Stress (biology)

Physiological stress redirects here.

confused with physical stress.

It is not to be tain equilibrium (homeostasis), a steady state that exists

more as an ideal and less as an achievable condition. Environmental factors, internal or external stimuli, continually disrupt homeostasis; an organisms present condition is a state of constant ux moving about a homeoFor other kinds of stress see stress.
static point that is that organisms optimal condition for
Physiological or biological stress is an organisms re- living. Factors causing an organisms condition to diverge
sponse to a stressor such as an environmental condi- too far from homeostasis can be experienced as stress. A
tion or a stimulus. Stress is a bodys method of react- life-threatening situation such as a major physical trauma
ing to a challenge. According to the stressful event, the or prolonged starvation can greatly disrupt homeostasis.
bodys way to respond to stress is by sympathetic nervous On the other hand, an organisms attempt at restoring
system activation which results in the ght-or-ight re- conditions back to or near homeostasis, often consumsponse. Because the body cannot keep this state for long ing energy and natural resources, can also be interpreted
periods of time, the parasympathetic system returns the as stress. In such instances, an organisms ght-or-ight
bodys physiological conditions to normal (homeostasis). response recruits the bodys energy stores and focuses atIn humans, stress typically describes a negative condition tention to overcome the challenge at hand.
or a positive condition that can have an impact on a per- The ambiguity in dening this phenomenon was rst recsons mental and physical well-being.
ognized by Hans Selye (1907-1982) in 1926. In 1951 a

commentator loosely summarized Selyes view of stress

as something that "in addition to being itself, was also
the cause of itself, and the result of itself.[4][5]

Etymology and historical usage

First to use the term in a biological context, Selye continued to dene stress as the non-specic response of the
body to any demand placed upon it. As of 2011 neuroscientists such as Bruce McEwen and Jaap Koolhaas
believe that stress, based on years of empirical research,
should be restricted to conditions where an environmental demand exceeds the natural regulatory capacity of an
organism.[6] Despite the numerous denitions given to
stress, homeostasis appears to lie at its core.

The term stress had none of its contemporary connotations before the 1920s. It is a form of the Middle English
destresse, derived via Old French from the Latin stringere, to draw tight.[1] The word had long been in use in
physics to refer to the internal distribution of a force exerted on a material body, resulting in strain. In the 1920s
and '30s, biological and psychological circles occasionally
used the term to refer to a mental strain or to a harmful
environmental agent that could cause illness.
Walter Cannon used it in 1926 to refer to external factors
that disrupted what he called homeostasis.[2] But "...stress
as an explanation of lived experience is absent from both
lay and expert life narratives before the 1930s.[3] Physiological stress represents a wide range of physical responses that occur as a direct eect of a stressor causing
an upset in the homeostasis of the body. Upon immediate disruption of either psychological or physical equilibrium the body responds by stimulating the nervous,
endocrine, and immune systems. The reaction of these
systems causes a number of physical changes that have
both short and long term eects on the body.

3 Biological background

Stress can have many profound eects on the human

biological systems.[7] Biology primarily attempts to explain major concepts of stress using a stimulus-response
paradigm, broadly comparable to how a psychobiological
sensory system operates. The central nervous system
(brain and spinal cord) plays a crucial role in the bodys
stress-related mechanisms. Whether one should interpret
these mechanisms as the bodys response to a stressor
or embody the act of stress itself is part of the ambiguity in dening what exactly stress is. Nevertheless,
the central nervous system works closely with the bodys
2 Biological need for equilibrium endocrine system to regulate these mechanisms. The
sympathetic nervous system becomes primarily active
Homeostasis is a concept central to the idea of stress. during a stress response, regulating many of the bodys
In biology, most biochemical processes strive to main- physiological functions in ways that ought to make an or1

NEUROANATOMY

ganism more adaptive to its environment. Below there metabolism. During a stress response, the hypothalafollows a brief biological background of neuroanatomy mus secretes various hormones, namely corticotropinand neurochemistry and how they relate to stress.
releasing hormone, which stimulates the bodys pituitary
gland and initiates a heavily regulated stress response
pathway.[9]

Neuroanatomy
4.1.2 Amygdala
The amygdala is a small, almond"-shaped structure,
two of which are located bilaterally and deep within
the medial temporal lobes of the brain. The amygdalae
are part of the brains limbic system, with projections
to and from the hypothalamus, hippocampus, and locus
coeruleus among other areas. Thought to play a role in
the processing of emotions, the amygdalae have been implicated in modulating stress response mechanisms, particularly when feelings of anxiety or fear are involved.[10]

4.1.3 Hippocampus
The hippocampus[11] is a structure located bilaterally,
deep within the medial temporal lobes of the brain, just
below each amygdala,[12] and is a part of the brains limbic system. The hippocampus is thought to play an important role in memory formation. There are numerous
Human
brain
(hypothalamus=red,
amygdala=green,
connections to the hippocampus from the cerebral cortex,
hippocampus/fornix=blue, pons=gold, pituitary gland=pink)
hypothalamus, and amygdala, among other regions. During stress, the hippocampus is particularly important, in
that cognitive processes such as prior memories can have
4.1 Brain
a great inuence on enhancing, suppressing, or even independently generating a stress response. The hippocampus
The brain plays a critical role in the bodys perception of is also an area in the brain that is susceptible to damage
and response to stress.[8] However, pinpointing exactly brought upon by chronic stress.[13]
which regions of the brain are responsible for particular aspects of a stress response is dicult and often unclear. Understanding that the brain works in more of a
4.1.4 Prefrontal cortex
network-like fashion carrying information about a stressful situation across regions of the brain (from cortical senThe prefrontal cortex, located in the frontal lobe, is the
sory areas to more basal structures and vice versa) can
anterior-most region of the cerebral cortex. An imporhelp explain how stress and its negative consequences are
tant function of the prefrontal cortex is to regulate cogniheavily rooted in neural communication dysfunction. In
tive processes including planning, attention and problem
spite of this, several important brain structures implicated
solving through extensive connections with other brain rein playing key roles in stress response pathways are degions. The prefrontal cortex can become impaired during
scribed below:
the stress response.[14][15]
4.1.1

Hypothalamus
4.1.5 Locus coeruleus

The hypothalamus is a small portion of the brain located

below the thalamus and above the brainstem. One of
its most important functions is to help link together the
bodys nervous and endocrine systems. This structure has
many bidirectional neural inputs and outputs from and to
various other brain regions. These connections help to
regulate the hypothalamus ability to secrete hormones
into the bodys blood stream, having far-reaching and
long-lasting eects on physiological processes such as

The locus coeruleus is an area located in the pons of the

brainstem that is the principal site of the synthesis of
the neurotransmitter norepinephrine, which plays an important role in the sympathetic nervous systems ght-oright response to stress. This area receives input from the
hypothalamus, amygdala, and raphe nucleus among other
regions and projects widely across the brain as well as to
the spinal cord.

