According to a randomized placebo-controlled study published in Psychoneuroendocrinology. 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 daily 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 pleasurable.
People with anhedonia tend to lose interest in hobbies they once enjoyed, socializing, or 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.
Inflammation is a natural response of the immune system to infections and injury, 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 felt by receiving it, called “liking.” Previous studies suggest that inflammation may reduce motivation to seek 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 a vital 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 their motivation to seek social contact and their sensitivity to positive social cues. To do this, they conducted a double-blind, placebo-controlled trial in healthy women. Researchers focused on women because they are particularly vulnerable to depression, and previous studies have shown that women may be more prone than men to depressed mood after an inflammatory challenge.
Participants were 40 healthy women aged 25 to 44, recruited from the Los Angeles area as part of a larger clinical trial. None currently had a 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 by intravenous injection, and 22 received a saline injection 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 knew directly who received endotoxin and who received the placebo.
Before the injection and every hour afterward, participants provided blood samples, which allowed researchers to measure inflammatory markers and reported symptoms of fatigue and nausea. Before the injection and again two hours later, around the peak of the inflammatory response, they performed two tasks measuring sensitivity to positive social cues.
In the first task, participants watched videos of faces gradually changing from a neutral expression to one of anger, fear, or joy, and tried to identify the emotion as quickly as possible. In the second task, which measures where people’s attention is attracted, participants briefly saw pairs of emotional and neutral faces and then responded to a dot that appeared at 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 alone, or watch short movie clips. They completed these assessments at an earlier screening visit and again two hours after the injection. Anhedonia was assessed using a questionnaire before the injection and two and four hours afterwards.
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 the women’s willingness to do the puzzle, watch movie clips, or sit quietly. Both effects occurred after researchers took into account symptoms of physical illness and fatigue.
The increase in anhedonia was short-lived, with scores returning to baseline levels four hours after injection, although inflammatory markers remained elevated. Among women who received endotoxin, greater increases in the inflammatory protein TNF-α during the first hour were associated with greater increases in anhedonia and greater declines in desire to chat.
The 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 the women who received endotoxin did not improve. However, the placebo group had been slightly less accurate at the start, so the authors believe this result should be interpreted with caution. Endotoxin had no effect on where participants’ attention was focused in the second task.
“The results suggest that an 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 scientific understanding of the psychological effects of inflammation. It should be noted, however, that the study participants were all women aged 25 to 44 and the sample was small. Results in men and other age groups may 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. A reduced desire to socialize during acute illness may also reflect a coping effort to conserve energy. Finally, social motivation was measured by asking participants how much they would like to do certain activities, rather than observing whether they actually sought social contact.
The article, “Effects of an 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.
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