Stress.pdf

STRESS, PART 1 Dr Nils Muhlert Course Overview Week Lecturer Title 1 Dr Pobric Intro 2 Dr Pobric Structure of the CNS 3 Dr Pobric Structure & Function of cells 4 Dr Muhlert Stress (1) 5 Dr Muhlert Stress (2) 6 Dr Ruigrok Emotion (1) 7 Dr Ruigrok Emotion (2) 8 Dr Annie Pye...

STRESS, PART 1 Dr Nils Muhlert Course Overview Week Lecturer Title 1 Dr Pobric Intro 2 Dr Pobric Structure of the CNS 3 Dr Pobric Structure & Function of cells 4 Dr Muhlert Stress (1) 5 Dr Muhlert Stress (2) 6 Dr Ruigrok Emotion (1) 7 Dr Ruigrok Emotion (2) 8 Dr Annie Pye Sleep 9 Dr Ruigrok Autism 10 Dr Pye Substance abuse Teaching week 12 Online Revision Lecture overview ¨  What is stress? ¨  Why should we study the effects of stress? ¨  The HPA axis ¨  Effects of stress on immune systems What is stress ¨  Commonly viewed as: What stresses you? ¨  Exams, grades ¨  Deadlines ¨  Traffic ¨  Family relationships ¨  Facebook posts ¨  Careers ¨  What is not a significant stressor in your lives? ¤  Being eaten What stresses a zebra? ¨  Serious physical injury ¨  Predators (e.g. lions) ¨  Starvation ¨  Sapolsky 1994 “Why zebras don’t get ulcers” What is stress? ¨  ‘Stress’ is very imprecise ¨  Stressor = a situation that ‘causes stress’ to a system (e.g. aversive event) ¨  Stress reactivity = the way we respond to a stressor. 2022 Liz Truss - ended up avoiding PM questions when under substantial stress 2011 Donald Trump - after a scathing review, Trump sent the journalist a picture of herself with ‘face of a dog!,’ scrawled on it. Why study stress? ¨  How does our body change when we feel stress? ¤  Changes in breathing n  increased risk of asthma attack/ emphysema n  Hyperventilation during stress – increased risk of panic attack in those with panic disorder. ¤  Exacerbate existing mental health conditions ¤  Changes in eating behaviour ¤  Diarrhea/ constipation Why study stress ¨  Chronic stress ¤  Muscles of body – constant state of guardedness ¤  Tension-type headache/ migraines ¤  Long-term heart/ blood problems n  Hypertension n  Heart attack Everson-Rose et al. 2014 ¨   Multi-ethnic study of atherosclerosis ¨   Population-based study of 6749 adults ¤  Aged 45-84 years, free of cardiovascular disease ¨   Followed-up over average 8.5 years ¨   Stress measured as burden in 5 domains: ¤  Health problems ¤  Health problems of others ¤  Job or ability to work problems ¤  Relationships ¤  Finances Everson-Rose et al. 2014 ¨  Chronic stress (i.e. burden) at baseline predicted increased likelihood of stroke over the follow-up period (10% increase) ¤  Held after accounting for race, age, sex, education. What is the stress response? ¨  Walter Cannon (1871-1945) ¤  Chair of Dept. Physiology, Harvard n  In 1915, coined the term ‘fight or flight response ’ Arousal Increased blood supply & sugar Violent burst of energy Fight or flight responses ¨  Short term gain ¨  …but when continuous we can experience negative consequences Causes of stress Acute Chronic Physical Injury Hunger, cancer Psychological deadline Chronic work pressure Social humiliation Chronic isolation Causes of mortality ¨  1900 – infectious disease & childbirth ¤  Pneumonia ¤  Tuberculosis ¤  Influenza ¤  Childbirth (young women) ¨  2007? ¤  Cumulative damage n  Heart disease n  Cancer n  Cerebrovascular disorders Physiology of the stress response ¨  Hypothalamus ¨  Pituitary gland ¨  Adrenal gland ¨  =‘HPA axis’ CRH ACTH Cortisol Perceived Threat The hypothalamus ¨  Centrally located in the brain ¨  Generally involved in homeostasis ¤  Thermoregulation n  Sweating, panting, shivering ¤  Circadian rhythms ¤  Satiety & feeding The hypothalamus ¨  Bard (1928) examined the effects of lesions on cats ¤  Removed most of cerebral cortex either with or without the hypothalamus ¨  Intact hypothalamus, led to undirected rage ¨  We can see this just by stimulating this region Stimulating