Week 10 Flashcards
Stress
• Any stimulus that disrupts the body’s internal balance (i.e.,
physiological homeostasis)
• Any deviation from homeostasis
• The mental and physical state induced by a stressor
Stress – the state
Stressor – the thing that causes the state
Stress Response – the link between the stressor and stress
The Stress Response
• Fight or flight – survival mechanism – react quickly to life threatening
situation
• Rapid recognition of potentially harmful stimuli to mobilize the
defence responses
• An array of neural and endocrine systems that mobilise physiological
and psychological resources allowing response to the present
challenge to homeostasis and overall well being
• Complex but orchestrated and rapid
• The stress response is incredibly ancient evolutionarily
• All vertebrates respond to stressful situations by releasing hormones,
such as epinephrine and glucocorticoids
➢ Mobilize energy resources
➢ Increase blood pressure
➢ Turn off everything that’s not essential to surviving right now -
digestion, growth, reproduction
➢ Think more clearly
➢ Learning and memory are enhanced
➢ Sensory thresholds sharpened
Good Stress / Bad Stress
If stress is so good, then why the bad rap?
• All stressors – single stress response – Evolution is a tinkerer!!
• Many modern life stressors are not life threatening
• Many modern life stressors are social
• Many modern life stressors are psychological
• We neither fight nor flee
If stress is so good, then why the bad rap?
• Worries, social pressure, sitting in traffic
• All elicit the same stress response as
escaping a tiger – release of epinephrine
and cortisol
• Stress response evolved to get you out
of a bad situation
• Short term adaptive, long term harmful
Good Stress / Bad Stress- If stress is so good, then why the bad rap?
• Good stress – mild, transient, not a complete loss of control • Bad stress – severe or chronic and coupled with lack of predictability or perceived lack of control • Chronic psychological stress implicated in ill health Optimal good stress: • Occurs in a safe environment • Is transient and mild • Involves a plausible but not guaranteed reward • You have control • Results in arousal, alertness, stimulation
Good Stress / Bad Stress- Bad stress – severe or chronic and coupled with lack of predictability or
perceived lack of control
• What if the stressor is always there? • What if you can’t get away? • What if you believe that nothing you do will change things anyway?
Good Stress / Bad Stress- Long-term
The long-term activation of the stress-response system and the
overexposure to cortisol and other stress hormones that follows can
disrupt almost all your body’s processes
➢ Digestive problems
➢ Headaches
➢ Heart disease
➢ Sleep problems
➢ Weight gain
➢ Immune system impairment
➢ Accelerated chromosomal DNA aging (telomeres)
➢ Memory and concentration impairment
➢ Anxiety, depression, and other mental health issues
Stress- Introduction
Bad -Visual System Scotoma Cataracts Glaucoma Retinal detachment Cortical blindness Colour blindness Macular degeneration Retinoblastoma -Attention Contralateral Neglect -Auditory System Sensorineural deafness -Pain Congenital Insensitivity to Pain -Motor System Motor Neuron Disease Good -Performance Enhancing -Beneficial -Rise to a challenge -Protective -Keeps you alive -Adaptive
Bad Stress
-77% regularly experience physical symptoms caused by stress -48% reported lying awake at night due to stress -One in seven Australians will experience depression in their lifetime -One in five Australians have taken time off work in the past 12 months because they felt stressed, anxious, depressed or mentally unhealthy -One quarter of Australians will experience an anxiety condition in their lifetime -73% regularly experience psychological symptoms caused by stress
Gastric Ulcers
• Lesions of stomach lining leading to pain, bloating, nausea
• One of the first psychosomatic disorders - stress
• Warren and Marshall – H. Pylori
• Marshall ingested and developed
gastritis and ulcers
• H. Pylori – 90% of ulcers
• Nobel Prize in 2005
But most people have H. Pylori and only 10% get an ulcer
• Another factor increases susceptibility
of stomach wall to damage from H.
