Stress (biology)

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"Physiological stress" redirects here. It is not to be confused with physical stress.
For other kinds of stress see stress.

Physiological or biological stress is an organism's response to a stressor such as an environmental condition or a stimulus. Stress is a body's method of reacting to a challenge. According to the stressful event, the body's way to respond to stress is by sympathetic nervous system activation which results in the fight-or-flight response. Because the body cannot keep this state for long periods of time, the parasympathetic system returns the body's physiological conditions to normal (homeostasis). In humans, stress typically describes a negative condition or a positive condition that can have an impact on a person's mental and physical well-being.


There is likely a connection between stress and illness. Theories of the stress–illness link suggest that both acute and chronic stress can cause illness, and several studies found such a link.[1] According to these theories, both kinds of stress can lead to changes in behavior and in physiology. Behavioral changes can be smoking and eating habits and physical activity. Physiological changes can be changes in sympathetic activation or hypothalamic pituitary adrenocorticoid activation, and immunological function.[2] However, there is much variability in the link between stress and illness.[3]

Stress can make the individual more susceptible to physical illnesses like the common cold.[4] Stressful events, such as job changes, may result in insomnia, impaired sleeping, and health complaints.[5] Research indicates the type of stressor (whether it's acute or chronic) and individual characteristics such as age and physical well-being before the onset of the stressor can combine to determine the effect of stress on an individual.[1] An individual's personality characteristics (such as level of neuroticism),[6] genetics, and childhood experiences with major stressors and traumas [7] may also dictate their response to stressors.[1]



However, it is possible for individuals to exhibit hardiness—a term referring to the ability to be both chronically stressed and healthy.[11] Many psychologists are currently interested in studying the factors that allow hardy individuals to cope with stress and evade most health and illness problems associated with high levels of stress. Stress can be associated with psychological disorders such as general anxiety disorder, depression, and post-traumatic stress disorder. However, it is important to note that everyone experiences some level of stress, and diagnosis of stress disorders can only be performed by a licensed practitioner.

It has long been believed that negative affective states, such as feelings of anxiety and depression, could influence the pathogenesis of physical disease, which in turn, have direct effects on biological process that could result in increased risk of disease in the end. However recent studies done by the University of Wisconsin-Madison and other places have shown this to be untrue, it isn't stress itself that causes the increased risk of illness or death, it is actually the perception that stress is harmful.[12][13] For example, when humans are under chronic stress, permanent changes in their physiological, emotional, and behavioral responses are most likely to occur.[6][14] Such changes could lead to disease. Chronic stress results from stressful events that persist over a relatively long period of time, such as caring for a spouse with dementia, or results from brief focal events that continue to be experienced as overwhelmingly long after they are over, such as experiencing a sexual assault.


Even though psychological stress is often connected with illness or disease, most healthy individuals can still remain disease-free after confronting chronic stressful events. Also, people who do not believe that stress will affect their health do not have an increased risk of illness, disease, or death.[13] This suggests that there are individual differences in vulnerability to the potential pathogenic effects of stress; individual differences in vulnerability arise due to both genetic and psychological factors. In addition, the age at which the stress is experienced can dictate its effect on health. Research suggests chronic stress at a young age can have lifelong impacts on the biological, psychological, and behavioral responses to stress later in life.[15] Recent studies have shown that severe psychological stress resulting in PTSD can also significantly affect parenting perception, behavior, neural activity and HPA-axis physiology in response to stressful parent-infant interactions.[16] These recent studies support the existence of intergenerational effects of early chronic psychological stress.[17]


Etymology and historical usage[edit]


Walter Cannon used it in 1926 to refer to external factors that disrupted what he called homeostasis.[19] But "...stress as an explanation of lived experience is absent from both lay and expert life narratives before the 1930s".[20] Physiological stress represents a wide range of physical responses that occur as a direct effect 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 effects on the body.[citation needed]

Biological need for equilibrium[edit]

Homeostasis is a concept central to the idea of stress.[21] In biology, most biochemical processes strive to maintain 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 organism’s present condition is a state of constant flux moving about a homeostatic point that is that organism’s optimal condition for living.[22] Factors causing an organism’s condition to diverge too far from homeostasis can be experienced as stress. A life-threatening situation such as a major physical trauma or prolonged starvation can greatly disrupt homeostasis. On the other hand, an organism’s attempt at restoring conditions back to or near homeostasis, often consuming energy and natural resources, can also be interpreted as stress.[23]

