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Stress has a different meaning for different people under different conditions. The first and most generic definition of stress was that proposed by Hans Selye: "Stress is the nonspecific response of the body to any demand." Other definitions have evolved to cater for different situations-for example, cognitive. This article explores the basis for these definitions and their validity, and outlines the neuroendocrine mechanisms that subserve the stress response. The concept of homeostasis, 'stability through constancy' as the main mechanism by which the body copes with stress, has given way to allostasis, 'stability through change' brought about by central neural regulation of the set points that adjust physiological parameters to meet the stressful challenge. Furthermore, this article reviews relatively new stress concepts based on findings that (1) polymorphisms in certain genes involved in neurotransmission, as well as epigenetic factors, may determine individual susceptibility to stressful life events, and (2) fetal malnutrition may predispose individuals to the metabolic syndrome (obesity, hypertension, dislipidemia, and diabetes type 2) that has reached epidemic proportions in many countries. Finally, studies of heat shock proteins show that Selye's generic definition is applicable to the stress response in all three phylogenetic domains of organisms ranging from bacteria to man.
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Stress: Concepts, Definition and History
G Fink, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia
Ó2017 Elsevier Inc. All rights reserved.
Introduction and Historical Outline of Stress Concepts 1
Hans Selye 1
Epidemiology 2
Thrifty Phenotype Hypothesis 2
Brain Plasticity 2
Genetic Susceptibility to Stress: Gene x Environment Interaction 2
Neuroendocrine and Autonomic Nervous Control of Stress Response 3
Glucocorticoids Discovery and Clinical Importance 3
Denitions of Stress 4
SelyesDenition of Stress a Further Consideration 5
General Adaptation Syndrome 5
Stressors Features of and Lack of Stressor Sign 5
Non Specicity of Stress Response 6
Stress-Induction Across Phyla: Heat Shock Proteins 6
Concepts of Stress and Disease 6
Future Developments of Stress Concepts 7
References 7
Further Reading 9
Introduction and Historical Outline of Stress Concepts
Stresshas been dubbed the Health Epidemic of the 21st Centuryby the World Health Organization and is estimated to cost
American businesses up to $300 billion a year. The effect of stress on our emotional and physical health can be devastating. In
a recent USA study, over 50% of individuals felt that stress negatively impacted work productivity. Between 1983 and 2009, Stress
levels increased by 1030% among all demographic groups in the USA.
Aristotle, Hippocrates and the other Ancients were aware of stress and its adverse effects. However, Claude Bernard was the rst
formally to explain how cells and tissues in multicelled organisms might be protected from stress. One of the worlds greatest phys-
iologists, Bernard, working in Paris during the second half of the 19th century, rst pointed out (1859) that the internal medium of
the living organism is not merely a vehicle for carrying nourishment to cells. Rather, it is the xity of the milieu intérieur which is the
condition of free and independent life.That is, cells are surrounded by an internal medium that buffers changes in acid-base, gaseous
and CO
) and ion concentrations and other biochemical modalities to minimize changes around biologically determined set-
points, thereby providing a steady state. Fifty years later, Walter Bradford Cannon, working at Harvard, suggested the designation
homeostasis (from the Greek homoios or similar and stasis or position) for the coordinated physiological processes that maintain
most of the steady states in the organism. Cannon popularized the concept of homeostasis in his 1932 book Wisdom of the Body.
Cannon, also coined the term ght-or-ight to describe an animals response to threats. The concept of ght-or-ight, also called
the acute stress response, proposes that animals react to threats with a general discharge of the sympathetic nervous system, priming
the animal for ghting or eeing. This response was later recognized as the rst stage of a general adaptation syndrome (GAS) rst
postulated by Hans Selye to be a universal stress response among vertebrates and other organisms.
Hans Selye
Born in Vienna in 1907, Hans Hugo Bruno Selye, also known as the father of stress,began his stress research while still
a medical student in 1926. He observed that patients with a variety of illnesses had many of the same non-specicsymptoms
that were a common response to stressful stimuli experienced by the body. These clinical observations together with experi-
ments on laboratory rats underpinned Selyes concept of the GAS which led Selye to assert that prolonged exposure to stress
resulted in diseases of adaptation.That is, chronic stress, by causing the overproduction of chemicals and hormones,
produced gastro-duodenal ulcers and high blood pressure. Although the GAS hypothesis was subsequently shown to be incor-
rect, it did put stress on the map and also highlighted the fact that stress had major effects on the immune system as well as on
the adrenal glands.
Change History: January 2016. G Fink made some changes to the text, title of the manuscript, updated Further Reading and References section.
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In addition to providing the rst clear denition of stress, Hans Selye was also the rst to recognize that homeostasis could
not by itself ensure stability of body systems under stress. He coined the term heterostasis (from the Greek heteros or other) as
the process by which a new steady state was achieved by treatment with agents that stimulate the physiological adaptive mech-
anisms. Heterostasis, could be regarded as the precursor for the concept of allostasis,rst advanced by Peter Sterling and Joseph
Eyer in the 1980s (Sterling and Eyer, 1988;McEwen, 1998;Schulkin, 2004). That is, homeostasis, which has dominated phys-
iological and medical thinking since the 19th century, is thought to provide stability through constancy.Allostasis, on the
other hand, provides stability through changebrought about by regulation of the set-points that adjust physiological param-
eters to meet the stress/challenge.
A different tack, focused on cognition, was taken by the eminent and inuential Berkeley University Psychologist, Richard
Lazarus. At a time when psychology tried to understand human behavior by rst understanding simple organisms engaging in
simple behaviors learned by associations, rewards or punishments, Lazarus instead emphasized the importance of studying cogni-
tion which he extended into stress and coping (Lazarus, 2000,2006).
Epidemiology has been and remains central to stress studies. Numerous epidemiological studies have tried to dene the effects of
social, workplace and lifestyle on stress, health and well being. Indeed, job stress is by far the major source of stress for American
adults and has escalated progressively over the past few decades. Increased levels of job stress as assessed by the perception of having
little control but many demands have been demonstrated to be associated with increased rates of heart attack, hypertension, obesity,
addiction, anxiety, depression and other disorders. In New York, Los Angeles and other municipalities, the relationship between job
stress and heart attacks is recognized, so that any police ofcer that suffers a coronary event on or off the job is assumed to have
a work related injury and is compensated accordingly.
