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Martha Louzada EPI 6181 April 2, 2008

Association between psychological factors and immune impairment on development of cancer: is it real?. Martha Louzada EPI 6181 April 2, 2008. Biological Theories.

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Martha Louzada EPI 6181 April 2, 2008

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  1. Association between psychological factors and immune impairment on development of cancer: is it real? Martha Louzada EPI 6181 April 2, 2008

  2. Biological Theories • How can influences such as stress, social networks, coping, social capital, translate into changes in a person's biology that lead to illness and ultimately, death? • There are several theories trying to link mind and body or • Focus of these theories: psyche and disease • to try to find what are the connectors (limbic, immune and endocrine) between mind and body; • how and if they interrelate • how positive or negative influences of the psyche impair homeostasis promoting the development of diseases

  3. Questions • Can stress, anxiety, depression, social support, and optimistic view alter our ability to resist infection, autoimmune diseases or cancer? • What are the biological pathways through which psychological state or characteristic will influence in disease susceptibility? • Can we alter immunity and therefore disease susceptibility through psychological intervention?

  4. History • In the last 20 years striking advances in the biomedical technology have occurred and extended the frontiers between mind and the body identifying the intricate connections between brain-based emotions and the function of neuroendocrine and immune systems • James Papez in 1937 • 1950, McLean generalized Papez’s ideas into a theory of the limbic system an integrated set of subcortical structures in the brain whose precise role in expression and modulation of emotion were explored through electrical and chemical stimulation of specific anatomical structures and regions

  5. 1981 David Felten: Discover a “hard-wire connection between the immune system and the CNS (trace nerves to bone marrow, lymph nodes, thymus and the spleen) • Psychoneuroimmunology (PNI): study of interrelations between the CNS and the immune system (David Felten, 1981) • Existence of neurologic terminations directly into lymphoid tissues in the spleen and release of neurochemicals in this location • 2000 Bellinger: NA innervation of BM, thymus and spleen and nodes in animal models (immune system cells have adrenergic receptors • receptors for NE ): Herbert, 1994; Bachen, 1995 • Human research: establish the association between psychological states and immunity

  6. Immunity and DiseaseHow the immune system works

  7. How the immune system works • Protects the body from potentially harmful substances. • The inflammatory response is part of innate immunity. It occurs when tissues are injured by bacteria, trauma, toxins, heat or any other cause Redness, swelling and pain: result of increased blood flow in the injuried area that brings cells from the immune system to combat the intruder

  8. Detection of invaders active defense

  9. Humoral immunity ANTIbody GENerating

  10. Going back to PNI Distress, depression, anxiety, social support, optimistic view Interrelations are bidirectional CNS Endocrine System IMMUNE SYSTEM

  11. How do psychological factors influence immunity and disease?

  12. How could psychological factors influence immunity and disease? Psychological characteristic or state CNS innervations Hormonal response Behavioral change Immune change Stressful events Coping Smoking Poor dietary habits poor sleeping Disease susceptibility Cohen et al, Ann Rev Psychol, 1996

  13. Influence of psychological factors in immune-mediated disease • Stress: when demands imposed by events exceed individual capacity to cope (short-circuit) • A psychological stress response will occur and will influence the immune system Medical students Soon after vacation and soon after an exam Decreased activity of immune response (NK activity, lymphocyte production of cytokines and lymphocyte proliferation, increased prodution if herpes Ab) Glaser, Behav. Neurosci, 1986 Volunteers ingested a ptn capsule (Ag) for 12 weeks Daily diaries and daily saliva samples (IgA) + events = > IgA - events = < IgA Stone, Health Psychol., 1994

  14. Influence of psychological factors in immune-mediated disease • Affect: depressive disorders behaviour • Mood states: anxiety • Personality: pessimistic, power motivation, repression/denial (HIV) • Interpersonal relationships: support-induced changes in immune function?? Drink Smoke Poor sleep Poor exercise Immune system

  15. 16 divorced females vs 16 married females: higher levels of herpesvirus Ab, lower NK cells activity • 32 divorced males vs 32 married males: more infections and higher titers of herpesvirus Ab Kielcolt-Glaser et al., Psychosom. Med., 1987 Kielcolt-Glaser et al ,Physiol. Behav., 2003

  16. Do psychological factors influence immune system-mediated disease? • Is the presence of a disease-causing agent sufficient to cause disease? • Disease = immune system compromised or unable to recognize a foreign material • Infectious diseases • Auto-immune diseases • Cancer NO

  17. Psychology, Immunology and Cancer • Cancer: large and heterogeneous group of diseases: genetic basis (tumor supressor genes)/ environment influence • Second leading cause of death in USA • Results from a gap in the immune system capability of recognizing this self- defective cells cancer cell tries to fool the immune system

  18. Psychological var – NK - metastasis

  19. Psychology, Immunology and Cancer • Link psychological status and NK cell activity and lymphoid cells production • Depression is associated with impaired immune function (low NK) • Results are not consistent to whether and how depression contributes to cancer development and predicts survival

  20. 2020 men followed for 20 yrs those with higher scores of depression had 2-fold risk of dying of cancer (Shekelle, 1981) Notes from Dr JL Larry U of T

  21. Greater access to social support - Better prognostic indicators (Levy, 1975) - Longer survival (Funch And Marshal, 1983) • Social isolation : - men vs women: worse survival rates (Reynolds and Kaplan, 1990) • Non metastatic breast ca + fighting spirit or denial: longer survival than fatalism or helpless response (Greer, Psychol Med., 1991)

  22. Questions • Can stress, anxiety, depression, social support, and optimistic view alter our ability to resist infection, autoimmune diseases or cancer? • What are the biological pathways through which psychological state or characteristic will influence in disease susceptibility? • Can we alter immunity and therefore disease susceptibility through psychological intervention?

  23. RCT 66 melanoma pt psychol intervention vs no intervention • Intervention: stress management, coping skills, and discussion about disease: 6 x 90’ sessions • 6 mo after intervention ended the intervention group showed reduced psychological stress, increased NK activity and other lymphocytes • No impact on mortality Fawzy et al, Arch Gen Psychiat,1993

  24. Conclusions • No question that psyche, CNS and immunity are interrelated • Psychological factors alters the immune system • Effects of Psychological factors on cancer onset or progression intermediated by the immune system is a question that remains unanswered

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