Psychoneuroimmunology

Psychoneuroimmunology

1. Brain > Behaviour > Immune System or Immune System > Brain > Behaviour

2. Types of immunity:

   • Mucosal immunity
     • Natural Immunity (all purpose immune cells that attack pathogens), general response: inflammation
       • Specific immunity: greater specificity but less speed than natural immunity
         • Specific cellular immunity: against intracellular pathogens e.g. viruses
           • Humoral immune response: against extracellular pathofens e.g. bacteria

3. Assessing the functioning of the immune system

   • Cell counts, Antibody level, Proliferation response (number of antigen specific cells produced), Activation latent viruses
     • Cellular immunity limits primary infection & keep latent virus under control. Re activation can be used as indicator of immune functioning
       • Antibody levels:
         • HSV - 1, EBV and CMV antibodies elevated prior to and durin exams (Glaser et al 86 & 87)
           • Higher levels of antibodies to EBV among separated and divorced (Kielcot - Glaser et al 87)
             • Higher levels of HSV - 1 in depressed patients (Cappel et al)

4. Evidence for links between brain and immune system:

   • Direct innervation of lymphoid tissue e.g. the spleen
     • Hypothalamic stimulation > changes immune response, Immune responses > alter hypothalamic function
       • Dementia: reduced immune system functioning

5. Conditioning of an immune response: CS (drink flavour), US (immune suppression)

   • Antigen + CS = immune suppression

6. Immunological effects of acute stress

   • Kusnekov et al 92: footshock in mice = reduction in immunity to Herpes simplex
   • Bachen et al 92: Stroop task = reduction in lymphocyte nubers and capacity to proliferate in response to artificial antigens
   • Sieber et al 92: Uncontrollable noise = reduction in NK cell activity in subjects who perceived they had no control over the noise,
     • No NK cell activity reduction when perceived to have control over noise
   • Glaser et al 87: during exam period medical students reported more infectious illnesses and had lower CF4+ cells
   • Dorian et al 82: During exams = elevated B and T lymphocytes, lower cortisol levels and poorer mitogen responsivity
   • Schedlowski et al 93: NK cell activity parachute jump. Immediately after raised, 1 hour later less than at initial measure. Corr with noradrenaline levels

7. Immunological effects of chronic stress

   • Irwin et al 90: Experience of clinical depression associated with 50% reduction in NKCC
   • Irwin et al 92: hospitalisation: at admission NKCC lower than control. Six months discharge - sig increase in NKCC similar to control group
     • Caregiver stress: KIecolt-Glaser 87: carers of alzheimers patients: decline in T cell %, no. of T herlper cells and elevated antibody levels to Epstein-Barr Virus
       • Bereavement: Irwin 88: Reduced NK cell activity and increased plasma cortisol in bereaved women comp to control. Decline in NK cell activity when anticipating bereavement.

8. Stress and sIgA: Secretory Immunoglobulin A

   • Defends against a range of infections, especially respiratory tract infections
     • sIgA = most abundant immunoglobulin, provides barrier to invasion
       • High levels of stress = low levels of sIgA?
         • McClelland et al 82: -0.26 corr between stress & sIgA in prisoners
         • Mouton et al 89: students, corr significant during exams
         • Graham et al 88: Nurses, no relationships between anxiety, hassles GHQ and sIgA
           • Fowlie et al 93: irritable bowel syndrome & anxiety - no relationship
             • Evans et al 93: students, sig corr between daily hassles over 2 weeks & sIgA
               • Stone et al 87: students, no relationship between sIgA and mood
                 • CONCLUSION: few studies show negative corr between stress and sIgA but do not consider other psychosocial factors or health behaviours, salivary flow or clear def of stress.
                   • Within subject studies:
                     • Jemmott & Magloire 88: Lower sIgA during exam than before or after
                       • Mouton et al 89: higher sIgA just after exam than 1 3/4 hrs or days later
                         • CONCLUSION: short lived increase followed by decrease of sIgA?
                   • sIgA Regulatory mechanisms:
                     • Long term effect of stress = immunosuppression, mediated by increased activity of hypothalamic pituitary adrenocortical system
                     • Acute stress = increased noradrenaline, salivatory gland secretion, increased sIgA