Thrifty Phenotype Hypothesis
However, of the recent epidemiological studies that have generated new stress concepts, the most important perhaps remains that of
David Barker (Barker, 1995), which led to the hypothesis that fetal undernutrition in middle to late gestation programs later coro-
nary heart disease. This concept was soon extended by Hales and Barker (2001) in their thrifty phenotype hypothesis.The latter
proposes an association between poor fetal and infant growth and the subsequent development of type 2 diabetes and the meta-
bolic syndrome, which afict communities in epidemic proportions. Poor nutrition in early life, it is postulated, produces perma-
nent changes in glucose-insulin metabolism. These changes include insulin resistance (and possibly defective insulin secretion)
which, combined with effects of obesity, aging and physical inactivity, are the most important factors in determining type 2 dia-
betes. Many studies worldwide have conrmed Barkers initial epidemiological evidence, although the strength of the relationships
has varied between studies. As well as intrauterine growth restriction, maternal obesity and diabetes can be associated with disease
of the individual later in life (Rando and Simmons, 2015). Furthermore, paternal exposures can result in the later development of
metabolic disorders in the offspring, and human and animal studies suggest intergenerational transmission of the maternal or
paternal phenotype (Rando and Simmons, 2015). Several changes in epigenetic marks identied in offspring provide a likely mech-
anism by which early molecular changes result in persistent phenotypic changes (Keating and El-Osta, 2015), although additional
mechanisms yet to be uncovered cannot be excluded.
Brain Plasticity
Early life exposures, fetaland perinatal, could result in biological embedding byway of at least three plausible mechanisms: brain plas-
ticity, epigenetics (especially DNA methylation; Demetriou et al., 2015), and hormonal action. There are numerous examples of brain
plasticity, perhaps one of the most dramatic being the recruitment of new neurons and the increase in hippocampal gray matter in
scatter-hoarding animals which need to remember the location of food caches (Barnea and Nottebohm, 1994;Barnea et al., 2006)
and London Cab drivers (Maguire et al.,2006;Woollett et al., 2009) for whom spatial memory is of paramountimportance. Hormonal
effects are exemplied by the possible effect of excess androgen in causing the polycystic ovary syndrome phenotype (Gur et al., 2015).
Genetic Susceptibility to Stress: Gene x Environment Interaction
With recent advances in genomics, the concept of susceptibility genes that increase the vulnerability of individuals to stressful life
events has attracted considerable research interest. Thus, for example, the work of Avshalom Caspi and associates (Caspi et al.,
2002) suggested that a polymorphism in the MAOA (monoamine oxidase A) gene promoter, which reduces MAOA expression, inu-
ences vulnerability to environmental stress, and that this biological process can be initiated by childhood abuse. Furthermore, in what
seemed to be a landmark paper Caspi et al. (2003) reported that a polymorphism in the promoter of the serotonin transporter (SERT
or 5-HTT) gene can render individuals more susceptible to stressful life events. Because SERT is also the therapeutic target for popular
antidepressant drugs, the selective serotonin reuptake inhibitors, the publication by Caspi et al. (2003) led to a urry of research publi-
cations and subsequent meta-analyses to assess the replicability of the ndings. However, the overall conclusions from primary and
meta-analyses on genetic x environmental interactions suggest that it is unlikely that there is a stable gene x environment interaction
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involving the SERT, life stress and mental disorders (Fergusson et al., 2011). Whether the uncertainty regarding the suggested link bew-
een the SERT gene promoter polymorphism and susceptibility to stress reects an artifact or problems in posthoc analysis is discussed
by Rutter et al. (2009) who conclude that the totality of the evidence on GXE is supportive of its reality but more work is needed to
understandproperly how5HTT allelic variations affect response to stressors and to maltreatment.In fact, recent data suggest that there
is a stable gene x environment interaction involving MAOA, abuse exposure and antisocial behavior across the life course (Fergusson
et al., 2012) as proposed in the earlier paper by Caspi et al. (2002).
Single nucleotide polymorphisms in the gene for the CRF receptor-1 have been tentatively linked to suicidal thoughts and
behavior, depression, panic disorder and fear (Ben-Efraim et al., 2011;Ishitobi et al., 2012;Wasserman et al., 2008,2009,
2010;Weber et al., 2015). Recent genetic and functional magnetic resonance imaging (fMRI) studies have shown that a func-
tional deletion variant of ADRA2B, the gene encoding the alpha 2b-adrenergic receptor, is related to enhanced emotional
memory in healthy humans and enhanced traumatic memory in war victims (Rasch et al., 2009). The ADRA2B deletion
variant, which acts primarily as a loss-of-function polymorphism, is related to increased responsiveness and connectivity of
brain regions implicated in emotional memory (Rasch et al., 2009;de Quervain et al., 2007). In normal subjects, only carriers
of ADRA2B deletion variant showed increased phasic amygdala responses to acute psychological stress, illustrating that genetic
affects on brain function can be context (state) dependent (Cousijn et al., 2010). In twin studies, Tambs et al. (2009) have
investigated the genetic interactions and the 5 types of anxiety disorder. A recent report by Zannas et al. (2015) suggests that
cumulative lifetime stress may accelerate epigenetic aging, possibly driven by glucocorticoid-induced DNA methylation.
Taken together, the above examples illustrate that our understanding of gene x environment interactions in stress and stress-
related disorders is still at an early phase. Nonetheless, these ndings have heuristic importance for further thinking and research
on genetic-environmental interactions that determine the response to stress and the development of mental disorders.
Neuroendocrine and Autonomic Nervous Control of Stress Response
In parallel with these stress concepts, major neuroendocrine advances revealed the physiological substrate for homeostasis, allosta-
sis and the stress response mechanisms. The autonomic nervous and the hypothalamic-pituitary-adrenocortical (HPA) systems
subserve the afferent and efferent limbs of the stress response in vertebrates, and are also central to maintaining homeostasis
and effecting allostasis. The term autonomic nervous system was coined in 1898 by the Cambridge Physiologist, John Newport
Langley, who was also renowned for his development (in parallel with Paul Ehrlich) of receptor theory. Controlled by the brain,
and utilizing as neurotransmitters epinephrine and norepinephrine (sympathetic nervous component) or acetylcholine (parasym-
pathetic component), the role of the autonomic nervous system in ght-or-ight and homeostasis (especially cardiovascular) was
clearly explained by Walter Cannon.
The story of our understanding of the HPA, and the concept of the neurohumoral hypothesis of anterior pituitary control, is
tortuous (Fink, 2012,2015). The pituitary gland had long been regarded, by luminaries such as the great Harvard neurosurgeon
Harvey Cushing, as the autonomous controller of the adrenal cortex, the thyroid and the gonads. That is, the anterior pituitary
gland was considered to be the conductor of the endocrine orchestra.This view was reinforced by the dramatic effects of exper-
imental hypophysectomy in rodents made feasible by the parapharyngeal surgical approach to the pituitary developed by PE
Smith around 1930. However, at about the same time experiments were in progress that triggered a cascade of studies which would
eventually prove that the anterior pituitary gland is not autonomous; rather, it is controlled by the brain. These experiments,
carried out by William Rowan working alone in Edmonton Alberta in the late 1920s, showed that migration in birds was
controlled by the gonads, and that gonadal size in birds was increased many-fold by increases in day-length. Day-length and
the effects of other exteroreceptive factors, such as stress, on endocrine function together with the effects of brain tumors and trauma
in the human, lead to an acceptance of the concept that the pituitary gland is under central nervous system (CNS) control.