Pylori
• H. Pylori attacks the stomach wall, but
usually this is easily fixed
• Unless stomach (more generally
digestive) operations have been turned
right down to deal with a threat
• Stress
Main Characters
Hypothalamus
Pituitary
Amygdala
Adrenal Cortex- Releases cortisol - the major
glucocorticoid in humans
Adrenal Medulla- Releases epinephrine (also
known as adrenaline
The Stress Response
• The stress response is incredibly ancient evolutionarily
• All vertebrates – fish, birds, reptiles, mammals
• Encounter a stressor – any perceived threat - a tiger, a mean boss, a
worrying thought
• Sensory information to the amygdala – interprets – if perceive a
threat then signal hypothalamus
• Secrete hormones (epinephrine and glucocorticoids) to respond
Two pathways
Sympathetic-adrenal-medullary (SAM) system Fast response Short acting Epinephrine Jump start Hypothalamus-pituitary-adrenal (HPA) axis Slow response Lasting Cortisol Keep things going
The Stress Response
SAM
HPA
SAM System
Efferent Nerves
- Parasympathetic Nervous system
- Sympathetic Nervous System
ANS Efferents
Change the body’s internal state Sympathetic • Fight or flight • Stimulate organs and release hormones to wind things up • Mobilise energy sources • Increase blood flow and respiration • Suppress non-essentials From chest, mid-lower back Parasympathetic • Rest and digest • Counteract sympathetic to wind things down • Stimulate digestion and restorative functions • Conserve energy From brain, lower back
SAM System
• Direct adrenergic innervation of organs (epinephrine and norepinephrine)
• Stimulate the adrenal medulla to release epinephrine into bloodstream –
efficient to replace neural activity for sustained response
• Very fast response – before conscious awareness
• Wind things up and supress non-essentials but also senses sharpen, improve
mood, encourage creative thinking, problems feel more like challenges
• SNS slow to shut down – need to actively counteract - PSNS
• No ill effects from the short-term response (although persistent epinephrine
surges can damage blood vessels)
HPA Axis
• As initial surge of epinephrine subsides, the hypothalamus activates
the second component of the stress response system
• Release of cortisol by adrenal cortex
• Measure of circulating cortisol most common physiological measure
of stress
• Primary function – increase blood glucose
• Support an extended fight or flight response
HPA Axis - Cortisol
• Important steroid hormone – almost all cells in the body have cortisol
receptors
• Sleep/wake cycle
• Low blood sugar
• Stress
• Metabolic effects
• Release glucose stores in muscle and liver
• Modifies fat and protein metabolism – fatty acid mobilisation and
gluconeogenesis (create more glucose)
• Alters immune system responses
• Reduce inflammation
• Hyperactivity results in immune suppression
• Suppresses the digestive system, the reproductive system and growth
processes
• Negative feedback control – cortisol acts on both the hypothalamus and the
pituitary to turn the HPA axis DOWN
Three Determinants of HPA Activity
Three main determinants of HPA axis activity control the amount of
cortisol a person is exposed to during adulthood
• Genetic factors
• Early-life environment
• Current life stress
Also, sex and age differences in stress response
Three Determinants of HPA Activity
Genetic factors
• DNA variations in genes encoding neurotransmitters involved in HPA
axis regulation.