9. HIV cross sectional studies:

   • Persson et al 91: lower levels of support assoc with lower cell counts
   • Lamping et al 92: no rel between support and HIV symptoms or CD4+ counts
   • Goodkin et al 92: greater NK cell cytoxicity in men with active coping style
     • Kemeny et al 89: no assoc between depressed HIV men who were bereaved and mitogen responsivity, CD4+ or CD8+.
       • However, HIV men not bereaved = poorer mitogen, CD4+ and elevated CD8+
         • Gorman et al 91: no rel between cortisol levels and CD4+ counts

10. Longitudinal studies

    • Catan 89: more stress = more symptom reporting 9 months later but no rel between stress at baseline and CD4+
    • Kessler et al 91: no rel CD4+ or symptoms with stress
      • Burack et al 93: clinical depression at baseline = 40% greater decline in CD4+ cells over 4 years than not depressed
        • Weiss 92: greater depression and less suppression of anger = more rapid disease progression & CD4+ decline 5-6 years later
          • Lyketsos et al 93: no assoc between baseline depression and CD4+ decline 8 years later

11. Meta-analysis

    • Chida & Vedhara 2009: small positive assoc between adverse psychosocial factors and HIV progression
      • Personality and coping effect on progression, but no effect of social support.

12. Long term survivor studies:

    • Solomon et al: 87: Deceased HIV pneumonia with those who survived: Survivors problem solving, social support, active coping - realistic acceptance
      • Remien et al 92: LTS more flexible coping mechanisms
        • Marguth et al 93: LTS experiences fewer stressful events
          • CONCLUSIONS: Studies of HIV stress and immune function show conflicting results
            • Confounding factors such as effects of mediation, different samples
              • LTS studies suggest psychosocial factors affect progression of HIV

13. Meta analysis stress and immune system: Segerstrom & Miller 2004

    • Acute stress: lasting minutes = adaptive upregulation of natural immunity, downregulation of specific immunity aspects
      • Brief natural stressors: e.g. exam - suppress cellular immunity, little effect on humoral immunity
        • Chronic stressor: suppression of cellular and humoral, effects are stressor specific, subjectvie reports do not corr with immune change
          • Physical vulnerability increased effect of stress on immune system e.g. age

14. Relaxation and immune function: increases ability of neutrophils to active killer cells

    • clinical significance not clear
      • Kiecolt-Glaser 85: relaxation reduced distress and increased NK cell activity, antibody titres to latent viruses decreased.
        • Effects not seen at one month follow up.
          • Kiecolt-Glaser 86: rel between freq or relaxation and immune function during exams
            • Freq of relaxation corr with % helper cells
              • All p's showed immunosuppression during exams
    • Jasnoski & Kugler 87: sIgA increases immediately after relaxation
      • CONCLUSIONS: effects small and transient, may reduce symptoms of stress
        • Doesn't address cause, regular practice needed.

15. Wiedenfeld et al 90: snake phobia

    • Taught coping skills to interact with snake
      • Lymphocyte count increased over session
        • Those who mastered coping skills quickly showed rapid changes in immune function

16. CBT in early breast cancer stages: McGregora et al 2004:

    • Better emotional well being, improved lymphocyte proliferation
      • Stres reduction HIV infection: Antoni et al 2002
        • 10 wk stress management course = CD4+ increase
          • Coates et al 89: no effects of stress management on immune.
            • However, p's more immunocompromised than other studies
    • Meta-analysis Scott-Sheldon et al 2008: no effect of stress management on immune or hormonal processes

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