5.1
4.1.6

Corticotropin-releasing hormone
Raphe nucleus

5.1 Corticotropin-releasing hormone

The raphe nucleus is an area located in the pons of the

brainstem that is the principal site of the synthesis of the
neurotransmitter serotonin, which plays an important role
in mood regulation, particularly when stress is associated
with depression and anxiety. Projections extend from this
region to widespread areas across the brain, namely the
hypothalamus, and are thought to modulate an organisms
circadian rhythm and sensation of pain among other processes.

Corticotropin-releasing hormone is the neurohormone secreted by the hypothalamus during a stress response that
stimulates the anterior lobe of the pituitary gland by
binding to its corticotropin-releasing hormone-receptors,
causing the anterior pituitary to release adrenocorticotropic hormone.

The Spinal Cord

Adrenocorticotropic hormone is the hormone secreted by

the anterior lobe of the pituitary gland into the bodys
blood stream that stimulates the cortex of the adrenal
gland by binding to its adrenocorticotropic hormonereceptors, thus causing the adrenal gland to release cortisol.

4.2

Spinal cord

The spinal cord plays a critical role in transferring stress

response neural impulses from the brain to the rest of
the body. In addition to the neuroendocrine blood hormone signaling system initiated by the hypothalamus, the
spinal cord communicates with the rest of the body by innervating the peripheral nervous system. Certain nerves
that belong to the sympathetic branch of the central nervous system exit the spinal cord and stimulate peripheral
nerves, which in turn engage the bodys major organs and
muscles in a ght-or-ight manner.

4.3

Pituitary gland

The pituitary gland is a small organ that is located at the

base of the brain just under the hypothalamus. This gland
releases various hormones that play signicant roles in
regulating homeostasis. During a stress response, the pituitary gland releases hormones into the blood stream,
namely adrenocorticotropic hormone, which modulates a
heavily regulated stress response system.

5.2 Adrenocorticotropic hormone

5.3 Cortisol
Cortisol is a steroid hormone, belonging to a broader
class of steroids called glucocorticoids, produced by the
adrenal gland and secreted during a stress response. Its
primary function is to redistribute energy (glucose) to regions of the body that need it most (i.e., the brain and major muscles during a ght-or-ight situation). As a part
of the bodys ght-or-ight response, cortisol also acts to
suppress the bodys immune system.
Cortisol is synthesized from cholesterol in the adrenal
cortex.[16] Its primary function is to increase blood sugar
through gluconeogenesis, suppress the immune system
and aid in fat and protein metabolism.[17]

5.4 Norepinephrine

Norepinephrine is a neurotransmitter released from locus

coeruleus when stimulated by the hypothalamus during
4.4 Adrenal gland
a stress response. Norepinephrine serves as the primary
chemical messenger of the central nervous systems symThe adrenal gland is a major organ of the endocrine sys- pathetic branch that prepares the body for ght-or-ight
tem that is located directly on top of the kidneys and is response.
chiey responsible for the synthesis of stress hormones
that are released into the blood stream during a stress response. Cortisol is the major stress hormone released by 5.5 Serotonin
the adrenal gland.
Serotonin is a neurotransmitter synthesized in the raphe
In addition to the locus coeruleus existing as a source
nucleus of the pons of the brainstem and projects to most
of the neurotransmitter norepinephrine within the central
brain areas. Serotonin is thought to play an important
nervous system, the adrenal gland can also release norerole in mood regulation. Stress-induced serotonin dyspinephrine during a stress response into the bodys blood
functions have been associated with anxiety, fear and
stream, at which point norepinephrine acts as a hormone
depression-like symptoms.
in the endocrine system.

Neurochemistry

5.6 Neuropeptide Y
Neuropeptide Y is a protein that is synthesized in the hy-

BIOLOGICAL MECHANISMS

pothalamus and acts as a chemical messenger in the brain.

Traditionally, it has been thought to play an important
role in appetite, feeding behavior, and satiety, but more
recent ndings have implicated Neuropeptide Y in anxiety and stress, specically, stress resiliency.[18]