The ambiguity in defining this phenomenon was first recognized by Hans Selye (1907-1982) in 1926. In 1951 a commentator loosely summarized Selye's view of stress as something that "…in addition to being itself, was also the cause of itself, and the result of itself."[24][25]


Biological background[edit]

Stress can have many profound effects on the human biological systems.[27] 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 body's stress-related mechanisms. Whether one should interpret these mechanisms as the body’s response to a stressor or embody the act of stress itself is part of the ambiguity in defining what exactly stress is. Nevertheless, the central nervous system works closely with the body’s endocrine system to regulate these mechanisms. The sympathetic nervous system becomes primarily active during a stress response, regulating many of the body’s physiological functions in ways that ought to make an organism more adaptive to its environment. Below there follows a brief biological background of neuroanatomy and neurochemistry and how they relate to stress.[citation needed]


Human brain (hypothalamus=red, amygdala=green, hippocampus/fornix=blue, pons=gold, pituitary gland=pink)


The brain plays a critical role in the body’s perception of and response to stress.[28] However, pinpointing exactly which regions of the brain are responsible for particular aspects of a stress response is difficult and often unclear. Understanding that the brain works in more of a network-like fashion carrying information about a stressful situation across regions of the brain (from cortical sensory areas to more basal structures and vice versa) can help explain how stress and its negative consequences are heavily rooted in neural communication dysfunction. In spite of this, several important brain structures implicated in playing key roles in stress response pathways are described below:




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 brain’s 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.[30]


The hippocampus[31] is a structure located bilaterally, deep within the medial temporal lobes of the brain, just below each amygdala,[32] and is a part of the brain’s limbic system. The hippocampus is thought to play an important role in memory formation. There are numerous connections to the hippocampus from the cerebral cortex, hypothalamus, and amygdala, among other regions. During stress, the hippocampus is particularly important, in that cognitive processes such as prior memories can have a great influence on enhancing, suppressing, or even independently generating a stress response. The hippocampus is also an area in the brain that is susceptible to damage brought upon by chronic stress.[33]

Prefrontal cortex[edit]


Locus coeruleus[edit]


Raphe nucleus[edit]


The Spinal Cord
Human spinal cord

Spinal cord[edit]

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 body’s major organs and muscles in a fight-or-flight manner.

Pituitary gland[edit]

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 significant 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.

Adrenal gland[edit]

Adrenal gland

The adrenal gland is a major organ of the endocrine system that is located directly on top of the kidneys and is chiefly 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 the adrenal gland.

In addition to the locus coeruleus existing as a source of the neurotransmitter norepinephrine within the central nervous system, the adrenal gland can also release norepinephrine during a stress response into the body’s blood stream, at which point norepinephrine acts as a hormone in the endocrine system.


Corticotropin-releasing hormone[edit]


Adrenocorticotropic hormone[edit]



The atomic structure of the steroid, 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 fight-or-flight situation). As a part of the body’s fight-or-flight response, cortisol also acts to suppress the body’s immune system.

Cortisol is synthesized from cholesterol in the adrenal cortex.[37] Its primary function is to increase blood sugar through gluconeogenesis, suppress the immune system and aid in fat and protein metabolism.[38]


Norepinephrine is a neurotransmitter released from locus coeruleus when stimulated by the hypothalamus during a stress response. Norepinephrine serves as the primary chemical messenger of the central nervous system’s sympathetic branch that prepares the body for fight-or-flight response.



Neuropeptide Y[edit]


Biological mechanisms[edit]

Nervous system[edit]

Peripheral nervous system (PNS)

The peripheral nervous system (PNS) consists of two subsystems: the somatic nervous system and the autonomic nervous system. When a physical stressor acts upon the body the sensory-somatic nervous system is triggered through stimulation of the body's sensory nerves. The signal acts as a nerve impulse and travels through the body in a process of electrical cell-to-cell communication until it reaches the automatic nervous system. Activation of the automatic nervous system immediately triggers a series of involuntary chemical responses throughout the body. Preganglionic neurons release the neurotransmitter acetylcholine (ACh). This stimulates postganglionic neurons which release noradrenaline. The noradrenaline flows directly into the bloodstream ensuring that all cells in the body's nervous and endocrine systems have been activated even in areas which the ganclionic neurons are unable to reach.