The neural lobe of the pituitary gland is comprised of nerve projections from the paraventricular and supraoptic nuclei of the
hypothalamus: these projections terminate on systemic blood vessels into which they release the nanopeptide neurohormones,
vasopressin and oxytocin. In contrast, the anterior pituitary gland receives no direct innervation from the brain. Rather, the CNS
control of the anterior pituitary gland is mediated by neurohormones synthesized and released from hypothalamic neurons and
transported to the anterior pituitary gland by the hypophysial portal vessels. Proof of the neurohumoral hypothesis of anterior pitu-
itary control came, rst, from the elegant pituitary stalk section and pituitary grafting experiments of Geoffrey Harris and Dora
Jacobsohn, secondly, the characterization of some of the neurohormones by Andrew Schally and Roger Guillemin, for which
they were awarded the 1977 Nobel Prize for Physiology and Medicine, and, thirdly, the demonstration, rst by my group, that these
neurohormones were indeed released into hypophysial portal blood (Fink, 2012,2015;Fink and Sheward, 1989;Fink et al., 1971).
Corticotropin releasing hormone (CRH), a 41 amino acid peptide that mediates neural control of adrenocorticotropic hormone
(ACTH) release from pituitary corticotropes, was isolated and sequenced by Wylie Vale et al. (1981). A series of physiological
studies, including measurements of neurohormone release into hypophysial portal blood in vivo, have conrmed earlier views
that arginine vasopressin acts synergistically with CRH to control ACTH release (Fink, 2012;Fink et al., 1988).
Glucocorticoids Discovery and Clinical Importance
Finally, no outline of the history of stress concepts would be complete without mention of the characterization of the adrenocortical
glucocorticoids and their function. The glucocorticoids are steroid hormones whose secretion by the adrenal cortex is controlled by
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ACTH. The hormones of the adrenal cortex were isolated, identied, and synthesized independently by Edward Kendall (at the
Mayo Foundation) and Tadeus Reichstein (at Zurich) and their associates. The availibility of large amounts of synthetic steroids
enabled their physiological effects to be studied. Ultimately, Philip Hench was able to test the glucocorticoid, cortisone, in the
human and demonstrated that it was a powerful anti-inammatory agent. Also from the Mayo Foundation, Hench had previously
observed that rheumatoid arthritis was sometimes relieved during pregnancy and in some patients with jaundice, leading him to
conclude that the pain-alleviating substance was a steroid. Kendall, Hench, and Reichstein jointly were awarded the Nobel Prize for
Physiology and Medicine for 1950, and synthetic glucocorticoids continue to be used to treat arthritis, asthma, autoimmune condi-
tions and other inammatory disorders in the human (Raju, 1999).
Definitions of Stress
Stress has a different meaning for different people under different conditions. The rst and most generic denition of stress is that
proposed by Hans Selye:
Stress is the non-specic response of the body to any demand.
Selye repeatedly emphasized the fact that the continued use of the word stress as a non-specic response to any demand was most
appropriate. Selye argued that stress is not identical to emotional arousal or nervous tension since stress can occur under or in response
to anesthesia in man and animals, and can also occur in plants and bacteria that have no nervous system. This point is elaborated
below in the context of stress-induced heat shock proteins that play a key role in cytoprotection across all three phylogenetic domains.
The word stress,as used by Selye, is accepted in all foreign languages, including those in which no such word existed previously.
Stress, Selye underscored, is not something to be avoided. Indeed, it cannot be avoided, since just staying alive creates some
demand for life-maintaining energy. Even when man is asleep, his heart, respiratory apparatus, digestive tract, nervous system
and other organs must continue to function. Complete freedom from stress can be expected only after death.
There has been much controversy and debate about Selyes concepts and particularly Selyes view that stress is best regarded as
a non-specic response. Because of their heuristic value, these points will be further considered below.
Other denitions, reviewed in detail by Selye in his Stress in Health and Disease (1976), include the following:
1. In behavioral sciences, stress is regarded as the perception of threat, with resulting anxiety discomfort, emotional tension, and
difculty in adjustment.
2. In the group situation, lack of structure or loss of anchor makes it difcult or impossible for the group to cope with the
requirements of the situation, and the problem of leadership and interpersonal behavior becomes one of evolving or supplying
a structure or anchor and of supplying the expertness for coping with the demands of the situation.
3. Stress can also be dened in terms of pure neuroendocrinology. Eugene Yates, for example, dened stress as any stimulus that
will provoke the release of ACTH and adrenal glucocorticoids. Presumably, the same might apply to the equally powerful
sympathetic markers of stress, underscored earlier by Walter Cannon.
4. Selye also mentions Richard Lazarus, famous for his work in cognitive psychology and focus on the emotions. Lazarus under-
scores the difculties of reaching a precise overarching denition of stress by setting out the following different meanings of the
term: In spite of consistent confusion about the precise meaning of the term, stress is widely recognized as a central problem in
human life. Scientists of many disciplines have conceptualized stress but each eld appears to have something different in mind
concerning its meaning. For the sociologist, it is social disequilibrium, that is, disturbances in the social structure within which
people live. Engineers conceive of stress as some external force which produces strain in the materials exposed to it. Physiologists
deal with the physical stressors that include a wide range of stimulus conditions that are noxious to the body. In the history of
psychological stress research, there has been no clear separation between physical stressors which attack biological tissue systems
and psychological stressors which produce their effects purely because of their psychological signicance.
5. In their seminal review The Stressed Hippocampus, synaptic plasticity and lost memories,Kim and Diamond (2002) suggest
a three-component denition of stress that can be applied broadly across species and paradigms. First, stress requires heightened
excitability or arousal, which can be operationally measured using electroencephalography, behavioral (motor) activity or
neurochemical (adrenaline, glucocorticoid) levels. Second, the experience must also be perceived as aversive. Third, there is lack
of control. Having control over an aversive experience has a profound mitigating inuence on how stressful the experience feels.
The element of control (and predictability) is the variable that ultimately determines the magnitude of the stress experience
and the susceptibility of the individual to develop stress-induced behavioral and physiological sequelae.
Thus, the magnitude of neurocognitive stress (S) approximates to the product of:
lExcitability/Arousal (E)
lPerceived aversiveness (A)
lUncontrollability (U)
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Selye’s Definition of Stress a Further Consideration
As intimated above, Hans Selye was the rst to use the word stress in the context of biomedicine, and dene the concept and
phenomenon of stress in a generic and non-specic manner. Selyesdenition and concept of stress has remained controversial.
