Perspectives on psycho-neuro-immunology in oncology
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0973-1075.25916
Source of Support: None, Conflict of Interest: None
Psycho-oncology and psycho-neuro-immunology are both powerful new disciplines. Although a lot of literature exists in both of these fields the evidence is often controversial. This paper gives a brief perspective on the origins of psycho-neuro-immunology and discusses how our current understanding of this subject can be translated into clinical practice in an Indian setting.
Keywords: Psycho-oncology, psycho-neuro-immunology, spirituality, emotional intelligence, immunomodulation.
Psycho oncology is bi-directional. There is the impact of cancer on the individual, the family and other carers - what we call psychosocial impact. Then there is the influence of what we bring to the situation, as individual or collective behaviour and environmental influences that modulates or contributes to the risk of cancer and cancer outcomes - what we refer to as the psychobiological aspects. This article strives to provide an overview of the interface between two fairly new but powerful scientific disciplines: psycho oncology and psychoneuroimmunology. Research in this area has been scattered, at times inconclusive and often controversial; however, we will sift through some of the available evidence to bring in coherence to the concept and locate rationales for possible clinical application.
The origins of psychoneuroimmunology
Fatalistic attitudes towards malignancies in the past have been gradually discarded in favor of increasingly open dialogue between physicians and patients with the advent of a wider range of treatment options over the last few decades. This spawned new areas of scientific study that looked at reactions of individuals to cancer and psychological/ behavioural factors that influence cancer risk and survival. The origin of psychoneuroimmunology as a discipline is traditionally traced to the publication of the first edition of Psychoneuroimmunology in 1982. In addition to covering the scant amount of research on the subject that was available at that time, it contained a seminal chapter written by Ader and Cohen. This chapter reviewed behaviorally conditioned suppression of the immune system and provided strong support for the integration of the "somatic" and "psychological" aspects of immunity.
After exploring the association between environmental, infective, dietary and life style factors, tumor growth was induced in vitro/in laboratory animals, using toxic substances (carcinogens), high fat diets, radiation and viruses. Biologists found it useful to conceptualize the cancerous cell as a confused cell with accumulated genetic misinformation and predispositions that was constantly struggling unsuccessfully in most human bodies to express itself. The immunosurveillance theory was introduced to explain the forces that modulate the expression of these cancer cells and the immune system was implicated as a key player in whether the individual would succumb to the disease. This was partially corroborated by the higher incidence of cancer seen in known states of immunosuppression e.g., AIDS and immunos-uppressive therapy.
We now know that the sympathetic noradrenergic nerve fibers innervate the thymus, spleen, lymph nodes and bone marrow and that neuropeptide receptors occur on all mobile cells of the immune system. Furthermore, products of the activated immune cells are able to transmit signals directly to leucocytes and indirectly via neuroendocrine and autonomic nervous pathways., The dendritic cells of the immune system identify the mutated cancerous cell, send warning messages to the other components of the immune system, viz, the peptides, interleukins, interferon, natural killer cells [NKC] and T-cells which rush to the site and destroy the malignant cells.
What factors influence the working of the immune system in different individuals?
Several studies have correlated emotions with immunity, cancer and cancer outcomes. Some of the evidence that points in this direction is discussed here.
Sustained stress is known to produce high flat cortisol levels with depletion of interleukins and decreased natural killer cell activity. Those with severe job stress in the previous ten years were five and a half times more likely to have developed a malignancy compared to those without such stress in their lives. When mental attitude was studied as an additional prognostic factor among breast cancer patients, it suggested that those who displayed a fighting spirit or an active coping style survived longer than those who had hopeless, helpless or stoic attitudes. Depression has been found to decrease the lymphocyte mitogen response and natural killer cell activity although the results are controversial. Interestingly, alexithymia,an overly respectful, cooperative coping style and a passive/helpless coping style have been associated with an increased likelihood of dysplasia. Alexithymic patients also had lower cytotoxic T lymphocyte counts.
In 1982, Robert Ader, demonstrated that after conditioning mice by pairing saccharin [a conditioned stimulus] with an immuno-suppressant; cyclophosphamide [an unconditioned stimulus], exposure to saccharin alone could induce immuno-suppression. Today it is well established that there are reciprocal connections between the CNS and the immune system.,,,, Like the brain, the immune system was found to have a profound capacity for learning, memorizing and sorting out huge amounts of information. Both are dependant on information from each other and along with other systems, they establish a feedback loop between the emotions, nervous, endocrine and immune systems for the regulation of the ongoing physiological responses [Table - 1]. Current research is focusing on identifying chemicals that can be used to modify this feedback loop: a process referred to as immunomodulation. It is as yet unclear how best to translate available information into consistent and reproducible cancer regression or increased survival strategies.
