Health Psychology - Stress
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Hans Selye: The Father of Stress - Rat Experiment (5)
**When the rats experienced stress in multiple situations, he found: • Enlarged adrenal glands (the adrenals produce adrenaline as well as cortisol) • Shrunken lymph nodes (The lymph nodes are part of the immune system and house lymphocytes, which are white blood cells -- the body's"security system" as they patrol for infectious micro-organisms) • Bleeding ulcers ▪ he was one of the first people to really look at these issues ▪ he also looked at his control group, which he had injected with *saline*, and this caused --enlarged adrenal glands --shrunken lymph nodes --bleeding ulcers >>WHY did the rats have the same reactions in each group? ▪ he realized that maybe he wasn't a good animal handler, and that injecting these rats and handling them was causing them to be stressed out --He then engaged these animals in all sorts of stress ▪ he would put them in a cold room ▪ put them in a hot room ▪ make them do exercise -->they all had similar responses to the stressful situations -->the main three: 1. shrunken lymph nodes , 2. enlarged adrenal glands, 3. bleeding ulcers
Stress Defined (2)
*Stress* = negative emotional experience accompanied by predictable biochemical, physiological, cognitive, and behavioral changes that are directed either toward altering the stressful event or accommodating to its effect. (Taylor, p. 113) ▪ people in the field debate, where's the line between stress & an emotion
Example Trier Social Stress Test
*Three Conditions:* 1. Standard Manipulation (social evaluative threat: SET) 2. Control Condition 1 - Person present but not paying attention (PRES) 3. Control Condition 2 -Give speech alone in room (non-SET) >>Cortisol can reliably be measured in the saliva ▪ It really seems that you need the combination of *self evaluation*, speech and the audience starting at you to get these results **Check** >>Dickerson et al 2008 Negative social evaluation, but not mere social presence, elicits cortisol responses to a laboratory stressor task - HP Background: Recent research has supported the premise that performance conditions characterized by social-evaluative threat, in which an aspect of the self could be judged by others, are associated with cortisol responses. However, it remains unclear whether this effect is due to negative social evaluation per se or simply the presence of another during a performance situation. Method: In the present study, 89 undergraduates delivered a speech in 1 of 3 conditions: in front of an evaluative audience panel (social-evaluative threat [SET]), in the presence of an inattentive confederate (PRES), or alone in a room (non-SET). Results: Consistent with hypotheses, participants in the SET condition demonstrated a significant cortisol response, while those in the non-SET and PRES conditions did not show increases in this hormone. Further, participants in the SET condition who reported greater posttask levels of self-conscious cognitions and emotions demonstrated the greatest increases in cortisol. Conclusion: These findings suggest that the mere social presence of others is not driving the changes in cortisol observed under social-evaluative threat; instead, explicit negative social evaluation may be responsible for increases in this health-relevant physiological parameter
Laboratory Psychological Stress Induction
*Trier Social Stress Test* ▪ Part I >>Informed will be giving an impromptu speech on why you would be a good job candidate >> ~5 minutes prep time >>Audience is non-receptive & in white lab coats ▪ Part II >>Immediately after speech, do mental arithmetic (ex. count backwards from 2476 by 13) >>Experimenter is very demanding -->Activates HPA axis, Sympathetic Nervous System and triggers Inflammation ▪ There is a lack of control and there is self evaluation >>This is a good stressor and it is used in a lot of studies
Adrenal Gland (4)
- Page 15-21 ▪ The *adrenal cortex* causes the secretion of corticosteroids like cortisol ▪ When you're stressed, you typically need energy to respond to that stress --you need glucose to go to your muscles , need to increase mobilization --acutely this is a good thing, but chronically this can be bad → can lead to diabetes *ask about the catecholamines*
Controllability
- Perceived lack of controllability heightens stress response Standard experiment: Subject performs mental arithmetic while hearing intermittent loud noise. - if have a button to stop noise, experience less stress (even if don't use the button) ▪ In rodents, the lack of control over a stressor (e.g. shock) can lead to learned helplessness, an animal model of depression - also leads to ulcers, elevated glucocorticoids, adrenaline, and faster tumor growth - Experiencing the same shock, but having control does not induce learned helplessness or other physiological ailments
Stress Enhancement of Memory
- Subjects received either placebo or Propranolol (a Beta-Blocker) - Beta-Blockers bind to the Beta-andrenergic receptor and prevent the actions of norepinephrine and epinephrine - Subjects presented with a story on consecutive slides 1. Week later given memory test: - free recall - multiple choice recognition >>Cahill et al McGaugh 1994 Beta-adrenergic activation and memory for emotional events - Nature Substantial evidence from animal studies suggests that enhanced memory associated with emotional arousal results from an activation of beta-adrenergic stress hormone systems during and after an emotional experience. To examine this implication in human subjects, we investigated the effect of the beta-adrenergic receptor antagonist propranolol hydrochloride on long-term memory for an emotionally arousing short story, or a closely matched but more emotionally neutral story. We report here that propranolol significantly impaired memory of the emotionally arousing story but did not affect memory of the emotionally neutral story. The impairing effect of propranolol on memory of the emotional story was not due either to reduced emotional responsiveness or to nonspecific sedative or attentional effects. The results support the hypothesis that enhanced memory associated with emotional experiences involves activation of the beta-adrenergic system.
