The following is a summary of “Systemic Inflammation and Anhedonic Responses to an Inflammatory Challenge in Adults With Major Depressive Disorder: A Randomized Controlled Trial,” published in the April 2025 issue of American Journal of Psychiatry by Savitz et al. 

Researchers conducted a retrospective study to assess whether a lipopolysaccharide (LPS)-induced inflammatory challenge worsens anhedonia in major depressive disorder based on high (≥3 mg/L) or low (≤1.5 mg/L) C-reactive protein (CRP) levels. 

They randomly assigned 68 participants with major depressive disorder in a 1:1 ratio to receive LPS (0.8 ng/kg) or placebo in a parallel-group double-blind design. Baseline CRP stratified participants into 4 groups: high-CRP LPS (N = 13), low-CRP LPS (N = 19), high-CRP placebo (N = 13), and low -CRP placebo (N = 19). They collected blood at baseline, 1, 1.5, 3.5, 6, 24 hours, and 1-week post-injection with psychological assessments. The primary outcome was the change in Snaith-Hamilton Pleasure Scale (SHAPS) score from baseline to 1.5 hours. Secondary outcomes included the Montgomery-Åsberg Depression Rating Scale (MADRS) and serum IL-6, IL-10, and tumor necrosis factor (TNF). Data were analyzed using linear mixed models. 

The results showed greater increases in SHAPS scores and IL-6 levels from baseline to 1.5 hours in the high-CRP LPS group than in the low-CRP LPS group. No differences were seen for TNF or IL-10. A significant group-by-condition-by-time interaction was observed, indicating a greater decrease in MADRS scores from baseline to 24 hours in the high-CRP group. 

Investigators appeared biologically primed to respond more strongly to inflammatory stimuli. They showed greater anhedonic responses, indicating psychological sensitization in those with systemic inflammation. 

Source: psychiatryonline.org/doi/10.1176/appi.ajp.20240142