Immune system modulation can probably be attempted via different strategies; one being through neuroendocrine chemical agents at the intermediate and target sites. However the evidence here is still largely experimental. Another strategic intervention would be to target cognitions and emotions that would then influence downstream events. As discussed earlier, these would involve transformation in the psychological status in order to improve the health of the biological system. Radical as this approach might seem to some let us examine the evidence that has accrued in its favour. Speigel et al found that psychological interventions could not only improve mood, coping and pain perception, but that women who participated in this intervention also lived longer.
A structured psycho-education therapy for melanoma patients reduced the psychological distress, positively influenced immune changes and improved survival., Others have found that laughter with the expression of full range of positive emotions that includes humor, hope, love, faith, strong will to live, determination and purpose, can be a significant and indispensable aspect of the total fight for recovery. Norman Cousins has been a strong proponent of hope, joy and laughter in health and disease.
Hermandez Reif found massage therapy reduced anxiety, mood swings and improved NKC and lymphocyte numbers in stage 1 and 2 breast cancer patients.
The experience of any illness has a significant subjective component. Destructive emotions can not only destroy the human spirit but also, from the evidence provided above, probably have detrimental effects on the physical person. Different emotional responses are accompanied by divergent neuro-hormonal patterns that are further modulated by the underlying personality characteristics. Thus scientists have been forced to go beyond psychology in order to study transformation in attitudes. What can possibly affect the patterns of thinking or reactions to experiences in different individuals? Even though individuals are similar in structure and perceptual capabilities, they differ in attitudes. The differences in the emotional make up and mental outlook is determined by the spiritual sieve through which the experiences pass into the person; the understanding of the meaning/purpose of life. The individual spirit may either choose to be pronoiac (everyone conspiring to help) or paranoia (everyone conspiring to harm). Reactions to illness, events and attitudes in therapy are easily understood in this context. A few studies support this hypothesis by showing an inverse relationship between spiritual well being and anxiety in adult cancer patients and beneficial effects for elevated mood states,,, guided relaxation, mindfulness based stress reduction and meditation,,, on immune system functioning and in cancer therapy.
Psychoneuroimmunomodulation is a modern reflection of the ideas of ancient civilizations, that the mind is involved in the defense against diseases. There are references of this concept in the literature of many ancient civilizations. The Upanishads conceptualize human existence at five levels, each subtler and more expansive that the previous. The grossest is the body, followed by life energy, mind, intelligence and bliss levels of existence. many diseases begin at the mind level. Yoga vasishta gives the term "Adhija Vyadhi" [disease born out of stress] to those manifestations, which arise out of thinking patterns based on ego/ignorance and describes how it affects energy patterns within physiological systems and finally culminates in what we notice as disease. It prescribes nurturing of self discipline and pure thinking along with meditation and self awareness for a healthy and energetic life. Therapy will be more effective and comprehensive if directed at all levels of human existence [Table - 2]. Mindfulness Based Stress Reduction System and meditation therapies are based on this principle of being aware of being and doing; within and without.
Bringing spiritual and emotional intelligence to medical care is fraught with challenges. The evidence base will continue to be plagued by the inherent difficulties in conducting investigations with human emotions. Some difficulties are created by the culture in which modern medicine is practiced, perceived reward structures and the difficulties in funding such activities. Also not all care givers nor patients are willing to explore beyond the more tangible, superficial levels of existence.
A significant danger is the possibility of unproductive ideology in the opposite direction: the notion that people can cure themselves of any disease simply by making themselves happy or thinking positive thoughts or that they are somehow to blame for having fallen ill in the first place. This can create unnecessary angst and should be avoided.
The ultimate purpose of medicine is to assist all beings in experiencing a positive joyful and healthy life; to cure disease is the relative purpose. The different parts of the body are overlapping networks forming exquisitely organized whole. There is evidence to suggest connections between immune function and concomitant stress, though the complete chain of causation leading to physical pathology is yet to be established. It is possible that the outer world through several experiences in life remolds our inner world. Just like the disturbing stress arousal response, there must be a healing "relaxation response". Intelligence can thus create a physiology where the healing activity is assisted. It also appears that the body does not differentiate carefully between various types of stressors in determining its response. It may, therefore, follow that nonspecific psychological interventions may benefit physiology. Moderate alterations in an individual's social and emotional burden may slow down or reverse many stress related changes in the neuroendocrine-immune axis function. There is a definite need for integration of the growing body of research findings in Psychoneuroimmunology, into coherent models for clinical application.
[Table - 1], [Table - 2]