Epinephrine and Norepinephrine: Public Speaking Stress
- both *epinephrine* and *norepinephrine* increase during stress ----------------------------------------------------------------------------------------- Nater, Ditzen, Strahler, Ehlert 2013 Effects of orthostasis on endorcrine responses to psychosocial stress - Intl Jnl Psychophys Standardized psychological procedures have been designed to induce physiological stress responses. However, the impact of standing (orthostasis) on the physiological reaction after psychological stress remains unclear. The purpose of the current analysis was to examine and quantify the relative contribution of orthostasis to the physiological stress response by comparing a "standing with stress" to a "standing without stress" condition. Weinvestigated the effect of standingwith andwithout stress on responses of the sympathetic-adrenomedullary (SAM) system and the hypothalamic-pituitary-adrenal (HPA) axis using a standardized psychosocial stress protocol (Trier Social Stress Test) and a non-stress condition in a repeated measures design. Subjects (N = 30)were exposed to both conditions in randomized order and had to maintain a standing, upright position for 10 minutes. In the "standing with stress" condition, significant increases in repeatedly assessed plasma norepinephrine (NE) and epinephrine (EP), as well as in saliva cortisol were found, while in the "standing without stress" condition, no significant changes in plasma epinephrine and saliva cortisol were observed. Calculations of the relative contribution of orthostasis to physiological stress responses revealed that 25.61% of the NE increase, 82.94% of the EP increase, and 68.91% of the cortisol increase, could be attributed to psychosocial stress adjusted for the effects of orthostasis and basal endocrine output. Although these results are indicative for a marked endocrine reaction that is caused by psychosocial stress alone, our findings show that the contribution of orthostasis must be taken into account when interpreting endocrine data collected in a psychosocial stress test.
*Do catecholamines predict health outcomes?*
-- Yes >>they recruited military soldiers (everyone required to do it) , had to do a mental arithmetic test under pressure (count backwards from 3476 by 13) >>20 years later they find these people and measure their blood pressure
Glucocorticoids
--glucocorticoids is a larger category, cortisol is more specific - cortisol is a type of glucocorticoid?
So now you have this cortisol flowing through your bloodstream... how do you get it to shut off? (2)
--this is a negative feedback system, like a thermostat, there's a sensor for when it gets too hot the heat will turn off >>there's a sensor in your *hippocampus* that tells you when there's too much cortisol and it helps the cortisol levels go back down
Physiology of the Stress Response
1. Hypothalamic-Pituitary-Adrenal (HPA) axis - Acts in minutes to hours 2. Autonomic Nervous System - Acts in seconds 3. Oxytocin (Tend and Befriend Model of Stress - Variable time course
Biochemical Measures
>>Aren't the health outcomes themselves, but may lead to them
Heart Rate and HRV to the TSST
>>Boesch et al Steptoe 2014 Mood and autonomic responses to repeated exposure to the Trier Social Stress Test for Groups (TSST-G) - PNE Introduction: A group version of the Trier Social Stress Test (TSST-G) was introduced as a standardized, economic and efficient tool to induce a psychobiological stress response simulta-neously in a group of subjects. The aim of the present study was to examine the efficacy of the TSST-G to repeatedly induce an affective and autonomic stress response while comparing two alternative protocols for the second examination. Methods and materials: Healthy young male recruits participated twice in the TSST-G 10 weeks apart. In the first examination, the TSST-G consisted of a combination of mental arithmetic and a fake job interview (TSST-G-1st; n = 294). For the second examination, mental arithmetic was combined with either (a) a defensive speech in response to a false shoplifting accusation (TSST-G- 2nd-defence; n = 105), or (b) a speech on a more neutral topic selected by the investigators (TSST- G-2nd-presentation; n = 100). Affect ratings and salivary alpha-amylase (sAA) were determined immediately before and after the stress test, while heart rate (HR) and heart rate variability (HRV) were measured continuously. Results: TSST-G-1st resulted in a significant increase of negative affect, HR, and sAA, and a significant decrease in positive affect and HRV. TSST-G-2nd, overall, resulted in a significant increase of HR and sAA (the latter only in response to TSST-G-2nd-defence) and a decrease in HRV, while no significant affect alterations were found. When comparing both, TSST-G-2nd-defence and -2nd-presentation, the former resulted in a stronger stress response with regard to HR and HRV. Discussion: The findings reveal that the TSST-G is a useful protocol to repeatedly evoke an affective and autonomic stress response, while repetition leads to affective but not necessarily autonomic habituation. When interested in examining repeated psychosocial stress reactivity, a task that requires an ego-involving effort, such as a defensive speech, seems to be significantly superior to a task using an impersonal speech.
