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

• 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

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 DiseaseHow 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

IMMUNE SYSTEM

CNS

Distress, depression, anxiety, social support, optimistic view

Interrelations are bidirectional

EndocrineSystem

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 susceptibilityStressful eventsCopingSmokingPoor dietary habitspoor 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 studentsSoon after vacation and soon after an examDecreased 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 weeksDaily 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 behaviour

• Mood states: anxiety• Personality: pessimistic, power motivation,

repression/denial (HIV)• Interpersonal relationships: support-induced

changes in immune function??

Drink SmokePoor sleepPoor exercise

Immune system

• 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., 1987Kielcolt-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?

• Disease = immune system compromised or unable to recognize a foreign material

• Infectious diseases• Auto-immune diseases • Cancer

NO

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

Notes from Dr JL Larry U of T

2020 men followed for 20 yrs those with higher scores of depression had 2-fold risk of dying of cancer (Shekelle, 1981)

• 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