the hypothalamus ¤  Clearly involved in ‘fight or flight response ¤  The hypothalamus also releases stress hormones: ¤  Corticotropin releasing hormone (CRH) ¨   https://www.youtube.com/watch?v=Kj2MqEMpj4U The pituitary gland ¨  Located beneath the hypothalamus ¤  The ‘master gland’ ¤  Weighs 0.5g ¨  Releases: ¤  Somatotrophins (e.g. HGH, Growth) ¤  Thyrotrophins (TSH, metabolism) ¤  Gonadotrophins (LH, FSH, fertility) ¤  Corticotropins (adrenocorticotropic hormone - ACTH, stress response) Adrenal glands ¨  Sit on top of your kidneys ¨  Release a set of hormones involved in stress: ¤  Cortisol n  Released in response to ACTH n  Metabolism n  Immune system suppression ¤  Epinephrine Too much cortisol ¨  Cushing’s syndrome ¤  Often from too much treatment with cortisol ¤  Rapid weight gain – trunk & face ¤  Acne ¤  Reduced libido or infertility ¤  Thin skin ¤  Chronic tiredness Too little cortisol ¨  Addison’s disease ¨  Often caused by adrenal gland failing to produce enough cortisol ¤  Weight loss ¤  Weakness/ lethargy ¤  In some cases à adrenal crisis (low blood pressure, Confusion/ psychosis, loss of consciousness) n  Adrenal crisis is typically brought about by stressors Epinephrine/ Adrenaline ¨  Sympathomedullary system ¤  Hypothalamus à autonomic nervous system à adrenaline Sleeping, eating, relaxation Epinephrine/ adrenaline ¨  From adrenal medulla ¤  Releases stored forms of energy in muscles (protein à glucose) ¤  Stimulates heart & other organs ¨  Responsible for ‘fight or flight response’ ¨  Involved in the 4 f ’s: fight, fright, flight, and sex Selye’s General Adaptation Syndrome ¨  Hans Selye (1956) ¤  Animal experiments ¤  Chronic exposure to stressors led to sequence of 3 stages: n  Alarm n  Resistance n  Exhaustion Alarm ¨  Arousal of the Autonomic Nervous System ¨  Primarily during first encounter with stressor ¤  Resistance to stressor drops below normal with potential for shock ¨  At this point, hormones like epinephrine & cortisol are released into the bloodstream ¨  Sympathetic nervous system activated Resistance ¨  Continued exposure to stressor ¤  Resistance – Parasympathetic system returns physiological functions to normal levels ¤  Blood glucose, epinephrine & cortisol all remain high ¤  Heart rate, blood pressure, breathing all increased ¨  Over time, resistance to stressor increases, levels out at normal levels. ¨  Resistance = adaptation to environmental stressors Exhaustion ¨  If the stressor continues beyond the body’s capacity, the stressor depletes the available resources. ¨  Loss of ability to adapt to situations ¨  Susceptible to illness, and even death Dread ¨  Dentists ¨  Exams ¨  Footshocks ¨  Sometimes waiting is worse than the experience itself – dread ¤  fMRI study by Berns et al. 2006, Science Berns – Neurobiology of Dread ¨  29 Participants underwent MRI ¤  Waiting for a cutaneous electrical shock to the foot ¤  Set out maximum tolerable voltage ¤  Trials started with info about voltage level & wait ¤  To start, 100% of trials had voltage ¤  Choice phase = e.g. 90% voltage in 3 secs or 60% voltage in 27 secs ¤  Analysis of choices – some chose more voltage now than to wait (extreme dreaders). fMRI activations ¨   More voltage = greater activation in pain network ¨  Extreme dreaders show earlier & more sustained activity in pain network between cue & shock Stress response & consequences Adaptive Stress disorder Mobilisation of energy Fatigue, diabetes Increased cardiovascular tone Stress-induced hypertension Suppression of digestion Peptic ulcers Suppression of growth Psychogenic dwarfism Suppression of reproduction Amenorrhea, impotency Suppression of immune system Increased disease risk Sharpening of cognition Neuron death Effects of stress on growth ¨  Stress (or psychosocial) dwarfism Chronic stress & brain structure ¨  Neurons of the hippocampus in rats Maras & Baram, 2012, Trends in Neuroscience The immune system ¨  Protects the body from infection ¤  Invading bacteria ¤  Viruses ¤  Foreign bodies ¨  Derives from white blood cells ¤  Bone marrow – B lymphocytes ¤  Thymus gland – T lymphocytes ¨  Stress – via cortisol – can directly suppress activity of immune system Chronic stress & the immune system ¨  Keller 1983, Science ¤  Inescapable shock = reduced B & T cells ¨  Removal of adrenal gland ¤  No immune change to shock ¤  But normal immune response to antigen (bacterial protein) 0 1 2 3 4 5 6 7 8 9 No shock Shock Magnitude of immune response Condition Adrenalectomised Control 0 10 20 30 40 50 60 70 80 90 100 No antigen Antigen Magnitude of immune response Condition Adrenalectomised Control Chronic stress & the immune system ¨  Kiecolt-Glaser et al. 1993 ¤  Bereavement, caring for others with Alzheimer’s disease, marital disease tend to reduce immune system functioning Chronic stress & healing ¨  Kiecolt-Glaser et al., 1995 ¤  13 caregivers for relatives with dementia ¤  13 controls ¤  Matched for age, household income ¤  Gave them ‘punch biopsy’ Chronic stress & healing ¨  Wounds took longer to heal in caregivers Exams & the immune system ¨  Glaser et al., 1987 ¤  Blood samples from 40 1 st year medical students n  During exam periods, and 1 month before exams ¤  During exams, immune system responses weakened n  Heightened risk of contracting acute infections n  Increased risk of Epstein Barr virus Psychological modifiers of stress response ¨  Outlets for frustration ¨  Sense of predictability ¨  A perception of life improving ¨  Social support Outlets for frustration ¨  Jay Weiss (1971) ¤  Rats receive mild shocks n  Prolonged stress response = increased heart rate, cortisol – increased number of peptic ulcers ¤  Other rats allowed to gnaw on wooden bar, eat or drink or run on wheel = fewer ulcers Weiss (1971) J Comp Physiol Psychol 1: 1-13 Sense of predictability ¨  Rats hear warning bell before shock = fewer ulcers ¨  If food is received at random vs intermittent intervals = glucocorticoid levels increase ¨  If the rat is given a lever & can avoid shock – stress reponse is reduced (even if lever is disconnected) ¨  People given annoying noise – those given button to press to stop noise – reduced blood pressure, even when button isn’t pressed. Sense of control ¨  Rodin & Langer, 1977 ¤  Studied people in nursing homes n  Group A – make decisions for yourself n  E.g. where to receive guests n  When to watch films n  Which houseplant to look after n  Group B – no instructions to make decisions n  Received plant, staff looked after it. ¤  After 1.5 years, group A more cheerful, active, alert, half as many had died! Sense of life improving ¨  Rats given shocks Group A Group B Day 1 10 shocks/ hour 50 shocks/ hour Day 2 25 shocks/ hour 25 shocks/ hour Day 2 outcome High blood pressure Lower blood pressure Social support ¨   Primates ¤  After a stress response n  when around strangers have greater cortisol levels n  When around friends – lower cortisol levels ¨   People ¤  Stressor (public speaking, argument with strangers) n  When alone – high cortisol levels n  When a supportive friend is present – lower cortisol response (Heinrichs et al., 2003) ¨   Observational studies ¤  People with spouse live longer n  When spouse dies, risk of dying increases ¤  Parental bereavement & mortality n  Higher risk of disease/ mortality, particularly mothers, following child’s death (Cohen-Mansfield et al. 2013) Conclusions ¨  Stress comes in the form of physical or psychosocial stressors ¨  The way we respond to stress is our stress reactivity ¨  The body responds to stress through the HPA axis & sympathetic nervous system ¨  Prolonged stress can negatively affect the immune system STRESS, PART 2 Dr Nils Muhlert Lecture overview ¨  Recap of last week’s lecture ¨  Determining