Oxytocin: the "cuddle" hormone? (3)
>>Grewen KM, Girdler SS, Amico J, Light KC. Effects of partner support on resting oxytocin, cortisol, norepinephrine, and blood pressure before and after warm partner contact. Psychosom Med. 2005 Jul-Aug;67(4):531-8. Light KC, Grewen KM, Amico JA. More frequent partner hugs and higher oxytocin levels are linked to lower blood pressure and heart rate in premenopausal women. Biol Psychol. 2005 Apr;69(1):5-21 Kendrick KM, Fabre-Nys C, Blache D, Goode JA, Broad KD. The role of oxytocin release in the mediobasal hypothalamus of the sheep in relation to female sexual receptivity. J Neuroendocrinol. 1993 Feb;5(1):13-21. Melis MR, Argiolas A. Central control of penile erection: a re-visitation of the role of oxytocin and its interaction with dopamine and glutamic acid in male rats. Neurosci Biobehav Rev. 2011 Jan;35(3):939-55.
Oxytocin and the Trier Social Stress Test
>>Heinrichs et al 2003 Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress - Biological Psychiatry Background: The presence of social support has been associated with decreased stress responsiveness. Recent animal studies suggest that the neuropeptide oxytocin is implicated both in prosocial behavior and in the central nervous control of neuroendocrine responses to stress. This study was designed to determine the effects of social support and oxytocin on cortisol, mood, and anxiety responses to psychosocial stress in humans. Methods: In a placebo-controlled, double-blind study, 37 healthy men were exposed to the Trier Social Stress Test. All participants were randomly assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before stress, and either social support from their best friend during the preparation period or no social support. Results: Salivary free cortisol levels were suppressed by social support in response to stress. Comparisons of pre and poststress anxiety levels revealed an anxiolytic effect of oxytocin. More importantly, the combination of oxytocin and social support exhibited the lowest cortisol concentrations as well as increased calmness and decreased anxiety during stress. Conclusions: Oxytocin seems to enhance the buffering effect of social support on stress responsiveness. These results concur with data from animal research suggesting an important role of oxytocin as an underlying biological mechanism for stress-protective effects of positive social interactions. Social Support Provision Two weeks before the experiment, subjects were randomly instructed in writing either to bring their best friend (male or female) along with them to the experimental session ("social support") or to come alone ("no social support"). Support providers were told that their task during the experiment was to be as helpful as possible during the 10-min preparation for the speech task (see Stress Procedure) and offer both instrumental and emotional support. More specifically, they were told that they would know best what kind of supportive behaviors would fit the individual coping preferences of the subject. Support providers were present only during preparation of the stressor.
Stress, Memory, & the Hippocampus
>>Lupien, SJ., et al. McEwen, Meaney "Cortisol levels during human aging predict hippocampal atrophy and memory deficits." Nature Neuroscience, v. 1 issue 1, 1998, p. 69-73 Elevated glucocorticoid levels produce hippocampal dysfunction and correlate with individual deficits in spatial learning in aged rats. Previously we related persistent cortisol increases to memory impairments in elderly humans studied over five years. Here we demonstrate that aged humans with significant prolonged cortisol elevations showed reduced hippocampal volume and deficits in hippocampus-dependent memory tasks compared to normal-cortisol controls. Moreover, the degree of hippocampal atrophy correlated strongly with both the degree of cortisol elevation over time and current basal cortisol levels. Therefore, basal cortisol elevation may cause hippocampal damage and impair hippocampus-dependent learning and memory in humans.
Physical Stressors
>>These stressors are things that all animals (human and not) might list as stressful, e.g., heat, cold, pain, fatigue, injury, hunger, predators.
What would happen if a patient had hippocampal damage?
>>They wouldn't be able to calm down from the stress bc that is a structure in the negative feedback loop that shuts off the cortisol in the blood stream
Health outcomes
>>Things that you get diagnosed with --cancer, cardiovascular disease, etc.