For some, his denition is too biological and ignores cognitive and psychological factors, a criticism that seems to stem from
the mistaken idea that cognition is not brain/biologically based (a reversion to Rene Descartesoutmoded doctrine that mind
and body are separate). For others, Selyesdenition is too general. Selye systematically rebutted some of these and other criticisms
(Selye, 1975). Here we review the basis for Selyesdenition of stress, and consider whether the criticisms leveled at Selyes stress
concept are valid. Overall, our observations suggest that Selye fully understood so-called psychological or cognitive stress, and that
the generality of Selyes stress denition has facilitated the molecular, genotypic and phenotypic analysis of stress and stress
responses across all species from bacteria to man.
General Adaptation Syndrome
Hans Selye rst put stress on the map with the GAS. In search of a new hormone, Selye injected extracts of cattle ovaries into rats. The
injection caused the following characteristic triad:
1. the adrenal cortex became enlarged and discharged lipid secretory granules
2. the thymus, spleen, lymph nodes and all other lymphatic structures showed severe involution
3. deep bleeding ulcers appeared in the stomach and duodenum
Selye at rst thought that these effects were due to a new hormone in the extracts. But soon found that all toxic substances
extracts of kidneys, spleen, and even toxicant not derived from living tissue produced the same syndrome.
Selye surmised that the response to the injection of toxic substance reected his classroom conceptof the syndrome of just
being sickThat is, adrenal enlargement, thymico-lymphatic involution and gastrointestinal ulcers were the omnipresent signs of
damage to the body when under attack. The three changes thus became (for Selye) the objective indices of stress and the basis for the
development of the entire stress concept.
First described in a note to Nature in 1936 (Selye, 1936), the GAS has three stages: alarm; resistance; exhaustion. In the alarm
stage, the body shows changes characteristic of the rst exposure to the stressor these changes generally coincide with the sympa-
thetic discharge that enables the ght-or-ight phenomenon of Cannon. If the stressor continues and is compatible with adaptation,
features of the alarm reaction disappear and resistance develops. Prolonged exposure to the stressor may result in exhaustion and
nally death.
One of the most important ndings of GAS is the stress-induced thymico-lymphatic involution which highlighted for the rst
time that stress has a major impact on the immune system and that was in 1936 more than 20 years before the discoveries of
lymphocyte recirculation by James Gowans and acquired immunological tolerance by MacFarlane Burnet and Peter Medawar!
Selyes discovery began the eld of neuroimmunomodulation.
Selye soon became aware of the fact that the adrenal enlargement of the GAS was associated with increased secretion of gluco-
corticoids (cortisol or corticosterone) that induce glycogenolysis, thereby supplying a readily available source of energy for the
adaptive reactions necessary to meet the demands made by the stressors. In addition, they facilitate various other enzymatically
regulated adaptive metabolic responses and suppress immune reactions as well as inammation, assisting the body to coexist
with potential pathogens.Selye asserted that glucocorticoids are needed for the acquisition of adaptation primarily during the
alarm reaction. Selyes view that glucocorticoids enhance and mediate the stress response has been upheld with the additional
concepts that glucocorticoids play a permissive role that primes the bodys stress response systems and also prevent overshoot of
the defense systems. Overshoots in the bodys defense system are perhaps most dramatically seen in major inammatory cataclysms
called cytokine storms and the consequent systemic inammatory response syndromes that play a key role in the lethality of avian
inuenza and have also occurred in response to the injection of certain antibodies (Suntharalingam et al., 2006). Exogenous
synthetic glucocorticoids such as methylprednisolone remain a mainstay of the treatment of cytokine storms.
The GAS is clearly a consequence of extreme stress. The three components of the GAS have not withstood the test of time as
indices of stress as Selye had originally proposed. Rather, the main biological markers of stress have long been behavioral observa-
tions and tests and measures of sympathetic and HPA activation. In the case of the latter the measurement of glucocorticoid concen-
trations in blood, either alone or in parallel with plasma concentrations of ACTH, have been used as the main biological indices of
stress. So, in spite of its heuristic value, and its importance for triggering the concept of stress-induced neuroimmunomodulation,
the concept of the GAS has lost scientic currency.
Stressors Features of and Lack of Stressor Sign
Selye, in Stress in Health and Disease (Selye, 1976), underscored the fact that Stress is part of our daily human experience, but it is
associated with a great variety of essentially dissimilar problems, such as surgical trauma, burns, emotional arousal, mental or phys-
ical effort, fatigue, pain, fear, the need for concentration, the humiliation of frustration, the loss of blood, intoxication with drugs or
environmental pollutants, or even the kind of unexpected success that requires an individual to reformulate his lifestyle. Stress is
present in the businessman under constant pressure; in the athlete straining to win a race; in the air-trafc controller who bears
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continuous responsibility for hundreds of lives; in the husband helplessly watching his wifes slow, painful death from cancer; in
a race horse, its jockey and the spectator who bets on them.Selye went on to argue that while all these subjects face quite different
problems they respond with a stereotyped pattern of biochemical, functional and structural changes essentially involved in coping
with any type of increased demand upon vital activity, particularly adaptation to new situations.
Selye also asserted that stressors have no sign as faras evoking the stress response. That is the response will be the same whether the
agent or situation being faced is pleasant or unpleasant; all that counts is the intensity of the demand for readjustment or adaptation
that it creates.Selye underscored this point with the following poignant example: The mother who is suddenly told that her only son
died in battle suffers a terrible mental shock; if years later, it turns out that the news was false and the son unexpectedly walks into her
room alive and well, she experiences extreme joy. The specic resultsof the two events, sorrow and joy, are completely different, infact
they are opposite to each other, yet their stressor effect the nonspecic demand for readjustment to a new situation is the same.
Non Specicity of Stress Response
Selye seemed to have been driven to nd specicity in the response to different types of stressors. Thus, in Stress in Health and Disease
(Selye, 1976) he wrote:
It is difcult to see at rst how such essentially different things as cold, heat, drugs, hormones, sorrow and joy could provoke an identical biologic
reaction. Nevertheless this is the case; it can now be demonstrated by highly objective, quantitative biochemical and morphologic parameters that
certain reactions are totally non-specic and common to all types of agents, whatever their superimposed specic effects may be.