GR begin to become activated, neurons in the amygdala,

hippocampus, and prefrontal cortex become over stimulated. This stimulation of the neurons triggers a ghtor-ight response which allows the brain to quickly process information and therefore deal with life-threatening
situations. If the stress response continues and becomes
chronic, the hyperactivity of the neurons begins to physically change the brain and have severe damaging eects
6 Biological mechanisms
on ones mental health. As the neurons begin to become
stimulated, calcium is released through channels in their
6.1 Nervous system
cell membranes. Although initially this allows the cells
chemical signals to continue to re, allowing nerve cells to
Peripheral nervous system (PNS)
remain stimulated, if this continues the cells will become
overloaded with calcium leading to over-ring of neuron
The peripheral nervous system (PNS) consists of two sub- signals. The over-ring of the neurons is seen to the brain
systems: the somatic nervous system and the autonomic as a dangerous malfunction; therefore, triggering the cells
nervous system. When a physical stressor acts upon to shut down to avoid death due to over stimulation.
the body the sensory-somatic nervous system is triggered
through stimulation of the bodys sensory nerves. The sig- Decline in both neuroplasticity and long term potentianal acts as a nerve impulse and travels through the body tion (LTP) occurs in humans after experiencing levels of
in a process of electrical cell-to-cell communication un- high continual stress. To maintain homeostasis the brain
til it reaches the automatic nervous system. Activation is continuously forming new neural connections, reorgaof the automatic nervous system immediately triggers a nizing its neural pathways, and working to x damages
series of involuntary chemical responses throughout the caused by injury and disease. This keeps the brain vital
body. Preganglionic neurons release the neurotransmit- and able to perform cognitive complex thinking. When
ter acetylcholine (ACh). This stimulates postganglionic the brain receives a distress signal it immediately begins
neurons which release noradrenaline. The noradrenaline to go into overdrive. Neural pathways begin to re and
ows directly into the bloodstream ensuring that all cells rewire at hyper-speed to help the brain understand how
in the bodys nervous and endocrine systems have been to handle the task at hand. Often, the brain becomes
activated even in areas which the ganclionic neurons are so intently focused on this one task that it is unable to
comprehend, learn, or cognitively understand any other
unable to reach.
sensory information that is being thrown at it during this
time. This over stimulation in specic areas and extreme
Central nervous system (CNS)
lack of use in others causes several physiological changes
in the brain to take place which overall reduce or even
The central nervous system (CNS) is made up of the destroy the neuroplasticity of the brain. Dendritic spines
brain and the spinal cord. The brain is equipped to found of the dendrite of neurons begin to disappear and
process stress in three main areas: the amygdala, the many dendrites become shorter and even less complex in
hippocampus, and the prefrontal cortex. Each of these ar- structure. Glia cells begin to atrophy and neurogenesis ofeas is densely packed with stress corticosteroid receptors ten ceases completely. Without neuroplasticity, the brain
which process the intensity of physical and psychological loses the ability to form new connections and process new
stressors acting upon the body through a process of hor- sensory information. Connections between neurons bemone reception. There are two types of corticosteroid re- come so weak that it becomes nearly impossible for the
ceptors: mineralocorticoid receptors and glucocorticoid brain to eectively encode long term memories; therereceptors. The mineralocorticoid receptors (MR) have fore, the LTP of the hippocampus declines dramatically.
an extremely high anity for cortisol. This means that
they are at least partially stimulated at all times and therefore are entirely activated almost immediately when a true Endocrine system
stressor is disrupting the homeostasis of the body. The
second type of receptor, glucocorticoid receptors (GR), When a stressor acts upon the body, the endocrine syshave a low anity for cortisol and only begin to become tem is triggered by the release of the neurotransmitter
activated as the sensation of stress reaches its peak inten- noradrenaline by the autonomic nervous system. Norasity on the brain.
drenaline stimulates the hypothalamic-pituitary-adrenal
Stress dramatically reduces the ability of the blood brain
barrier (BBB) to block the transfer of chemicals including hormones from entering the brain from the bloodstream. Therefore when corticosteroids are released into
the bloodstream they are immediately able to penetrate
the brain and bind to rst the MR and then the GR. As the

axis (HPA) which processes the information about the

stressor in the hypothalamus. This quickly signals the
pituitary gland and nally triggers the adrenal cortex. The
adrenal cortex responds by signaling the release of the
corticosteroids cortisol and corticotropin releasing hormone (CRH) directly into the bloodstream.

6.3

Immune response

Immune system

HPA-axis stress-response cascade via feedback inhibition. This prevents additional cortisol from being released. This is biologically identied as a normal, healthy
The most important aspect of the immune system are Tstress mechanism in response to a situation or stressor a
cells found in the form of T-helper and T-suppressor cells.
biological coping mechanism for a threat to homeostasis.
Cortisol, once released into the bloodstream, immediately begins to cause division of T-Suppressor cells. This It is when the bodys HPA-axis cannot overcome a chalrapid cell division increases the number of T-Suppressor lenge and/or is chronically exposed to a threat that this
cells while at the same time suppressing T-helper cells. system becomes overtaxed and can be harmful to the
This reduces immune protection and leaves the body vul- body and brain. A second major eect of cortisol is to
suppress the bodys immune system during a stressful sitnerable to disease and infection.
uation, again, for the purpose of redistributing metabolic
resources primarily to ght-or-ight organs. While not a
major risk to the body if only for a short period of time, if
6.2 Hypothalamic-pituitary-adrenal
under chronic stress, the body becomes exceptionally vul(HPA) axis
nerable to immune system attacks. This is a biologically
negative consequence of an exposure to a severe stressor
Main article: Hypothalamicpituitaryadrenal axis
The HPA axis is a multi-step biochemical pathway where and can be interpreted as stress in and of itself a detriinformation is transmitted from one area of the body to mental inability of biological mechanisms to eectively
the next via chemical messengers. Each step in this path- adapt to the changes in homeostasis.
way, as in many biochemical pathways, not only passes
information along to stimulate the next region but also
receives feedback from messengers produced later in the 6.3 Immune response
pathway to either enhance or suppress earlier steps in the
pathway this is one way a biochemical pathway can reg- Cortisol can weaken the activity of the immune system.
Cortisol prevents the proliferation of T-cells by renderulate itself, via a feedback mechanism.
ing the interleukin-2 producer T-cells unresponsive to
When the hypothalamus receives signals from one of
interleukin-1 (IL-1), and unable to produce the T-cell
its many inputs (e.g., cerebral cortex, limbic system,
growth factor.[35]Cortisol also has a negative-feedback
visceral organs) about conditions that deviate from an
eect on interleukin-1.[36] IL-1 must be especially useideal homeostatic state (e.g., alarming sensory stimuful in combating some diseases; however, endotoxic baclus, emotionally charged event, energy deciency), this
teria have gained an advantage by forcing the hypothalacan be interpreted as the initiation step of the stressmus to increase cortisol levels (forcing the secretion of
response cascade. The hypothalamus is stimulated by
CRH hormone, thus antagonizing IL-1). The suppressor
its inputs and then proceeds to secrete corticotropincells are not aected by glucosteroid response-modifying
releasing hormones. This hormone is transported to its
factor (GRMF),[37] so the eective setpoint for the imtarget, the pituitary gland, via the hypophyseal portal sysmune cells may be even higher than the setpoint for phystem (short blood vessels system), to which it binds and
iological processes (reecting leukocyte redistribution to
causes the pituitary gland to, in turn, secrete its own meslymph nodes, bone marrow, and skin). Rapid administrasenger, adrenocorticotropic hormone, systemically into
tion of corticosterone (the endogenous Type I and Type
the bodys blood stream. When adrenocorticotropic horII receptor agonist) orRU28362 (a specic Type II recepmone reaches and binds to its target, the adrenal gland,
tor agonist) to adrenalectomized animals induced changes
the adrenal gland in turn releases the nal key messenin leukocyte distribution. Natural killer cells are not afger in the cascade, cortisol. Cortisol, once released, has
fected by cortisol.[38]
widespread eects in the body. During an alarming situation in which a threat is detected and signaled to the hypothalamus from primary sensory and limbic structures, 6.3.1 Eect of stress on the immune system
cortisol is one way the brain instructs the body to attempt
to regain homeostasis by redistributing energy (glucose) Stress is the bodys reaction to any stimuli that disturbs its
to areas of the body that need it most, that is, toward crit- equilibrium. When the equilibrium of various hormones
ical organs (the heart, the brain) and away from digestive is altered the eect of these changes can be detrimenand reproductive organs, during a potentially harmful sit- tal to the immune system.[19] Much research has shown a
uation in an attempt to overcome the challenge at hand. negative eect stress has on the immune system, mostly
After enough cortisol has been secreted to best restore
homeostasis and the bodys stressor is no longer present
or the threat is no longer perceived, the heightened levels of cortisol in the bodys blood stream eventually circulate to the pituitary gland and hypothalamus to which
cortisol can bind and inhibit, essentially turning o the