What would happen if a patient had a tumor of the pituitary ? (3)
>>This would affect the release of ACTH which in turn would affect the release of cortisol into the bloodstream --some people with tumors , have hyperfunctional responses --they would most likely release too much cortisol
Oxytocin & Stress
>>de Jong et al Hellhammer, Neumann 2015 Salivary oxytocin concentrations in response to running, sexual self-stimulation, breastfeeding and the TSST- The Regensburg Oxytocin Challenge (ROC) study - PNE Intranasal oxytocin (OXT) application is emerging as a potential treatment for socio-emotional disordersassociated with abnormalities in OXT system (re-) activity. The crucial identification of patients with suchabnormalities could be streamlined by the assessment of basal and stimulus-induced OXT concentrationsin saliva, using a simple, stress-free sampling procedure (i.e. an OXT challenge test). We therefore estab-lished the Regensburg Oxytocin Challenge (ROC) test to further validate salivary OXT concentrations asa practical, reliable and sensitive biomarker.OXT concentrations were quantified by radioimmunoassay in samples collected at home by healthyadult male and female volunteers before and after running ("Run") or sexual self-stimulation ("Sex"). Inlactating women, salivary OXT concentrations were quantified before, during and after breastfeeding.Salivary OXT along with salivary cortisol and heart rate were monitored in healthy adult participantsundergoing the Trier Social Stress Test (TSST).The home-based "Run" and "Sex" challenges as well as the laboratory-based TSST caused quantifiable,rapid, and consistent increases in salivary OXT (approximately 2.5-fold after 10-15 min), which weresimilar for men and women. Breastfeeding did not result in measurably increased salivary OXT levels,probably because the short pulses of OXT release characteristic for lactation were missed.Taken together, ROC tests reliably assess the responsiveness of the OXT system (i.e., the increase insalivary OXT concentrations as compared to basal levels) to challenges such as "Run" and "Sex" at homeor psychosocial stress (TSST) in the laboratory. Further studies with larger sample numbers are essentiallyneeded in order to reveal individual differences in ROC test outcomes depending on, for example, genetic or environmental factors.
Does how you respond in the laboratory to this test predict anything about health outcomes you may have in the future ?
>>relationship is assumed, but difficult to document >>might be related .... is this really conclusive ? --referring to TSST
What would happen if you had damage to the adrenal gland?
>>they probably wouldn't be able to release as much cortisol
What would happen if a patient had amygdala damage ? (3)
>>they wouldn't have as strong of a stress response because that is one of the areas that activates the HPA axis >>they probably wouldn't be able to release as much cortisol as they need to >>stress is good in the short term
Blood Pressure Reactivity & CVD Mortality
Carroll et al Phillips 2012 Increased blood pressure reactions to acute mental stress are associated with 16-year cardiovascular disease mortality - Psychophys Exaggerated cardiovascular reactions to acute psychological stress may be involved in the etiology of cardiovascular pathology. The present analysis examined the association between the magnitude of systolic and diastolic blood pressure reactions to stress and cardiovascular disease mortality. Participants were 431 (229 women) from the West of Scotland Twenty-07 Study, aged 63 years at the time of stress testing, where blood pressure was measured during resting baseline and mental arithmetic stress. Participants' vital status was tracked for the next 16 years, during which time 38 had died of cardiovascular disease. Both systolic and diastolic blood pressure reactions were positively associated with cardiovascular disease mortality. This association could reflect the long-term erosive effects of exaggerated reactivity on the vasculature as well as its short-term capacity to trigger acute cardiovascular events.
What is oxytocin doing during a stress response?
Heinrichs et al 2003 Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress - Biological Psychiatry *Background:* The presence of social support has been associated with decreased stress responsiveness. Recent animal studies suggest that the neuropeptide oxytocin is implicated both in prosocial behavior and in the central nervous control of neuroendocrine responses to stress. This study was designed to determine the effects of social support and oxytocin on cortisol, mood, and anxiety responses to psychosocial stress in humans. Methods: In a placebo-controlled, double-blind study, 37 healthy men were exposed to the Trier Social Stress Test. All participants were randomly assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before stress, and either social support from their best friend during the preparation period or no social support. *Results*: *Salivary free cortisol levels were suppressed by social support in response to stress*. Comparisons of pre and poststress anxiety levels revealed *an anxiolytic effect of oxytocin.* More importantly, the combination of oxytocin and social support exhibited the lowest cortisol concentrations as well as increased calmness and decreased anxiety during stress. *Conclusions: Oxytocin seems to enhance the buffering effect of social support on stress responsiveness.* These results concur with data from animal research suggesting an important role of oxytocin as an underlying biological mechanism for stress-protective effects of positive social interactions. Social Support Provision Two weeks before the experiment, subjects were randomly instructed in writing either to bring their best friend (male or female) along with them to the experimental session ("social support") or to come alone ("no social support"). Support providers were told that their task during the experiment was to be as helpful as possible during the 10-min preparation for the speech task (see Stress Procedure) and offer both instrumental and emotional support. More specifically, they were told that they would know best what kind of supportive behaviors would fit the individual coping preferences of the subject. Support providers were present only during preparation of the stressor.
