Download Martha Louzada

Association between psychological
factors and immune impairment on
development of cancer: is it real?
Martha Louzada
EPI 6181
April 2, 2008
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 psyche and disease
• Focus of these theories:
 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
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?
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
• 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
Immunity and Disease
How the immune system works
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
Detection of invaders
active defense
Humoral immunity
ANTIbody GENerating
Going back to PNI
Distress, depression, anxiety, social support, optimistic view
Interrelations are bidirectional
Endocrine
System
CNS
IMMUNE SYSTEM
How do psychological factors
influence immunity and disease?
How could psychological factors
influence immunity and disease?
Psychological characteristic or state
CNS innervations Hormonal response
Behavioral change
Immune change
Disease susceptibility
Stressful events
Coping
Smoking
Poor dietary
habits
poor sleeping
Cohen et al, Ann Rev Psychol, 1996
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
Influence of psychological factors in
immune-mediated disease
• Affect: depressive disorders
Drink Smoke
Poor sleep
Poor exercise
behaviour
Immune system
• Mood states: anxiety
• Personality: pessimistic, power motivation,
repression/denial (HIV)
• Interpersonal relationships: support-induced
changes in immune function??
• 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
Do psychological factors influence
immune system-mediated disease?
• Is the presence of a disease-causing agent
sufficient to cause disease? NO
• Disease = immune system compromised or
unable to recognize a foreign material
• Infectious diseases
• Auto-immune diseases
• Cancer
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
Psychological var – NK - metastasis
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
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
• 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)
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?
• 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
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