through studies where participants were subjected to a

variety of viruses. In one study individuals caring for a
spouse with dementia, representing the stress group, saw
a signicant decrease in immune response when given an
inuenza-virus vaccine compared to a non-stressed control group.[19][20] A similar study was conducted using

a respiratory virus. Participants were infected with the

virus and given a stress index. Results showed that an increase in score on the stress index correlated with greater
severity of cold symptoms.[19] Studies with HIV have also
shown stress to speed up viral progression. Men with HIV
were 23 times more likely to develop AIDS when under
above average stress.[19]
Stress aects the immune system in many ways. The immune system protects the body from viruses, bacteria,
and anything that is dierent or that the body does not
recognize. The immune system sees these as intruders
and it sends messages to attack. The white blood cells,
leukocytes, are very important to the immune system.[21]
White blood cells have several types including B cells, T
cells, and natural killer cells. B cells secrete antibodies.
T cells attack intruders and natural killer cells attack cells
that have been infected by viruses. These leukocytes produce cytokines which ght infections.[21] But they also are
the immune systems communicator in telling the brain
that the body is ill. When an individual is stressed or
going through a stressful experience the immune system
starts to produce natural killer cells and cytokines.[22]
When levels of cytokines are higher they combat infections and therefore the brain gets communicated the body
is ill and it produces symptoms as if the individual was ill.
These symptoms include fever, sleepiness, lack of energy,
no appetite, and basically u like symptoms. These symptoms mean the body is ghting the illness or virus.[21] This
is useful for when the body goes through the stress from
an injury. But the body has now evolved to do this process
during stressful events such as taking exams, or even going through a life changing event such as a death of a family member or a divorce.[22] That is why many times when
individuals are stressed because of life changing events or
situations such as those, they get these symptoms and believe they are sick when in reality it can be because the
body is under stress.[22]
6.3.2

Eects of chronic stress

Main article: Chronic stress

Chronic stress is dened as a state of prolonged tension
from internal or external stressors, which may cause various physical manifestations e.g., asthma, back pain,
arrhythmias, fatigue, headaches, HTN, irritable bowel
syndrome, ulcers, and suppress the immune system.
Chronic stress takes a more signicant toll on the body
than acute stress does. It can raise blood pressure, increase the risk of heart attack and stroke, increase vulnerability to anxiety and depression, contribute to infertility, and hasten the aging process. For example, results
of one study demonstrated that individuals who reported
relationship conict lasting one month or longer have a
greater risk of developing illness and show slower wound
healing. Similarly, the eects that acute stressors have
on the immune system may be increased when there is

BIOLOGICAL MECHANISMS

perceived stress and/or anxiety due to other events. For

example, students who are taking exams show weaker
immune responses if they also report stress due to daily
hassles.[23] While responses to acute stressors typically do
not impose a health burden on young, healthy individuals,
chronic stress in older or unhealthy individuals may have
long-term eects that are detrimental to health.[24]

6.3.3 Mechanisms of chronic stress

Studies revealing the relationship between the immune
system and the central nervous system indicate that
stress can alter the function of the white blood cells involved in immune function known as lymphocytes and
macrophages. People undergoing stressful life events,
such as marital turmoil or bereavement, have a weaker
lymphoproliferative response. People in distressed marriages have also been shown to have greater decreases in
cellular immunity functioning over time when compared
to those in happier marriages.[25] After antigens initiate
an immune response, these white blood cells send signals,
composed of cytokines and other hormonal proteins, to
the brain and neuroendocrine system.[26] Cytokines are
molecules involved with cell signaling.
Cortisol, a hormone released during stressful situations,
aects the immune system greatly by preventing the production of cytokines. During chronic stress, cortisol is
over produced, causing fewer receptors to be produced
on immune cells so that inammation cannot be ended.
A study involving cancer patients parents conrmed this
nding. Blood samples were taken from the participants.
Researchers treated the samples of the parents of cancer
patients with a cortisol-like substance and stimulated cytokine production. Cancer patient parents blood was signicantly less eective at stopping cytokine from being
produced.[27]

6.3.4 Chronic stress and wound healing

The immune system also plays a role in stress and the
early stages of wound healing. It is responsible for preparing the tissue for repair and promoting recruitment of certain cells to the wound area.[23] Consistent with the fact
that stress alters the production of cytokines, Graham et
al. found that chronic stress associated with care giving
for a person with Alzheimers Disease leads to delayed
wound healing. Results indicated that biopsy wounds
healed 25% more slowly in the chronically stressed group,
or those caring for a person with Alzheimers disease.[19]

6.3.5 Chronic stress and development

Chronic stress has also been shown to impair
developmental growth in children by lowering the
pituitary gland's production of growth hormone, as in

7.2

Coping

children associated with a home environment involving sonal expectations, and resources to cope with the stress.
serious marital discord, alcoholism, or child abuse.[28]
Alarming experiences, either real or imagined, can trigger a stress response.[34]
6.3.6

Chronic stress and memory

Chronic stress is seen to aect the parts of the brain

where memories are processed through and stored. When
people feel stressed, stress hormones get over-secreted,
which aects the brain. This secretion is made up of
glucocorticoids, including cortisol, which are steroid hormones that the adrenal gland releases, although this can
increase storage of ashbulb memories it decreases long
term potentation (LTP).[29] Prolonged Stress can also be
harmful to our body. That is because stress releases cortisol, and cortisol causes metabolic activity throughout the
body. Metabolic activity is raised in the hippocampus.
Overstimulation and toxins then are more likely to kill or
damage neurons in the hippocampus.[30] The hippocampus is important in the brain for storing certain kinds
of memories and damage to the hippocampus can cause
trouble in storing new memories but old memories, memories stored before the damage, are not lost.[31] Also high
cortisol levels can be tied to the deterioration of the hippocampus and decline of memory that many older adults
start to experience with age.[30]

7.2 Coping
Main article: Stress management
Responses to stress include adaptation, psychological
coping such as stress management, anxiety, and
depression. Over the long term, distress can lead to
diminished health and/or increased propensity to illness;
to avoid this, stress must be managed.
Stress management encompasses techniques intended to
equip a person with eective coping mechanisms for
dealing with psychological stress, with stress dened as a
persons physiological response to an internal or external
stimulus that triggers the ght-or-ight response. Stress
management is eective when a person uses strategies to
cope with or alter stressful situations.
There are several ways of coping with stress,[35] such as
controlling the source of stress or learning to set limits
and to say no to some of the demands that bosses or
family members may make.

