Hormones and Behavior 43 (2003) 2–15
emergency responses depends upon other factors such as
parasite load, diseases, social status, permanent injury, pollution, etc. These can lead to permanent additional “costs”
that potentially provide a “handicap” in the face of environmental change, unpredictable events, etc.
Historically, within both the basic biological and biomedical sciences, the concepts of stress and homeostasis
have been used in ambiguous ways that obfuscate a number
of important aspects of the impact of experience and genes
on life cycles in general, and health and disease in particular. The energy required to fuel daily and seasonal routines
includes major life history stages such as breeding, unpredictable events that can lead to stress, and the permanent
handicaps accrued from disease, injury, etc. These form a
continuum with important transitional points that determine
whether the individual can cope or triggers facultative physiological and behavioral responses designed to reduce costs.
Failure to do either results in symptoms of what we call
“allostatic overload,” as discussed below.
Our goal here is to propose the inclusion of four terms,
“allostasis,” “allostatic state,” “allostatic load,” and “allostatic overload” in a basic framework for the organization
and management of life cycles. These terms are offered as
organizing principles for understanding the management of
life cycles in diverse habitats and varying degrees of unpredictability in basic biology. They also include the influence
of genetic risk factors, early life events, lifestyle and healthrelated behaviors and stressful experiences, including social
conflict and social hierarchies, on the processes of physiological adaptation and the exacerbation of disease.
The process of allostasis that leads adaptation/acclimation of the organism in the short run underlies all of what we
shall discuss. We will explore how costs to the body (referred to as allostatic load) can eventually result in allostatic
overload, i.e., the balance between energy expenditure and
energy input. We understand fully that this is a simplistic
approach and many other nutritional components (essential
fatty acids and amino acids, minerals, etc.) are important.
These indeed could also be modeled, but here we use the
term “energy” in a very general sense that encompasses all
potentially limiting resources. Moreover, we focus on glucocorticosteroids as hormonal mediators that reflect how the
individual responds to the challenges imposed by the external world as well as by the internal environment. We do so
in full recognition of the fact that glucocorticosteroids are
only one of many interconnected hormonal mediators and
that a full description of what we are outlining will require
inclusion of these mediators as well.
First, we consider situations in which energy available to
the organism is exceeded by demands of the environment.
Second, we consider situations when energy available to the
individual is not exceeded, but other factors such as social
competition and conflict become paramount. Before elaborating on these ideas, we need to define some terminology.
3
Definition of terms
Homeostasis
Homeostasis is the stability of physiological systems that
maintain life, used here to apply strictly to a limited number
of systems such as pH, body temperature, glucose levels,
and oxygen tension that are truly essential for life and are
therefore maintained within a range optimal for the current
life history stage.
Allostasis
Allostasis is achieving stability through change. This is a
process that supports homeostasis, i.e., those physiological
parameters essential for life defined above, as environments
and/or life history stages change. This means that the “setpoints” and other boundaries of control must also change.
There are primary mediators of allostasis such as, but not
confined to, hormones of the hypothalamo–pituitary–adrenal (HPA) axis, catecholamines, and cytokines. Allostasis
also clarifies an inherent ambiguity in the term “homeostasis” and distinguishes between the systems that are essential
for life (“homeostasis”) and those that maintain these systems in balance (“allostasis”) as environment and life history stage change.
We note, however, that another view of homeostasis is
the operation of coordinated physiological processes that
maintain most of the steady states of the organism (Cannon,
1929). In this interpretation, homeostasis and allostasis
might seem to mean almost the same thing. The reason they
do not is that the notion of “steady state” is itself vague and
does not distinguish between those systems essential for life
and those that maintain them. It also does not differentiate
changes in state to enable reproduction (and other life cycle
processes) that are not required for immediate survival (e.g.,
Bauman, 2000; Kuenzel et al., 1999; Mrosovsky, 1990).
Allostatic state
The allostatic state refers to altered and sustained activity
levels of the primary mediators, e.g., glucocorticosteroids,
that integrate physiology and associated behaviors in response to changing environments and challenges such as
social interactions, weather, disease, predators, pollution,
etc. Originally proposed for understanding physiological
aspects of drug abuse (Koob and LeMoal, 2001), an allostatic state results in an imbalance of the primary mediators,
reflecting excessive production of some and inadequate production of others. Examples are hypertension, a perturbed
cortisol rhythm in major depression or after chronic sleep
deprivation, chronic elevation of inflammatory cytokines
and low cortisol in Chronic Fatigue Syndrome, and imbalance of cortisol, CRF, and cytokines in the Lewis rat that
increases risk for autoimmune and inflammatory disorders.
Allostatic states can be sustained for limited periods if food
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intake and/or stored energy such as fat can fuel homeostatic
mechanisms. For example, bears and other hibernating animals preparing for the winter become hyperphagic as part
of the normal life cycle and at a time (summer and early
autumn) when food resources can sustain it. In contrast,
facultative hyperphagia in response to environmental perturbations (impending storms or increased predator pressure) may not always be supported by local resources. If
imbalance continues for longer periods, and becomes independent of maintaining adequate energy reserves, then
symptoms of allostatic overload appear.
Allostatic load and allostatic overload
The cumulative result of an allostatic state (e.g., facultative fat deposition in an animal responding to unexpected
environmental change) is allostatic load. It can be considered the result of the daily and seasonal routines organisms
have to obtain food and survive and extra energy needed to
migrate, molt, breed, etc. Within limits, they are adaptive
responses to seasonal and other demands. However, if one
superimposes additional loads of unpredictable events in the
environment such as disease, human disturbance, and social
interactions, then allostatic load can increase dramatically.
We envision two distinctly different outcomes. First, if
energy demands exceed energy income, and what can be
mobilized from stores, then Type 1 allostatic overload occurs. For example, breeding birds use increasing food abundance in spring to raise young. If inclement weather then
increases the cost of maintaining homeostasis in addition to
the demands of breeding, and at the same time reduces food
available to fuel this allostatic load, then negative energy
balance results in loss of body mass and suppression of
reproduction (Wingfield et al., 1983). Another example is
the mass movement of seabirds to islands in the face of a
severe storm that limited access to food. The increased
allostatic load of dealing with the storm in the face of
reduced energy income resulted in Type 1 allostatic overload (Smith et al., 1994).
