Week 10

Question 1

Stress

Answer 1

• 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

Question 2

The Stress Response

Answer 2

• 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

Question 3

Good Stress / Bad Stress

Answer 3

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

Question 4

Good Stress / Bad Stress- If stress is so good, then why the bad rap?

Answer 4

• 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

Question 5

Good Stress / Bad Stress- Bad stress – severe or chronic and coupled with lack of predictability or
perceived lack of control

Answer 5

• 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?

Question 6

Good Stress / Bad Stress- Long-term

Answer 6

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

Question 7

Stress- Introduction

Answer 7

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

Question 8

Bad Stress

Answer 8

-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

Question 9

Gastric Ulcers

Answer 9

• 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

Question 10

Main Characters

Answer 10

Hypothalamus
Pituitary
Amygdala
Adrenal Cortex- Releases cortisol - the major
glucocorticoid in humans
Adrenal Medulla- Releases epinephrine (also
known as adrenaline

Question 11

The Stress Response

Answer 11

• 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

Question 12

Two pathways

Answer 12

Sympathetic-adrenal-medullary
(SAM) system
Fast response
Short acting
Epinephrine
Jump start
Hypothalamus-pituitary-adrenal
(HPA) axis
Slow response
Lasting
Cortisol
Keep things going

Question 13

The Stress Response

Answer 13

SAM

HPA

Question 14

SAM System

Answer 14

Efferent Nerves

• Parasympathetic Nervous system
• Sympathetic Nervous System

Question 15

ANS Efferents

Answer 15

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

Question 16

SAM System

Answer 16

• 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)

Question 17

HPA Axis

Answer 17

• 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

Question 18

HPA Axis - Cortisol

Answer 18

• 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

Question 19

Three Determinants of HPA Activity

Answer 19

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

Question 20

Three Determinants of HPA Activity

Genetic factors

Answer 20

• DNA variations in genes encoding neurotransmitters involved in HPA
axis regulation.
• Heritable influences account for 62% of the variance in basal
glucocorticoid levels

Question 21

Three Determinants of HPA Activity

Early-life environment

Answer 21

• 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

Question 22

Three Determinants of HPA Activity

Current Life Stress

Answer 22

• 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

Question 23

• 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

Answer 23

• 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

Question 24

Chronic Stress

Answer 24

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

Question 25

Psychosocial Short Stature

Answer 25

• 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.

Question 26

Brain - Cortisol Damage

Answer 26

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

Question 27

Brain - Cortisol Damage | Hippocampus

Answer 27

• 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

Question 28

Brain - Cortisol Damage | Amygdala

Answer 28

• 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

Question 29

Brain - Cortisol Damage | Prefrontal Cortex

Answer 29

• 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

Question 30

Turning the Stress Response OFF

Answer 30

• 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

Question 31

Stress and Social Bonds

Answer 31

• 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

Question 32

Social Isolation

Answer 32

• 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

Question 33

Amygdala

Answer 33

``` 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 ```

Question 34

Anxiety

Answer 34

• 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

Question 35

Anxiety Disorders

Answer 35

• 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

Question 36

Anxiety Disorders - Examples

Answer 36

* Generalised Anxiety Disorder * Phobic * Panic * Obsessive Compulsive Disorders * Post Traumatic Stress Disorder

Question 37

• Generalised Anxiety Disorder

Answer 37

* 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

Question 38

• Phobic

Answer 38

* intense excessive fear of specific stimuli | * similar to GAD but triggered by specific object or situation

Question 39

• Panic

Answer 39

• rapid onset extreme fear and severe stress symptoms • panic attack – intense fear plus somatic symptoms – palpitations, shortness of breath, sweating, dizzy

Question 40

• Obsessive Compulsive Disorders

Answer 40

• 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

Question 41

• Post Traumatic Stress Disorder

Answer 41

• 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

Question 42

Anxiety and Stress

Answer 42

• 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

Question 43

Depression

Answer 43

• 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.

Question 44

Depression and Stress

Answer 44

• 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

Question 45

Depression and Stress | Genetic-stress model

Answer 45

• 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

Question 46

Stress Management

Answer 46

• 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)