A persons capacity to tolerate the source of stress may

be increased by thinking about another topic such as a
hobby, listening to music, or spending time in a wilderStudies of female monkeys at Wake Forest University ness.
(2009) discovered that individuals suering from higher
A way to control stress is rst dealing with what is causstress have higher levels of visceral fat in their bodies.
ing the stress if it is something the individual has control
This suggests a possible cause-and-eect link between the
over. Other methods to control stress and reduce it can
two, wherein stress promotes the accumulation of visbe: to not procrastinate and leave tasks for last minute,
ceral fat, which in turn causes hormonal and metabolic
do things you like, exercise, do breathing routines, go out
changes that contribute to heart disease and other health
with friends, and take a break. Having support from a
[32]
problems.
loved one also helps a lot in reducing stress.[30]
6.3.7

Stress and visceral fat

A study was done and it showed that the power of having support from a loved one or just social support, low7 Psychological concepts
ered stress in the individuals. They gave painful shocks
to married womens ankles. On some trials women were
Main article: Stress (psychological)
able to hold their husbands hand, on other trials they held
a strangers hand, and then held no ones hand. When the
women were holding their husbands hand, the response
reduced in many brain areas. When holding the strangers
7.1 Eustress
hand the response reduced a little but not as much as when
they were holding their husbands hand. Social support
Selye published in year 1975 a model dividing stress into helps reduce stress but even more if the support is from a
eustress and distress.[33] Where stress enhances function loved one.[30]
(physical or mental, such as through strength training or
challenging work), it may be considered eustress. Persistent stress that is not resolved through coping or adapta- 7.3 Cognitive appraisal
tion, deemed distress, may lead to anxiety or withdrawal
(depression) behavior.
Lazarus[36] argued that, in order for a psychosocial sitThe dierence between experiences that result in eustress uation to be stressful, it must be appraised as such. He
and those that result in distress is determined by the dis- argued that cognitive processes of appraisal are central in
parity between an experience (real or imagined) and per- determining whether a situation is potentially threatening,

8 CLINICAL SYMPTOMS AND DISORDERS

constitutes a harm/loss or a challenge, or is benign.

Increased frequency of urination

Both personal and environmental factors inuence this

primary appraisal, which then triggers the selection of
coping processes. Problem-focused coping is directed
at managing the problem, whereas emotion-focused coping processes are directed at managing the negative emotions. Secondary appraisal refers to the evaluation of the
resources available to cope with the problem, and may
alter the primary appraisal.

Indigestion
Changes in blood glucose
Nausea, dizziness
Chest pain, rapid heartbeat
Loss of sex drive

In other words, primary appraisal includes the percep Frequent colds

tion of how stressful the problem is and the secondary
Irregular periods.
appraisal of estimating whether one has more than or less
than adequate resources to deal with the problem that affects the overall appraisal of stressfulness. Further, cop- Behavioral symptoms
ing is exible in that, in general, the individual examines
the eectiveness of the coping on the situation; if it is not
Eating more or less
having the desired eect, s/he will, in general, try dierent strategies.[37]
Sleeping too much or too little
Isolating oneself from others

Clinical symptoms and disorders

8.1

Symptoms

Procrastinating or neglecting responsibilities

Using alcohol, cigarettes, or drugs to relax
Nervous habits (e.g. nail biting, pacing)

Signs of stress may be cognitive, emotional, physical, or

behavioral.
Cognitive symptoms
Memory problems
Inability to concentrate

8.2 DSM-IV TR
8.2.1 Diagnosis
Main articles: Holmes and Rahe stress scale and Stress
(psychological)

Poor judgment
Pessimistic approach or thoughts
Anxious or racing thoughts
Constant worrying
Emotional symptoms
Moodiness
Irritability or short temper
Agitation, inability to relax
Feeling overwhelmed
Sense of loneliness and isolation
Depression or general unhappiness
Physical symptoms
Aches and pains
Diarrhea or constipation

A renewed interest in salivary alpha amylase as a marker

for stress has surfaced. Yamaguchi M, Yoshida H (2005)
have analyzed a newly introduced hand-held device called
the Cocorometer developed by Nipro Corporation of
Japan. They state that this can be reliably used to analyze the amylase levels and is denitely a cheaper alternative as compared to the more expensive ELISA kits. The
working consists of a meter and a saliva collecting chip,
which can be inserted into the meter to give the readings.
The levels of amylase obtained have been calibrated according to standard population, and can be categorized
into four levels of severity.[38]
Measuring stress levels independent of dierences in
peoples personalities has been inherently dicult: Some
people are able to process many stressors simultaneously,
while others can barely address a few. Such tests as the
Trier Social Stress Test attempted to isolate the eects of
personalities on ability to handle stress in a laboratory environment. Other psychologists, however, proposed measuring stress indirectly, through self-tests.
Because the amount of stressors in a persons life often
(although not always) correlates with the amount of stress
that person experiences, researchers combine the results

8.3

Generalized anxiety disorder

of stress and burnout self-tests. Stress tests help determine the number of stressors in a persons life, while
burnout tests determine the degree to which the person
is close to the state of burnout. Combining both helps researchers gauge how likely additional stressors will make
him or her experience mental exhaustion.[39]
8.2.2

Health risk factors

Both negative and positive stressors can lead to stress.

