Smile! It is for free!

Despite employing unknown mechanisms, scientific studies have conclusively established that a tight connection between immune system and psychological and cognitive factors exists1-6. The so called “positive emotions” and overall happiness can strengthen our immune system and improve our well-being. Intriguingly, our body is even able to react differently to diverse types of well-being. Ancient philosophers distinguished between two main forms of well-being:

  • Hedonic well-being which represents the sum of an individual’s positive affective experiences
  • Eudaimonic well-being which is an inner process that results from striving toward meaning and a noble purpose beyond simple self-gratification

A recent study, published in the international peer-reviewed journal PNAS, found out that hedonic and eudaimonic well-beings are able to activate distinct gene regulatory programs. These distinctive programs were detected in the peripheral blood mononuclear cells of 80 healthy adults via gene expression profiles7.To a similar extent, positive expectations can have a huge effect on our health. Going back to the 18th century the so called “animal magnetism”, also known as mesmerism, was extremely famous and benefit from this practice can be fairly attributed to the positive and encouraging emotions transmitted by the therapist to the patient. Even Arthur Schopenhauer in his essay “Versuch über das Geistersehn und was damit zusammenhängt“ (Research on ghosts, witches and everything connected with it), appoints curative effects to the power of the mind (or suggestion).

Nowadays, after 50 long years of scientific research using placebo controls is clear that positive expectation toward clinical progress can improve patient’s prognosis. It is a matter of fact that placebo can increase survival and recovery of the patients: however, the underlying mechanisms remain elusive, albeit a link with brain reward circuitry has been proposed. A new study from the Technion–Israel Institute of Technology, Israel, finally shows the existence of a causal link between the reward system in the brain and the innate and adaptive immunity in mice. Indeed, switching on the reward system through activation of a specific cerebral area was sufficient to dramatically boost innate and adaptive immune responses against the pathogen E.Coli8.

But how the brain communicated to the immune cells?

The region activated in this study comprises neurons projecting within zones of the brain that regulates the autonomic nervous system (ANS). This system controls involuntary processes (e.g blood pressure), which are crucial for our survival. Particularly, an important branch of the ANS is the sympathetic nervous system (SNS) whose neurones reach all lymphoid organs of the body. When the authors of the study blocked this system, immune protection was abolished despite reward system activation.

Marina Corral Spence/Nature Publishing Group

As for the process by which immune system can control social behaviour (more info here), all the activities that imply an activation of the VTA system, such as having sex, socializing and traveling, tremendously expose our body to pathogens. From the evolutionary point of view is extremely helpful to have a system that on the one hand control reward circuitry and on the other strengthen our immune system.

This causal link between reward system activation and immune system found by Ben-Shaanan and colleagues, partly explains why placebo effects and positive experience can be so clinically relevant. In future, this entire field has to be seriously taken into account for improving clinical outcomes.

Davide Mangani



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  • Segerstrom, S.C. & Miller, G.E. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol. Bull. (2004).
  • Barak, Y.The immune system and happiness. Rev. (2006).
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  • Segerstrom, S.C. & Sephton, S.E.Optimistic expectancies and cell-mediated immunity: the role of positive affect. Sci. (2010).
  • Fredrickson, al. A functional genomic perspective on human well-being. Natl. Acad. Sci. USA (2013).
  • Ben-Shaanan, al. Activation of the reward system boosts innate and adaptive immunity Med. (2016).