Autonomic Nervous System (4)
PNS acts as a break - decreases heart rate - decreases blood pressure - decreases
Physiology of the Stress Response: - What are the chemical & biological pathways that are involved in handling stress? (6)
Physiology of the Stress Response 1. Hypothalamic-Pituitary-Adrenal (HPA) axis - Acts in minutes to hours 2. Autonomic Nervous System - Acts in seconds 3. Oxytocin (Tend and Befriend Model of Stress) - Variable time course
Psychological Stressor
These stressors are things that generally only humans would consider stressful, e.g., grades, job security, money, relationships, traffic
Acute Stressors
These stressors demand immediate attention and don't last long. They tend to appear suddenly. - Usually physical stressors
Chronic Stressors
These stressors do not require immediate attention, but last a long time and are a constant source of worry. - Usually psychological
Neural Drivers of Autonomic Activation
Wager, TD., et al. "Brain mediators of cardiovascular responses to social threat- part I- Reciprocal dorsal and ventral sub-regions of the medial prefrontal cortex and heart-rate reactivity." NeuroImage, v. 47 issue 3, 2009, p. 821-35. Chronic perception of threat has been shown to increase the risk of heart disease (Bosma, 1998; Jain et al., 2001; Rozanski et al., 1988; Sheps, 2002), cause hippocampal deterioration (Smith et al., 1995; Stein-Behrens et al., 1994; Watanabe et al., 1992) and impairments in declarative memory (McEwen and Sapolsky, 1995), promote proinflammatory immune responses (Kiecolt-Glaser and Glaser, 2002), and contribute to cognitive and physical aging (Mcewen, 2007), among other adverse effects. Both threat states and their negative connotations for health are captured in early concepts of "stress" (Selye, 1956) and the more recent concept of "allostatic load" (Mcewen, 2007)— the notion that a) the brain actively maintains homeostasis through the activation of brain, autonomic, and endocrine systems, and b) chronic load on these systems by persistent threat has deleterious effects on the brain and body, contributing to a variety of health problems (Kiecolt-Glaser et al., 2002). SET challenges in patients with coronary artery disease have been shown to induce myocardial ischemia (Rozanski et al., 1988) and affect clinical measures of cardiac dysfunction, including left ventricular ejection fraction (LVEF) (Jain et al., 2001, 1998). Ischemic responses to SET have been shown to predict the incidence of fatal and non-fatal cardiac events over a 5-year follow-up (Jiang et al., 1996; Sheps, 2002).
Stress Appraisal
• According to one stress theory, what is stressful is not what event occurs, but how we perceive and interpret that event. • The process of perceiving and interpreting the event is called appraisal. >>When coping abilities less than demands you experience stress
Chronic Stress and Hippocampal Neurons
• Constant exposure to cortisol shrinks hippocampal neurons
Cortisol assessed in the wild (not laboratory): Diurnal Cortisol & Longevity
▪ 104 women with breast cancer ▪ Saliva sampled for cortisol over 3 consecutive days ▪ Followed for 7 years >>- Suggests that the high levels of daily cortisol output (unable to shutoff?) has negative health consequences. Also been related to longevity. ▪ the experimenters give you different tubes to spit into at different times throughout the day bc cortisol levels re measured in saliva -->the normal cycle is that the cortisol should go up in the morning and then taper off throughout the day -->what happens if you're chronically stressed is that it doesn't go down -->it goes up and it stays up ▪ it seems that this diurnal study does predict longevity -->elevation of cortisol due to persistent stress can have negative health effects >>Sephton, Sapolsky, Kraemer, & Spiegel 2000 Diurnal Cortisol Rhythm as a predictor of breast cancer survival - Jnl NCI Background: Abnormal circadian rhythms have been observed in patients with cancer, but the prognostic value of such alterations has not been confirmed. We examined the association between diurnal variation of salivary cortisol in patients with metastatic breast cancer and subsequent survival. We explored relationships between cortisol rhythms, circulating natural killer (NK) cell counts and activity, prognostic indicators, medical treatment, and psychosocial variables. Methods: Salivary cortisol levels of 104 patients with metastatic breast cancer were assessed at study entry at 0800, 1200, 1700, and 2100 hours on each of 3 consecutive days, and the slope of diurnal cortisol variation was calculated using a regression of log-transformed cortisol concentrations on sample collection time. NK cell numbers were measured by flow cytometry, and NK cell activity was measured by the chromium release assay. The survival analysis was conducted by the Cox proportional hazards regression model with two-sided statistical testing. Results: Cortisol slope predicted subsequent survival up to 7 years later. Earlier mortality occurred among patients with relatively "flat" rhythms, indicating a lack of normal diurnal variation (Cox proportional hazards, P = .0036). Patients with chest metastases, as opposed to those with visceral or bone metastases, had more rhythmic cortisol profiles. Flattened profiles were linked with low counts and suppressed activity of NK cells. After adjustment for each of these and other factors, the cortisol slope remained a statistically significant, independent predictor of survival time. NK cell count emerged as a secondary predictor of survival. Conclusions: Patients with metastatic breast cancer whose diurnal cortisol rhythms were flattened or abnormal had earlier mortality. Suppression of NK cell count and NK function may be a mediator or a marker of more rapid disease progression.
