Obesity, low-grade inflammation, and inflammatory response to immune challenge modulate willingness to expend effort for reward

Abstract

Background

Inflammation is increasingly considered a vulnerability factor for deficits in reward motivation. It remains unclear if such motivational changes differ between acute and chronic low-grade inflammation. Given obesity’s link to chronic low-grade inflammation, the present study a priori tested the effects of obesity and low-grade inflammation (elevated CRP concentrations), as well as acute inflammation (experimental immune challenge using lipopolysaccharide), on motivation for a monetary reward. Moreover, the wear-and-tear induced by chronic inflammation could amplify motivational changes induced by immune challenge. Thus, we also tested the a priori hypotheses that acute inflammation is associated with more strongly altered reward motivation for individuals with higher low-grade inflammation, and for obese than normal-weight individuals.

Methods

Obese (n = 14) and normal-weight (n = 21) young adults, all without current or past history of medical or psychiatric conditions, were intravenously injected with a bacterial endotoxin (lipopolysaccharide, LPS [0.8 ng/kg body weight]) to trigger an acute inflammatory response, and placebo (saline) in a counterbalanced, randomized, crossover design. The Effort Expenditure for Reward Task (EEfRT) was administered 2 h following each injection to assess reward motivation. Blood was sampled pre- and post-injection to quantify concentrations of inflammatory proteins (interleukin [IL]-6 and C-reactive protein [CRP]).

Results

Obesity and higher low-grade inflammation (baseline CRP) were associated with overall reduced motivation to expend effort for reward in the placebo condition. Interactions with reward magnitude were observed, so that this effect occurred at smaller reward values, but not when reward values increased. However, these interaction effects were not significant in a posteriori sensitivity analyses. LPS-induced inflammatory responses (IL-6 concentrations during EEfRT) were associated with a weaker influence of reward magnitude on increasing effort. Unexpectedly, we did not detect the amplification effect of obesity and its associated low-grade inflammation on the ability of lipopolysaccharide to modulate reward motivation.

Conclusions

Lipopolysaccharide-induced and low-grade inflammation may alter how effort is allocated towards reward: low-grade inflammation reduced the willingness to expend effort, while acute inflammation dampened reward sensitivity. This study offers a nuanced understanding of inflammatory processes underlying alterations in reward motivation.