• Heritable influences account for 62% of the variance in basal
glucocorticoid levels
Three Determinants of HPA Activity
Early-life environment
• Pre and post-natal influences
• Maternal stress modifies HPA axis responsivity of infant and adult offspring
• Childhood trauma associated with alterations in HPA axis function
• Animal models show neonatal stress results in a epigenetic modification of a
receptor gene with long-lasting effects on cortisol responsivity - rats that
received poor maternal care showed deficits in receptors in the
hippocampus and impaired shut off of the HPA stress response
• Mild to moderate early life stressors enhance HPA regulation and promotes
life long resilience to stress
Three Determinants of HPA Activity
Current Life Stress
• Severe, chronic stress in adulthood alter HPA axis dynamics and
increase the cortisol burden
• Chronic stress triggers a shift in the normal circadian rhythm of
cortisol release – increased baseline
• Makes the HPA axis more sensitive, resulting in higher cortisol
exposure or greater cortisol burden following each stressful episode
• Severe, chronic stress in adulthood alter HPA axis dynamics and
increase the cortisol burden
• Chronic stress triggers a shift in the normal circadian rhythm of
cortisol release – increased baseline
• Makes the HPA axis more sensitive, resulting in higher cortisol
exposure or greater cortisol burden following each stressful episode
• Romania under Ceausescu (1960’s to 1989) – contraception and
abortion forbidden; childless couples taxed – high birth rate
• Huge number of children to orphanages – horrific conditions –
isolation, neglect, maltreatment
• Failed to meet even the most basic needs of the children
• Intense and pervasive stress during development
• McLaughlin et al. (2015) – 138 children – 3 groups – orphanage;
orphanage but removed to high quality foster care; local controls
• Electrocardiogram, impedance cardiograph, and neuroendocrine data
collected during laboratory based challenge tasks
• Main finding – blunted SAM and HPA responses to lab stressors –
both social and non-social
• Normal response if removed into foster care before 24 months –
critical period
Chronic Stress
Adaptive
• Mobilise energy stores
• Increase blood supply
• Enhanced cognition
• Enhanced immunity, reduced
inflammation
• Suppression of growth
• Suppression of digestion
• Suppression of reproduction
Disorder
• Metabolic dysfunction, inefficient energy use, muscle wasting, type 2 diabetes
• Stress hypertension, atherosclerosis,
heart disease
• Memory loss, disconnection of neural networks, reduced neurogenesis, selective neurodegeneration
• Amygdala expansion → increased anxiety
• Depletion of dopamine → anhedonia → depression
• Increased risk of some infectious diseases (probably no increase in cancer risk)
• Osteoporosis, osteoarthritis,
psychogenic dwarfism
• Increased risk of ulcers, increased fat deposition
• Females – irregular cycles, loss of cycles, failure of implantation; males – decreased testosterone, erectile dysfunction; everyone – loss of libido
Psychosocial Short Stature
• Extreme stress and emotional deprivation endured during childhood
• Symptoms appear after age two and continue into the early teenage years
• Failure to thrive despite adequate nutrition - short stature, immature
skeletal age, and improper body weight for height
• Low growth hormone but resistant to treatment with GH
• When a child leaves an abusive home environment, growth hormone
insufficiency can be reversed.
• Undergo rapid “catch-up growth” to what is likely their genetically
predetermined height.
Brain - Cortisol Damage
Chronic stress negatively impacts the brain in many ways
• Mediated by cortisol
• Acts directly on receptors and indirectly via excitatory
neurotransmitters, BDNF, other intra- and extracellular mediators
• Structural remodelling (plasticity) of
• Hippocampus
• Amygdala
• Prefrontal Cortex
• Remodelling is reversible, but more difficult with age
Brain - Cortisol Damage
Hippocampus
• Contextual information about the circumstances under which stress response has
been activated in the past - contributes to threat appraisal by the amygdala;
important in learning and memory, and in regulation of mood
• HC particularly susceptible to stress – high density of glucocorticoid receptors
• Reduce dendritic branching; reduce adult neurogenesis; modify synapse
structure; loss of grey matter
• May be a protective function against permanent damage
• Disrupt performance of HC dependent tasks
• HC part of system that tells HT to turn off cortisol – loss of regulation
Brain - Cortisol Damage
Amygdala
• Amygdala based fear circuitry mediates defensive behaviours and
physiological responses to danger
• Emotional significance of sensory signals learned and maintained
