Systemic Inflammation as a Modulator of Anhedonia in Major Depressive Disorder: Insights from an LPS Challenge Trial

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This randomized controlled trial demonstrates that in adults with major depressive disorder (MDD), those with elevated systemic inflammation—as indicated by high baseline serum C-reactive protein (CRP)—show increased anhedonic symptoms following a standardized inflammatory challenge with lipopolysaccharide (LPS). Significant elevations in interleukin-6 (IL-6) accompanied this symptom exacerbation, suggesting a biologically primed inflammatory sensitization influencing reward-related neuropsychological processes.

Secondary findings indicated dynamic depressive symptom changes over 24 hours, emphasizing the complex temporal relationship between inflammation and mood in MDD. These findings support targeting inflammation in precision psychiatry approaches for anhedonia in depression.