Second, Type 2 allostatic overload occurs if energy demands are not exceeded and the organism continues to take
in or store as much or even more energy than it needs. This
may be a result of stress-related food consumption, choice
of a fat-rich diet, or metabolic imbalances (prediabetic state)
that favors fat deposition. There are other cumulative
changes in other systems, e.g., neuronal remodeling or loss
in hippocampus, atherosclerotic plaques, left ventricular hypertrophy of the heart, glycosylated hemoglobin, and other
proteins by advanced glycosylation end products as a measure of sustained hyperglycemia. High cholesterol with low
HDL may also occur, and chronic pain and fatigue, e.g., in
arthritis or psoriasis, associated with imbalance of immune
mediators. Thus it may be possible to distinguish between
allostatic load in the normal life cycle (incorporating unpredictable events in the environment) and allostatic overload
that exceeds the capacity of the individual to cope, albeit in
the two distinctive directions described above. This is particularly severe if the overload is permanent such as with
injury, disease, and some lifestyles. These are all secondary
outcomes that can be measured and are associated with
increased risk for a disease.
Using these definitions as a starting point, we now discuss the overused term “stress” and how, in its place, the
concept of allostasis may allow us to consider the life cycle
in general as a continuum from daily routines to allostatic
overload and the accompanying pathologies. Within the
framework of allostasis, a narrower and more precise definition of stress has an important place. This is particularly
heuristic because it allows us to include individual variation
due to experience, genetics, and social status. It incorporates
thresholds and transitions among physiological and behavioral states that also vary from individual to individual.
Despite this complexity, the framework illustrates that similar hormone systems may be involved. Furthermore, the
framework allows formulation of clear predictions that can
be tested experimentally.
What do we mean by “stress”?
Stress is often defined as a threat, real or implied, to
homeostasis. In common usage, stress usually refers to an
event or succession of events that cause a response, often in
the form of “distress” but also, in some cases, referring to a
challenge that leads to a feeling of exhilaration, as in “good”
stress. But, the term “stress” is full of ambiguities. It is often
used to mean the event (stressor) or, sometimes, the response (stress response). Furthermore, it is frequently used
in the negative sense of “distress,” and sometimes it is used
to describe a chronic state of imbalance in the response to
stress. Here stress will be used to describe events that are
threatening to an individual and which elicit physiological
and behavioral responses as part of allostasis in addition to
that imposed by the normal life cycle. The response to stress
can now be included in the process of allostasis with concomitant load and the two types of overload.
The most commonly studied physiological systems that
respond to stress are the HPA axis and the autonomic
nervous system, particularly the sympathetic response of the
adrenal medulla and the sympathetic nerves. These systems
respond in daily life to stressful events, as well as to the
diurnal cycle of rest and activity, even though they are
frequently identified as “stress response systems.” Behaviorally, the responses to stress may consist of “fight or
flight” reactions or, in humans, involve health-related behaviors such as eating, alcohol consumption, smoking, and
other forms of substance abuse. Another type of reaction to
a potentially stressful situation is an increased state of vigilance, enhanced by anxiety and worrying particularly when
the threat is ill-defined or imaginary and when there is no
clear alternative behavioral response that would end the
threat. Behavioral responses to stress and these states of
B.S. McEwen, J.C. Wingfield / Hormones and Behavior 43 (2003) 2–15
anxiety are capable of exacerbating and potentiating physiological mediators of health outcomes.
What are some examples of allostasis?
Sterling and Eyer (1988) used variations in blood pressure as an example: in the morning, blood pressure rises
when we get out of bed and blood flow is maintained to the
brain when we stand up in order to keep us conscious. This
type of allostasis helps to maintain oxygen tension in the
brain. There are other examples: catecholamine and glucocorticosteroid elevations during physical activity mobilize and replenish, respectively, energy stores needed for
brain and body function under challenge. These adaptations
maintain essential metabolism and body temperature. Examples in other contexts include changes in food intake,
osmoregulatory processes and metabolism that females undergo when lactating (Bauman, 2000), or dramatic shifts of
metabolism, muscle morphology, and complex patterns of
behavior in migrating birds (Kuenzel et al., 1999). These are
clearly adjustments to demands of state dictated by life
history stage, environmental conditions, and social context.
Allostatic processes can also go beyond immediate homeostasis, and maintenance of body temperature and pH, to
broader aspects of individual survival, e.g., from pathogens
or physical danger. For the immune system, acute stressinduced release of catecholamines and glucocorticosteroids
facilitate the movement of immune cells to parts of the body
where they are needed to fight an infection or to produce
other immune responses (Dhabhar and McEwen, 1999).
Finally, in the brain, glucocorticosteroids and catecholamines act in concert to promote the formation of
memories of events of potentially dangerous situations so
that the individual can avoid them in the future
(Roozendaal, 2000).
Protection vs damage
From the standpoint of survival and health of the individual, the most important feature of mediators associated
with allostasis is that they have protective effects in the
short run. However, they can have damaging effects over
longer time intervals if there are many adverse life events or
if hormone secretion is dysregulated as in a sustained allostatic state that leads to allostatic overload (McEwen, 1998).
In contrast to Selye (1956), this view holds that mediators of
allostasis have a spectrum of actions that depend on the time
courses over which they are being produced, and other
events that are taking place at the same time — that is, the
“general adaptation syndrome” is not really so general, after
all (Goldstein and Eisendorfer, 2000; Goldstein and Pacak,
2000). Below we illustrate how the immediate effects of the
secretion of mediators of allostasis such as glucocorticosteroids and catecholamines are largely protective and adap-
5
tive. We then note the damaging consequences that result
from overproduction and/or dysregulation of the same mediators (see also Sapolsky et al., 2000). Some of the examples given above to illustrate “allostasis” will be repeated
below.
Glucocorticosteroids, so named because of their ability
to promote conversion of protein and lipids to usable carbohydrates, serve the body well in the short run by replenishing energy reserves after a period of activity such as
running away from a predator. Glucocorticosteroids also act
on the brain to increase appetite for food and to increase
locomotor activity and food-seeking behavior (Leibowitz
and Hoebel, 1997), thus regulating behaviors that control
energy intake and expenditure. This is very useful when we
have to run 2 miles, but it is not beneficial when we grab a
bag of potato chips while writing a grant or a paper. Inactivity and lack of energy expenditure creates a situation
where chronically elevated glucocorticosteroids can impede
the action of insulin to promote glucose uptake. One of the
results of this interaction is that insulin levels increase and,
together, high insulin and glucocorticosteroid concentrations promote the deposition of body fat. This combination
of hormones also promotes formation of atherosclerotic
plaques in coronary arteries (Brindley and Rolland, 1989).
