Stress

(Dhabar et al., 1996)

Acute stress to challenges enhances the traffic of lymphocytes and macrophages.

(Dhabar et al., 1996)

Allostasis enhances responses where immunologic memory is established.

(Hortwitz & Hortwitz, 1993)

Allostatic load is important in highlighting the relationship between disease and chronic stress. Important in treatment/diagnosis of many illnesses, enabling patients to change their behavioural patterns appropriately (i.e. stopping smoking/drinking alcohol/complete more exercise).

Stress

A pattern of psychological, biological and behavioural responses caused by stressors.

General Adaptation Syndrome

(Seyle, 1956)

(Sapolsky, 2004)

Adrenaline alters blood platelets which makes them more likely to clot. This can also cause atherosclerosis.

Increased arousal alters emotional and cognitive processing

Adrenaline and noradrenaline activate the reticular formation (involved in general arousal) and other brain regions such as the amygdala via the brain stem. Cortisol receptors located in the amygdala, hippocampus and prefrontal cortex allow increased arousal and emotional/cognitive processing.

(AHA, 2010)

Hypertension is a major risk factor for CHD (coronary heart disease).

(Sapolsky, 1992; Kim & Diamond, 2002)

Repeated stress causes dendritic atrophy of pyramedial neurons in CA3 regions of the hippocampus. An excess of glutocorticoids stimulates an excess of glutamate, causing an influx of calcium in hippocampal synapse CA3-CA1. This kills cells and hippocampal neurons.

(Smith, 2006)

The stress response is complex and varied with exact responses depending upon the stressor, timing, person and how reactions materialise.

The nature and duration of the stressors influence immune activity. Allostatic load thus disrupts immunity. Short-term acute stress produces beneficial immune changes, but chronic stress suppresses immune function.

(Segerstrom & Miller, 2004)

Chronic stress is...

...linked to the development of insulin resistance (Raikkonen et al., 1996) and coronary heart disease (Bjorntorp et al., 1990). [Although animal studies - not 100% generalisable].

(Marucha et al., 1998)

11 dental students given punch biopsies in mouths once during vacation, and again 3 days prior to an exam. Wounds took 3 days (40%) longer to heal during the exam condition. Infers that stress is not always adaptive and can suppress immune systems in terms of healing.

Disruption

Any changes to the stress response (increased or reduced responding) resulting from chronic stress can disrupt delicately balanced immune responses.

(Kim & Diamond, 2002)

Brief exposure to a brief, naturalistic stressor reduced prime-burst potentiation and impaired spatial memory in rats.

Chronic activation

Chronic activation of the stress response can result in negative consequences, and is thus maladaptive.

(Kiecolt-Glaser, 2002)

Chronic psychological stress most frequently implicates health.

(Cohen et al., 1998)

Chronic stress associated with greater susceptibility to illness.

(Sparrenberger et al., 2009)

Chronic stress is associated with hypertension.

(McEwen, 2000; Sandi, 2004)

Chronically stressed rats show dendritic atrophy in the hippocampus and neurogenesis is inhibited. Dendrites therefore waste away, and no new neurons are formed.

Cortisol effects on heart muscles

Cortisol enhances the effects of adrenaline and noradrenaline by allowing more oxygen and energy into the blood. Fuel rich blood reaches muscles and organs quicker, facilitating the body to be ready for action.

Cortisol and energy

Cortisol mainly (and adrenaline) break down stored energy into usable forms. For example, glycogen is broken down into glucose, and fat to fatty acids.

(Sapolsky, 1992)

Cushing's disease - tumours on the adrenal glands caused by an excess secretion of cortisol - is associated with the atrophy of the hippocampus.

(Fleshner & Laudenslager, 2004)

Cytokines have been classified with stress hormones (adrenal). However, much research has been done on animals and this is not 100% generalisable, whilst being unethically unjust to induce stress.

(Evans & Kim, 2007)

Early experiences of neglect in children correlates a variety of brain and endocrine system abnormalities.

(Meaney et al., 1994)

Early stress causes an overreaction of the HPA axis and SNS in animals and an under-reaction in those animals exposed to neonatal handling.

(Seyle, 1956)

Emphasised the dual nature of stress. Short-term stress is adaptive by mobilising resources. Long-term stress is maladaptive as it can lead to health implications such as enlarged adrenal glands.