The intensity and duration of stress changes depending on
the circumstances and emotional condition of the person
suering from it (Arnold. E and Boggs. K. 2007). Some
common categories and examples of stressors include:

9
The areas of the brain aected in generalised anxiety
disorder (advanced)
Patients with generalised anxiety disorder (GAD) exhibit
increased metabolic rates in several brain regions compared with healthy controls. Hyperactive neurotransmitter circuits between the cortex, thalamus, amygdala
and hypothalamus have been implicated in the disorder.
Hypofunction of serotonergic neurones arising from the
dorsal raphe nucleus and GABAergic neurones that are
widely distributed in the brain may result in a lack of
inhibitory eect on the putative GAD pathway. Furthermore, overactivity of noradrenergic neurones arising
from the locus coeruleus may produce excessive excitation in the brain areas implicated in GAD.[46]

Sensory input such as pain, bright light, noise, temperatures, or environmental issues such as a lack The septohippocampal circuit
of control over environmental circumstances, such
as food, air and/or water quality, housing, health, Based on early neuroanatomical observations and studies with psychoactive drugs, the septohippocampal cirfreedom, or mobility.
cuit has been proposed as a model for anxiety disorders.
Social issues can also cause stress, such as struggles The circuit that links the septum, amygdala, hippocamwith conspecic or dicult individuals and social pus and fornix is thought to process external stimuli and
defeat, or relationship conict, deception, or break regulate the behavioural response through wider projecups, and major events such as birth and deaths, tions in the brain. Hyperstimulation of this putative bemarriage, and divorce.
havioural inhibition circuit, through dysfunctional noradrenergic and serotonergic neurotransmission, has been
Life experiences such as poverty, unemployment,
implicated in producing anxiety, and increased arousal
clinical depression, obsessive compulsive disorder,
and attention.[47]
heavy drinking,[40] or insucient sleep can also
cause stress. Students and workers may face performance pressure stress from exams and project dead- The noradrenaline pathways in generalised anxiety disorder
lines.
Adverse experiences during development (e.g. prenatal exposure to maternal stress,[41][42] poor attachment histories,[43] sexual abuse)[44] are thought to
contribute to decits in the maturity of an individuals stress response systems. One evaluation of the
dierent stresses in peoples lives is the Holmes and
Rahe stress scale.

8.3

Generalized anxiety disorder

In generalised anxiety disorder (GAD) there is increased

noradrenaline transmission from both the locus coeruleus
and the caudal raphe nuclei. The locus coeruleusnoradrenaline system is associated with anxiety and may
mediate the autonomic symptoms associated with stress
such as increased heart rate, dilated pupils, tremour and
sweating.[48]
Serotonergic pathways showing the eects of generalised anxiety disorder

Main article: Generalized anxiety disorder

The areas of the brain aected by generalised anxiety
disorder

Serotonergic nuclei are found in the rostral and caudal

raphe nuclei. Neurones ascend from the rostral raphe nuclei to the cerebral cortex, limbic regions and basal ganglia. The activity of neurones innervating the pre-frontal
cortex, basal ganglia and limbic region is decreased in
generalised anxiety disorder (GAD). The activity of descending neurones from serotonergic nuclei in the brainstem is unaected in GAD. This altered neurotransmitter
balance contributes towards the feeling of anxiety associated with GAD.[49]

During passive activity, patients with generalised anxiety

disorder (GAD) exhibit increased metabolic rates in the
occipital, temporal and frontal lobes and in the cerebellum and thalamus compared with healthy controls. Increased metabolic activity in the basal ganglia has also
been reported in patients with GAD during vigilance
GABAergic pathways showing the eects of genertasks. These nding suggest that there may be hyperacalised anxiety disorder
tive brain circuits in GAD.[45]

10

8 CLINICAL SYMPTOMS AND DISORDERS

GABA is the main inhibitory neurotransmitter in the central nervous system (CNS). GABAergic inhibition is seen
at all levels of the CNS, including the hypothalamus, hippocampus, cerebral cortex and cerebellar cortex. The activity of GABAergic neurones is decreased in generalised
anxiety disorder.[50]

stimuli or it may aect fear-related processing by stimulating other regions of the brain implicated in anxiety and
fear behaviours i.e. amygdala, hippocampus, hypothalamus, cortex and spinal cord.[56]

8.4

Physiologists dene stress as how the body reacts to a

stressor, real or imagined, a stimulus that causes stress.
Acute stressors aect an organism in the short term;
chronic stressors over the longer term. General adaptation syndrome (GAS), developed by Hans Selye, is a
prole of how organisms respond to stress; the general
adaptation syndrome is characterized by three phases: a
nonspecic mobilization phase, which promotes sympathetic nervous system activity; a resistance phase, during
which the organism makes eorts to cope with the threat;
and an exhaustion phase, which occurs if the organism
fails to overcome the threat and depletes its physiological
resources.[57]

Panic disorder

Main article: Panic disorder

The areas of the brain aected in panic disorder

8.5 General adaptation syndrome

There are a number of areas of the brain aected in

panic disorder. Decreased serotonin activity in the
amygdala and frontal cortex induces symptoms of anxiety, whereas decreased activity in the periaqueductal
gray results in defensive behaviours and postural freezing. The locus coeruleus increases norepinephrine release mediating physiological and behavioural arousal, Alarm is the rst stage, which is divided into two phases:
while the hypothalamus mediates the sympathetic ner- the shock phase and the antishock phase.[58]
vous system.[51][52][53]

Shock phase: During this phase, the body can enThe areas of the brain aected in panic disorder (advanced)dure changes such as hypovolemia, hypoosmolarity,
hyponatremia, hypochloremia, hypoglycemiathe
stressor eect. This phase resembles Addisons disease. The organisms resistance to the stressor drops
Hyperactive neurotransmitter circuits between the cortex,
temporarily below the normal range and some level
thalamus, hippocampus, amygdala, hypothalamus and
of shock (e.g. circulatory shock) may be experiperiaqueductal gray matter have been implicated in panic
enced.
disorder. Hypofunction of serotonergic neurones arising
from the rostral raphe nucleus may result in a lack of in Antishock phase: When the threat or stressor is idenhibitory eect on the putative panic pathways in the brain.
tied or realized, the body starts to respond and
While, overactivity of norepinephrine neurons arising
is in a state of alarm. During this stage, the lofrom the locus coeruleus may produce excessive excitacus coeruleus/sympathetic nervous system is actition in the regions implicated in panic disorder. Physiovated and catecholamines such as adrenaline are
logical symptoms of the panic response are medicated by
being produced, hence the ght-or-ight response.
the autonomic nervous system through connections with
The result is: increased muscular tonus, increased
the locus coeruleus and hypothalamus.[51][52][53][54][55]
blood pressure due to peripheral vasoconstriction
and tachycardia, and increased glucose in blood.
The serotonin pathways in panic disorder
There is also some activation of the HPA axis, producing glucocorticoids (cortisol, aka the S-hormone
The principal serotonin centres in the brain are the cauor stress-hormone).
dal and rostral raphe nuclei. Transmission of serotonin
from the rostral raphe nuclei to the pre-aquaductal grey,
Resistance is the second stage and increased secreamygdala, temporal lobe and limbic cortex is decreased
tion of glucocorticoids play a major role, intensifying
in panic disorder compared with normal. Serotonin
the systemic responsethey have lypolytic, catabolic
transmission to other target regions of the brain remain
and antianabolic eects: increased glucose, fat and
unchanged.[56]
aminoacid/protein concentration in blood. Moreover,
they cause lymphocytopenia, eosinopenia, neutrophilia
The norepinephrine pathways in panic disorder
and polycythemia. In high doses, cortisol begins to act
as a mineralocorticoid (aldosteron) and brings the body
In panic disorder there is increased norepinephrine trans- to a state similar to hyperaldosteronism. If the stressor
mission from both the locus coeruleus and the caudal persists, it becomes necessary to attempt some means of
raphe nuclei. The locus coeruleus-norepinephrine sys- coping with the stress. Although the body begins to try to
tem may have a signicant role in processing fear-related adapt to the strains or demands of the environment, the