• Opposite effect than on HC - increase plasticity and expansion of
dendritic processes
• Bad since increases fear acquisition and decrease extinction – learn
more readily to be afraid and less readily detect safety – anxiety
disorder
Brain - Cortisol Damage
Prefrontal Cortex
• Provides top-down control of emotional responses and amygdala
restraint
• Dendritic shrinkage in mPFC - impaired cognitive flexibility
• Dendritic expansion in OFC - salience of reward or punishment so
possibly increased vigilance to possible new stressors
• Impaired amygdala restraint during stress
Turning the Stress Response OFF
• Basic mechanism – Parasympathetic Nervous System
• Post threat, PSNS rapidly dampens stress response and cortisol levels
fall
• Direct innervation of organs (acetylcholine) and hormones to the
adrenal cortices to supress cortisol
• BUT … hierarchical dominance of SNS over PSNS – often requires
conscious effort to initiate relaxation response
• Relaxation response can be triggered – deep abdominal breathing,
focus on word, visualisation, yoga, etc
Conscious control of the stress response – prefrontal cortex
• Amygdala response not very nuanced – all or none qualities of defensive
reactions
• Amygdala threat appraisal is negatively biased – missing a real threat is worse
than misinterpreting something non-threatening
• Moderate stress levels - PFC activates inhibitory amygdala neurons
• Cognitive reinterpretation of stimuli possible
• Threatening or exciting
• Overwhelming or challenging
• BUT … intense stress - excessive NE output suppresses PFC restraint on the
amygdala- amygdala storm
Stress and Social Bonds
• Compared to most animals, humans not that great at fighting or fleeing - no sharp teeth, claws or thick hide, pretty slow
• Fight and flight both potentially leave young at risk – human young particularly vulnerable - stress response must protect offspring in times of danger and not just the individual
• Under conditions of threat, people come together to protect one another - impulse to affiliate part of the human stress response
• Humans evolved to use social relationships as a primary resource to
deal with stressful times – tend and befriend
• Social affiliation – release of oxytocin
• Oxytocin reduces cortisol response to stress and supresses HPA axis
• Oxytocin reduces threat induced amygdala activation and fear conditioning
• To exhibit a social response to stress, arousal must be controlled to avoid
aggression or flight
• Supportive contacts reduce stress response but hostile or unsupportive
increase it
• Affiliation is vital so expect systems to maintain it – sensitive to social threats
and loss of social contact
Social Isolation
• More than one in six people report feeling lonely in any given year and 1.5
million people have been lonely for a decade or more (Household, Income
and Labour Dynamics in Australia (HILDA))
• Social isolation is stressful – we are built to be social
• Being lonely is stressful
• Without social support stress is less manageable
• Unmanaged stress becomes chronic
• Chronic stress impairs systems that deal with stress
• Higher levels of loneliness are associated with higher levels of social
interaction anxiety, less social interaction, poorer psychological wellbeing
and poorer quality of life
• Increased risk of mortality - 26%
• Physical symptoms - lack of energy, sleep problems, diet problems,
headaches, illness, aches and pains and worsening of medical conditions
• Poor mental health including depression, lower levels of self-worth, life
satisfaction and subjective wellbeing
• Substance abuse
Amygdala
Amygdala based fear circuitry mediates defensive behaviours and physiological responses to danger • All sensory input – indirect and direct • Emotional significance of sensory signals learned and maintained • PFC inputs – suppress fear • HC inputs – mediate learning about context of fear related events (esp. location) Amygdala based fear circuitry mediates defensive behaviours and physiological responses to danger • Brain stem outputs control emotional responses (behavioural and physiological) – HT for SAM/HPA responses; PAG for defensive responses • Cortical outputs influence cognitive function – attention, perception, memory, decision making
Anxiety
• Fear– adaptive response to threat and usually transient
• Anxiety– longer lasting response to signals or vague indications –
adaptive arousal, vigilance, preparedness increases good for
surviving danger
• Hyperarousal (exaggerated startle response); heightened SNS arousal
and motor tension
• Adaptive since motivates effective coping behaviours
• Fear is good and anxiety is good
Anxiety Disorders
• BUT … if it persists or occurs out of proportion to possible threat –