(McEwen, 2004)

Exposure to stress affects the structure of the brain in many ways, however the hippocampus is particularly susceptible to stress induced effects. This may be due to the dense population of glutocorticoid receptors in the hippocampus.

(Seeman et al., 1994)

Failure to shut off our allostatic responses, resulting in allostatic load, causes our allostatic systems to become exhausted.

(Schulkin et al., 1994)

Feelings of anticipation and worry can also contribute to allostatic load as anxiety drives the secretion of cortisol and adrenaline. Anxiety which is prolonged is likely to result in allostatic load (Schulkin et al., 1994).

Gastric ulcers

Gastric ulcers occur more commonly in those who are under stress - stressors produce gastric ulcers in lab animals (Pinel, 2013). Helicobactor pylori infection alone is insufficient to produce ulcers, as 75% of healthy individuals display signs of helicobactor pylori.

(McEwen, 1998)

Graphs of elevated/insufficient physiology. McEwen isolated four problematic response patterns resulting from chronic exposure to stress, that lead to allostatic load and poor health. These were 'frequent hits'; 'lack of adaptation'; 'prolonged response'; and 'inadequate response'.

(Sarrafino, 2011)

Higher levels of circulating fats/glucose leads to the formation of plaques (atherosclerosis). Cortisol and adrenaline break down glycogen to glucose, and fat into fatty acids. This leads to higher levels of circulating fats which create plaques. Plaques lead to an increased risk of myocardial infarction and strokes.

Allostatic load - cardiovascular problems

Hypertension (chronically elevated blood pressure) damages blood vessels. As the stress response increased blood pressure, allostatic load may therefore cause hypertension.

(Cohen et al, 1991; Brunner, 1996)

Immune system functioning is a target of psychological stress, causing increased vulnerability to infections such as the common cold.

(Cahill & McGaugh, 1998)

In animals post-training injection of adrenaline enhanced memory for that training; in humans, drugs that block adrenaline eliminate the enhancement of emotional memories; and in animals, infusion of glutocorticioid agonists after training improves memory.

(Pinel, 2013)

In the 1990's it was discovered that brief stressors produce psychological reactions that participate in the body's inflammatory responses. Brief stressors produce increased cytokines (a group of peptide hormones). Cytokines are released by many cells and participate in a variety of physiological and immunological responses (such as inflammation and fever).

(Segerstrom & Miller, 2004)

In their meta-analysis of over 300 studies, they found that acute stress (lab tests of stress) up-regulated parameters of innate immunity by rises of phagocytes and Natural Killer cells in blood. This demonstrates preparation for infection/injury.

Allostatic response

Inactivation of the stress response returns systems to baseline levels of cortisol and adrenal hormones (happens when threat has passed). However, if inactivation is insufficient an over-exposure to stress hormones occurs leading to allostatic load and pathological consequences.

(Munk et al., 1984)

Inadequate responses by some allostatic systems trigger compensatory increases in others. If cortisol does not increase in response to stress, the secretion of inflammatory cytokines increases.

(Hagglof et al, 1991)

Inbred rats exposed to repeated stress demonstrated an increased incidence of diabetes.

(Lupien et al., 1998)

Indications from research within humans that long-term or intense stress is associated with damage to the brain. Within an elderly sample, elevated blood cortisol is associated with poor memory performance and a reduction in hippocampal volume.

LTP and Stress (ST)

Influx of (Ca2+) calcium at NDMA receptors sets off a series of cellular process that lead to LTP. In the short term, intermediate levels of stress hormones enhance LTP by stimulating the activity of glutamate receptors, causing the depolarisation of the calcium channel (Kim & Diamond, 2002).

(Boyar et al., 1994)

Intense athletic training leads to an elevated stress response. This causes weight loss, amenorrea, anorexia nervosa.

(Thompson et al., 1987)

LTP is impaired in rats exposed to chronic stress

Chronic stress

Leads to allostatic load which is a cumulative load of minor, day-to-day stressors.

Failure of acute/innate immune responses

Leads to the activation of specific responses and chronic inflammation

LTP and Stress (LT)

Long-term intense stimulation of the same neurons causes (Ca2+) calcium to enter the cell in such large amounts that it is toxic to the cell. This can cause dendritic atrophy and cell death (Kim & Diamond, 2002). Supported by McEwen (2000) - chronic stress shows dendritic atrophy in rats.

