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HPA axis & Stress

HPA axis & Stress. What is STRESS?. TIME PRESSURE. Elderly Individual or Young child …Not stressed. ...No. What is STRESS?. Hans Selye : Non Specific Response --> « Looking sick » 1968 : Mason --> A specific response to particular components of a situation.

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HPA axis & Stress

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  1. HPA axis & Stress

  2. What is STRESS? TIME PRESSURE Elderly Individual or Young child …Not stressed ...No...

  3. What is STRESS? Hans Selye : Non Specific Response --> « Looking sick » 1968 : Mason --> A specific response to particular components of a situation e.g. Sky Divers vs their trainors

  4. Stressful Situation : -Novelty -Unpredictability -Sense of Control -Threat to the Ego

  5. Stressful Situation : -Novelty -Unpredictability -Sense of Control -Threat to the Ego Individual Differences Stress is thus a personal experience...

  6. Stressful Situation : Response of the organism -Perspiration -Increase Heart Rate … Counsciousness of the stress Adrenaline “Warrior” DC. Mayor Barry who just learned that he was accused with possession of drugs

  7. Stressful Situation : Response of the Organisms -Direct Access to the brain -Impacts on all Systems (Immune, metabolic, etc). … No consciousness of the stress Cortisol “Spy”

  8. Stress : Explaining Individual Difference -Stress and Types of Personality (1970-80) Based on the link between stress and heart disease -Personality Type A vs Type B -escessive drive -time urgency … waiting line -impatience -aggressivity -hostility -sense of competition …. Everything that is not A

  9. Stress : Explaining Individual Difference TYPE A -escessive drive -time urgency … waiting line -impatience -aggressivity -hostility -sense of compétition cynical RUMINATIONS Repressed Anger 1990: the only factor that was proven to have a REAL impact

  10. Stress : Explaining Individual Difference Anticipation of stress…. As bad as stress itself…. …anxiety …¨the fear of being scared¨

  11. Stress : Importance of ruminations IMPORTANCE OF RUMINATION OR ANXIETY Ruminate, Ruminate, Ruminate Anxiety, Anxiety, Anxiety Release of cortisol & adrenaline

  12. STRESS: Important to differentiate Good Stress: Vigilance Good Stress: Vigilance Bad Stress: Fatigue -Basal Stress -Stress Reactivity

  13. STRESS: Important to differentiate -Acute Stress -Chronic Stress Ex. Job Interview

  14. Impact of Chronic Stress Habituation Sensitization

  15. ACUTE STRESS Fight Flight Adaptation/Coping Avoidance Problem Solving Method Good for Acute Stress …Bad for chronic stress

  16. CHRONIC STRESS -Frequent acute stress -Unique but uncontrolled stress -Inefficient Coping If paired with risk factors, (environment, heredity etc) Development of diseases -dermatology (eczema) -cognitive (memory problems) -pulmonary (asthma) -psychiatric (anxiety., depression) -immunology (infections) "Bulldozer" Effect

  17. STRESS… « Bulldozer Effect » The impact of stress on physical & mental health will be NON SPECIFIC e.g. Schizophrenia and stress e.g. Depression and stress e.g. Immune system and stress Stress is seen like a BULLDOZER putting us at the Edge of the mountain …risk factor for any other attack to the organism

  18. Fight Adaptation/Coping Problem Solving (emotion vs cognition) Individual Differences -Novelty -Unpredictability -Sense of control -Threat to ego -Yoga -Sport -Walk the dog … A well-defined problem Is a problem almost solved….

  19. Methods for Induction of Stress : Animals Physical VS psychological Stress Large Interindividual Differences Everyone will Respond

  20. Methods for Induction of Stress : Animals Rat ; animal mostly used. PHYSICAL STRESSORS Intensity Noise Restraint Swim Shocks

  21. Methods for Induction of Stress : Animals Rat ; animal mostly used. PSYCHOLOGICAL STRESSORS Nature Handling Novelty (open-field) Social Conflict

  22. Different Models of stress in animals Learned Helplessness Fear Conditioning Group 1 : Can control transmission of shocks e.g. press a lever Shock received in a particular environment One-trial learning If same environment without shock-cage, initiation of fear in rat (Model of PTSD) Group 2 : Cannot control transmission of shocks LEARNED HELPLESSNESS (Model of depression) control

  23. Methods for Induction of Stress : Animals Acute Chronic Many days Avoid Habituation : different stressors every day -Delay between stress days From 1-2 min to 6-8 hrs.