The lack of specicity of Selyesdenition of stress has been the subject of considerable criticism. Indeed, Pacak and Palkovits
(2001) carried out a series of experiments that demonstrate that different stressors activate different stress biomarkers and different
regions of the brain. Thus, for example, low blood glucose concentrations (glucopenia) or hemorrhage activate both the sympa-
thetic and HPA systems; hyperthermia, cold and formalin injection selectively activate the sympathetic system. On the basis of these
data, Pacak and Palkovits conclude that each stressor has its own specic neurochemical signature. However, since these stress
indices are limited to just two neurohumoral systems, and since for most stressors there is at least some overlap in response, it
is not clear that this approach invalidates Selyesdenition, Stress is the non-specic response of the body to any demand, which would
probably be unassailable had Selye omitted the term non-specic.
Stress-Induction Across Phyla: Heat Shock Proteins
Whatever the shortcomings Selyesdenition of stress for the human, it is probably appropriate for the vast majority of living organ-
isms. Living cells are classied into three main evolutionary lines, or phylogenetic domains; Bacteria (eubacteria), Archaea (formerly
archaebacteria), and Eucarya (eukaryotes which encompass all plants and animals through to man). The cellular response to stress
in all three phylogenetic domains is represented at the molecular level by the stress-induced synthesis of stress or heat shock proteins
(Hsps), of which molecular chaperones and proteases represent two well-characterized families. The heat shock response was
discovered in 1962 by Ferruccio Ritossa, who observed a pattern of Drosophila salivary gland chromosome puffs that were induced
in response to transient exposure to elevated temperatures (Ritossa, 1962,1996). Since then, many studies have shown that the heat
shock response is ubiquitous and highly conserved in all organisms from bacteria to plants and animals. It is an essential defense
mechanism for protection of cells from a wide range of stressors, including heat shock, alcohols, ischemia, inhibitors of energy
metabolism, heavy metals, oxidative stress, fever, or inammation, which depending on amplitude and duration can all cause
cell death by apoptosis or necrosis. The heat shock response can protect against stress-induced cell death by way of a cell-
protective process known as thermotolerance or cytoprotection, in which exposure of cells to mild stress conditions, sufcient to
induce the expression and accumulation of Hsps, protects against a subsequent challenge from another stress that is, by itself, lethal.
Although their precise function remains to be determined, the high degree of conservation of these Hsps across species, coupled
with their importance in cell survival in various conditions, suggests that Hsps are critical for both normal cellular function and
survival after a stress. Several cytoprotective functions have been attributed to Hsps and, in particular, the HSP70 family. These
include (1) the folding of proteins in various intracellular compartments, (2) the maintenance of structural proteins, (3) the refold-
ing of misfolded proteins, (4) translocation of proteins across membranes and into various cellular compartments, (5) the preven-
tion of protein aggregation, and (6) the degradation of unstable proteins. Hsps also serve as modulating signals for immune and
inammatory responses, and may have a role in cytokine production.
So, for the heat shock response to stressful stimuli, Selyes Stress is the non-specic response of the body (or cell) to any demand would
appear to be appropriate.
Concepts of Stress and Disease
There is a vast literature on the role or possible role of stress in the causation and/or excacerbation of disease in most organ systems
of the body. Here attention will focus on mental disorders. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) of
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the American Psychiatric Association recognizes two stress disorders: Acute Stress Disorder and Posttraumatic Stress Disorder. For
the diagnosis of Acute Stress disorder the individual, while experiencing the trauma or after the event, must have at least three of
several dissociative symptoms such as a subjective sense of numbing, detachment, or absence of emotional responsiveness, reduc-
tion in awareness of surroundings, depersonalization, or dissociative amnesia. Following the trauma, the traumatic event is persis-
tently reexperienced, the individual avoids stimuli that may arouse recollections of the traumatic event, and has anxiety or increased
arousal. The trauma causes clinically signicant distress or impairment in social, occupational, or other important areas of
Posttraumatic Stress Disorder (PTSD) is dened as a condition in which a traumatic event is persistently reexperienced in the
form of intrusive recollections, dreams or dissociative ashback episodes. Cues to the event lead to distress and are avoided, and
there are symptoms of increased arousal. To meet the diagnostic criteria of the DSM-5, the full symptom picture must be present
for more than 1 month, and the disturbance must cause clinically signicant distress or impairment in social, occupational, or other
areas of functioning.
PTSD has only been accepted ofcially as a mental disorder since 1980, when it was included, amid considerable controversy, in
the DSM-III. References to the after effects of psychological trauma (1) date back as far as the third century BC, (2) achieved
prominence during the early period of the railroad in Britain when rail travel, then precarious and physically traumatic, gave rise
to a syndrome called railway spine or postconcussion syndrome, and (3) were regarded as the basis for hysteria around the turn
of the 19th Century by neurologists and psychiatrists such as Jean-Martin Charcot, Pierre Janet and Sigmund Freud. Long before
PTSD was included in any diagnostic system, Charles Dickens wrote A Tale of Two Cities, which (published in 1859) can be
considered as an early case report of PTSD (Huber and te Wildt, 2005). Interest in PTSD increased dramatically during the First
World War: Charles Samuel Myers was the rst to coin the term and report case histories of shell shock(Myers, 1915) which
described a condition that aficted many troops who screamed and wept uncontrollably, froze and could not move, became
mute and unresponsive and lost their memory, sensations and capacity to feel. Pat Barkers monumental trilogy, Regeneration,
deals poignantly with the psychological traumas of war and the nature of shell shock. The condition occurred again in vast
numbers of people as a consequence of the Second World War. However, it was the psychological trauma experienced by
Vietnam veterans and their demand for compensation that lead to the inclusion of PTSD in the DSM-III as a condition that
occurred both in civilian (eg, rape trauma syndrome, battered woman syndrome, abused child syndrome) and military trauma
response syndromes.
Future Developments of Stress Concepts
Thisbriefaccountofsomeofthedenitions and concepts of stress show that there is still much to be done in the area of stress
research. Thus, with respect to gene-environmental interactions, work on susceptibility genes has just begun, and there is still
room for expanding our knowledge about the role in stress of epigenetic factors and other mechanisms of gene control such
as RNA interference. On the basis of previous theories, it seems likely that BarkersFetal originshypothesis might be honed
and revised and may lead to a robust understanding of the metabolic syndrome and diabetes type 2. New powerful computer
analysis of brain imaging and electrical recording may help to resolve the many questions that surround consciousness and
cognition. The vexed cause- and effect questions regarding the inuence of stress in mental disorders, cancer and other diseases
need to be answered. We have witnessed in the last 25 years how Selyes cherished and widely accepted axiom that stress is the
cause of gastric ulceration (one of the three components of the GAS) was modied by the careful observations and courageous
perseverance of Barry Marshall and Robin Warren who demonstrated that, in fact, many gastro-duodenal ulcers are caused by
a microbe, Helicobacter pylori, that is, readily amenable to treatment with antibiotics. And yet, some types of stress, especially
physical trauma, can in the absence of Helicobacter pylori cause gastric ulceration (Fink, 2011). Thus, the relative potency for ulcer
causation of stress compared with Helicobacter pylori, and the possible interaction between the two causes needs to be determined.