Laboratory Stress Reactivity (Norepinephrine) & Hypertension (resting blood pressure) 18 years later
▪ 99 Norwegian military recruits (military service required so sample is nationally representative). ▪ Mental Arithmetic Test ▪ Blood sampled during arithmetic test to measure norepinpehrine levels ▪ 18 year's later resting blood pressure was measured ▪ Graph shows the blood pressure of those who were in the lowest, middle, or upper third of the norepinephrine response 18 years previously. ---------------------------- >>Flaa et al 2008 Sympathoadrenal stress reactivity is a predictor of future blood pressure- an 18-year follow-up study - Hypertension In the present study we hypothesized that arterial catecholamine concentrations during rest and 2 laboratory stress tests were independent predictors of blood pressure at an 18-year follow-up. At entry, blood pressure, heart rate, and arterial plasma epinephrine and norepinephrine concentrations were measured in 99 healthy men (age: 19.3_0.4 years, mean_SD) at rest, during a mental arithmetic test, and during a cold pressor test. After 18.0_0.9 years of follow-up, resting blood pressure was measured. The norepinephrine and epinephrine concentrations during the mental arithmetic explained 12.7% of the variation of future systolic blood pressure after adjusting for initial resting blood pressure, family history, body mass index, and systolic blood pressure during the stress test in a multiple regression analysis (adjusted R2_0.651; P_0.001). To conclude, the present study shows that sympathetic nervous activity during mental arithmetic predicts future blood pressure, indicating a possible causal factor in the development of essential hypertension independent of the initial blood pressure.
Hans Selye: General Adaptation Syndrome (5)
▪ A non-specific response of the body to *any* demand placed upon it. ▪ Three stages to the syndrome: - Alarm - Resistance - Exhaustion ]- there's a general *alarm phase* - there's a triggering of a response ▪ over time you develop a resistance to it ▪ finally, in the exhaustion stage, your body just gets depleted
Allostatic Load
▪ Allostasis = "maintaining stability (or homeostasis) through change" ▪ Allostatic load = as stressors compile and build up over time, the body doesn't go back to the same original homeostasis. There becomes a new baseline that is unhealthy.
Stress Enhancement of Memory - Graph
▪ Cahill et al McGaugh 1994 Beta-adrenergic activation and memory for emotional events - Nature Substantial evidence from animal studies suggests that enhanced memory associated with emotional arousal results from an activation of beta-adrenergic stress hormone systems during and after an emotional experience. To examine this implication in human subjects, we investigated the effect of the beta-adrenergic receptor antagonist propranolol hydrochloride on long-term memory for an emotionally arousing short story, or a closely matched but more emotionally neutral story. We report here that propranolol significantly impaired memory of the emotionally arousing story but did not affect memory of the emotionally neutral story. The impairing effect of propranolol on memory of the emotional story was not due either to reduced emotional responsiveness or to nonspecific sedative or attentional effects. The results support the hypothesis that enhanced memory associated with emotional experiences involves activation of the beta-adrenergic system.
