Presentation on theme: "Psychoneuroimmunology"— Presentation transcript:
1 Psychoneuroimmunology Margaret E. Kemeny, Ph.D.Jason Satterfield, Ph.D.
2 Stress and Coping Assessment: A Caregiver Case Example Objectives:“Pull forward” stress & disease basics from MS1Illustrate clinically-relevant strategies to assess stress and coping prior to learning PNI basics
3 Mark Simmons is a 62yo man who was diagnosed with Alzheimer’s Disease at the age of Prior to that time he worked full time as a civil engineer. He and his wife Marsha (aged 56) live at home. Marsha works part-time at home as an accountant as well as serving as Mark’s primary care-giver.Both Mark and Marsha are your patients. Marsha has been having frequent URI’s and appears worn and fatigued.
4 How Can Stress Cause Disease? Recall from Prologue – stress can contribute to disease through 3 overlapping pathways. All three are important to understand and address. The interventions used for each may differ. Today’s lecture focuses on the physio pathway. But before thinking about stress-disease pathways, it is important to develop a process for detecting and assessing stress in our patients.
5 What should trigger a stress and coping assessment? Signs of emotional distress, depression, or anxietyMultiple somatic complaints – insomnia, appetite, pain, fatigueFrequent colds, infections, slow healing timesStressor onset or changeFrom your FPC and preceptor patient interviews, it is now probably very clear that time is short in nearly every clinical visit. You simply can’t assess for everything every time. You learned to generally ask about stress – like with the Mrs. Henderson case – but we haven’t really specified when to do a stress assessment or what questions would be highest yield. Here are some of the clues that should tip you off to do a stress assessment.
6 Stress Assessment Step 1: Ask about frequency “How often have you felt nervous or stressed out in the past month?”Step 2: Ask about cause (i.e. stressor)“What’s been causing you to feel stressed out?” Be sure to ask, “And is there anything else?”We recommened a fairly quick 5 step stress assessment – frequency, cause, duration, impact, and coping.
7 Stressor 1: Caregiving, grief for husband Frequency: “I feel stressed out nearly all the time. It’s just so hard for us right now.”Stressor 1: Caregiving, grief for husbandStressor 2: Ms. Simmons is worried about her own health.Stressor 3: Finances are worrisome but not at crisis point.Ms. Simmons health issues = Ms. Simmons often feels fatigued, has trouble sleeping, catches colds/URI, feels physically run down and “unwell.” She is emotionally exhausted but feels guilty for worrying about herself.
8 Stress Assessment Step 3: Ask about duration “How long has this been going on?”Step 4: Ask about impact“How has this stress been affecting you?” Be sure to ask about both the social and occupational domains – “How has it affected your relationships? Your performance at work? Any other effects?”
9 Stress Assessment Step 5: Ask about coping strategies “What have you been doing to cope with this stressful situation? How well has that been working for you?”Be sure to ask, “How can we help you get through this difficult time? What would be most helpful for me to do right now?”Remember that coping mechanisms can be adaptive or maladaptive. We need to know if a person if coping by drinking more, staying up late, etc. We also need to know if they are successfully tapping into available coping resources such as social supports or programs.
10 Duration: Mr. Simmons began having difficulties about 4-5 years ago Duration: Mr. Simmons began having difficulties about 4-5 years ago. In the past year, the caregiving demands have been rapidly escalating. Ms. Simmons has been ill herself over the past 6-8 months. Their financial stress is just now starting.Impact: Ms. Simmons has trouble sleeping, fatigue, irritability, and frequent colds/URI’s. She neglects her health, avoids some of her friends, and had to cut way back on her accounting job.Coping strategies: She uses an in-home health aid 20hrs/wk. She watches TV late at night to relax. She keeps a journal when she has time.Mr. Simmons requires round-the-clock supervision because he is unable to eat, bath or dress himself and will often leave the house and get lost if unattended. No other family members live in the area to share care-giving responsibilities. While home-health assistants provide basic care 4 hours per day 5 days a week, Marsha is responsible for the majority of care and has little time or energy for social or other activities.
