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

Document Type

Article

Publication Date

6-1-2025

Identifier

DOI: 10.1176/appi.ajp.20240142

Abstract

OBJECTIVE: The authors sought to determine whether an inflammatory challenge with lipopolysaccharide (LPS) differentially impacts symptoms of anhedonia in participants with major depressive disorder with high (≥3 mg/L) and low (≤1.5 mg/L) serum C-reactive protein (CRP) concentrations.

METHODS: Sixty-eight participants with major depressive disorder were randomly assigned, in a 1:1 ratio, to receive LPS (0.8 ng/kg body weight) or placebo (saline) in a parallel-group double-blind design. Participants were stratified according to baseline CRP concentrations, yielding four groups: high-CRP LPS (N=13), low-CRP LPS (N=19), high-CRP placebo (N=13), and low-CRP placebo (N=19). Blood was sampled at baseline, at 1, 1.5, 3.5, 6, and 24 hours, and 1 week after LPS or saline administration, with concurrent assessment of psychological outcomes. The primary outcome measure was the Snaith-Hamilton Pleasure Scale (SHAPS), and the primary contrast of interest was the change between baseline and 1.5 hours (peak of the inflammatory response) in the high-CRP versus low-CRP groups receiving LPS. Secondary outcomes included the Montgomery-Åsberg Depression Rating Scale (MADRS) and serum levels of three cytokines: interleukin-6 (IL-6), IL-10, and tumor necrosis factor (TNF). Data were analyzed with linear mixed models.

RESULTS: Significantly greater increases in self-reported anhedonia (on the SHAPS) and IL-6 levels were observed between baseline and 1.5 hours in the high-CRP versus low-CRP LPS groups. There were no significant differences for TNF and IL-10. The MADRS was not administered at 1.5 hours; secondary analyses showed a significant group-by-condition-by-time interaction driven by a greater decrease in MADRS scores between baseline and 24 hours in the high-CRP group.

CONCLUSIONS: Depressed individuals with systemic inflammation appeared to be biologically primed to respond more strongly to inflammatory stimuli, and psychologically, this sensitization impacted the symptom of anhedonia, the primary outcome.

Journal Title

The American journal of psychiatry

Volume

182

Issue

6

First Page

560

Last Page

568

MeSH Keywords

Humans; Depressive Disorder, Major; Anhedonia; Male; Female; Lipopolysaccharides; Double-Blind Method; C-Reactive Protein; Adult; Inflammation; Middle Aged; Tumor Necrosis Factor-alpha; Interleukin-6

PubMed ID

40264292

Keywords

Depressive Disorders; Inflammation; Major Depressive Disorder

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