Psychoneuroimmunology (PNI)

1. Psychoneuroimmunology(PNI) By Fabiola Tatone EPI 6181, December 4, 2006

2. 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.

3. 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 Immune System System

4. 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.

5. Stress & Immune function: Taken from J.L.Jarry’s (2002) Health Psychology slides at U.of T.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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).

11. 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.

12. 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!

13. 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