11 Stress Assessment Recap Be sure to ask about the 5 elementsFrequencyCauseDurationImpact – include social and occupationalCoping – the good, the bad, and how we can help
12 Our Plan for Ms. Simmons?Schedule f/u appt for 1-2 wks to discuss adjunctive tx or stress management programs.Give her a depression screener to complete before next visit.Give referral to social work to arrange respite and assist with shared care scheduling.Give URL for local support group and ask her to consider joining. Will discuss next time.“Watchful waiting” re insomnia and other somatic sx possibly related to stress (no meds yet)
13 How Can Stress Contribute to Disease? 1How Can Stress Contribute to Disease?
14 Psychoneuroimmunology: 2Psychoneuroimmunology:Investigations of the bidirectional linkages between the CNS, the endocrine system and the immune system, and the clinical implications of these linkages.
15 STRESSOR NO YES CRH 3 HYPOTHALAMIC ACTIVATION Psychological Stress? MODERATING VARIABLESGenetic predispositionPrevious life experiencesCopingSocial supportNOPsychological Stress?YESHYPOTHALAMICACTIVATIONCRHPITUITARY FACTORSACTHLOOKS PERFECT! THANKS.SYMPATHETIC ACTIVATIONNorepinephrineMedullaCortexAdrenal GlandsEPINEPHRINEGLUCOCORTICOIDSIMMUNE SYSTEM
16 4Noradrenergic fibers innervateimmune organs (lymph node,thymus, spleen, bone marrow)Release NE in close proximity toimmune cells (greater density in Tcell areas)Leukocytes express a and badrenergic receptorsNE and E can influence leukocyteactivity e.g., macrophageproduction of TNFa
17 NE and epinephrine can alter lymphocyte migration: 5Immediate exposure (30 min) # lymphocytes,natural killer cellsLonger exposure (days) # natural killer cells
18 6NE can alter innate and adaptive immune function in organs and in circulation:“Fine tunes” immune responses, allowing for quick adjustments (within minutes)Shift from Th1 to Th2
19 STRESSOR NO YES CRH 7 HYPOTHALAMIC ACTIVATION Psychological Stress? MODERATING VARIABLESGenetic predispositionPrevious life experiencesCopingSocial supportNOPsychological Stress?YESHYPOTHALAMICACTIVATIONCRHPITUITARY FACTORSACTHLOOKS PERFECT! THANKS.SYMPATHETIC ACTIVATIONNorepinephrineMedullaCortexAdrenal GlandsEPINEPHRINEGLUCOCORTICOIDSIMMUNE SYSTEM
20 8Leukocytes express glucocorticoid receptors; cortisol acts on glucocorticoid receptors to have the following effects (as with synthetic GCs):inhibit lymphocyte proliferationinhibit production of pro-inflammatory cytokinesShift from Th1 to Th2 cell activity by stimulating synthesis of IL-10, IL-4
21 Definition of Stressors 9Definition of StressorsStressors:environmental or internal demands which tax or exceed a person’s resources
22 10Stressor Time WindowsImmediate acute phase (within minutes of stressor onset); the “fight/flight” responseShort-term stressors (that last for days or weeks)Ex.: exams*, moving, being firedChronic stressors (that last for months or years)Ex.: caregiving for a family member with Alzheimer’s Disease, marital discord, poverty
23 Redistribution of immune cells (increase in leukocytes in blood) 11Innate Immune System Mobilization in the Immediate Acute Phase of a Stressor (fight/flight): min to hrs post stressor onsetRedistribution of immune cells (increase in leukocytes in blood)Increase in innate, non-specific immunity (increased NK cell activity)(Decrease in specific immunity)
24 Increase in Th2 humoral immunity (e.g., Th2 cytokine production) 12Alterations in Specific Immunity following Exposure to Short-term Stressors: days or weeks post stressor onsetDecrease in Th1 cellular immune response (e.g., proliferative response of lymphocytes)Increase in Th2 humoral immunity (e.g., Th2 cytokine production)
25 13Alterations in Non-specific and Specific Immunity following Exposure to Chronic Stressors: months to years post stressor onsetDecrease in both Th1 cellular and Th2 humoral immune response (e.g., lower antibody titers to hepatitis B vaccines*)Decrease in innate, non-specific immune responses (except inflammatory activity)Persistent inflammatory activity (e.g., increased pro-inflammatory cytokine production)*antibody response can be enhanced with stress reduction intervention
26 Immune effects are stronger in those who: 14Effects of Stress on the Immune System Depend not Only on Timing but Characteristics of the PersonImmune effects are stronger in those who:Are olderMore depressedLess supported
27 15Health behaviors (below) are affected by stress but immune effects of stress exposure are not due only to these effects.Drug useAlcohol UseExerciseDietMedication adherenceSleep loss
28 16Sympathetic Nervous System (SNS) mediation of immune effects of immediate acute phase of stressors (minutes to hours): the fight/flight response
29 17SNS mediation of immune effects of immediate acute phase stressor—parachute jump
30 18Somehow this really ended up looking really blurry for some reason, why did the lines get so jumbly, they werent on my slide. Maybe just by making it smaller it might help? Also this slide doesn’t have the bottom part with exit and -4 etc like the one I had so see if you cant get that back. .
