Abstract

Increasing evidence from animal and human studies suggests that inflammation may be involved in mood disorders. Sickness behavior and emotional changes induced by experimental inflammatory stimuli have been extensively studied in humans and rodents to better understand the mechanisms underlying inflammation-driven mood alterations. However, research in animals and humans have remained compartmentalized and a comprehensive comparison of inflammation-induced sickness and depressive-like behavior between rodents and humans is lacking. Thus, here, we highlight similarities and differences in the effects of bacterial lipopolysaccharide administration on the physiological (fever and cytokines), behavioral and emotional components of the sickness response in rodents and humans, and discuss the translational challenges involved. We also emphasize the differences between observable sickness behavior and subjective sickness reports, and advocate for the need to obtain both subjective reports and objective measurements of sickness behavior in humans. We aim to provide complementary insights for translational clinical and experimental research on inflammation-induced behavioral and emotional changes, and their relevance for mood disorders such as depression.

Highlights

  • In this mini-review, we provide a short historical introduction of the concept of sickness behavior and of the links between sickness behavior and symptoms of depression in the past 30 years, and introduce the model of LPS-induced experimental inflammation

  • There is a clear lack of objective measurements of sickness behavior in humans

  • Sickness feelings are an essential part of sickness behavior, measuring objective changes that occur and correlate with sickness feelings and mood alterations in controlled experimental human studies would allow to further understand LPS-induced behavioral changes observed in animals

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Summary

Introduction

In this mini-review, we provide a short historical introduction of the concept of sickness behavior and of the links between sickness behavior and symptoms of depression in the past 30 years (part 1.1), and introduce the model of LPS-induced experimental inflammation (part 1.2). We provide a comparison of LPS-induced physiological changes, such as cytokine production and fever induction (part 2), LPSinduced sickness behavior, focusing on reduced activity/increased fatigue, lowered food consumption and appetite, and social withdrawal (part 3), and LPS-induced mood-related changes, such as depressivelike and anxiety-like behaviors (part 4) between animals and humans. We end with the conclusion that, in spite of difficult points of comparison, there are many similarities between animal and human sickness behavior (Fig. 1) and recommendations for future research (part 5)

Sickness behavior and symptoms of depression
Translational issues of the model of LPS-induced experimental inflammation
LPS-induced cytokine and fever responses in rodents and humans
LPS-induced sickness behavior in rodents and humans
LPS-induced depressive-like and anxiety-like behavior in rodents and humans
Conclusion
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