Association between psychological factors and immune impairment on development of cancer: is it real

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Association between psychological factors and
immune impairment on development of cancer is it
real?

• Martha Louzada
• EPI 6181
• April 2, 2008

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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

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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?

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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 Papezs 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

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• 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

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Immunity and DiseaseHow the immune system works
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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
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(No Transcript)
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Detection of invaders active
defense
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Humoral immunity
ANTIbody GENerating
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Going back to PNI
Distress, depression, anxiety, social support,
optimistic view
Interrelations are bidirectional
CNS
Endocrine System
IMMUNE SYSTEM
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How do psychological factors influence immunity
and disease?
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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
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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 gt IgA - events lt IgA
Stone, Health
Psychol., 1994
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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
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• 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
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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
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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

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Psychological var NK - metastasis
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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

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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
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• 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)

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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?

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• 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
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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