Endocrine system


Central nervous system (CNS)




Immune system

The most important aspect of the immune system are T-cells found in the form of T-helper and T-suppressor cells. Cortisol, once released into the bloodstream, immediately begins to cause division of T-Suppressor cells. This rapid cell division increases the number of T-Suppressor cells while at the same time suppressing T-helper cells. This reduces immune protection and leaves the body vulnerable to disease and infection.

Hypothalamic-pituitary-adrenal (HPA) axis[edit]

Basic hypothalamic–pituitary–adrenal axis summary (corticotropin-releasing hormone=CRH, adrenocorticotropic hormone=ACTH).





Immune response[edit]

Cortisol can weaken the activity of the immune system. Cortisol prevents the proliferation of T-cells by rendering the interleukin-2 producer T-cells unresponsive to interleukin-1 (IL-1), and unable to produce the T-cell growth factor.[35]Cortisol also has a negative-feedback effect on interleukin-1.[36] IL-1 must be especially useful in combating some diseases; however, endotoxic bacteria have gained an advantage by forcing the hypothalamus to increase cortisol levels (forcing the secretion of CRH hormone, thus antagonizing IL-1). The suppressor cells are not affected by glucosteroid response-modifying factor (GRMF),[37] so the effective setpoint for the immune cells may be even higher than the setpoint for physiological processes (reflecting leukocyte redistribution to lymph nodes, bone marrow, and skin). Rapid administration of corticosterone (the endogenous Type I and Type II receptor agonist) orRU28362 (a specific Type II receptor agonist) to adrenalectomized animals induced changes in leukocyte distribution. Natural killer cells are not affected by cortisol.[38]

Effect of stress on the immune system[edit]

Stress is the body’s reaction to any stimuli that disturbs its equilibrium. When the equilibrium of various hormones is altered the effect of these changes can be detrimental to the immune system.[40] Much research has shown a negative effect stress has on the immune system, mostly 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 significant decrease in immune response when given an influenza-virus vaccine compared to a non-stressed control group.[40][41] 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.[40] Studies with HIV have also shown stress to speed up viral progression. Men with HIV were 2–3 times more likely to develop AIDS when under above average stress.[40]

Stress affects the immune system in many ways. The immune system protects the body from viruses, bacteria, and anything that is different 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.[42] 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 fight infections.[42] 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.[43] 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 flu like symptoms. These symptoms mean the body is fighting the illness or virus.[42] 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.[43] 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.[43]

Effects of chronic stress[edit]

Main article: Chronic stress

Chronic stress is defined 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".[citation needed] Chronic stress takes a more significant 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 conflict lasting one month or longer have a greater risk of developing illness and show slower wound healing. Similarly, the effects that acute stressors have on the immune system may be increased when there is 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.[44] 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 effects that are detrimental to health.[45]

Mechanisms of chronic stress[edit]

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.[46] 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.[47] Cytokines are molecules involved with cell signaling.


Chronic stress and wound healing[edit]

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.[44] 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 Alzheimer’s 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 Alzheimer’s disease.[40]

Chronic stress and development[edit]


Chronic stress and memory[edit]

Chronic stress is seen to affect the parts of the brain where memories are processed through and stored. When people feel stressed, stress hormones get over-secreted, which affects 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 flashbulb memories it decreases long-term potentation (LTP).[50] 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.[51] 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.[52] 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.[51]

Stress and visceral fat[edit]


Psychological concepts[edit]


Selye published in year 1975 a model dividing stress into eustress and distress.[54] Where stress enhances function (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 adaptation, deemed distress, may lead to anxiety or withdrawal (depression) behavior.



Main article: Stress management



There are several ways of coping with stress,[56] 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 study was done and it showed that the power of having support from a loved one or just social support, lowered stress in the individuals. They gave painful shocks to married women’s ankles. On some trials women were able to hold their husbands hand, on other trials they held a strangers hand, and then held no one’s hand. When the women were holding their husbands hand, the response reduced in many brain areas. When holding the strangers hand the response reduced a little but not as much as when they were holding their husbands hand. Social support helps reduce stress but even more if the support is from a loved one.[51]

Cognitive appraisal[edit]




Clinical symptoms and disorders[edit]



Cognitive symptoms

  • Memory problems
  • Inability to concentrate
  • 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
  • Increased frequency of urination
  • Indigestion
  • Changes in blood glucose
  • Nausea, dizziness
  • Chest pain, rapid heartbeat
  • Loss of sex drive
  • Frequent colds
  • Irregular periods.