Relevance to the Self
▪ Cortisol response to the Trier Social Stress Test is most associated with the degree to which oneself feels evaluated. --Ratings of feeling ashamed, embarrassed, humiliated, self-conscious foolish, stupid more related to response than negative affect (e.g. anxious, upset, distressed). ▪ Setbacks in important life domains: -If you value achievement, setbacks in career or academic performance are most stressful -If you value relationships, setbacks in romantic relationships or friendships most likely to cause stress
Adrenaline/Epinephrine (3)
▪ Greek: "top-kidney" = epi & nephron = epinephrine ▪ Latin: "top-Kidney" = ad & renal = adrenaline >>These are the exact same molecule and are produced by the adrenal medulla, which is located right on top of the kidney. >>Norepinephrine (a.k.a. noradrenalin) and epinephrine (a.k.a. adrenalin) are not the same molecule. -- Both are in class of molecules called *catecholamines*
Heart Rate Variability (HRV)
▪ HRV is a measure of parasympathetic nervous system function --it is not a chemical measure like all the others talked about --Parasympathetic counters the sympathetic nervous system ▪ ventromedial PFC activates parasympathetic system via vagus nerve innervation of the heart ▪ HRV is relatively easily measured with low cost devices (e.g. Polar Heart Rate Monitor). >>Greater variation (i.e. higher Heart Rate Variability) in your EKG reflects greater parasympathetic influence --Deep slow breathing activates the parasympathetic nervous system --Stress decreases HRV, Relaxation increases HRV
Does cortisol reactivity to the TSST matter for health outcomes? (4)
▪ Health outcomes refer to specific disease states or clinically relevant symptom reports (e.g. what we care about clinically) ▪ Biochemical measures are generally NOT health outcomes (they may be associated with or even cause health outcomes, but they are not health outcomes in and of themselves). ▪ For the most part, there is only weak evidence that cortisol reactivity in the laboratory predicts health outcomes like cardiovascular disease, depression, or cancer. --relationship is often assumed, but difficult to document -----------------------------
Physiological Effects of Stress - Maladaptive Chronic Effects of SNS & HPA Activation:
▪ Hypertension ▪ Insulin resistance ▪ Ulcers ▪ Dwarfism ▪ Impotence/Amenorrhoea ▪ Chronic Pain Disorders ▪ Memory Loss & Hippocampal Shrinkage ▪ Cancer, Cardiovascular Disease, Depression, Infections
Exam Stress
▪ In Germany, students are required to do multiple oral exams to graduate: - *Examination Day:* Cortisol was measured just before the oral exam and afterwards - *Control Day:* Cortisol measured at the same time of day and at same time points *Cortisol was higher on exam day before and after the exam* ▪ the main thing to compare here is the examination day and the control day ▪ they usually measure cortisol levels with saliva >>the pre level is higher bc you're anticipating/thinking about/worrying about the stressor ▪ it's not just the stressors you're exposed to, but the stressors that you're thinking about and worrying about >>Schoofs et al 2008 Neuroendocrine stress responses to an oral academic examination - Stress Public speaking tasks have been widely used as laboratory stressors in human research. Fewer studies have investigated similar real life situations like oral examinations and results have been inconsistent. The present study investigated salivary cortisol (as a marker of hypothalamus-pituitary-adrenal (HPA) activity) and salivary alpha-amylase (sAA as a marker of sympathetic nervous system (SNS) activity) within the context of a university examination. Subjects were 40 undergraduate students who participated in an oral examination. Of these, 20 also participated in a second examination within a few weeks. Cortisol and sAA were measured immediately before and after the examination and on a control day. Additionally, subjects filled out personality questionnaires. A strong anticipatory increase in salivary cortisol and sAA as well as more modest further increases between the pre- and post-measurements were detected during the examination. Sex or oral contraceptive use had no influence on either measure. In addition, no significant differences between the first and second examination were observed. The findings indicate the neuroendocrine stress responses to laboratory stressors and to heralded real life stressors as well as the modulatory variables involved differ from each other
Hypothalamic-Pituitary Adrenal (HPA) Axis (5)
▪ Let's say you perceive something as a stressor: --the *Hypothalamus* gets triggered/activated by the stressor --it released *CRH*, which gets sent to the *anterior pituitary* --> *ACTH* gets sent form the anterior pituitary to the *adrenal gland* in the kidney -->adrenal gland releases *cortisol* into the bloodstream
Chemical Signaling in the Body Neurotransmitter (2) vs. Hormone (3)