Free-living animals responding to storms, change in social status, or human disturbance that result in reduced
access to resources such as food and shelter increase glucocorticosteroid secretion to facilitate foraging and promote
gluconeogenesis (especially from muscle). There is also an
inhibition of processes not essential for survival (e.g., reproduction), an increase in activity associated with moving
away from the perturbation or finding shelter, and promotion of night restfulness with a savings in energy (e.g.,
Wingfield, 1994; Wingfield and Ramenofsky, 1999; Wingfield et al., 1998). In some species such as hummingbirds,
increases in glucocorticosteroids are correlated with torpor,
another energy-saving mechanism (Hiebert et al., 2001a,b).
In seabirds, chicks fed a lower quality diet have elevated
glucocorticosteroid levels (Kitaysky et al., 1999). Furthermore, corticosterone treatment of normal chicks results in
higher rates of begging for food, resulting in their parents
foraging more to find additional food. This is particularly
fascinating because one individual influences another in an
effort to relieve allostatic overload (Kitaysky et al., 2002).
Glucocorticosteroids act in concert with peptides in the
CNS, such as CRF, ␤-endorphin, NPY, arginine vasotocin,
and others, and catecholamines to orchestrate these complex
physiological and behavioral responses to perturbations of
the environment (Wingfield and Romero, 2000).
For the heart, we see a similar paradoxical biphasic role
of allostasis mediators. Our blood pressure rises and falls
during the day as physical and emotional demands change,
providing adequate blood flow as needed (Sterling and
Eyer, 1988). Yet repeatedly elevated blood pressure resulting from additional allostatic load promotes the generation
of atherosclerotic plaques, particularly when combined with
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a supply of cholesterol, lipids, and oxygen-free radicals that
damage the coronary artery walls (Manuck et al., 1995).
Beta adrenergic receptor blockers are known to inhibit this
cascade of events and to slow down the atherosclerosis that
is accelerated in dominant male cynomologus monkeys exposed to an unstable dominance hierarchy (Manuck et al.,
1991). Thus catecholamines and the combination of glucocorticosteroids and insulin can have dangerous effects on
the body besides their important short-term adaptive roles
(Brindley and Rolland, 1989).
The nervous system interprets which events are “stressful” and determines behavioral and physiological responses
to the stressor, and it shows a similar paradoxical biphasic
action of the mediators of allostatic load. In the brain, strong
emotions frequently lead to “flash-bulb” memories, e.g.,
where we were and what we were doing when we heard of
John Lennon’s assassination, the horrible events of September 11, 2001, or remembering the location and events associated with a very positive life event like proposing marriage or receiving a promotion or award. Both
catecholamines acting via beta adrenergic receptors and
glucocorticosteroid hormones acting via intracellular receptors play an important role in establishing these long-lasting
memories. A number of brain structures participate along
with the autonomic nervous system (Cahill et al., 1994;
Roozendaal, 2000). The amygdala plays an important role
in this type of memory (LeDoux, 1996), aided by the autonomic nervous system, which picks up a signal from circulating epinephrine (Cahill et al., 1994), and by the hippocampus, which helps us remember “where we were and
what we were doing” at the time the amygdala was turned
on in such a powerful way (LeDoux, 1996; Roozendaal,
2000).
Thus, epinephrine and glucocorticosteroids promote the
memory of events and situations that in the future may be
dangerous. This is an adaptive and beneficial function. The
paradox for the brain comes when there is repeated stress
over many days or when allostatic load forces glucocorticosteroid levels to remain high because of adrenal overactivity, poor “shut off” in relation to negative feedback, or
the diurnal rhythm. Then there is atrophy of pyramidal
neurons in the hippocampus and dentate gyrus (McEwen,
1999; Sousa et al., 2000) and inhibition of ongoing neurogenesis in the dentate gyrus (McEwen, 1999) as well as a
possible loss of glial cells (Rajkowska et al., 1999). After
very prolonged periods of allostatic load, as in subordinate
monkeys living in a dominance hierarchy, allostatic overload may occur and pyramidal neurons may actually die
(Uno et al., 1989). Through some or all of these processes,
the hippocampus undergoes a shrinkage in size, with impairment of declarative, contextual, and spatial memory,
and this can be picked up in the human brain by neuropsychological testing accompanied by MRI in such conditions
as recurrent depressive illness, Cushing’s syndrome, posttraumatic stress disorder, mild cognitive impairment in aging, and schizophrenia (McEwen, 1999).
Allostasis as a concept to unify approaches to
perturbations of the environment in biological and
biomedical contexts
There are potentially two complementary views of allostasis, allostatic states, allostatic load, and allostatic overload. One involves how organisms in their natural environment search for basic needs such as food and shelter,
thereby enhancing overall fitness. In these cases individuals
must orchestrate daily and seasonal needs in relation to
environmental conditions and social status, as well as deal
with unpredictable events in the environment. Failure to
deal with these problems results in death, thus providing
strong selection for mechanisms that allow organisms to
cope. The other view involves the impact of complex social
organization on human health and longevity of its members
under conditions where social organization predominates
over basic needs as a factor that causes stress. It is fascinating to consider whether these two historically divergent
approaches, medical research on the one hand and basic
biology on the other, have some common ground in the
concept of allostasis and mechanisms underlying coping.
This could be of particular importance over the next few
decades as global change not only will influence the environment that animals live in, but will also have a profound
impact on our own lives.
While allostasis and allostatic states apply to all situations that involve physiological and behavioral responses to
challenge, the cumulative costs to the organism are very
much dependent upon the balance between energy supplies
and demands, and upon additional factors involving social
competition and perceived, as well as actual inequality. We
now consider two types of allostatic load and overload.
Allostatic load and type 1 overload to cope with
unpredictable environmental events that threaten food
availability and quality of shelter—mechanisms to
avoid and resist stress
All organisms must adjust their physiology, morphology,
and behavior in response to changing environments —
physical and social, predictable and unpredictable. This
allows an individual to avoid or resist the potential for stress
(Sapolsky et al., 2000; Wingfield et al., 1998; Wingfield and
Romero, 2000). The rapid behavioral and physiological
changes in response to perturbations have been collectively
called the “emergency” life history stage, which serves to
enhance lifetime fitness (Wingfield et al., 1998). Glucocorticosteroids interacting with other hormones in the HPA
cascade initiate and orchestrate events within this stage
within minutes to hours.