Chronic stress and memory

Long-term stress can inhibit synaptic plasticity in the same circuitry, damage neurons and impair memory (Kim & Diamond, 2002)

(Cohen et al., 1999) Severe Symptomatic Response

Participants completed a stress measure and were infected with an influenza virus. Higher stress at baseline was associated with greater symptom scores and higher IL-6 (cytokine production). IL-6 involved in inflammatory immune response, which aids the body to rid itself of viruses/infections. IL-6 produces symptoms such as fever. Need enough for former, whilst minimising the latter. Can infer that stress interferes with the body's ability to turn off cytokine production. If IL-6 stays on, there is a greater over-expression of symptoms.

(Cohen et al., 1991)

Participants exposed to low dose of common cold virus, and stayed at a research unit for 7 days. Those with higher levels of psychological stress prior to exposure to the virus were 45% more likely to develop the cold.

(Gerin, 1995)

People may be genetically predisposed to heightened stress responses. People who had elevated blood pressure after a maths test had a parent with hypertension.

(Baum et al., 1993)

Post-traumatic stress can produce chronic stress and drive physiological responses.

(Weinstock, 2008)

Prenatal stress can adversely affect neural and endocrine development before birth.

Transactional Model of Stress

Primary appraisal (stimulus encountered - if benign no stress response). If a threat is encountered > secondary appraisal takes place, whereupon one evaluates their ability to cope with the stressor. If coping mechanisms are adequate, no stress response. If coping mechanisms are inadequate, the stress response is activated. Therefore, outcomes of appraisals determine the nature and magnitude of our stress response.

Allostatic load

Prolonged stress. A frequent/prolonged activation of the same stress response. This can result in damage/disruption to biological systems.

(Wang et al., 2010)

Reduced hippocampal volume is associated with Post-Traumatic Stress.

(Cohen, 1999)

Reduced responding leads to allostatic load (damage/disruption to our biological systems) and poor health as cortisol deficiencies affect the immune system. This is because stress hormones such as cortisol leads to reduced regulation of the immune system, causing an over-expression of symptoms.

Innate immunity

Responds will all purpose cells that attack many different pathogens (disease causing antigens). All purpose cells (phagocytes, macrophages, and NK/natural killer cells) attack pathogens within minutes or hours (French et al., 2010).

Specific immunity

Responds with immune cells that only target specific antigens. Such cells can take up to several days to respond to and destroy cells. The specific immune system contains three types of lymphocytes: 1) B lymphocytes produce antibodies; 2) T-helper cells produce cytokines which regulate immune responses; and 3) T-cytotoxic cells which destroy cells. Responses to antigens cause inflammatory symptoms such as swelling or redness.

Chronic stress in caregivers

Segerstrom & Miller (2004) also found that chronic stress (caregiver of handicapped) saw immunosuppression by observable decreases in both innate and specific immunity.

Acute stress and memory

Short term increases in stress hormones can facilitate the formation of memories of emotional events (Cahill & McGaugh, 1998).

(Robles, Glaser, Kiecolt-Glaser, 2005)

Short-term cytokine induced inflammatory responses help the body combat infection, but long-term cytokine release is associated with adverse health consequences.

(Kiecolt-Glaser et al., 1995)

Skin blisters (3.5mm punch biopsy wounds) induced in caregivers and controls. Caregivers took 9 days (24%) longer to heal than controls and had lower levels of IL-1 (cytokine interleukin) in blood. IL-1 attracts phagocytes to wounds which then remove infectious agents. Found object evidence that stress may have a large enough impact to influence immunity responses as signalling IL-1 appears suppressed in caregivers.

Acute stress

Solved by allostasis and activation of the fight-or-flight

Stressors

Stimuli that we perceive to be aversive or threatening. Individuals differ in what they perceive to be stressors, and what produces their stress response.

(Sandi, 2004)

Stress has been shown to: reduce dendritic branching in the hippocampus; reduce adult neurogenesis in the hippocampus; modify the structure of some hippocampal synapses; and disrupt performance on hippocampus-dependent tasks.

Effects of adrenaline and noradrenaline on heart muscles

Stress hormones adrenaline and noradrenaline interact with beta receptors on the heart muscles, increasing heart rate and also interacting with receptors governing blood vessel dilation.

