Somatization: A psychoneuroimmune perspective

doi:10.1016/j.psyneuen.2005.03.011

Psychoneuroendocrinology

Volume 30, Issue 10, November 2005, Pages 947-952

https://doi.org/10.1016/j.psyneuen.2005.03.011 Get rights and content

Summary

The concept of somatization has a long history in psychosomatic medicine. What is missing, however, is an understanding of the way patients are able to perceive and represent somatic symptoms. Recent advances in psychoneuroimmunology offer new perspectives in this area. Proinflammatory cytokines produced by cells of the innate immune system in response to pathogen-associated molecular patterns and to endogenous danger signals act on the central nervous system via afferent and humoral pathways to trigger a brain cytokine system that organizes the sickness response in its subjective, behavioral, and metabolic components. There is evidence that prolonged activation of this system can precipitate the development of depressive disorders in vulnerable patients. The mechanisms that are responsible for the transition from sickness to depression involve alterations in tryptophan metabolism. There is also some indication that the brain cytokine system can become sensitized in response to non-immune stressors or to immune stressors occurring early in life. All these new findings have the potential to contribute to a renewed biopsychological approach to somatization and somatoform disorders.

Introduction

Somatic symptoms occur in many medically based conditions and are at the origin of the patient's will to consult with a physician and receive appropriate etiological and/or symptomatic treatments. Somatoform symptoms present like somatic symptoms but they do not have any identified medical cause and are often associated with psychopathology. Somatization is the tendency to express emotional problems in somatoform symptoms. There have been many attempts to define and measure somatization, characterize patients at risk, and identify possible causal environmental events including cultural factors (Portegijs et al., 1996, Hollifield et al., 1999, Lundh and Simonsson-Sarnecki, 2001, North, 2002). The purpose of the present review paper is not to discuss the concept of somatization and the way it relates to subjective health complaints, but to approach somatization from a very different perspective based on the new biopsychological knowledge gained during the last 15 years on the mechanisms allowing the brain to perceive and represent what is going in the body. The implicit assumption is that this information could be of help to understand the biopsychological basis of somatization. More specifically, I propose that somatization might be nothing else than the outward manifestation of sensitization of the brain cytokine system that is normally activated in response to activation of the innate immune system and mediates the subjective, behavioral and physiological components of sickness (Dantzer, 2001).

Section snippets

Sickness is represented in the brain

The basic mechanisms that explain why we feel sick and behave in a sick way when we are ill have been elucidated during the recent years (Fig. 1). Activation of innate immune cells by pathogen-associated molecular patterns results in the synthesis and release of proinflammatory cytokines. This is possible because innate immune cells have membrane receptors that recognize these pathogen-associated molecular patterns. These receptors belong to the family of Toll-like receptors (TLR) (Beutler, 2004

Danger signals can trigger the cytokine system in the brain

Details of the brain cytokine system have been worked out by studying the brain effects of pathogen-associated molecular patterns or recombinant cytokines. However, more and more evidence points to the possibility that the peripheral innate immune system and probably the brain cytokine system can be triggered by ‘danger’ signals.

This concept has been initially developed by Polly Matzinger. It proposes that the immune system always sees a pathogen within the context of danger signals that are

Cytokine-induced sickness is a motivational state

The behavioral alterations that develop during sickness are not just the result of a decreased ability to react to the external world and engage in physical activities. Cytokines actually function as a motivational signal that tells the brain to change the organism priorities in face of the threat represented by pathogens or danger signals. This reorganization of priorities results in changes at the subjective, behavioral and physiological levels (Fig. 2). Malaise, abrogation of costly energy

Prolonged activation of the brain cytokine system induces mood disorders

An important implication of the motivational aspect of cytokine-induced sickness behavior is that it makes sickness behavior reintegrate the realm of physiology. There is nothing wrong with being sick during an infection in the same way that it is normal to experience fear when there is a danger. Sickness becomes abnormal or pathological when its intensity is disproportionate in relation to its eliciting factors or when it occurs in the absence of any immune triggering stimulus.

Normally, the

Implications and conclusion

Humans like animals have in their brains a molecular and cellular system that is geared to represent the dangers occurring in various parts of the body that are monitored by the innate immune system. This system coordinates the organism's response to these dangers. The discovery of the brain cytokine system opens new avenues for understanding mechanisms of perception and representation of symptoms. The brain cytokine system organizes the subjective, behavioral and metabolic components of the

Acknowledgements

The author's work reported in this review paper has been supported by INRA, CNRS and NIH (MH 71349).

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Somatization: A psychoneuroimmune perspective

Summary

Introduction

Section snippets

Sickness is represented in the brain

Danger signals can trigger the cytokine system in the brain

Cytokine-induced sickness is a motivational state

Prolonged activation of the brain cytokine system induces mood disorders

Implications and conclusion

Acknowledgements

Brain Behav. Immun.

Physiol. Behav.

Brain Behav. Immun.

Mol. Immunol.

Brain Behav. Immun.

Auton. Neurosci.

Psychoneuroendocrinology

Psychosomatics

Trends Neurosci.

Auton. Neurosci.

Am. J. Pathol.

J. Neuroimmunol.

Brain Res.