stress reactivity ¨  Effects of stress on memory ¨  Coping with stress ¨  Enjoying stress Physiology of the stress response ¨   We learned about Stressors and Stress- reactivity ¨   Stressors can generate a stress-response, releasing adrenal hormones ¨   Hypothalamus ¨   Pituitary gland ¨   Adrenal gland ¨   =‘HPA axis’ CRH ACTH Cortisol Perceived Threat Sympathomedullary response ¤  And release of adrenaline via sympathetic branch of autonomic nervous system Brain neurotransmitters ¨  Also, the release of Adrenaline acts with noradrenaline ¤  Noradrenaline prepares brain & body for action ¤  Lowest release in sleep, highest during stress ¨  In the brain, noradrenaline primarily released from Locus Coeruleus ¤  As a neurotransmitter, NA can enhance formation and retrieval of memory Early changes in stress-reactivity ¨  Early events can affect how we respond to stress Prenatal stress ¨  Dutch Hunger Winter (End of WWII, 1944-45) ¤  Nazis pushed back ¤  Dutch tried to aid Allies for liberation ¤  As punishment, Nazis cut off all food transport (5 months) ¨  Typical food consumption ¤  400-800 calories/ day ¨  After liberation, sudden increase in food Prenatal stress ¨  Effects – cohort of people with increased risk of heart disease, type 2 diabetes aged 50 years ¨  Pregnancy during famine ¤  Fetus ‘learns’ that food is scarce ¤  Metabolism of fetus has permanent shift n  “Metabolic imprinting” ¤  Afterwards, fetus becomes good at storing consumed food, retaining salt from diet. ¤  Developed ‘thrifty’ metabolism Finnish study on birthweight ¨  Kajantie et al., 2002 ¤  Large cohort study of 421 men, born 1924-33 ¤  Birthweight & size was recorded, evaluated cortisol levels aged ~70 years ¤  The lower the birthweight (adjusted for height), the higher the basal cortisol levels in adults. n  Particularly for premature birth. ¨  Early exposure to stress programs your stress- reactiveness. Effects of prenatal stress ¨  When pregnant rats experience significant stress… ¨  How are offspring affected? ¤  Test anxiety in new environment: n  Food placed in middle of bright cage n  Placed in with new rats ¤  Prenatally stressed rats show: n  Freezing in bright lights, difficulties learning & take longer to socially interact n  All evidence of greater anxiety n  Amygdala shows greater glucocorticoid receptors Lee et al., 2007 Brain Res Effects of POSTnatal stress ¨  Plotsky & Meaney, 1993 ¤  maternal separation of rats ¤  As adults, rats showed increased glucocorticoid response to stress. n  Greater fearfulness ¨  As discussed last week, stress in infancy can reduce growth hormones – lower adult height Romanian orphanages ¨  Gunnar et al., 2001 ¤  Compared daytime cortisol measures in children from: n  Romanian orphanages for >8 months n  Romanian orphanages for <= 4 months n  Canadian children ¤  Studied at 7-8 years old 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 Wakeup Noon Evening Cortisol levels Romanian orphanage Early adopted Canadian Summary so far ¨  Perceived threats can trigger a stress response ¤  HPA axis ¤  Release of adrenaline & noradrenaline from adrenal medulla and brain ¨  Both prenatal and postnatal events can affect the production & baseline rates of stress-hormones (e.g. cortisol) Studying the effects of stress in adults ¨  Which brain areas are involved in perceiving threats? ¨  Which brain areas help to regulate these emotions? ¨  How can we study stress in adults ¤  Physical stress ¤  Psychological stress Experimental tests of stress ¨  What can be done to test the effects of stress? ¤  Damnatio ad bestias ? ¤  Make people endure pain? ¤  Infect people with diseases? Feed them to the beasts! ¨  Not quite ¨  Nili et al. 2010 ¨  People with snake phobias recruited – put in MRI scanner with snakes Nili et al. 2010 ¨  At each point, participants chose whether to bring the live snake closer – or