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Year : 2006  |  Volume : 12  |  Issue : 1  |  Page : 29-33

Perspectives on psycho-neuro-immunology in oncology

Department of Anaesthesiology, St. John's National Academy of Medical Sciences, Bangalore - 560 034, Karnataka, India

Correspondence Address:
Nandini Vallath
Department of Anaesthesiology, St. John's National Academy of Medical Sciences, Bangalore - 560 034, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1075.25916

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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.

How to cite this article:
Vallath N. Perspectives on psycho-neuro-immunology in oncology. Indian J Palliat Care 2006;12:29-33

How to cite this URL:
Vallath N. Perspectives on psycho-neuro-immunology in oncology. Indian J Palliat Care [serial online] 2006 [cited 2021 May 12];12:29-33. Available from:

  Introduction Top

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.[1] 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.[2]

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[3] 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[4] and that neuropeptide receptors occur on all mobile cells of the immune system.[5] Furthermore, products of the activated immune cells are able to transmit signals directly to leucocytes and indirectly via neuroendocrine and autonomic nervous pathways.[6],[7] 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.[8] 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.[9] 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.[10] Depression has been found to decrease the lymphocyte mitogen response and natural killer cell activity[11] 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.[12]

In 1982, Robert Ader,[13] 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.[13],[14],[15],[16],[17] 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.

  Psychoneuroimmunomodulation Top

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.[18]

A structured psycho-education therapy for melanoma patients reduced the psychological distress, positively influenced immune changes and improved survival.[19],[20] 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.[21]

Hermandez Reif[22] found massage therapy reduced anxiety, mood swings and improved NKC and lymphocyte numbers in stage 1 and 2 breast cancer patients.

  Spirituality and Psyche Top

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[23] and beneficial effects for elevated mood states,[14],[15],[16] guided relaxation,[24] mindfulness based stress reduction and meditation[25],[26],[27],[28] on immune system functioning and in cancer therapy.

  Bringing Spiritual and Emotional Intelligence to Medical Care Top

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[29] 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[30] 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.

  Conclusion Top

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.[31] 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.

