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Psychoneuroimmunology
(PNI)
By Fabiola Tatone
EPI 6181, December 4, 2006
Psychoneuroimmunology (PNI)
What is it?
“The field that studies the interactions between the central nervous
system, the endocrine system and the immune system; the impact
of behavior/stress on these interactions; and the implications for
health of these interactions” - Ronald Glaser
From 1919, stress was noted to influence the progression of
pulmonary tuberculosis.
In 1974, Robert Ader conducted the first experiments showing that
the brain directly influences the immune system by using classical
conditioning in rats. Ader paired an inert substance such as
saccharine (the Conditioned Stimulus) with an immunosuppressive
substance that decreases T-lymphocytes, cyclophosphamide (the
Unconditioned Stimulus) and demonstrated that the harmless
substance caused immunosuppression and rats died.
How psychological factors affect
our immune system & vice-versa:
The nervous system affects the endocrine system via the pituitary gland, controlling hormone secretion.
The endocrine system modulates the immune system through the hormones secreted by the pituitary and adrenal
glands. This hypothalamus-pituitary-adrenal axis (HPA) plays a central role, as immune cells are equipped with
receptors for HPA molecules, and are altered in number, function, and distribution as a result of the hormones
secreted.
Through the autonomic nervous system, the nervous system also has direct effects on the immune system via the
thymus gland, the spleen, and bone marrow.
Cytokines (communication molecules of the immune system), are secreted by immune system cells and are one of
the components that fight foreign invaders, regulate the production of immune cells and also impact the central
nervous system and the HPA axis.
Cytokines also drive our physiological ‘illness response’, affecting our mood, fever, eating, and sleeping patterns,
along with other associated behaviours. This response to illness is evident at the neuronal level, demonstrating
changes in neuronal firing rates and neurotransmitter turnover when presented with an immune challenge; this
provides evidence for a bi-directional circuit.
Thus, yes, it’s complex! :
CNS
Endocrine
System
Immune
System
Stress & the Immune System
In laboratory studies, short-term stressors such as making a speech,
are shown to inhibit an effective immune system response in as little
as 5 minutes.
Longitudinal studies show that individuals who experience
significant stressors at one point or another have increased rates of
illnesses and long-term immune suppression over time; this
association is present even after controlling for confounding factors
such as smoking and substance abuse.
The effect of stress has been investigated for the most part as a
main effect, however other studies also show that it may interact
with other factors (e.g. personality) in its effect on illness.
Stress & Immune function: Taken from J.L.Jarry’s (2002)
Health Psychology slides at U.of T.
Mood & the Immune System
Negative emotions induced by stress also impact the immune
system.
Studies show that negative emotions such as sadness, grief, and
helplessness, suppress immune function, such that individuals who
are ill are 3 times more likely to die as a result of their illness if they
are depressed, in comparison to those who are ill and not
depressed.
Studies on the effects of mood on cancer have shown that cancer
patients who are depressed have lower natural killer cell activity
(NKCA) in comparison to their non-depressed counterparts. These
findings come from 2 types of longitudinal studies: 1) studies
following cancer-free people over time, measuring their mood and
possible cancer onset; 2) studies following individuals already
diagnosed with cancer and monitoring how their mood is associated
with cancer progression.
Social Support & the Immune System
Emotional and instrumental support have also
been shown to relate to proper immune function.
Theorell et al. (1995) found that HIV-positive
men with low levels of social support had a more
rapid decline in T-helper cell counts over a
period of 5 years than did HIV-positive men with
high levels of social support.
Effects on Immune Function
Other factors including, anxiety, sleep deprivation,
abortion, divorce, family illness, unemployment,
personality, coping style, psychiatric illness, and war
have also been shown to impact immune function.
(summarized by Reilly & McCabe, 1997).
Conversely, the immune system and disease can be
positively influenced by relaxation, humour, hypnosis,
meditation, and positive attitudes. These techniques
induce a physiological “relaxation response” (as opposed
to the stress “fight-or-flight” response), reducing blood
pressure, respiratory rate, heart rate, etc.
What does this mean for health practice?
Clinical Interventions
Therapeutic interventions such as hypnosis, psychotherapy, and stress management
techniques have demonstrated benefits in alleviating symptoms of chronic illnesses
such as cancer, and latent viral infections such as herpes. Immunological changes
are also documented as a result of these interventions.