Characteristic components of the emergency life history
stage in birds include: redirection of behavior from a normal
life history stage to increased foraging, irruptive-type migration during the day, enhanced restfulness at night, ele-
B.S. McEwen, J.C. Wingfield / Hormones and Behavior 43 (2003) 2–15
vated gluconeogenesis, and recovery once the perturbation
passes. These states allow an individual to avoid potential
deleterious effects of perturbations (i.e., reduce allostatic
load) that may result from chronically elevated levels of
circulating glucocorticosteroids over days and weeks. Several field studies in diverse habitats indicate that free-living
populations have elevated circulating levels of glucocorticosteroids when in an emergency life history stage (Wingfield and Romero, 2000).
Expression of the emergency life history stage may not
always be advantageous, however. There is accumulating
evidence from birds that the adrenocortical responses to
labile perturbation factors are modulated both seasonally
and at individual levels. These changes may have ecological
bases such as reproductive state, social status, body condition, etc. It is possible that different control mechanisms in
the HPA cascade may mediate changes in response to specific environmental and social conditions. Some simple
models based on food available in the habitat, body condition, social status, and life history stage may provide a
common framework to experimentally test sensitivity of the
HPA axis to perturbations under different conditions (Wingfield and Ramenofsky, 1999). The accumulating data clearly
indicate that there has been strong selection for mechanisms
that allow individuals to respond to environmental perturbations in an adaptive manner that avoids the deleterious
effects of stress. The data also raise the question of whether
we should refer to glucocorticosteroids as stress or antistress hormones, reminding us of the discussion of protective and damaging effects mediated by stress hormones (see
also Sapolsky et al., 2000).
Some simple energy models allow development of a
common framework for the energetic costs of the normal
life cycle, including reproduction, migration, and other critical events (Fig. 1). These energetic requirements (E) are
very broad and include actual energy needs, as well as other
factors such a minerals, vitamins, essential amino acids,
etc., as one. The basic existence of an individual requires a
minimum energy level (EE) to maintain homeostasis in any
life history stage. However, as the environment changes
homeostatic mechanisms must be adjusted accordingly, or
else the individual would be unable to adapt. The energy
required to make these predictable changes (EI) under ideal
conditions during the day and night, or during the changing
seasons, is regulated allostasis. EI can increase during reproduction or decrease during hibernation and is always
below the energy in the environment (EG) that is available
for the individual to eat.
In Fig. 1a, these energy levels are represented as straight
lines over time. In the real world these possibly change as
indicated in Fig 1b. For example, at higher latitudes the
amount of food available in the environment increases in
spring and summer and decreases in autumn and winter.
Existence energy (EE) and the energy required to go out and
forage, obtain, and process food (EI) will decline in spring
and summer (as, for example, environmental temperature
7
Fig. 1. A framework for modeling energetic requirements (E) of organisms
during their life cycle. This energy requirement, E, includes all potential
nutritional requirements including energy per se. They are grouped together here for convenience although essential components of nutrition
could also be modeled. In this and all figures, EE represents the energy
required for basic homeostasis. EI represents the extra energy required for
the individual to go out, find, process, and assimilate food under ideal
conditions. EG represents the amount of energy (in food) available in the
environment (from Wingfield et al., 1998; Wingfield and Ramenofsky,
1999). (a) These requirements are represented as straight lines. (b) The
changes in energy levels have been adjusted to represent probable changes
in relation to seasons. EG would be expected to rise dramatically in spring
and summer and then decline through autumn and winter when primary
productivity is low. EE would be lowest in summer when ambient temperatures are highest. EI should be fairly constant (under ideal conditions) and
varies in parallel with EE. (c) Bearing in mind that energy levels will vary
in potentially complex ways, EE and EI are held as straight lines for
simplicity. Here we introduce additional costs incurred after a perturbation
(such as a storm) that increases costs above EE ⫹ EI. This line (EO)
represents the energy required to go out and find food, process it, and
assimilate nutrients under nonideal conditions. Allostatic load increases as
EO persists in time. If it exceeds EG then Type 1 allostatic overload begins,
resulting in elevation of plasma glucocorticosteroid levels. This should
trigger an emergency life history stage that results in alternate physiology
and behavior intended to reduce allostatic overload. (d) If we then represent
the effects of EO in more naturally fluctuating conditions, then in winter
Type 1 allostatic overload occurs rapidly.
increases) and increase again in autumn and winter (when
temperature declines; Fig. 1b). Thus, the margin between EE
⫹ EI (costs of living day to day) and resources in the
environment (EG) is much greater at some times of year than
others. This allows the individual to migrate, breed, molt,
etc., all of which require extra energy, at some times of year
but not others. Additionally, some animal populations use
the period of food excess to store fat for migration, hibernation, etc.
If an additional event occurs in the environment such as
bad weather, change in habitat, etc. (see Wingfield, 1994),
then the energy required to obtain food can increase under
these non ideal conditions (EO; Fig. 1c) and glucocorticosteroid secretion also increases. As long as the sum of EE,
EI, and EO remains below EG then the individual can continue to pursue its normal life cycle. If EE ⫹ EI ⫹ EO
exceeds EG then negative energy balance may increase
8
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glucocorticosteroid secretion further, resulting in a change
of physiology and behavior designed to promote survival
(the emergency life history stage; Wingfield and Ramenofsky, 1999). Allostatic load increases as EE ⫹ EI ⫹ EO
increases and becomes allostatic overload, Type 1, when it
exceeds EG (Fig. 1c). If the same perturbation (EO) occurs in
winter, then Type 1 allostatic overload is reached very
quickly (Fig. 1d) compared to summer (Fig. 2a). Additionally, if environmental conditions, or social status, increase
EE ⫹ EI, then the same EO can result in Type 1 allostatic
overload even in summer (Fig. 2b). A similar result is
obtained if EG is decreased (Fig. 2c). If EE ⫹ EI increases
along with a decrease in EG, then in winter the individual
may be in Type I allostatic overload constantly requiring a
major response—the emergency life history stage (Fig. 2d).
Even in summer EO may result in Type 1 allostatic overload
very quickly (Fig. 2d).
Various environmental factors can result in permanent
elevation of EE and EI, or at least the individual’s ability to
obtain energy necessary to fuel allostatic load, and thus are
cumulative (Chitty, 1996; Wingfield, 1994; Wingfield et al.,
Fig. 2. A schematic representation of the effects of EO, a line showing an
increase in energy costs required to go out and find food, process, and
assimilate it under nonideal conditions. If this occurs in late spring (a), then
the seasonal increase in EG and decreases in EI and EE can cover the costs
of EO. (b) A model of the effects if permanent injury, disease, or deleterious lifestyle increase EE ⫹ EI close to resources available (EG), then the
individual may be close to Type 1 allostatic overload through the Winter
and even in Spring and Summer will be susceptible to a perturbation (EO)
resulting in overload. A perturbation (EO) occurring in winter, or a time
when resources are at low ebb, would result in almost immediate allostatic
overload. (c) A scenario in which EG is reduced dramatically. This can
happen in nature as a result of climate change or other perturbation.
