Inflammation briefly dampens pleasure and the desire to socialize, placebo-controlled study finds

Experimentally inducing inflammation in healthy women temporarily increased symptoms of anhedonia, a reduced ability to feel pleasure, and lowered their desire to socialize, according to a randomized, placebo-controlled study published in Psychoneuroendocrinology. The inflammation had more limited effects on how the women responded to smiling faces.

Depression is one of the leading causes of disability worldwide, affecting not only people’s emotional well-being but also their ability to enjoy everyday activities and maintain social relationships. One of its most troubling symptoms is anhedonia, the reduced ability to experience pleasure or interest in things that were previously enjoyable.

People experiencing anhedonia tend to lose interest in hobbies they once loved, in socializing, or in other activities that once brought them satisfaction. Although the causes of anhedonia are not fully understood, growing evidence suggests that inflammation may play an important role in it.

Inflammation is a natural response of the immune system to infections and injuries, but it can also influence how the brain processes emotions, motivation, and rewards. Researchers distinguish between two important aspects of reward processing: the motivation to pursue something desirable, often called “wanting,” and the pleasure experienced when receiving it, known as “liking.” Previous studies suggest that inflammation can reduce motivation to pursue rewards, although its effects on the actual experience of pleasure are less consistent. This may be particularly important for social interactions, since positive experiences such as receiving approval, feeling accepted, or seeing a friendly smile play an essential role in psychological well-being.

Study author Chloe C. Boyle of the Norman Cousins Center for Psychoneuroimmunology at the University of California, Los Angeles, and colleagues wanted to test whether inducing acute inflammation would affect how people process social rewards, including both their motivation to seek out social contact and their sensitivity to positive social cues. To do so, they conducted a double-blind, placebo-controlled trial in healthy women. The researchers focused on women because they are particularly vulnerable to depression, and previous studies have found that women may be more prone than men to depressed mood after an inflammatory challenge.

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The participants were 40 healthy women between 25 and 44 years of age, recruited from the Los Angeles area as part of a larger clinical trial. None had a current psychiatric illness, smoked, or took antidepressants or medications known to affect the immune system. Eighteen were randomly assigned to receive a low dose of endotoxin through an intravenous injection, and 22 received an injection of saline solution as a placebo.

Endotoxin is a component of the outer membrane of Gram-negative bacteria that triggers a short-lived inflammatory response when it enters the bloodstream. Neither the participants nor the researchers working with them directly knew who had received endotoxin and who had received the placebo.

Before the injection and every hour afterward, participants provided blood samples, which allowed the researchers to measure inflammatory markers, and reported symptoms of fatigue and feeling sick. Before the injection and again two hours later, around the peak of the inflammatory response, they completed two tasks measuring sensitivity to positive social cues.

In the first task, participants watched videos of faces gradually shifting from a neutral expression to an angry, fearful, or happy one, and tried to identify the emotion as quickly as possible. In the second task, which measures where people’s attention is drawn, participants briefly saw pairs of emotional and neutral faces and then responded to a dot that appeared in the location of one of them.

To measure social motivation, participants rated how much they would like to do each of four short activities: chat with another person, complete a puzzle game, sit quietly by themselves, or watch short film clips. They completed these ratings at an earlier 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 received endotoxin reported more anhedonia and less desire to chat with another person than women who received the placebo. The effect on motivation appeared specific to social activity, as endotoxin did not significantly change how much women wanted to do the puzzle, watch film clips, or sit quietly. Both effects held after the researchers accounted for physical sickness symptoms and fatigue.

The increase in anhedonia was short-lived, with scores returning to their original levels four hours after the injection, even though inflammatory markers remained elevated. Among women who received endotoxin, larger increases in the inflammatory protein TNF-α during the first hour were associated with larger increases in anhedonia and larger drops in the desire to chat.

Effects on sensitivity to positive social cues were more limited. Women in the placebo group became slightly more accurate at recognizing happy faces the second time they completed the emotion recognition task, while women who received endotoxin did not improve. However, the placebo group had been somewhat less accurate at the start, so the authors say this finding should be interpreted with caution. Endotoxin had no effect on where participants’ attention was drawn in the second 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 study contributes to the scientific understanding of the psychological effects of inflammation. However, it should be noted that the study participants were all women between 25 and 44 years of age, and the sample was small. Findings in men and other age groups might differ.

Additionally, endotoxin produces a brief, intense inflammatory response that differs from the more persistent, lower-level inflammation seen in some people with depression, and the authors note that the relevance of their findings to clinical depression requires further study. Reduced desire to socialize during acute illness may also reflect an adaptive effort to conserve energy. Finally, social motivation was measured by asking participants how much they would like to do certain activities, rather than by observing whether they actually sought out social contact.

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.