▪ Neurotransmitter = chemical messenger that is used to communicate between 2 (or a few) cells of the nervous system >>Examples: -norepinephrine (noradrenaline) ▪ hormone = chemical messenger that acts over longer distances, typically via the bloodstream >>Examples: -*glucocorticoids* -humans: cortisol (ie. hydrocortisone) -rats: corticosterone) -epinephrine (ie. adrenaline) -oxytocin *The difference b/w a neurotransmitter & a hormone is:* ▪ Hormones travel over a long distance ▪ Neurotransmitters are very localized
Take Home Message
▪ On the one hand, the stress response is good.... ▪ Without the stress response, you would never survive an acute stressor --On the other hand, too much of the stress response is bad... ▪ Constantly running the stress response for psychological stressors does not help you deal with those stressors, and causes a slow accumulation of damage that can lead to serious illness
Physiological Effects of Stress - Adaptive Acute Effects of SNS & HPA activation
▪ Raises Heart Rate & Blood Pressure ▪ Mobilizes Energy ▪ Slows Digestion ▪ Slows Growth ▪ Slows Reproduction ▪ Inhibits Pain ▪ Enhances Memory ▪ Triggers Immune System
Physical Exercise & Cortisol - Cycling experiment (6)
▪ Subjects (n = 12) came to laboratory on 3 separate days ▪ Stationary cycle for 30 min in each session at different intensities (40%, 60%, or 80% intensity) ▪ Blood sample taken before or after exercise; cortisol measured ▪ What does stress do ? --It prepares you to respond to a stressor *--physical movement increases cortisol* ------------------------------------------------------------------------------------------ >>Hill et al 2008 Exercise and circulating cortisol levels - intensity threshold effect - Journal of Endocrinological Investigation This study examined the influence of exercise intensity upon the cortisol response of the hypothalamic-pituitary adrenal (HPA) axis. Specifically, we examined exercise at intensities of 40, 60, and 80% maximal oxygen uptake (VO2max) in an attempt to determine the intensity necessary to provoke an increase in circulating cortisol. Twelve active moderately trained men performed 30 min of exercise at intensities of 40, 60, and 80% of their VO2max, as well as a 30-min resting-control session involving no exercise on separate days. Confounding factors such as time of day — circadian rhythms, prior diet — activity patterns, psychological stress, and levels of exercise training were controlled. Cortisol and ACTH were assessed in blood collected immediately before (pre-) and after (post-) each experimental session. Statistical analysis involved repeated measures analysis of variance and Tukey posthoc testing. The percent change in cortisol from pre- to post-sampling at each session was: resting-control, 40, 60, and 80% sessions (mean±SD) =−6.6±3.5%, +5.7±11.0%, +39.9±11.8%, and +83.1±18.5%, respectively. The 60% and 80% intensity magnitude of change was significantly greater than in the other sessions, as well as from one to another. The ACTH responses mirrored those of cortisol, but only the 80% exercise provoked a significant (p<0.05) increase pre- to post-exercise. The calculated changes in plasma volume for the resting-control, 40%, 60%, and 80% sessions were: +2.2±3.0%, −9.9±5.0%, −15.6±3.5%, and −17.2±3.3%, respectively. Collectively, the cortisol findings support the view that moderate to high intensity exercise provokes increases in circulating cortisol levels. These increases seem due to a combination of hemoconcentration and HPA axis stimulus (ACTH). In contrast, low intensity exercise (40%) does not result in significant increases in cortisol levels, but, once corrections for plasma volume reduction occurred and circadian factors were examined, low intensity exercise actually resulted in a reduction in circulating cortisol levels.
Autonomic (e.g. "Automatic") Nervous System (2)
▪ Sympathetic = fight or flight ▪ Parasympathetic = rest & digest
Neural Triggers of the HPA Axis (2)
▪ The Anterior Cingulate & Amygdala is another structure that triggers that whole cascade that results in cortisol release into the bloodstream ▪ Hippocampus helps us shut off the release of cortisol
What does the general adaptation syndrome suggest? (3)
▪ This says that there is a general/non specific response to *any* stressor -->Selye argued that there was a *general response to stress* -->However, he did his experiments on mostly *physical stressors*
Exogenous Glucocorticoids (2)
▪ drugs -Hydrocortisone (is cortisol) -Prednisone (very similar to cortisol) >>you produce your own class of stress hormones >>there's another class where you can take certain drugs that trigger the same receptors and cause the same responses
Corticosteroids
▪ produced by adrenal cortex in your body) --Mineralocorticoids (Aldosterone) --Glucocorticoids:
Stress: Outline
▪Stress Defined ▪History: Hans Selye & the General Adaptation Syndrome ▪Physiology of the Stress Response - Hypothalamic-Pituitary-Adrenal (HPA) Axis - Autonomic Nervous System (Fight or Flight/Rest & Digest) - Oxytocin (Tend and Befriend) ▪Stress and Disease (Acute and Chronic Stress) ▪Psychology of Stress - Appraisal - Controllability, Predictability, and Relevance to Self ▪Measurement of Psychological Stress >>for stress and disease, the key thing is to separate acute and chronic stress