These and other biological questions about stress are likely to be tractable rational and rigorous biology will almost certainly
win the day.
However, the causes of human stress, acute and posttraumatic, are largely social and sociological, political and irrational (beliefs
in religious and racial superiority). Our continuing strife and conict reect in part mans innate, often irrational (limbic-brain
generated) aggressive drive for conquest, territory, acquisition, and reproduction of the species. Perhaps the fact that man is such
a smart political animal works against us, and could ultimately lead to our stressful self-destruction. It is not clear that anything
short of the impossible amygdalectomy at birth can protect man from this fate.
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Further Reading
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... Stress as defined by Hans Selye, Father of Stress is "a state manifested by a specific syndrome which consists of all the non-specifically induced changes within the biological system". 1 Lazarus, Psychologist also has defined stress as a process whereby an individual perceives and responds to events that he appraises as overwhelming or threatening to his well-being. 2 Stress can be considered a double-edged sword. 'Eustress' can be to better performance to an individual while 'distress' can lead to adverse mental health condition such as anxiety, burnout maladaptive coping such as substance abuse or suicide in worst case. ...
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Background: Stress can be considered as a double-edged sword. Various studies have provided evidence of stress amongst medical students. There have been no studies regarding prevalence of various stress factors among the medical students of the only private medical college in Manipur. Methods: A cross-sectional study was conducted at Shija Academy of Health Sciences, Langol amongst the first MBBS Batch 2022. Convenience sampling method was adopted. medical students stress questionnaire was used for assessing Stress and Maslach burnout inventory-student survey was used for assessing Burnout of the medical students. Results: A total of 148 medical students participated. For stress predictor domains, the academic related stressor was found to have the highest mean score (2.30±0.65). There were statistically significant associations between the social related stressor score with location of home of students and academic related stressor with self-graded academic performance. There was also significant association between group activities related stressor and self-graded academic performance of students. for burnout domains, the employment/occupational exhaustion had the highest mean score (26.54±9.37). Statistically significant associations were found between depersonalization with gender and location of home of students, and occupational exhaustion with self-graded academic performance of students. Conclusions: This study reveals the need for stress management modules development for students with special focus on academic and social related stressors.
... The word stress refers to a series of processes that involve the perception, assessment, and response to harmful events or stimuli. These stressors may be of a physical nature or those that arise from states of the mind (FINK, 2009). ...
Resumo: Chronic stress may change eating behavior and thus play a role in the development of obesity. Recent research targeting obesity prevention has evaluated meditation as a resource for regulating emotion. In this literature review, 20 studies conducted in the last decade, concerning the topics of overweight and obese population that used different types of meditation were examined. These articles were focused on changes in weight, eating behavior and psychological factors. The results showed that meditation reduced stress and promoted positive changes in eating behavior that help the individual to lose weight. However, the body of evidence as regards the effect on weight are still not conclusive and further research is necessary.Keywords: Eating Behavior. HPA axis. Stress. Meditation. Obesity. Resumo: O estresse crônico pode alterar o comportamento alimentar e, assim, desempenhar um papel no desenvolvimento da obesidade. Pesquisas recentes voltadas para a prevenção da obesidade avaliaram a meditação como um recurso para regular a emoção. Nesta revisão de literatura, foram examinados 20 estudos realizados na última década, sobre os temas da população com sobrepeso e obesidade que utilizaram diferentes tipos de meditação. Esses artigos foram focados em mudanças de peso, comportamento alimentar e fatores psicológicos. Os resultados mostraram que a meditação reduziu o estresse e promoveu mudanças positivas no comportamento alimentar que ajudam o indivíduo a perder peso. No entanto, o corpo de evidências em relação ao efeito sobre o peso ainda não é conclusivo e mais pesquisas são necessárias. Palavras-chave: Comportamento Alimentar. eixo HPA. Estresse. Meditação. Obesidade.
... The meaning of stress depends on the field of application, and it is different for different people in different situations. There has been much debate about this theme in the scientific community leading to a not unique definition of it [16]. Regarding the aviation sector, this concept can be associated with 'the response of the body to stimuli that affect the normal physiological balance of a person, causing physical, mental or emotional strain' [7]. ...
The relevant growth of human-machine interaction (HMI) systems in recent years is leading to the necessity of being constantly aware of the cognitive workload level of an operator, especially in a safety-critical context such as aviation. Since the confusion in the definition of this concept, this paper clarifies this terminology and also highlights its relationship with stress. Thus, we analysed the state-of-the-art of cognitive workload evaluations, showing three up-to-date methodologies: subjective, behavioural and physiological. In particular, the physiological approach is increasingly gaining attention in the literature due to today’s exponential growth of biomedical sensors. Therefore, a review of the most adopted physiological signals in the workload evaluation is provided, focusing on the aeronautical field. We conclude by highlighting the necessity of a multimodal approach for mental workload assessment as a result of this analysis.
... The distinguishing feature of all anxiety disorders is "excessive fear and anxiety followed by avoidance of an object or situation that poses no danger" [10]. Stress on the other hand is represented in feelings of emotional strain and unease when faced with challenging situations [11]. ...
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Background: Adolescence represents a critical period characterized by extensive changes across various domains. While some of the changes and behaviors that emerge during this period can have detrimental effects on adolescents' present and future health, mental health disorders continue to constitute a leading cause of morbidity among young individuals. Objective: Assess the prevalence and determinants of depression, anxiety, and stress among secondary school students in Saudi Arabia. Methods: This analytical cross-sectional study utilized an online questionnaire to collect responses from secondary school students in Saudi Arabia. The Arabic version of the Depression, Anxiety, and Stress Scale - 21 Items (DASS-21) was used to measure depression, anxiety, and stress levels. Data were analyzed using IBM Statistical Package for the Social Sciences software (SPSS, version 29.0, IBM Corp., Armonk, NY, USA). The study included 702 participants. Results: The prevalence of anxiety was 35.2%, followed by depression (30.8%) and stress (14.7%). Females had significantly higher anxiety and stress scores than males (P=0.004, and P=0.011, respectively). Students who were bullied in the last 30 days had significantly higher depression, anxiety, and stress scores than those who were not bullied (P<0.001 for all). Participants who experienced physical assault in the last 12 months had significantly higher depression, anxiety, and stress scores than those who did not (P<0.001 for all). Participants who had had fights in the last 12 months had significantly higher depression (P=0.004) and anxiety (P<0.001) scores than those who did not. Participants who felt unsafe on the way to school had significantly higher depression, anxiety, and stress scores than those who did not (P<0.001 for all). Conclusion: The study revealed prevalence rates of depression (30.8%), anxiety (35.2%), and stress (14.7%) among secondary school students in Saudi Arabia. The study highlights the importance of addressing social stressors such as bullying and physical assault and promoting a safe and supportive school environment to prevent mental health disorders in this population.