Additionally, in human society, socioeconomic status reduces resources
available (EG). Then in winter an individual may always be in Type 1
allostatic overload, and even in summer EG does not increase enough to
prevent allostatic overload if a perturbation occurs. The same perturbation
(EO) in winter would result in immediate Type 1 allostatic overload. (d) If
permanent injury, disease, or deleterious lifestyle increase EE ⫹ EI, and
socio-economic status or environmental perturbation reduces resources
available (EG), then the individual will be in Type 1 allostatic overload
through the winter and even into spring. Even in summer susceptibility to
a perturbation (EO) will result in rapid overload.
Fig. 3. Summary of Type 1 allostatic overload and glucocorticosteroid
secretion. Here EO increases dramatically and eventually EO ⫹ EE ⫹ EI
exceeds EG. Increasingly high glucocorticosteroid secretion then triggers
an emergency life history stage. The result of this is to suppress expression
of other life history stages, resulting in a net decrease of allostatic load
below EG. The animal can now survive the perturbation in positive energy
balance and glucocorticosteroid secretion subsides, avoiding pathologies
associated with chronic high levels.
1995; Wingfield and Ramenofsky, 1999). Examples include
injury that impairs an individual’s capacity to forage, body
size, location, or parasite load that reduces energy storage
and utilization as well (Dunlap, 1995a,b; Dunlap and Schall,
1995; Dunlap and Wingfield, 1995). Collectively, any permanent impairment, as well as the fluctuating energy requirements of the cycling environment and its perturbations,
make up allostatic load.
These theoretical models allow a common framework for
assessing how environmental conditions, social status, and
disease all contribute to allostatic load and vulnerability to
Type 1 allostatic overload. It is further suggested that although glucocorticosteroid secretion will increase as allostatic load increases, when EE ⫹ EI ⫹ EO exceeds EG, then
gluocorticosteroid secretion is very high and prolonged for
as long as the perturbation persists, and triggers the emergency life history stage (Fig. 3). If the perturbation is
chronic and the emergency life history stage cannot reduce
allostatic load, then development of serious pathological
effects and eventually death are possible.
Social status can also have dramatic effects on EE and
EG. Dominants will have greater access to restricted food
resources (increase EG), whereas subordinates will have less
access (decrease EG). Additionally, dominants may have the
best shelter, thus reducing EE, whereas subordinates will be
forced into suboptimal habitat, with a likely increase in EE.
Particularly dramatic effects can accrue when several environmental and social conditions combine (e.g., Fig. 2d). An
example is when unpredictable severe weather in winter
reduces food resources (EG) and subordinate status raises EE
⫹ EI in young European blackbirds, Turdus merula. These
subordinate young birds develop Type 1 allostatic overload
rapidly and emigrate south from their normal winter area in
southern Germany to a more benign environment in Italy.
Once at the new location EE ⫹ EI are once again less than
B.S. McEwen, J.C. Wingfield / Hormones and Behavior 43 (2003) 2–15
EG. Furthermore, only subordinate blackbirds had elevated
circulating levels of corticosterone (Schwabl et al., 1984,
1985). This is not a permanent emigration because the next
spring the latter birds migrate back to Germany to breed
when food resources (EG) are increasing again. On the other
hand, some environmentally forced emigrations of animals
may have resulted in permanent range changes, thus affecting gene pools in populations affected.
A related human example, involving socioeconomic status (SES), is a local or regional disaster such as a flood,
earthquake or drought that differentially affects people with
lower incomes and poorer housing than those with higher
economic status: e.g., the famous migration from Oklahoma
to California in the dust bowl of the 1930s, as captured by
John Steinbeck in The Grapes of Wrath. This migration
allowed for reproduction and survival of the emigrants in a
more hospitable environment and influenced the cultural
traditions and gene pool of present-day California. Although this is a compelling human example, it is not known
whether or not such facultative migrations in humans are
triggered by glucocorticosteroids.
One of the tenets of allostatic load and Type 1 overload
is that glucocorticosteroid secretion and perhaps other mediators of allostasis increase (Fig. 3). As glucocorticosteroid
levels in blood rise, then physiological and behavioral
changes occur, ensuring that sufficient energy is available to
fuel EO or other events of the life cycle such as migrating,
breeding, molting, etc. If perturbations force allostatic load
even higher so that EG is surpassed, resulting in Type 1
allostatic overload, and negative energy balance ensues,
plasma glucocorticosteroid levels continue to rise. When
they pass a certain threshold (probably variable across populations and among individuals; see Wingfield and Ramenofsky, 1999; Wingfield and Romero, 2000) they trigger
an emergency life history stage (Fig. 3), the function of
which is to redirect individuals to a survival mode. This
reduces allostatic load so that positive energy balance (EE ⫹
EI ⫹ EO ⬍ EG) is regained (Fig. 3). Glucocorticosteroid
secretion declines as a consequence, thus avoiding deleterious effects of chronic hyperadrenocorticism (Fig. 3).
Clearly Type 1 allostatic overload triggers responses that
make it possible for the individual to cope. In contrast, Type
2 allostatic load and overload do not lead to such a favorable
outcome, but, rather, are harbingers of disease, as will be
discussed below.
Allostatic load and type 2 overload—what happens
when competitive social structure predominates over
food and shelter as a source of challenge?
The distinction between views of Type 1 allostatic overload versus allostatic load in some forms of human disease
is that increasing energy requirement is the drive leading
eventually to allostatic overload when negative energy balance is reached (EE ⫹ EI ⫹ EO ⬎ EG; Figs. 1 and 2). Unless
9
the emergency life history stage reduces allostatic load (Fig.
3) to regain positive energy balance (EE ⫹ EI ⫹ EO ⬍ EG),
then cumulative effects become pathological. In modern
human society, we see positive energy balance that goes
awry with chronic abdominal fat and atherosclerosis. Even
inflammatory disorders can be linked, in part, to oxidative
stress and too much “fuel” in the body (Bierhaus et al.,
2001). These considerations are summarized in energy diagrams (Fig. 4) like those described above for Type 1
allostatic load and overload (Figs. 1, 2, and 4a).