Women with breast cancer have seen extended survival rates as a result of
participation in group therapy or self hypnosis.
However, it is important to note that direct associations are difficult to observe as a
result of confounding factors such as changes in diet, lifestyle, and medical
treatments.
Nonetheless, this does not discount the potential benefits obtained by considering
psychological, behavioural, and emotional interventions in addition to traditional
medical treatments when targeting an illness. As Roger Sturrock once mentioned:
“If you settle the patient, the illness then often settles”.
However, this in no way implies that our illnesses are purely a result of our poor
stress-management techniques. Stress management (as an example) is just an
important part of the dynamic picture.
The Placebo Effect
Many argue that the therapeutic interventions described are simply a
placebo effect: a body’s ability to heal itself as a result of the
confidence in an unknowingly inert intervention (e.g. a sugar pill).
The placebo effect is also defined as: “a change in a patient’s illness
attributable to the symbolic import of a treatment rather than a
specific pharmacologic or physiologic property”.
Benefits obtained through placebos have implicated the autonomic
nervous system (with improvements in hypertension, cardiac pain,
and headaches), the endocrine system (diabetes and menstrual
pain), and the immune system (colds, asthma, and cancer).
The Placebo Effect (cont’d…)
The placebo effect is considered by many to represent that an illness was “all in your
mind”. However, although the placebo may be chemically inactive, its effects are
evident beyond the psyche.
1) Through patient’s confidence in a treatment, placebos have been shown to reduce
stress, anxiety, and depression, all which have been reviewed to associate with
illness.
2) Placebo treatments may also work as conditioned stimuli, similar to Ader’s
experiments with saccharine in rats.
3) The placebo response may also act directly on the CNS with the release of the
body’s natural pain killers and narcotics (e.g. endorphins and enkephalins).
Thus, although the beliefs may be ‘all in the mind’, the effects of this belief alter an
individual’s biochemistry to mimic the effects of an active drug.
However, it is difficult to study the exact physiological mechanisms of placebo effect as its
effectiveness also depends on the patient’s faith in the treatment, reduction of
anxiety, and conditioning; no individual has the same response to a given placebo.
Just the same, the therapeutic potential of placebos merit important consideration.
Bi-directional Interactions between
the Brain and Nervous System
Evidence suggesting the presence of bi-directional pathways between the brain and immune
system cannot be ignored.
The two pathways connecting these systems are primarily the autonomic nervous system and the
HPA axis, and these communicate via chemical messengers from nerve cells, endocrine organs,
and immune cells.
Although most research has focused on how the sympathetic nervous system and HPA axis affect
the immune system, there is evidence that the reverse also occurs. The immune system impacts
the nervous system inducing “sickness behaviour” through fever, loss of appetite, an increase
need for sleep, etc. This results from active immune cells releasing cytokines, sending back
messages through the HPA and to the brain.
The implication of this bi-directional pathway suggests the possibility for future chemical
interventions to obstruct these chemical pathways so that, for example, stressful situations will be
prevented from interfering with our immune function, and sickness behaviour can be better
managed by interfering with it’s feed-back loop as well.
Does this all mean that people of lower SES, who tend to be more likely to experience stressful
life circumstances, will no longer show disparities in health once we find a way to block these
psychoneuroimmunological communication routes? …That will be left to us future researchers to
discover!
References
Azar B. A new take on psychoneuroimmunology. Monitor on Psychology,
2001;32(11). URL: http://www.apa.org/monitor/dec01/anewtake.html
Jarry JL. Psychoneuroimmunology [PPT-slides]. Health Psychology (PSY333). Dept.
of Psych. University of Toronto; 2002.
Kinser PA. Therapeutic placebo effect: A mind/body connection. 1999. URL:
http://serendip.brynmawr.edu/bb/neuro/neuro99/web1/Kinser.html
Kinser P. Psychoneuroimmunology and natural healing by the brain. 1999. URL:
http://serendip.brynmawr.edu/bb/neuro/neuro99/web2/Kinser.html
Reilly D., McCabe D. Creative consulting: Psychoneuroimmunlogy, the mindbody.
URL: http://www.studentbmj.com/back_issues/0402/education/97.html
Wachterman M. Psychoneuroimmunology: Bi-directional interactions between the
brain and the nervous system. 2000. URL:
http://serendip.brynmawr.edu/bb/neuro/neuro00/web1/Wachterman.html