  24. Methods for Induction of Stress : Humans PHYSICAL STRESSORS Physical fatigue ice Cold pressure test

  25. Methods for Induction of Stress : Humans PSYCHOLOGICAL STRESSORS TSST Public Speaking + Mental Arithmetics

  26. The HPA axis Hypothalamus - The Hypothalamic- Pituitary-Adrenal Axis (HPA axis) + CRF - Pituitary - + …2 types of GC receptors Type I Type II ACTH Adrenal Gland - + Glucocorticoids

  27. Localization of Steroid Receptors in the Brain Adrenal Steroid Receptors : DISTRIBUTION TYPE I TYPE II -Present in hippocampus -Present in hippocampus -Present in amygdala -Present in amygdala -Not in hypothalamus -Present in hypothalamus -Not in pituitary -Present in pituitary -Not present in high -Present in high concentrations concentrations in cortex in cortex, particulary in the (particularly frontal lobes) frontal lobes

  28. GENDER and STRESS : Animals Females are more reactive than males (cortisol responses 2-fold higher than males) CRF Secretion CRH ACTH Secretion ACTH Less Type II receptors so less feedback activity than males GCs Secretion GCs

  29. GENDER and STRESS FEMALES Female Adults OVX Females <10days OVX Injected with Androgens Injected with Androgens Stress reactivity similar to that of females Stress reactivity similar to that of males

  30. GENDER and STRESS MALES Male 20 days CSX Males 1day CSX Injected with E + P Injected with E + P Stress Reactivity similar to that of male Stress Reactivity similar to that of female

  31. GENDER and STRESS : Humans Physical Stressors : Females are more reactive than males Psychological Stressors : Males are more reactive than females TSST : Men higher response of ACTH and cortisol than women What could be the bias here?….

  32. The Menstrual Cycle Follicular Phase Luteal Phase

  33. GENDER and STRESS : Humans What could explain the gender difference in reactivity to psychological stress? One answer : Sex Steroids interacting with HPA axis If sex steroids interact with HPA axis, if mix women in the luteal and Follicular phase when comparing to males, you could loose the stress Effects as a function of the menstrual cycle Moreso…. WHAT you are measuring could have a very DIFFERENT effect on what you see…..

  34. Study : Kudielka et al., -4 groups Men  Women in Luteal Phase (High E + P)  Women in Follicular Phase (Higher E than P)  Women taking contraceptives (Higher E than P) -2 Challenges to the HPA axis  TSST (psychological stressor) -Measure ACTH and cortisol in blood & saliva  ACTH challenge (acute) -Measure Cortisol in blood and Saliva Why Blood vs Saliva? Possible impact of estrogen on CBG

  35. Results -->ACTH challenge • Saliva Cortisol Response • Luteal > Men > Follicular > Contraceptive Estrogen Blood Cortisol Response No group differences  TSST • Saliva Cortisol Response • Luteal = Men > Follicular = Contraceptive Estrogen Blood Cortisol Response No group differences Cue : Estradiol-induced changes in CBG In cases of high estrogen levels (as a function of P), leads to an increase in CBG, Binds more to cortisol, so less FREE cortisol measured in saliva Estrogen acts on CBG and NOT cortisol per see, so doesn’t affect blood cortisol levels (free + bound)

  36. GENDER and STRESS : Humans So, increased ESTROGEN levels is related to decreased FREE GC levels However, Increased GC levels also induces a decrease in GnRH GnRH CRF Impact of Stress on Reproduction - LH/FSH - ACTH - Gonadal Hormones GCs

  37. GENDER and STRESS : Mechanism synapses Specific role of CRF GnRH CRF - Hypothalamus LH/FSH ACTH CRF receptors Gonadal Hormones GCs When activated, inhibits secretion of gonadal hormones

  38. So, stress will inhibit reproductive function Females : decreased reproduction Males : decreased sperm count E.g. animal: transportation synapses Specific role of CRF GnRH CRF - Hypothalamus LH/FSH ACTH CRF receptors Gonadal Hormones GCs When activated, inhibits secretion of gonadal hormones

  39. Neuroendocrine demonstration of HPA impact on HPG Administration of CRF GnRH synapses Specific role of CRF GnRH CRF - Hypothalamus LH/FSH ACTH CRF receptors Gonadal Hormones GCs When activated, inhibits secretion of gonadal hormones

  40. Neuroendocrine demonstration of HPA impact on HPG Study by Berga et al., 1997 -->2 groups of interest : -Women with Functional Hypothalamic Amenorrhea (FHA) : anovulation because disrupted GnRH input -Women with anovulation due to other causes e.g. hyperprolactinemia, hyperandrogenic anovulation etc. (group Other Anovulation) Hypothesis : The anovulation (thus, infertility) observed in women with FHA is due to STRESS, ie the impact of GC on GnRH while this is not the case for the other women

  41. Neuroendocrine demonstration of HPA impact on HPG Study by Berga et al., 1997 Method : Measure of plasma cortisol and LH levels for 24 hours, at 15 min. intervals Results : Women with FAH have increased cortisol levels when compared to other women. Since this is the only group with increases GC levels, it is interpreted that the problem in GnRH secretion in these women is due to exposure to stress Conclusion : Stress management could help in these women

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