Systemic Inflammation and Anhedonic Responses to an Inflammatory Challenge in Adults With Major Depressive Disorder: A Randomized Controlled Trial

• DOI: 10.1176/appi.ajp.20240142
• Publication Date: 2025-04-23T07:00:31Z
• Authors: Jonathan Savitz; Leandra K. Figuer...; T. Kent Teague; Hung-Wen Yeh; Haixia Zheng; Rayus Kuplicki; Kaiping Burrows; Nour El-Sabbagh; MacGregor Thomas; Isaac Ewers; Yoon-Hee Cha; Salvador Guinjoan; Sahib S. Khalsa; Martin P. Paulus; Michael R. Irwin
• Keywords: Anhedonia; Inflammatory response

The authors sought to determine whether an inflammatory challenge with lipopolysaccharide (LPS) differentially impacts symptoms of anhedonia in participants major depressive disorder high (≥3 mg/L) and low (≤1.5 serum C-reactive protein (CRP) concentrations. Sixty-eight were randomly assigned, a 1:1 ratio, receive LPS (0.8 ng/kg body weight) or placebo (saline) parallel-group double-blind design. Participants stratified according baseline CRP concentrations, yielding four groups: high-CRP (N=13), low-CRP (N=19), (N=19). Blood was sampled at baseline, 1, 1.5, 3.5, 6, 24 hours, 1 week after saline administration, concurrent assessment psychological outcomes. primary outcome measure the Snaith-Hamilton Pleasure Scale (SHAPS), contrast interest change between 1.5 hours (peak response) versus groups receiving LPS. Secondary outcomes included Montgomery-Åsberg Depression Rating (MADRS) levels three cytokines: interleukin-6 (IL-6), IL-10, tumor necrosis factor (TNF). Data analyzed linear mixed models. Significantly greater increases self-reported (on SHAPS) IL-6 observed groups. There no significant differences for TNF IL-10. MADRS not administered hours; secondary analyses showed group-by-condition-by-time interaction driven by decrease scores group. Depressed individuals systemic inflammation appeared be biologically primed respond more strongly stimuli, psychologically, this sensitization impacted symptom anhedonia, outcome.