Sickness behavior is not all about the immune response: Possible roles of expectations and prediction errors in the worry of being sick

Brain Behav Immun. 2018 Nov:74:213-221. doi: 10.1016/j.bbi.2018.09.008. Epub 2018 Sep 11.


Background: People react very differently when sick, and there are only poor correlations between the intensity of the immune response and sickness behavior. Yet, alternative predictors of the individual differences in sickness are under-investigated. Based on the predictive coding model of placebo responses, where health outcomes are function of bottom-up sensory information and top-down expectancies, we hypothesized that individual differences in behavioral changes during sickness could be explained by individual top-down expectancies and prediction errors.

Methods: Twenty-two healthy participants were made sick by intravenously administering lipopolysaccharide (2 ng/kg body weight). Their expectations of becoming sick were assessed before the injection.

Results: Participants having lower expectations of becoming sick before the injection reacted with more emotional distress (i.e., more negative affect and lower emotional arousal) than those with high expectations of becoming sick, despite having similar overall sickness behavior (i.e., a combined factor including fatigue, pain, nausea and social withdrawal). In keeping with a predictive coding model, the "prediction error signal", i.e., the discrepancy between the immune signal and sickness expectancy, predicted emotional distress (reduction in emotional arousal in particular).

Conclusion: The current findings suggest that the emotional component of sickness behavior is, at least partly, shaped by top-down expectations. Helping patients having a realistic expectation of symptoms during treatment of an illness may thus reduce aggravated emotional responses, and ultimately improve patients' quality of life and treatment compliance. REGISTRATION: "Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences",, registration number: NCT02529592.

Keywords: Emotions; Expectation; Inflammation; Lipopolysaccharide; Negative mood; Placebo response; Prediction error; Predictive coding; Sickness behavior.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / physiology
  • Adult
  • Anxiety / psychology
  • Emotions / drug effects
  • Female
  • Forecasting / methods
  • Humans
  • Illness Behavior / drug effects
  • Illness Behavior / physiology*
  • Lipopolysaccharides / pharmacology
  • Male
  • Motivation / drug effects*
  • Motivation / physiology
  • Quality of Life
  • Stress, Psychological / immunology
  • Stress, Psychological / psychology*


  • Lipopolysaccharides

Associated data