8.7

Post-traumatic stress disorder (PTSD)

11

body cannot keep this up indenitely, so its resources are The principal serotonin centres in the brain are the caudal
gradually depleted.
and rostral raphe nuclei. Transmission of serotonin from
the rostral raphe nuclei to the thalamus, limbic cortex and
The third stage could be either exhaustion or recovery:
cerebral cortex is decreased in phobia compared with normal. The other major pathways for serotonin transmis Recovery stage follows when the systems compen- sion which involve the basal ganglia and cerebellum, and
sation mechanisms have successfully overcome the project down the spinal cord, remain unchanged.[59]
stressor eect (or have completely eliminated the
factor which caused the stress). The high glucose,
fat and aminoacid levels in blood prove useful for
8.7 Post-traumatic stress disorder (PTSD)
anabolic reactions, restoration of homeostasis and
regeneration of cells.
Main article: Posttraumatic stress disorder
PTSD is a severe anxiety disorder that can develop after
Exhaustion is the alternative third stage in the GAS exposure to any event that results in psychological trauma.
model. At this point, all of the bodys resources are This event may involve the threat of death to oneself or
eventually depleted and the body is unable to main- to someone else, or to ones own or someone elses phystain normal function. The initial autonomic nervous ical, sexual, or psychological integrity, overwhelming the
system symptoms may reappear (sweating, raised individuals ability to cope. As an eect of psychologheart rate, etc.). If stage three is extended, long- ical trauma, PTSD is less frequent and more enduring
term damage may result (prolonged vasoconstric- than the more commonly seen acute stress response. Dition results in ischemia which in turn leads to cell agnostic symptoms for PTSD include intrusion, avoidnecrosis), as the bodys immune system becomes ex- ance and hyperarousal -- re-experiencing the original
hausted, and bodily functions become impaired, re- trauma(s) through ashbacks or nightmares (intrusion),
sulting in decompensation.
emotional numbing or avoidance of stimuli associated
with the trauma, and increased arousal, such as diculty
The result can manifest itself in obvious illnesses, such as falling or staying asleep, anger, and hypervigilance. Forpeptic ulcer and general trouble with the digestive system mal diagnostic criteria (both DSM-IV-TR and ICD-10)
(e.g. occult bleeding, melena, constipation/obstipation), require that the symptoms last more than one month and
diabetes, or even cardiovascular problems (angina pec- cause signicant impairment in social, occupational, or
toris), along with clinical depression and other mental ill- other important areas of functioning.
nesses.

8.6

Phobia

The areas of the brain aected in phobia

The areas of the brain aected in post-traumatic

stress disorder
Sensory input, memory formation and stress response
mechanisms are aected in patients with PTSD. The regions of the brain involved in memory processing that are
implicated in PTSD include the hippocampus, amygdala
and frontal cortex. While the heightened stress response
is likely to involve the thalamus, hypothalamus and locus
coeruleus.[54][55]

There are a number of areas of the brain aected in phobia. Activation of the amygdala causes anticipatory anxiety or avoidance (conditioned fear) while activation of
the hypothalamus activates the sympathetic nervous system. Other regions of the brain involved in phobia include
the thalamus and the cortical structures, which may form
a key neural network along with the amygdala. Stimulation of the locus coeruleus increases noradrenaline release Memory
mediating physiological and behavioural arousal.[53]
Cortisol works with epinephrine (adrenaline) to create
memories of short-term emotional events; this is the proThe noradrenaline pathways in phobia
posed mechanism for storage of ash bulb memories, and
One hypothesis about the biological basis of phobia sug- may originate as a means to remember what to avoid in
gests that there is an excess of noradrenaline in the prin- the future. However, long-term exposure to cortisol damcipal noradrenergic pathways in the brain and that this ages cells in the hippocampus; this damage results in imcauses a down-regulation of post-synaptic adrenergic re- paired learning. Furthermore, it has been shown that corceptors. Transmission of noradrenaline from the cau- tisol inhibits memory retrieval of already stored informadal raphe nuclei and the locus coeruleus is increased in tion.
phobia.[59]
Atrophy of the hippocampus in posttraumatic stress disorder
The serotonin pathways in phobia

12

9 HISTORY IN RESEARCH

There is consistent evidence from MRI volumetric studies that hippocampal volume is reduced in posttraumatic
stress disorder (PTSD). This atrophy of the hippocampus
is thought to represent decreased neuronal density. However, other studies suggest that hippocampal changes are
explained by whole brain atophy and generalised white
matter atrophy is exhibited by people with PTSD.[61][62]

8.8

Depression

The areas of the brain aected in depression

9 History in research
The current usage of the word stress arose out of Selye's
1930s experiments. He started to use the term to refer
not just to the agent but to the state of the organism as
it responded and adapted to the environment. His theories of a universal non-specic stress response attracted
great interest and contention in academic physiology and
he undertook extensive research programs and publication eorts.[70]