... In an anxious or stress condition, our sympathetic nervous system respond same as in fight or flight condition and releases adrenalin, leading to stress sweating. 16 ...
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Fingerprint being a vital evidence plays an important role in identifying a criminal, because of its unique, permanence and inevitable nature. We acquire a variety of chance print on crime scene such as latent, patent and plastic that is 3 dimensional. It is not necessary that we get a whole fingerprint on scene of occurrence. The amount of fingerprint usually present is 5-10 %, and that too it may or may not be clear.2 According to many researchers, along with the ridge characteristics, pores are also unique and individual to a person. If we talk about procedure of sweat secretion in our body, our body in condition like physical heat or psychological stress and anxiety reacts in fight or flight manner, resulting excessive sweating in feet and palmer areas. The main idea of this study is to found out any correlation in the ridge as well as pores dimensions while doing an activity which causes stress or anxiety. Different instruments like digital microscope and Stereo microscope have been used for analysis purpose. In this project a total of 800 fingerprints were studied. After analyzing all the fingerprint it was seen that there is change in the pore and ridge dimension in different psychological condition. It can be concluded that there is significant deviation in both the case that is normal vs. stressed and normal vs. anxiety. Pore and Ridge dimension increases in anxiety and stressed condition as compared to normal state. Keywords: Forensic science, Fingerprint, Poroscopy, Ridge Thickness, Pore Dimension.
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Stress in urban life can be a breeding ground for mental disorders. In addition to being an important cause of physical and mental illness, urban stress also increases the rate of moral anomalies in the city and reduces the security of citizens. For this reason, it is necessary for urban planners and designers to consider the peace of mind of citizens as an important principle in their plans and designs, and to avoid actions that cause this mental disorder. However, although many studies in the last century have examined the relationship between urbanization and stress and effective solutions to it with different approaches, so far no studies on urban planning stress therapy to consider all the indicators affecting urban stress and there is no effective strategic planning based on the results. Moreover, Tehran is the sixth most stressful city in the world, according to the Zipjet Institute. For this reason, it is very important to conduct theoretical studies in this field and formulate urban planning for stress therapists in this city. But due to its large scope, doing such research requires a lot of time and money. For this purpose, in this study, after determining the general indicators, using the Delphi technique, District 8, District 1 of Tehran Municipality has been selected as the study sample. The research method in this research is descriptive-explanatory and is based on the purpose of applied research. Quantitative and qualitative methods were used to collect information and factor analysis was used to analyze them. Then the urban stressors have been identified and a strategic document has been presented.The findings of the research indicate that the stress factors caused by the access system, poor social and economic status, low security, lack of cohesion and social support, differentiation and social isolation, lack of resilience of the urban environment, lack of vitality of the environment, negative feelings of residents, discrimination and social displacement, stress caused by crowding, low sense of identity and belonging are the most important stressors in the study area. As a result, by considering these factors as micro-objectives, urban planning can reduce urban stress in the studied area to a great extent. This research develops the theoretical and empirical findings of previous studies. As a result, with the implementation of this research, the psychological pressure that is imposed on the citizens of this area can be reduced to a great extent. This research provides a suitable method for measuring and identifying urban stressors to urban planners who seek to reduce urban stress.. Applying the factor analysis approach in recognizing and analyzing urban contexts in terms of stress and developing a strategic document corresponding to stressful factors in other parts or the whole city of Tehran and developing a comprehensive mental health program in this city can be very effective in this field.
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Nas últimas décadas, a obesidade está associada a diversos fatores, um deles é o comportamento alimentar hedônico decorrente do estresse, tendo como consequência o consumo de alimentos de alta palatabilidade e menor saciedade, bem como aumento do conteúdo calórico em cada refeição e alimentação de fora, feito em redes de fast-food, sendo assim o objetivo do presente estudo foi identificar a influência do estresse no comportamento alimentar. Trata-se de uma revisão bibliográfica realizada a partir de materiais elaborados, como livros e artigos científicos pesquisados na base de dados do Scielo, Biblioteca Virtual da Saúde (BVS) e buscadores, como o Google Acadêmico, publicados entre 2000 e setembro de 2022. Este estudo aponta a associação entre sentir-se estressado e a melhora após o consumo de alimentos ricos em calorias, como açúcar e gordura. Esta associação pode se tornar um comportamento manifestado mais tarde com menos consciência, tornando-se um hábito. Por meio dessa associação aprendida, as pessoas podem começar a usar os alimentos para aliviar incômodos leves, a fadiga e o estresse crônico de baixo nível, acarretando em obesidade. Foi concluído, que há um impacto significativo no comportamento alimentar de adultos estressados, alterando qualitativamente o consumo alimentar, ocasionando obesidade.
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Covid 19, which has been rapidly spreading throughout Malaysia, especially in Sarawak, has put pressure on both the public and private health sectors. The Malaysian government has imposed a movement decree (MCO) to curb the deadly epidemic. This factor has caused the health sector to experience a large workload during the Covid 19 pandemic, the lack of health personnel also played a role. Due to the covid19 pandemic, it has caused health workers to suffer from mental health symptom problems. At the same time, studies conducted by other researchers agree that the pandemic has caused mental health problems for health sector workers around the world.this study was done to find the causes of mental health problems among health sector workers and provide a way for them to get out of mental health problems and also to measure the impact of mental health in their daily lives. The study was conducted online survey using Microsoft excel as a result of a study of 50 people involved in the data of this study and almost 80% of them had steress and burnout ,difficult to sleep at night and were exposed to the dangers of covid 19, in they did work during the covid19 a result of which the effects of this have caused them mental health problems. The researchers also recommend that the study be done in a comprehensive manner not only in the health sector but it should also be done in general . Keywords: mental health, frontliners workers, pandemic, coronavirus
In this chapter, concepts such as health, mental health, urban health, stress, environmental stress, and urban stress are fully described. Then, the relationships between these concepts and urban stress are identified through content analysis using MAXQDA software. Stress is a social pollutant, an unpleasant emotional state, an unspecific physiological and psychological response to perceived real and imagined threats and stress factors (environmental, social, and behavioral stimuli) to physical, mental, or social integrity, a mechanism preparing us for any reaction (biochemical, physiological, and behavioral response), and also making us evolve and adapt more to the environment. What it causes and what its effects are not always clear. It can be acute (appears suddenly through an unpredictable threat), or chronic (resulting from exposure to repeated threats). Although it is not harmful in general, exposure to chronic stress endangers our physical, mental, emotional, spiritual, and social health. It is an acute threat to the homeostasis (steady state) of an organism, which helps its physical and mental well-being. In fact, the nervous system alerts the body by increasing the heart rates and releasing some hormones (adrenaline and cortisol) and the body quickly turns to maximize its power. This automatic process is known as the “fight-or-flight” reaction or the “stress response.” Urban stress is actually the cumulative stress caused by the experience of living in unfavorable conditions of the urban environment and a general term related to the relationship between the urban environment and its impact on human mental health and a reaction to some threats perceived by undesirable urban events such as pollution, high population, extreme temperature, crowding, noise, destroyed landscape, excessive accumulation of solid waste, waste of time in commuting, etc., and if these conditions are beyond the urbanite’s tolerance, he will experience urban stress. The city both directly influences mental health and causes stress through social, economic, physical, environmental, housing, transportation, and individual stressors, and this stress reduces mental health. Of course, the city also influences mental health through the reduction of general or physical health, because the areas of health and mental health are largely interdependent. Mental health also affects the city both directly and through stress and public health. As a result, urban stress and physical health can mediate the effects of urbanization on mental health and the effects of mental health on the city. A better understanding of this relationship and the effect of mediators and trying to reduce the negative effects of cities on mental health will greatly help to best take advantage of urban life.KeywordsUrban healthUrban mental healthEnvironmental stressUrban stress
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Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1 as a risk factor for panic disorder (PD). Allelic variation of CRHR1 was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1 mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1 risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder.Molecular Psychiatry advance online publication, 1 September 2015; doi:10.1038/mp.2015.125.