further away – from them ¤  Control condition – toy bear Nili et al. 2010 - findings ¨  When choosing to let snake closer: ¨  Also, when fearful people chose to advance the snake, amygdala activity was reduced Detecting threats ¨  How does the brain recognise threats in the environment? ¨  Patrick Vuilleumier et al. 2001 ¨  fMRI study, participants decided: ¤  Are the vertical or horizontal boxes the same ¤  Either faces or houses Vuilleumier et al. 2001 ¨  Some faces were neutral, others were fearful ¨  Participants slower at judging houses if faces happened to be fearful 900 920 940 960 980 1000 1020 Fearful faces Neutral faces Response time (ms) Vuilleumier et al. fMRI evidence ¨  Regions responding to faces: ¨  Regions responding to houses: ¨  The amygdala was more active when incidentally viewing fearful faces: Fusiform gyrus Parahippocampal gyrus Regulating perceived threats ¨  Which brain areas are involved in regulating the stress response? ¤  Examine clinical cases of poor emotion regulation n  Post-traumatic stress disorder n  Social Anxiety Disorder n  Specific phobia ¤  Etkin & Wager, 2007 – meta-analysis of fMRI studies across these conditions Etkin & Wager, 2007 ¨  Patients showed either ¤  Increased activation in amygdala (phobia/ social anxiety) ¤  Decreased activity in medial prefrontal cortex (PTSD) Focus on the medial prefrontal cortex ¨  Midline of brain – in front of the motor cortex Studies of Emotion Regulation ¨  Etkin et al. 2011 Trends in Cog Sciences ¨  Examined brain responses to anxiety & fear ¨  Which brain regions are active when we consciously control our emotional response? Bottom-up Amygdal a Emotion regulation = balance ¨  ‘Bottom-up’ signalling from the Amygdala indicates threats in the environment ¨  ‘top-down’ regulation from the medial pre-frontal cortex prevents this from triggering constant stress-responses ¨  Further evidence? Bottom-up Top-down Amygdala Dorso- medial prefrontal Bottom-up Top-down Dorso -medial prefrontal Anterior c ingulate c ortex Am ygdala How does stress affect memory? ¨  Examined by studying stress during: ¤  Encoding ¤  Consolidation ¤  Retrieval Memory for stressful events ¨  Information encoded during stressful events is generally well remembered (e.g. Nice attacks) ¨  Particularly if information is relevant to stressor ¤  (i.e. learn to avoid house, after attack by dog). ¨  Normally adaptive BUT dysregulation could result in psychological trauma ¤  E.g. post-traumatic stress disorder, characterised by flashbacks . n  Feeling that traumatic event is recurring Stress at encoding ¨  Henckens et al., 2010 ¤  fMRI study – shown film clips (very violent or neutral) and pictures n  Later asked to remember pictures Effects of stress on encoding ¨  Stressful films led to better memory for pictures ¨  During Stress LOWER activity in hippocampus at encoding = better memory for those pictures ¨  Poor separation of event info from relevant stimuli may overwhelm hippocampal activity 0 10 20 30 40 50 60 70 80 90 100 Stress film Neutral film Memry retrieval at 24 hours Stress during consolidation ¨  The cold pressor test ¤  Hand plunged into ice cold water ¨  Cahill et al. 2003 ¤  How does stress AFTER learning affect memory ¨  Stress enhances consolidation of emotional pictures ¤  But not for neutral pictures Stress at retrieval ¨  The Trier Test ¤  Unexpected 5 min talk ¤  followed by 5 min arithmetic ¤  Combines feeling of peer evaluation with forced failure ¨  Memory retrieval during stress is impaired ¤  E.g. Guez et al., 2016 https://youtu.be/sud85cP4HiQ?t=11s Cortisol receptors in the hippocampus ¨  The hippocampus is involved in memory ¨  High density of glucocorticoid receptors ¨  As discussed last week, stress in rats is shown to affect hippocampal neurons ¨  Sensitivity of hippocampus to stress hormones may explain effects of stress ¨  Generally, adaptive! Coping