In Type 2 allostatic load, social conflict (for an example
of EO) leads to an allostatic state reflected in elevated
glucocorticosteroid levels; EO rises but never exceeds food
available (Figs. 4a and 4b). In fact, the crisis might even
increase food consumption, because as noted earlier, glucocorticosteroids increase appetite (e.g., stress-induced eating). If the crisis and resulting allostatic state are transitory
(e.g., a temporary social trauma for a human or invasion of
a territory by a predator for an animal) then the resulting
allostatic load will be temporary and will be reflected in a
transitory increase in glucocorticosteroids (Fig. 4a). If the
crisis resulting in increased EO is more chronic (e.g., low
social status for an animal or low SES for a human), then a
more long-lasting allostatic state ensues (Fig. 4b), with
chronically dysregulated glucocorticosteroid secretion,
chronically elevated food consumption, insulin resistance,
and increased deposition of fat. With the onset of these
conditions, Type 2 allostatic overload has begun.
Another situation is depicted in Figs. 4c and 4d, namely
one in which EE and EI increase due to an injury or deleterious lifestyle in humans or a temporary change in temperature coupled with injury in an animal. Glucocorticosteroid secretion increases as EE ⫹ EI increases and declines as
the perturbation passes (Fig. 4c). Because EG is never actually surpassed, the individual is able to cope. On the other
hand, in human conditions, and perhaps in animals in captivity, agriculture, etc., the sum of EE and EI may be permanently increased (Fig. 4d). This could be due to social
factors owing to SES interacting with disability, poor housing and working conditions, noise and danger from crime,
and other depredations. In these cases EE ⫹ EI remains high
but again never exceeds EG. Glucocorticosteroid secretion
also increases and remains permanently elevated, leading
once again to Type 2 allostatic overload. In other words,
environmental conditions lead to a chronic allostatic state,
but food resources are always abundant.
Type 2 allostatic overload may reconcile the observation
that we see positive energy balance with abdominal fat, but
development of atherosclerosis. Many inflammatory disorders can also be linked, in part, to oxidative stress and
excess fuel in the body. In these scenarios, EG is not reduced
to an extent that negative energy balance is a problem.
However, other stressors may be acting to increase glucocorticosteroid secretion independently of energy balance
resulting in protein breakdown despite a continued high
level of food intake. Extra energy is laid down as fat.
10
B.S. McEwen, J.C. Wingfield / Hormones and Behavior 43 (2003) 2–15
Fig. 4. Glucocorticosteroids are key biological mediators of both Type 1
and Type 2 allostatic load and overload, as shown in four different hypothetical scenarios. Depending on the circumstances associated with glucocorticoid elevation other hormones, e.g., insulin and related metabolic
hormones, will also be altered. When EG is not exceeded and individuals
are consuming excess calories, obesity, the metabolic syndrome, and Type
2 diabetes are the result. (a) Normal responses to challenge when EG is not
exceeded. EO represents the challenges of daily living in a difficult or
challenging environment. In animals in the wild, this would include demands of finding food and coping with weather. In human terms, this
includes the challenges of work and coping with a stressful living environment and interpersonal interactions. Glucocorticosteroid levels remain
low during normal events associated with EE ⫹ EI. As EO sets in, glucocorticosteroid secretion increases in parallel. (a) EO is transient; when EO
subsides, so does glucocorticosteroid secretion. Because EG is not exceeded, the individual does not need to trigger an emergency life history
stage, i.e., escape from the situation. (b) Type 2 allostatic overload as a
function of permanent perturbations in EO, which increases and remains
high. Glucocorticosteroid secretion also increases and stays chronically
high because of the continuous stress of the living and (in humans) working
environment. Because EG is not exceeded, the chronic elevation of glucocorticosteroids leads to an imbalance in other hormones — e.g., hyperinsulinemia—that can lead to hyperphagia and obesity. This is Type 2
allostatic overload. (c) Increases in allostatic load could be presented as a
transitory increase in EE ⫹ EI, such as is the case when individuals overeat,
become obese, and have more weight to carry around. Again glucocorticosteroid secretion would match this increase and subside as EE ⫹ EI return
to normal, such as after a successful diet and exercise program. Because EG
is never exceeded, then an emergency life history stage is not needed. In
these cases, EE and EI are elevated as a result of within-individual changes.
EO is an outside influence, such as social pressure, over and above EE ⫹ EI.
(d) Type 2 allostatic overload as a result of permanent increases in EE and
EI, as in a chronic state of obesity when individuals continue to consume
more calories than are needed and enter a state where oxidative stress is
elevated, as in Type 2 diabetes (Bierhaus et al., 2001). Glucocorticosteroid
secretion parallels this increase and chronically high levels result in the
same pathologies as in b.
There are animal models of this. The thrifty genes hypothesis has been proposed for many decades and asserts
that humans and perhaps all animals have genes for efficient
and potentially excessive energy accumulation. In fluctuating environments when food shortages (EG) are common,
this would be highly adaptive. In modern times with no food
shortage, at least in developed countries, it leads to chronic
obesity, hypertension, and diabetes (Lev-Ran, 2001; Neel,
1962; Neel et al., 1998). Many animals from fish to toads
and mammals get fat when food is available at high levels
and energy output is not elevated. Birds migrate and burn
off that fat. Hibernating animals also have extended periods
of not feeding and thus lose fat. But if events in life history
stages or general activity do not metabolize this, then obesity becomes chronic (Lev-Ran, 2001).
In some free-living birds, environmental perturbations
result in a dramatic increase in corticosterone secretion that
in turn facilitates foraging/feeding, promotes protein breakdown for gluconeogenesis, and increases associated activity
(Wingfield et al., 1998; Wingfield and Romero, 2000).
However, if birds are implanted with corticosterone to
mimic high levels attained in response to a stressor, they
gain fat. The implants create a chronic allostatic state but
without reduction of EG. These animals then show the same
behavioral responses but put on fat in large quantities (Gray
et al., 1990; Wingfield and Silverin, 1986). Normally that
fat would be metabolized in coping with the perturbation.
Over a prolonged period this could lead to other symptoms
of chronic stress but without a decrease in fat (Type 2
allostatic load).
When in the course of allostatic load do the changes
become irreversible? One example that comes to mind is
death of the migrating salmon after reproduction (Dickhoff,
1989). Males of tournament (lekking) species may spend
many years gaining experience in aggressive interactions,
etc., so that they have one, often brief, period as a dominant
male during which they gain many matings with females
(e.g., Wittenberger, 1981). To get to this point they incur
injuries and suppressed immune systems, and feed less.
Typically they accrue such allostatic load that they may not
recover and fail to breed in the next breeding season. This
is not a programmed death because other males do not die.