disorder
• Chronic fear in the absence of direct threat – common psychological
correlate of stress
• Maladaptive since disrupts normal functioning
• 5 classes of anxiety disorder – generalized, phobic, panic, OCDs, PTSD
• Generalized, phobic, panic, and OCDs run in families – twin studies
suggest substantial genetic component
Anxiety Disorders - Examples
- Generalised Anxiety Disorder
- Phobic
- Panic
- Obsessive Compulsive Disorders
- Post Traumatic Stress Disorder
• Generalised Anxiety Disorder
- stress response and extreme feelings of anxiety in absence of obvious cause
- chronic worry and vigilance not warranted by situation
- heightened SNS arousal and motor tension
• Phobic
- intense excessive fear of specific stimuli
* similar to GAD but triggered by specific object or situation
• Panic
• rapid onset extreme fear and severe stress symptoms
• panic attack – intense fear plus somatic symptoms – palpitations, shortness
of breath, sweating, dizzy
• Obsessive Compulsive Disorders
• recurrent and uncontrollable anxiety producing thoughts (obsessions) and
impulses (compulsions)
• responding (eg washing hands) dissipates the anxiety
• behaviours intended to neutralize negative thoughts and emotions from
obsessions – resisting compulsions leads to high anxiety
• Post Traumatic Stress Disorder
• recurrent and uncontrollable anxiety producing thoughts (obsessions) and
impulses (compulsions)
• responding (eg washing hands) dissipates the anxiety
• behaviours intended to neutralize negative thoughts and emotions from
obsessions – resisting compulsions leads to high anxiety
Anxiety and Stress
• Anxiety disorders often triggered by stressful event
• Genetic – heritability 30-40% but timing and focus reflect particular
experience
• Stress and anxiety high comorbidity – both thought to involve
heightened emotional response to stress
• Stress disorder impacts the amygdala, HC and PFC - response to
incoming sensory information
• Amygdala and ACC implicated in anxiety from functional imaging
studies
Depression
• Depression – affective disorder – disturbance of mood or emotion
• Prolonged feelings of sadness, emptiness, or hopelessness, loss of interest in
activities that were once enjoyed
• Changes in appetite (leading to overeating or not eating enough), changes in
sleeping patterns (sleeping too much or not being able to sleep), loss of energy,
and difficulty concentrating.
• Distinguish from normal sadness by severity, pervasiveness, duration, associated
symptoms
• Must have signs and symptoms nearly every day for at least 2 weeks
• Features vary widely – possibly multiple disorders with similar signs and
symptoms
• Monoamine theory – underactivity at serotonergic and noradrenergic
synapses
• MAO inhibitors, tricyclics, SSRIs and norepinephrine reuptake
inhibitors are all agonists of serotonin, norepinephrine or both
• But – inhibitory actions fast but weeks before effect on depressions -
rather than an absolute deficit, low 5-HT neurotransmission may
represent a risk factor for MDD
• Genetic - concordance 60% MZ twins, 15% DZ but no particular gene
linked variations in many genes, each with a small effect, combine to
increase the risk of developing depression.
Depression and Stress
• Depression and stress interrelated – stress can precede depression and
depression is stressful
• Depression and chronic stress share symptomatic features and
biochemical changes
• Depressed release more stress hormones – increased HPA activation
and impaired HPA suppression (cortisol feedback system)
• Alterations in HPA axis functioning in recovered depressed patients and
at-risk individuals
• Enlargement of amygdala and increased activity
• Association between brain-derived neurotrophic factor (BDNF) levels
and depression (animal models of depression and depressed patients)
• Altered immune function in depression (suppression)
• Antidepressants increase neurogenesis
Depression and Stress
Genetic-stress model
• Genetic susceptibility plus early stress sensitises system so over react
to mild stressors
• Environmental stressors reprogram biological systems through
epigenetic processes, such as DNA methylation, by altering the
expression of genes
• Stress shown to trigger attacks in sufferers rather than increasing
susceptibility in healthy – but, significant stressors appear to be more
frequently involved with initial episodes
Stress Management
• Stress is good (until its bad)
• PSNS – should dampen the SNS, but can be activated – calm down, breathe,
teach the PSNS
• PFC – conscious amygdala control – is it really stressful? Is it really dangerous?
• (Perceived) control of the situation
• Fight or flight – use the stress response – exercise
• Escape the stressor
• Be with your people (and make sure you have people)