31 NK cell # (CD16, CD56) and activity increased with jump 19Figure 3NK cell # (CD16, CD56) and activity increased with jumpEffect abolished with b-adrenergic antagonistNE levels correlated with NK cell # and functionSimilar effects in studies of acute stressors in the laboratoryThis and other studies show that NE is a critical mediator of the immune effects of the immediate fight/flight phase of the stress response
32 Hypothalamus CRH Anterior Pituitary ACTH Adrenal Cortex Cortisol 20HypothalamusCertain stressors can activate the HPA (more selective activation than ANS)-causing increased release of cortisol in blood, saliva an urineCRHAnterior PituitaryStressorsimmediate-acute phaseShort-term-days/weeksChronic-months/yearsACTHAdrenal CortexHPA appears to be an important mediator of effects of short-term and chronic stressors on the immune systemCortisol
33 Hypothalamus CRH Anterior Pituitary ACTH Adrenal Cortex Cortisol 21Cortisol suppresses immune functions such as pro-inflammatory cytokine production via the glucocorticoid receptor (GCR).HypothalamusCRHAnterior PituitaryACTHAdrenal CortexCortisolImmune CellGCR
34 Hypothalamus CRH Anterior Pituitary ACTH Adrenal Cortex Cortisol 22HypothalamusBut stress-> INCREASES pro-inflammatory cytokine productionOne mechanism: Glucocorticoid Resistance: stress induced downregulation of GCR; cortisol cannot restrain pro-inflammatory cytokine production so cytokine production increases (animal/human studies)CRHAnterior PituitaryACTHAdrenal CortexCortisolImmune CellGCR
35 23Glucocorticoid Resistance: Decreased ability for dexamethasone to suppress IL-6 production in vitro in chronically stressed individuals (parents of children with cancer)Miller et al., 2002
36 Are these stress-induced immunologic changes clinically significant? 24Are these stress-induced immunologic changes clinically significant?Do they contribute to disease onset or accelerate disease course?
37 25Above: A 3.5-mm mucosal wound used to study delayed closure associated with stress and immune mechanisms of effect.
39 27Healing time (as measured by response to hydrogen peroxide) is shown for each of the 11 subjects for the two time periods, summer vacation and examinations. Also high stress increased susceptibility to opportunistic bacterial infections in the wounds.
40 Mediators of Stress-related Changes in Wound Healing 28Mediators of Stress-related Changes in Wound Healingdiminished mononuclear cell trafficking to the wound sitereduced expression of cytokine, chemokine, growth factor genesdecreased production of pro-inflammatory cytokines in wound environment*
41 How Might Information From the Field of Psychoneuroimmunology Influence Your Clinical Practice? 29Ask about life stressors (short term and chronic), impact on functioningAsk about how a pt is coping, social supports. “Does it help?”Recognize that test results during chronically stressful times could be unreliable (repeat testing?)Recognize that vaccinations may be less protective during stressful times (consider other precautions)Recognize that wound healing may be influenced by stressRecognize that immune functions may be affected by the use of drugs that influence the ANS or glucocorticoids (e.g., b-blockers).Ask about therapy and make recommendations and/or referrals as needed (know what is available in the community).recognize the limitations in knowledge when patients ask about whether a given therapy (visualization, etc) can improve their immune system.