Another example is migration. Some bird species accumulate so much allostatic load while migrating to the breeding
grounds and then breeding that they never recover sufficiently to repeat the cycle the next year (Marshall, 1952).
In many animal populations there may be similar cases
of Type 2 allostatic load (overload), but the individuals
involved die quickly, thus providing strong selection for
mechanisms that limit allostatic load. We know from the
veterinarian literature that captive animals can develop similar symptoms (large fat stores, atherosclerosis) and thus
Type 2 allostatic load can involve “too much” positive
energy balance as in humans (Butterwick and Hawthorne,
1998; Krysiak et al., 2001; Shafrir, 1997). It is just that in
human society, and in captive animals, the selection pressure is not there. There is actually good evidence that fat
stores in wild animals incur a cost in terms of risk of
predation; i.e., the individual is not as maneuverable, gets
caught by a predator, and makes a good meal (e.g., Lind,
1999). Thus there is a trade-off with increasing fat stores
allowing a reserve for allostasis, but increasing allostatic
load in terms of predation risk.
B.S. McEwen, J.C. Wingfield / Hormones and Behavior 43 (2003) 2–15
Fig. 5. Gradients of four diseases as a function of socioeconomic status.
Four diseases show gradients across the full range of socioeconomic status.
Data for the following are shown: (a) Percentage diagnosed osteoarthritis
(Cunningham and Kelsey, 1984); (b) relative prevalence of chronic disease
(Townsend, 1974); (c) prevalence of hypertension (Kraus et al., 1980); (d)
rate of cervical cancer per 100,000 (DeVasa and Diamond, 1980). Republished from Adler et al. (1994) by permission.
Type 2 allostatic load—a human perspective
The situations depicted in Fig. 4 are an attempt to put
into an energy model the conditions that exist in the modern
industrialized world with its social hierarchies and differing
degrees of inequality. Modern Western society is characterized not by hunger and the search for basic creature comforts as by complex social structures. These involve living
and working environments that vary in quality, variable
access to recreation, and the existence of mass communications with a variety of messages about personal choices,
morality, and politics. As a result there are systematic variations in health and mortality across the range of income
and education collectively referred to as SES. These SES
gradients cannot be explained simply by access to health
care or individual factors such as amount of smoking (Adler
et al., 1993, 1994). The gradients of health across the range
of socioeconomic status relate to a complex array of risk
factors that are differentially distributed in human society
and that have a cumulative impact on behavioral and physiological allostatic load. Cardiovascular disease is among
the most prominent disorders showing an SES gradient.
However, cardiovascular disease is not the only disease with
an SES gradient. Figure 5 presents gradients of four disorders across a range of SES, showing that those at the highest
SES levels have the lowest incidence of all four disorders
compared to the mid-SES level, which, in turn, is lower than
the lowest level of SES. In other words, the gradient is
gradual and does not dip only at the lowest SES level.
Among the underlying causal factors for the SES gradient are economic hardship and early childhood experiences.
For example, a study of elderly people who had a lifetime of
sustained economic hardship pointed to a more rapid decline of physical and mental functioning (Lynch et al.,
11
1997b). Moreover, as noted, individuals with a history of
childhood abuse suffer greater mortality and morbidity from
a range of diseases (Felitti et al., 1998).
Undoubtedly the best example of SES influences upon
health is the Whitehall study of the British Civil Service. In
Whitehall, stepwise gradients of mortality and morbidity
were found across all six grades of the British Civil Service
in spite of the fact that all of the studied individuals had jobs
and access to health care (Marmot et al., 1991). There are
many factors that undoubtedly contribute to these gradients,
including factors in the living and working environment.
Not surprisingly, cardiovascular disease is a frequent outcome of these gradients and the psychosocial and environmental factors that are responsible for the allostatic load.
Based upon the discussion of depression and cardiovascular
disease, one must consider depression, as well as lack of
control as a major factor in the allostatic load that results in
hypertension, abdominal obesity, and atherosclerosis.
Hypertension was found to be a sensitive index of job
stress, particularly in factory workers, in other workers with
repetitive jobs and time pressures (Melin et al., 1997), and
in workers whose jobs were unstable due to departmental
privatization (M.G. Marmot, personal communication).
“Vital exhaustion” is a work-related behavioral state, reflecting lack of perceived control and a sense of helplessness, that correlates strongly with increased risk for cardiovascular disease (Everson et al., 1997; Keltikangas-Jarvinen
et al., 1996; Kop et al., 1998; Lynch et al., 1997a;
Raikkonen et al., 1996). Among indices of allostatic load,
plasma fibrinogen, which predicts increased risk of death
from CHD and stroke because it participates in clotting of
blood in coronary and cerebral blood vessels, is elevated in
men in lower British Civil Service grades (Markowe et al.,
1985).
Another stress-linked parameter of allostatic load that
varies across SES is abdominal obesity, measured as increased waist/hip ratio (WHR). Abdominal obesity is linked
to Type II diabetes and cardiovascular disease (Brindley and
Rolland, 1989) and can be enhanced in a primate animal
model by psychosocial stress (Manuck et al., 1991). WHR
is increased at the lower end of the SES gradient in Swedish
males (Larsson et al., 1989), and WHR also increases with
decreasing civil service grade in the Whitehall studies
(Brunner et al., 1997).
Immune system function is also a likely target of psychosocial stress. Recent evidence indicates that psychosocial stress—tensions in personal relationships and negative
life events—increases vulnerability to infections such as the
common cold (Cohen et al., 1997; Widom, 1999). Social
disruption in mice—placing an aggressive intruder in a
stable mouse colony— causes glucocorticiod resistance, i.e.,
reduced suppression of immune responses by exogenous
glucocorticoids, that is particularly apparent in subordinates
that are most likely to be wounded by the intruder (Stark et
al., 2001).
