A small, tightly controlled study in healthy women has shown that a brief inflammatory challenge can temporarily blunt the pleasure people derive from activities and reduce the desire to socialise. In a double-blind, placebo-controlled trial, researchers induced acute inflammation with an intravenous endotoxin dose and tracked mood and social motivation over several hours. By two hours after administration, participants given endotoxin reported higher anhedonia and a reduced wish to chat with others, compared with a saline placebo. The trial involved 40 women aged 25 to 44 and was conducted at the Norman Cousins Center for Psychoneuroimmunology at the University of California, Los Angeles.
Anhedonia, the reduced ability to feel pleasure, is a central symptom of depression and can blunt everyday activities and social interactions. Scientists have increasingly suspected that inflammation plays a role in this mood disturbance.
Participants were 40 healthy women aged 25 to 44, recruited from the Los Angeles area as part of a larger clinical trial. Eighteen were randomised to receive a low-dose endotoxin intravenously, while 22 received a saline placebo. Endotoxin triggers a brief inflammatory response; neither participants nor researchers knew who had received endotoxin.
Before the injection and hourly thereafter, blood samples were taken to measure inflammatory markers and participants reported fatigue and sickness. Two hours after injection, around the peak of the inflammatory response, they completed two tasks assessing sensitivity to positive social cues.
One task involved watching videos of faces that shifted from neutral to angry, fearful or happy expressions, and participants had to identify the emotion quickly. The second task used a dot-probe paradigm to see where attention was drawn to emotional versus neutral faces.
To gauge social motivation, participants rated how much they would like to engage in four activities: chat with another person, complete a puzzle game, sit quietly by themselves, or watch short film clips. These ratings were collected at a screening visit and again two hours after the injection. Anhedonia was assessed with a questionnaire before the injection and two and four hours afterward.
Two hours after the injection, women who had received endotoxin reported more anhedonia and less desire to chat than those given placebo. The effect appeared specific to social activity, as endotoxin did not significantly change how much participants wanted to do the puzzle, watch film clips, or sit quietly. The results remained after accounting for physical sickness symptoms and fatigue.
Among endotoxin recipients, larger increases in the inflammatory marker TNF-α during the first hour were associated with larger increases in anhedonia and larger drops in the wish to chat.
Effects on sensitivity to positive social cues were more limited. The placebo group became slightly more accurate at recognising happy faces on the second emotion-recognition run, while those who received endotoxin did not improve; however, the authors note the baseline difference between groups makes this finding difficult to interpret. Endotoxin had no effect on attention allocation in the dot-probe task.
“Findings suggest that acute inflammatory challenge induces anhedonia and reduces social motivation, with more limited effects on sensitivity to positive social cues, highlighting specific reward-related pathways through which immune activation may contribute to inflammation-associated depression,” the study authors concluded.
The researchers emphasised that the study’s limitations should be acknowledged: all participants were women aged 25–44, and the sample size was small. Results in men and other age groups may differ.
They also noted that endotoxin produces a brief, intense inflammatory response, unlike the more persistent, lower-level inflammation seen in some forms of depression, and that further work is needed to determine clinical relevance. The authors suggest that reduced social desire during acute illness could reflect an adaptive energy-conserving response. Social motivation was measured by self-reported preferences rather than observed social behaviour.
The paper, “Effects of acute inflammatory challenge on anhedonia and social reward processing: A randomized controlled trial of endotoxin,” was authored by Chloe C. Boyle, Flora Blandl, Naomi I. Eisenberger, Richard Olmstead, Joshua H. Cho, Dominique Piber, and Michael R. Irwin.