Behavioral symptoms

  • Eating more or less
  • Sleeping too much or too little
  • Isolating oneself from others
  • Procrastinating or neglecting responsibilities
  • Using alcohol, cigarettes, or drugs to relax
  • Nervous habits (e.g. nail biting, pacing)

DSM-IV TR[edit]





Health risk factors[edit]


Generalized anxiety disorder[edit]

The areas of the brain affected by generalised anxiety disorder

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 tasks. These finding suggest that there may be hyperactive brain circuits in GAD.[66]

The areas of the brain affected 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 effect 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.[67]

The septohippocampal circuit

Based on early neuroanatomical observations and studies with psychoactive drugs, the septohippocampal circuit has been proposed as a model for anxiety disorders. The circuit that links the septum, amygdala, hippocampus and fornix is thought to process external stimuli and regulate the behavioural response through wider projections in the brain. Hyperstimulation of this putative ‘behavioural inhibition’ circuit, through dysfunctional noradrenergic and serotonergic neurotransmission, has been implicated in producing anxiety, and increased arousal and attention.[68]

The noradrenaline pathways in generalised anxiety disorder

In generalised anxiety disorder (GAD) there is increased noradrenaline transmission from both the locus coeruleus and the caudal raphe nuclei. The locus coeruleus-noradrenaline system is associated with anxiety and may mediate the autonomic symptoms associated with stress such as increased heart rate, dilated pupils, tremour and sweating.[69]

Serotonergic pathways showing the effects of 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 unaffected in GAD. This altered neurotransmitter balance contributes towards the feeling of anxiety associated with GAD.[70]

GABAergic pathways showing the effects of generalised anxiety disorder

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.[71]

Panic disorder[edit]

Main article: Panic disorder
The areas of the brain affected in panic disorder

There are a number of areas of the brain affected 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, while the hypothalamus mediates the sympathetic nervous system.[72][73][74]

The areas of the brain affected in panic disorder (advanced)

Hyperactive neurotransmitter circuits between the cortex, thalamus, hippocampus, amygdala, hypothalamus and periaqueductal gray matter have been implicated in panic disorder. Hypofunction of serotonergic neurones arising from the rostral raphe nucleus may result in a lack of inhibitory effect on the putative panic pathways in the brain. While, overactivity of norepinephrine neurons arising from the locus coeruleus may produce excessive excitation in the regions implicated in panic disorder. Physiological symptoms of the panic response are medicated by the autonomic nervous system through connections with the locus coeruleus and hypothalamus.[72][73][74][75][76]

The serotonin pathways in panic disorder

The principal serotonin centres in the brain are the caudal and rostral raphe nuclei. Transmission of serotonin from the rostral raphe nuclei to the pre-aquaductal grey, amygdala, temporal lobe and limbic cortex is decreased in panic disorder compared with normal. Serotonin transmission to other target regions of the brain remain unchanged.[77]

The norepinephrine pathways in panic disorder

In panic disorder there is increased norepinephrine transmission from both the locus coeruleus and the caudal raphe nuclei. The locus coeruleus-norepinephrine system may have a significant role in processing fear-related stimuli or it may affect 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.[77]

General adaptation syndrome[edit]

A diagram of the General Adaptation Syndrome model.

Physiologists define stress as how the body reacts to a stressor, real or imagined, a stimulus that causes stress. Acute stressors affect an organism in the short term; chronic stressors over the longer term. General adaptation syndrome (GAS), developed by Hans Selye, is a profile of how organisms respond to stress; the general adaptation syndrome is characterized by three phases: a nonspecific mobilization phase, which promotes sympathetic nervous system activity; a resistance phase, during which the organism makes efforts to cope with the threat; and an exhaustion phase, which occurs if the organism fails to overcome the threat and depletes its physiological resources.[78]

Stage 1[edit]


  • Antishock phase: When the threat or stressor is identified or realized, the body starts to respond and is in a state of alarm. During this stage, the locus coeruleus/sympathetic nervous system is activated and catecholamines such as adrenaline are being produced, hence the fight-or-flight response. The result is: increased muscular tonus, increased blood pressure due to peripheral vasoconstriction and tachycardia, and increased glucose in blood. There is also some activation of the HPA axis, producing glucocorticoids (cortisol, aka the S-hormone or stress-hormone).