With regard to psychiatric disorders, there is some evi-
12
B.S. McEwen, J.C. Wingfield / Hormones and Behavior 43 (2003) 2–15
Table 1
Relative risk for three disorders involving the nervous system
Income
$0–19K
$20–34K
$35–69K
$ ⬎ 70K
Education
Years 0–11
Years 12
Years 13–15
Years ⬎ 16
Affective
Disorders
Anxiety
Disorders
Substance
Abuse
1.73*
1.13
1.01
1.00
2.12*
1.56*
1.50
1.00
1.92*
1.12
1.11
1.00
1.79*
1.38*
1.37*
1.00
2.82*
2.10*
1.60*
1.00
2.10*
1.80*
1.70*
1.00
Note. Data are compiled for both income and education based upon
Kessler et al. (1994) and Regier et al. (1993). Table prepared by Dr. Nancy
Adler, University of California, San Francisco, as a personal communication to the author. Reprinted from McEwen (2000) by permission.
dence that low SES is associated with mental distress and
depression, as well as other disorders such as schizophrenia
and substance abuse (Brown and Adler, 1998). However,
there are questions of causality; i.e., does SES cause the
disorder or does the disorder lead to low SES? In the case of
schizophrenia, personality disorders, substance abuse, and
severe cognitive impairment, it is very likely that the conditions themselves lead to a lower SES position (Brown and
Adler, 1998; Dohrenwend et al., 1992). On the other hand,
a low SES position, reflecting poor resources, living environment, and an unsatisfying job, are likely to be a cause of
depression and anxiety (Brown and Adler, 1998; Dohrenwend et al., 1992). Table 1 shows gradients of affective
disorders, anxiety disorders, and substance abuse, as a function both of income and of education. It is noteworthy that,
for education, all three disorders show a gradient in which
the lowest and middle levels of education all differ significantly from the highest level. However, for income, both
affective disorders and substance abuse show significant
differences only for the lowest income group, although
anxiety disorders show a more robust gradient in which all
three lowest levels of income differ significantly from the
highest income level.
It is important to point out that considerations of Type 2
allostatic load and social organization go beyond the confines of organized, stable social structures. In less stable
societies, conflict and social instability have been found to
accelerate pathophysiological processes and increase morbidity and mortality. For example, cardiovascular disease is
a major contributor to the almost 40% increase in the death
rate among Russian males in the social collapse following
the fall of Communism; in these studies, cardiovascular
disease is a prominent cause of death, along with alcoholism, suicide, and homicide (Bobak and Marmot, 1996; Notzon et al., 1998). In addition, self-reported health was related inversely to material deprivation and positively related
to education level and perceived control (Bobak et al.,
1998). As noted above, blood pressure surges and sustained
blood pressure elevations, which are likely to occur in
unstable and stressful social environments, are linked to
accelerated atherosclerosis as well as increased risk for
myocardial infarction (Manuck et al., 1995; Muller and
Tofler, 1990).
Conclusions
Most vertebrate organisms have regular patterns and
routines that involve obtaining food and carrying out life
history stages such as breeding, migrating, molting, hibernating, etc. These life history stages occur in set sequences
on a time scale of about 1 year. Each has energetic requirements that vary according to demand. Often, life history
stages such as reproduction and migration are energetically
demanding, whereas others rely on stored energy only (hibernation). The annual sequence of stages is geared to
maximize fitness by allowing individuals to breed at the
optimal time and in the best condition. Acquisition, utilization, and storage of energy reserves are critical to lifetime
reproductive success. Animals are also exposed to unpredictable perturbations of the environment that have the
potential to disrupt the life cycle and may even result in
development of pathologies if the perturbation becomes
chronic. Thus individuals must respond to challenges that
are both predictable, such as seasonal changes, and unpredictable, such as storms and natural disasters. Social organization also plays an important role in the integration of
life cycles.
Here we have discussed the concept of allostasis, maintaining stability through change, as a fundamental process
through which organisms actively adjust to these predictable and unpredictable events. It is a particularly heuristic
concept because it joins the energetic costs of life history
stages with those accompanying social challenges and perturbations of the environment into a continuum. Glucocorticosteroid secretion, catecholamines, and cytokines increase in parallel with this continuum — allostatic load.
One very attractive aspect of this idea is that the term
“stress” can now be restricted to the environmental perturbations that lead to allostatic load. The term allostasis subsumes stress as the process by which physiological stability
is maintained in the face of change. In the past the term
stress could refer to the environmental challenges as well as
the process of attempted adaptation and the result — development of pathologies. This often led to confusing phrases
such as the stress of reproduction or migration as opposed to
the stress of being chased by a predator, or the result of
social trauma. Clearly the former is part of the normal life
cycle whereas the latter are perturbations that go beyond the
norm. Allostasis forms a continuum between events of the
normal life cycle and unpredictable perturbations with clear
transition points and outcomes.
Allostatic load refers to the cumulative cost to the body
of allostasis as individuals adjust their morphology, physi-
B.S. McEwen, J.C. Wingfield / Hormones and Behavior 43 (2003) 2–15
ology, and behavior to environmental changes, social state,
etc. This can fluctuate as the animal changes life history
stage and as the seasons and other cycles progress. Allostatic overload is either a state in which the costs of the life
history stage and accompanying challenges exceed the food
resources available to provide sufficient energy (Type 1), or
a state in which deleterious challenges (e.g., social) are
chronic and lead to a sustained allostatic state independent
of seasonal changes in the environment (Type 2). Serious
pathophysiology can occur if overload is not relieved in
some way.
In the case of Type 1 allostatic overload, escape responses are triggered along with other self-preservation
measures, increasing the chances of reestablishing a new, or
temporary, life in a different environment. Using the balance between energy input and expenditure as the basis for
applying the concept of allostasis, we propose that in Type
1 allostatic overload, activation of the emergency life history stage and consequences of deprivation serve to direct
the animal into a survival mode that decreases allostatic
load and regains positive energy balance. This will allow the
individual to survive the perturbation in the best condition
possible and the normal life cycle can be resumed when the
perturbation passes. In Type 2 allostatic load there is sufficient or even excess energy consumption, but continued
social conflict and other types of social dysfunction drive
allostasis constantly. As a result, glucorticosteroid secretion
is chronically and differentially elevated, along with imbalances in other mediators, leading to pathophysiology. This
latter situation is the case in human society and certain
situations affecting animals in captivity. Unlike Type 1
allostatic overload, Type 2 allostatic load does not trigger an
escape response. Escape from Type 2 allostatic overload is
only possible when humans and animals suffering from
social conflict and embedded within social hierarchies can
learn to change their own behavior and alleviate the negative social conditions.
Acknowledgments
J.C.W. is grateful for several grants from the Division of
Integrated Biology and Neuroscience, and the Office of
Polar Programs, National Science Foundation. He also acknowledges a John Simon Guggenheim Fellowship, a Benjamin Meaker Fellowship (University of Bristol, UK), and a
Russell F. Stark University Professorship (University of
Washington). B.Mc. acknowledges the intellectual support
from colleagues in the MacArthur Research Network for
Socioeconomic Status and Health, Nancy Adler, UCSF,
Chair. In particular, Teresa Seeman, UCLA, and Burton
Singer, Princeton, have played a major role in formulating
and validating the concepts of allostasis and allostatic load.
He acknowledges grant support from the NIH.
13
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