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Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the "thrifty" phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS.
In contrast to homeostasis, allostasis refers to the relatively new idea of "viability through change." This book addresses basic physiological regulatory systems, and examines bodily regulation under duress. It integrates the basic concepts of physiological homeostasis with disorders such as depression, stress, anxiety and addiction. It will interest graduate students, medical students, and researchers in physiology, epidemiology, endocrinology, neuroendocrinology, neuroscience, and psychology.
This book is the first to address the most urgent issues, combining a solid basic research approach with applied individual and stress issues, including interventions. Throughout, the focus is on our latest knowledge about various causes of stress and its neuro-cognitive and biological implications. World-renowned authors from Europe as well as the US describe how stress affects the brain of young people as well as adults. They cover the topic from all perspectives, showing how stress affects life in general, from the societal and organizational level to the individual, organ and molecular level. While the book clearly points out stress as a risk factor to health, it also offers a number of evidence-based methods to cope with stress and even ride the positive energy of stress - both as an individual, as well as what managers can do to create a healthy and productive workplace. Written in a reader-friendly and appealing style, the book provides real-life examples from various laboratories, as well as such events as the Volvo Ocean Race, the largest around-the-globe sailing competition. Essential reading for clinicians and biologists, as well as for a wide range of students, including medicine and public health, but also managers and HR staff. With a Foreword by Nobel Laureate Professor Arvid Carlsson (Medicine 2000).
Like the first edition, the second edition of the Encyclopedia of Stress covers nearly every conceivable aspect and ramification of stress including a wide range of related topics such as neuroimmune interactions, cytokines, enzymatic disorders, effects on the cardiovascular system, immunity and inflammation, and physical illnesses. Over the last decade, scientists have presented convincing research showing that psychological stress increases vulnerability to disease. They now understand more clearly that stress may be the thread tying together illnesses that were previously believed to be unrelated. Bone loss, increased abdominal fat, and damaged memory cells in the hippocampus have been linked to elevated cortisol levels. Building on the success of the first edition, this completely revised work surveys the vast amount of research generated in the past five years, resulting in a substantial revision with over 30% new material and over 100 new entries. Expanded sections include Animal Studies, Anxiety and Depression, Drugs, Depression, Disasters, and Psychological and Other Therapies. Also available online via ScienceDirect (2007) - featuring extensive browsing, searching, and internal cross-referencing between articles in the work, plus dynamic linking to journal articles and abstract databases, making navigation flexible and easy. For more information, pricing options and availability visit
Introduction The linking between the social determinants and the health status of the people has been recognized for a very long time, although the last three decades has witnessed the rebirth of interest for this association. The number of scientific publications rose, the contents of which showed the social inequalities in health, hence their validity turns them into a mandatory topic in the field of public health. Objective To review the relevant information on the social determinants and inequalities in health policies. Data sources Literature and document review on-line and in electronic format about this topic. The subject headings such as social determinants, and health inequality and inequity were used for search in websites and pages from well-known centers and institutions. Data synthesis Brief historical account on the relationship between the health status of the people and their social conditions; assessments and critical comments on prestigious researchers ́ approaches. Those methods for the study of health inequalities were summarized and exemplified with the situation of these research works in Mexico. Conclusions More comprehensive and good evidence-supported processes of research on the social determinants are required. Also, it is necessary to recognize the importance of these research works to make decisions to overcome health problems using approaches that guide us to their determinants, but not only from the medical care viewpoint.
This chapter focuses on the principles of negative feedback control using the hypothalamic pituitary adrenal (HPA) system as an example. Feedback control systems are fundamental for the normal physiological functioning of the body. Glucocorticoid feedback inhibition of ACTH release protects the organism against the deleterious effects of hypercortisolemia. The HPA system, together with the sympathetic-medullary system, plays a pivotal role in the neuroendocrine response to stress. Thyroid negative feedback control is more complex than originally thought. It seems that most of thyroid negative feedback is actioned by an effect on TRH at the level of the paraventricular nucleus. There are several types of inherited enzymatic defects in cortisol synthesis known to result in congenital adrenal hyperplasia (CAH), also known as the adrenogenital syndrome. Disruption of the HPA negative feedback system has serious deleterious effects, a point illustrated by the congenital adrenogenital syndrome and hypercortisolemia associated with serious mental illnesses.
This chapter focuses on the principles of neural control of the anterior lobe of the pituitary gland. Derived embryologically from a neural downgrowth, the neural lobe is composed of axons that project from nerve cells in the hypothalamus and terminate on capillaries of the inferior hypophysial artery. Neurohemal junctions are the fundamental functional modules of the major central neuroendocrine system, the median eminence. They are composed of nerve terminals and capillaries that are closely juxtaposed and thereby facilitate the release of chemical messengers from nerve terminals into the bloodstream and vice versa. The neurohemal junctions in the median eminence, neurohypophysis and pineal gland facilitate the transport of neurohormones from the nerve terminals or nerve cell derivatives (pineal) into the bloodstream, whereas at the other CVOs, neurohemal junctions facilitate the sensing of blood hormones by nerve cells. Most of the neurohormones that mediate the neural control of anterior pituitary hormone secretion are peptides that are synthesized in discrete hypothalamic nuclei.