with stress ¨  Some people are better able to cope with stressful events than others ¤  Lazarus, 1991 - Depends on our cognitive appraisal of the situation: ¤  Two main factors n  Primary appraisal – How relevant is this situation to my needs? n  Secondary appraisal – What resources & options do I have for coping with this event? n  E.g. should I blame someone else? Appraising stressful situations ¨  Types of conflict - Lewin, 1935 ¨  Approach-approach conflict (least stressful) ¤  Should I go for dinner with friends, or to cinema with girlfriend ¨  Avoidance-avoidance conflict ¤  Do your homework, or go to bed without dinner ¨  Approach-avoidance conflict ¤  Should I propose (chance of acceptance or rejection) Personality factors & stress-reactivity ¨   How does procrastination help? ¤  Tice & Baumeister, 1997 ¤  Compared stress levels and exam results in students n  Divided into procrastinators/ non-procrastinators ¤  Early in year (and for the longest part of the year), n  procrastinators = lower stress, lower marks (but changed over time) ¨   Submissiveness protective against stressors (i.e. lower conflict) Whiteman, 1997 ¤  Longitudinal study of 1500 people – high submissiveness, lower heart disease Forms of eustress ¨  Why do some people seek to be stressed? ¨  Sensation seeking (form of impulsivity) varies in the general population Factors involved in thrill seeking ¨  Risky event ¤  Innervation of sympathetic branch of autonomic nervous system n  Release of adrenaline/epinephrine within 15 seconds ¤  Release of dopamine n  Greatest release, just prior to event Ways to increase dopamine release ¨  Tickling (Blakemore et al., 2000) ¤  Can you tickle yourself – does it make you laugh? ¤  Examined this seriously, by using a tickle-o-meter. Tickling yourself Tickling yourself via ‘robot’ Tickling yourself ¨   Tickling yourself – low tickle ratings ¨   Experimenter tickling yourself – high tickle rating ¨   Inserting a delay into your own tickles – if more than 3/10ths of a second, high tickle rating ¨   You can tickle yourself, but only when it’s unpredictable. ¤  You just need a lever & ‘robot’ ¨   Surprising, since stress is greatest in situations that are unpredictable/ lack of control Dopamine release ¨   Monkey studies (Schultz 2016) ¨   Bell sounds ¤  Monkey has to press lever 10 times n  10 seconds later, desirable food reward ¨   Dopamine neurons show biggest response not when the monkey receives reward ¤  Instead, at the sound of bell n  “I know that bell, IF I press the lever THEN I’ll get food. This’ll be great!” n  Dopamine release from ANTICIPATION of reward. Increasing dopamine release ¨  1. Signal, task, reward = modest dopamine release ¨  2. Signal, task, high probability of reward ¤  If outcome is likely to be good = huge dopamine release ¤  Intermittent reinforcement leads to greatest effects. ¨  As with tickling, lack of control & predictability & sense of anticipatory pleasure fuel dopamine release Stress & dopamine ¨  Cortisol can trigger dopamine release ¤  Specifically, the pleasure pathways of dopamine ¨  Piazza et al. 1996 ¤  Rats will press levers to receive glucocorticoids ¤  But only moderate rise ¤  Too much, dopamine depletion, anhedonia Effects of dopamine release ¨  Dopamine released in short burst, then returns to baseline (or slightly below) ¨  Greater thrill/ anticipation needed next time ¤  Rollercoasters ¤  Dating ¤  Drug abuse ¨  Overall, many of us seek brief transient stress Conclusions ¨  Areas of the brain like the amygdala respond to threats in the environment ¨  Our general stress reactivity can be influenced by prenatal and postnatal events ¨  Once a stress response is triggered, the body responds via HPA axis & sympathomedullary system ¨  How we cope & appraise events affects the extent of the stress response ¨  Sometimes, stress responses feel good!