(McGaugh, 2000)

Stress hormones enhance emotional memories by enhancing synaptic plasticity in areas involved in memory (connections between neurons become stronger with LTP). Activation of the amygdala is a crucial component of this process. Basolateral amygdala activation allows neural pathways to open, allowing glutocorticoids to each the neocortex, hippocampus, caudate nucleus and other brain regions.

(Cohen et al., 2005)

Stress may increase susceptibility to respiratory infection by disrupting the regulation of cytokines. However, this is a correlational finding. Participant's self-reports may have been subjective. Do they report more illness because they expect to be more ill, or genuinely because stress has changed their behaviour in ways that make them more susceptible to illness?

(Katz et al, 1970)

Study of women awaiting surgery for breast cancer found that stress levels were lower in those who were convinced that they didn't have it.

Psychoneuroimmunology

Studying interactions between psychological factors, the nervous system, and the immune system (Fleshner & Laudenslager, 2004).

Chronic stress can lead to our response systems becoming exhausted.

Supports Seyle's 1956 GAS model. Reduced cortisol response is evident with previous history of chronic stress in chronic fatigue (CF) sufferers (Fries et al., 2005).

(Kaplan et al., 1991)

Surges in blood pressure can accelerate atherosclerosis in primates.

(Muller et al., 1989)

Surges in blood pressure over weeks and months can trigger myocardial infarction.

Effects of stress upon the brain

The brain is a major target for stress hormones which alter activity in various regions. In short-term effects are adaptive as stress hormones contribute to increased alertness. Future responses may also be aided by enhancing memory of the arousal experiences, but chronic stress has negative effects on the brain.

(McEwen, 2004) in response to (Sandi, 2004)

The effects described by Sandi (2004) appear to be mediated by elevated glutocorticoid levels.

(French et al., 2010)

The immune system involves a variety of cells that identify and eliminate foreign matter in our bodies, known as antigens (Rabin, 2005). The immune system can be divided into the natural (innate/first line of action) and specific (slower/more tailored) immune responses.

(Kaplan et al., 1991)

The inability to shut off allostatic responses means that blood pressure fails to recover. This causes hypertension which in turn accelerates atherosclerosis.

(Cohen, 1999)

The negative consequence of enhanced inflammatory response is increased susceptibility to an over-expression of symptoms.

Allostasis

The stress response allows the body to deal with stressors by altering biological systems (i.e. increased cardiovascular activity is adaptive in the short term and maintains equilibrium). Allostasis is the ability to achieve stability through change. Change is crucial for survival (evolutionary). The SNS, HPA axis, cardiovascular/metabolic immune systems protect the body by responding to internal/external stress.

(Cannon, 1929)

The stress response serves a catabolic function by mobilising the body for fight-or-flight. The response is adaptive as it has evolved to enable us to deal with acute environmental threats requiring physical action to maintain homeostasis and equilibrium. (short-lived)

General Adaptation Syndrome

This suggests that a stressor causes 3 stages of response. Initially alarm: the stress response is initiated to meet and resist the stressor. This is adaptive, and equilibrium should be retained. The second stage (resistance) refers to a full scale mobilisation of resources to further resist the stressor is equilibrium was not retained in stage one. This is very costly to the body as an extensive consumption of resources occurs. The third stage, exhaustion, ensues if the stressor has still not been terminated. Resistance depletes bodily responses to exhaustion. Seyle associated resistance and exhaustion stages with heightened susceptibility to illness and death.

The Stress Response

Threat appraisal activates the ANS that alerts the SNS to stimulate the hypothalamus to release CRH (corticotropin-releasing-hormone). The release of CRH activates the pituitary gland to release ACTH (adreno-corticotropic hormone), which in turn alerts the adrenal glands located on top of each kidney. ACTH from the pituitary gland stimulates the adrenal cortex to release cortisol (a glutocorticoid). At the same time, neurons in the hypothalamus signal the adrenal medulla to release adrenaline and noradrenaline. These hormones push the body into hyper-alterness.

(Sapolsky, 2004)

Today's stressors are more long-lasting as they are often psychological and maintained by worry.

(Lazarus & Folkman, 1984)

Transactional Model of Stress - we constantly evaluate events we encounter in terms of their threat value.