  References Top

1.Karl Goodkin, Adrian Visser (editors). Psychoneuro-immunology. Stress, Mental Disorders and Health,1st edn. Washington: American Psychiatric press, 2000.  Back to cited text no. 1    
2.Ader R, Felten DL, Cohen N (editors). Psychoneuro-immunology, 2nd edn. New York: Academic Press, 1991.  Back to cited text no. 2    
3.Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res 1970; 13:1-27.   Back to cited text no. 3  [PUBMED]  
4.Felten DL, Felten SY, Carson SL, Olschowka JA, Livnat S. Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol 1985;135:755-65.  Back to cited text no. 4    
5.Pert CB, Ruff MR, Weber RJ, Herkenham M. Neuropeptides and their receptors: a psychosomatic network. J Immunol (suppl) 1985;135:820-6.   Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Hall NR, McGillis JP, Spangelo BL, Goldstein AL. Evidence that thymosins and other biological response modifiers can function as neuroactive immunotransmitters. J Immunol (suppl) 1985;135:806-11.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Cancer Care at the interface of Psycho oncology and Psychoneouroimmunology 81/maggies/files/psychology_paper.pdf accessed on 06.05.2006   Back to cited text no. 7    
8.O'Connor TM, O'Halloran DJ, Shanahan F. The stress response and the Hypothalamo Pituitary Axis; from molecule to melancholia. QJM 2000;93:323-33.  Back to cited text no. 8    
9.Courtney JG, Longnecker MP, Theorell T, Gerhardsson de Verdier M. Stressful life events and the Risk of Colorectal Cancer. Epidemiology 1993;4:407-14.  Back to cited text no. 9    
10.Pettingale KW, Morris T, Greer S, Haybittle JL. Mental attitudes to cancer: An additional prognostic factor. The Lancet 1985;30:750.  Back to cited text no. 10    
11.Irwin M, Daniels M, Bloom ST, Smith TL, Weiner H. Life events, depressive symptoms and immune function. Am J Psychiatr 1987;144:437-41.  Back to cited text no. 11    
12.Todarello O, Casamassima A, Daniele S, Marinaccio M, Fanciullo F, Valentino L, Tedesco N, Wepse LS , Simone G, Marinaccio L. Alexithymia, immunity and cervical intraepithelial neoplasia: replication. Psychother Psychosom 1997;66:208-13.  Back to cited text no. 12    
13.Ader R, Cohen N. Behaviourally conditioned immunosuppression and murine systemic lupus erythematosis. Science 1982;215:1534-6.  Back to cited text no. 13    
14.Felten DL, Felten SY. "Noradrenergic symphatetic neural interactions with the immune system: structure and function". Immunol Rev. 1987;100:225-60.   Back to cited text no. 14    
15.Schedlowski M, Kugler J, Schulz KH, Merz F, Riiter M, editors. Psychoneuroimmunology: "How the brain and the immune system communicate with each other". Wien, Pabst Science Publishers: Berlin, USA; 1994.  Back to cited text no. 15    
16.Blalock JE: The syntax of immune-neuroendocrine communication: Immunol Today 1994;15:504-11.   Back to cited text no. 16    
17.Song C. The effect of thymectomy and IL-1 on memory. Brain Behav Immun 2002;16:557-68.   Back to cited text no. 17    
18.Spiegel D, Bloom JR, Kraemer HC, Gatthei LE. Effect of psychological treatment on survival of patients with metastatic breast cancer. The Lancet 1989;2:888-91.   Back to cited text no. 18    
19.Fawzy FI,Kemeny ME, Fawzy NW, Elashoff R, Morton D, Cousins N, Fahey JL. A structured psychiatric intervention for cancer patients.II. Changes over time in immunologic measures. Arch Gen Psychiatr 1990;47:729-35.   Back to cited text no. 19    
20.Fawzy FI, Canada AL, Fawzy NW. Malignant melanoma: effects of a brief, structured psychiatric intervention on survival and recurrence at 10-year follow-up. Arch Gen Psychiatr 2003;60:100-3   Back to cited text no. 20    
21.Cousins, Norman. Head first: The Biology of Hope. E P Dutton: New York; 1989.   Back to cited text no. 21    
22.Hernandez-Reif M, Ironson G, Field T, Hurley J, Katz G, Diego M, Weiss S, Fietcher MA, Schanberg S, Kuhn C, Burman I. Breast cancer patients have improved immune and neuroendocrine function following massage therapy. J Psychosomat Res 2004;57:45-52.   Back to cited text no. 22    
23.Kaczorouski JM. Spiritual wellbeing and anxiety in adults diagnosed with cancer. Hosp J 1989;5:105-16.   Back to cited text no. 23    
24.Lekander M, Furst CJ, Rotstein S, Hursti TJ, Fredriksen M. Immune effects of relaxation during chemotherapy for ovarian cancer. Psychother Psychosomat 1997;66:185-9.   Back to cited text no. 24    
25.Itami, Jinroh, "Morita Concept and the Treatment of Cancer in Foreign Countries," J Morita Ther 1994;5:157-61.   Back to cited text no. 25    
26.Mears A. Regression of Cancer of the rectum after intensive Meditation. Med J Aust 1982;17:539-40.   Back to cited text no. 26    
27.Carlson LE, Speca M, Patel KD. Mindfulness based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate[ DHEAS] and melatonin in breast and prostate cancer out patients. Psychoneuroendocrinology 2004;29:448-74.   Back to cited text no. 27    
28.Jevning R, Wallace RK, Beidebach M. The physiology of meditation: a review. A wakeful hypometabolic integrated response Neurosci Biobehav Rev 1992;16:415-24.   Back to cited text no. 28    
29.Thaithireeya Upanishad. Ancient Indian Scripture 4000-5000 BC  Back to cited text no. 29    
30.Yoga vasishta. Ancient Indian scripture 4000 BC  Back to cited text no. 30    
31.Jeremy Geffen. The Journey Through Cancer: Chapter 1, Crown 2000.  Back to cited text no. 31    


[Table - 1], [Table - 2]

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