Stage 2[edit]

Resistance is the second stage and increased secretion of glucocorticoids play a major role, intensifying the systemic response—they have lypolytic, catabolic and antianabolic effects: increased glucose, fat and aminoacid/protein concentration in blood. Moreover, they cause lymphocytopenia, eosinopenia, neutrophilia and polycythemia. In high doses, cortisol begins to act as a mineralocorticoid (aldosteron) and brings the body to a state similar to hyperaldosteronism. If the stressor persists, it becomes necessary to attempt some means of coping with the stress. Although the body begins to try to adapt to the strains or demands of the environment, the body cannot keep this up indefinitely, so its resources are gradually depleted.

Stage 3[edit]

The third stage could be either exhaustion or recovery:

  • Recovery stage follows when the system's compensation mechanisms have successfully overcome the stressor effect (or have completely eliminated the factor which caused the stress). The high glucose, fat and aminoacid levels in blood prove useful for anabolic reactions, restoration of homeostasis and regeneration of cells.

The result can manifest itself in obvious illnesses, such as peptic ulcer and general trouble with the digestive system (e.g. occult bleeding, melena, constipation/obstipation), diabetes, or even cardiovascular problems (angina pectoris), along with clinical depression and other mental illnesses.


The areas of the brain affected in phobia

There are a number of areas of the brain affected 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 mediating physiological and behavioural arousal.[74]

The noradrenaline pathways in phobia

One hypothesis about the biological basis of phobia suggests that there is an excess of noradrenaline in the principal noradrenergic pathways in the brain and that this causes a down-regulation of post-synaptic adrenergic receptors. Transmission of noradrenaline from the caudal raphe nuclei and the locus coeruleus is increased in phobia.[80]

The serotonin pathways in phobia

The principal serotonin centres in the brain are the caudal and rostral raphe nuclei. Transmission of serotonin from the rostral raphe nuclei to the thalamus, limbic cortex and cerebral cortex is decreased in phobia compared with normal. The other major pathways for serotonin transmission which involve the basal ganglia and cerebellum, and project down the spinal cord, remain unchanged.[80]

Post-traumatic stress disorder (PTSD)[edit]

Regions of the brain associated with stress and posttraumatic stress disorder[81]

PTSD is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity, overwhelming the individual's ability to cope. As an effect of psychological trauma, PTSD is less frequent and more enduring than the more commonly seen acute stress response. Diagnostic symptoms for PTSD include intrusion, avoidance and hyperarousal -- re-experiencing the original trauma(s) through "flashbacks" or nightmares (intrusion), emotional numbing or avoidance of stimuli associated with the trauma, and increased arousal, such as difficulty falling or staying asleep, anger, and hypervigilance. Formal diagnostic criteria (both DSM-IV-TR and ICD-10) require that the symptoms last more than one month and cause significant impairment in social, occupational, or other important areas of functioning.

The areas of the brain affected in post-traumatic stress disorder

Sensory input, memory formation and stress response mechanisms are affected 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.[75][76]



Atrophy of the hippocampus in posttraumatic stress disorder

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 atrophy and generalised white matter atrophy is exhibited by people with PTSD.[82][83]


The areas of the brain affected in depression

Many 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.[84]

The hypothalamic-pituitary-adrenal (HPA) axis in depression

In depression, the hypothalamic-pituitary-adrenal (HPA) axis is upregulated with a down-regulation of its negative feedback controls. Corticotropin-releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocorticotropin hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands; adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including 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-inflammatory immune mediators and disturbances in neurotransmitter transmission.[85][86][87][88]

The serotonin pathways in depression

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 depression.[89]

The noradrenaline pathways in depression

In depression the transmission of noradrenaline is reduced from both of the principal noradrenergic centres – the locus coeruleus and the caudal raphe nuclei. An increase in noradrenaline in the frontal/prefrontal cortex modulates the action of selective noradrenaline reuptake inhibition and improves mood. Increasing noradrenaline transmission to other areas of the frontal cortex modulates attention.[90]

History in research[edit]







See also[edit]


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