While the work attracted continued support from advocates of psychosomatic medicine, many in experimental
physiology concluded that his concepts were too vague
and unmeasurable. During the 1950s, Selye turned away
from the laboratory to promote his concept through popular books and lecture tours. He wrote for both nonacademic physicians and, in an international bestseller entitled Stress of Life, for the general public.
The hypothalamic-pituitary-adrenal (HPA) axis in depression
A broad biopsychosocial concept of stress and adaptation oered the promise of helping everyone achieve
In depression, the hypothalamic-pituitary-adrenal (HPA) health and happiness by successfully responding to changaxis is upregulated with a down-regulation of its negative ing global challenges and the problems of modern
feedback controls. Corticotropin-releasing factor (CRF) civilization. Selye coined the term "eustress" for posiis hypersecreted from the hypothalamus and induces the tive stress, by contrast to distress. He argued that all peorelease of adrenocorticotropin hormone (ACTH) from ple have a natural urge and need to work for their own
that found favor with industrialists and
the pituitary. ACTH interacts with receptors on adreno- benet, a message
[70]
governments.
He
also coined the term stressor to recortical cells and cortisol is released from the adrenal
fer
to
the
causative
event
or stimulus, as opposed to the
glands; adrenal hypertrophy can also occur. Release of
resulting
state
of
stress.
cortisol into the circulation has a number of eects, inMany areas of the brain appear to be involved in
depression including the frontal and temporal lobes and
parts of the limbic system including the cingulate gyrus.
However, it is not clear if the changes in these areas cause
depression or if the disturbance occurs as a result of the
etiology of psychiatric disorders.[63]

cluding elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol
receptors become desensitized leading to increased activity of the pro-inammatory immune mediators and disturbances in neurotransmitter transmission.[64][65][66][67]
The serotonin pathways in depression

From the late 1960s, academic psychologists started to

adopt Selye's concept; they sought to quantify life stress
by scoring "signicant life events, and a large amount
of research was undertaken to examine links between
stress and disease of all kinds. By the late 1970s, stress
had become the medical area of greatest concern to the
general population, and more basic research was called
for to better address the issue. There was also renewed
laboratory research into the neuroendocrine, molecular,
and immunological bases of stress, conceived as a useful heuristic not necessarily tied to Selye's original hypotheses. The US military became a key center of stress
research, attempting to understand and reduce combat
neurosis and psychiatric casualties.[70]

Serotonin transmission from both the caudal raphe nuclei and rostral raphe nuclei is reduced in patients with
depression compared with non-depressed controls. Increasing the levels of serotonin in these pathways, by reducing serotonin reuptake and hence increasing serotonin
function, is one of the therapeutic approaches to treating The psychiatric diagnosis post-traumatic stress disorder
(PTSD) was coined in the mid-1970s, in part through the
depression.[68]
eorts of anti-Vietnam War activists and the Vietnam
Veterans Against the War, and Chaim F. Shatan. The
The noradrenaline pathways in depression
condition was added to the Diagnostic and Statistical
In depression the transmission of noradrenaline is re- Manual of Mental Disorders as posttraumatic stress disduced from both of the principal noradrenergic centres order in 1980.[71] PTSD was considered a severe and
the locus coeruleus and the caudal raphe nuclei. An ongoing emotional reaction to an extreme psychological
increase in noradrenaline in the frontal/prefrontal cortex trauma, and as such often associated with soldiers, pomodulates the action of selective noradrenaline reuptake lice ocers, and other emergency personnel. The stressor
inhibition and improves mood. Increasing noradrenaline may involve threat to life (or viewing the actual death of
transmission to other areas of the frontal cortex modu- someone else), serious physical injury, or threat to physical or psychological integrity. In some cases, it can also
lates attention.[69]

13
be from profound psychological and emotional trauma,
apart from any actual physical harm or threat. Often,
however, the two are combined.

[7] Schacter, Daniel L.; Gilbert, Daniel T.; Wegner, Daniel

M. (2011). Psychology (2nd ed.). New York: Worth Publishers. p. 13.7. ISBN 1429237198.

By the 1990s, stress had become an integral part of [8] Ulrich-Lai, Y. M.; Herman, J. P. (2009). Neural regulation of endocrine and autonomic stress remodern scientic understanding in all areas of physiology
sponses. Nature Reviews Neuroscience 10 (6): 397409.
and human functioning, and one of the great metaphors
doi:10.1038/nrn2647. PMID 19469025.
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techniques were developed. The term also became a
(2000). The stress response and the hypothalamiceuphemism, a way of referring to problems and elicitpituitary-adrenal axis: From molecule to melancholia.
QJM : monthly journal of the Association of Physicians
ing sympathy without being explicitly confessional, just
93 (6): 323333. doi:10.1093/qjmed/93.6.323. PMID
stressed out. It came to cover a huge range of phenom10873181.
ena from mild irritation to the kind of severe problems
that might result in a real breakdown of health. In pop- [10] Roozendaal, B.; McEwen, B. S.; Chattarji, S. (2009).
ular usage, almost any event or situation between these
Stress, memory and the amygdala. Nature Reviews Neuextremes could be described as stressful.[1][70]
roscience 10 (6): 423433. doi:10.1038/nrn2651. PMID
19469026.

10

See also

Defense Physiology
Trier Social Stress Test
Xenohormesis

11

Notes

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Carlson, N.R. & Heth, C.D. (2007). Psychology the

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Dantzer R., Kelley K. W. (1989). Stress and Immunity: An Integrated View of Relationships Between the Brain and the Immune System. Life
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Joe, Marian; Pu, Zhenwei; Wiegert, Olof; Oitzl,
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Khansari D. N., Murgo A. J. et al. (1990). Eects
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Renner Katherine H (2010). Eects of Naturalistic Stressors on Cognitive Flexibility and Working Memory Task Performance. Neurocase 16 (4):
293300. doi:10.1080/13554790903463601.

13 External links
The American Institute of Stress
Research on Work-Related Stress, European
Agency for Safety and Health at Work (EU-OSHA)
Self help guide (NHS Direct)

16

13

EXTERNAL LINKS

Adrenal gland

O
HO

OH

OH
H
H

O
The atomic structure of the steroid, Cortisol

Basic
hypothalamicpituitaryadrenal
axis
summary
(corticotropin-releasing hormone=CRH, adrenocorticotropic
hormone=ACTH).

Human spinal cord

17

A diagram of the General Adaptation Syndrome model.

Regions of the brain associated with stress and posttraumatic

stress disorder[60]

18

14

14
14.1

TEXT AND IMAGE SOURCES, CONTRIBUTORS, AND LICENSES

Text and image sources, contributors, and licenses

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File:Ambox_important.svg Source: http://upload.wikimedia.org/wikipedia/commons/b/b4/Ambox_important.svg License: Public domain Contributors: Own work, based o of Image:Ambox scales.svg Original artist: Dsmurat (talk contribs)
File:Cortisol2.svg Source: http://upload.wikimedia.org/wikipedia/commons/0/0d/Cortisol2.svg License: Public domain Contributors:
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14.3

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