Altered Cytokine Levels in the First Episode of Major Depression and in Antidepressant-Naïve Patients: A Systematic Review and Meta-Analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational case-control studies
PubMed 41226404 · doi:10.3390/ijms262110362
What was done
Following PRISMA guidelines, the authors searched PubMed, Scopus, and Web of Science through March 2025 for studies comparing peripheral inflammatory cytokine levels between healthy controls and adult patients with major depressive disorder (MDD) who were either in their first episode (FE) or antidepressant-naïve (DN). Random-effects meta-analyses were conducted, with subanalyses based on sample source (plasma vs. serum) and study quality.
What was found
The meta-analysis included 17 studies with 1,371 MDD patients. First-episode patients had significantly elevated levels of interleukin 6 (IL-6), interleukin 2 (IL-2), and tumor necrosis factor-alpha (TNF-α) compared to healthy controls. Drug-naïve patients showed significantly increased levels of IL-6, IL-2, interleukin 4 (IL-4), interleukin 10 (IL-10), TNF-α, and interferon-gamma (IFN-γ). For TNF-α, IL-2, interleukin 1-beta (IL-1β), and IL-4, results differed depending on sample matrix (plasma versus serum). The abstract reports no numerical effect sizes, confidence intervals, or exact p-values.
Why it matters
These findings indicate that immune-inflammatory dysregulation occurs at the earliest clinical stages of depression and is not merely an artifact of chronicity or pharmacological treatment.
Limits
The abstract provides no numerical effect estimates, dispersion metrics, or healthy control sample sizes. The underlying literature relies on cross-sectional case-control designs, lacks standardized sample collection protocols, and exhibits notable heterogeneity based on whether plasma or serum was assayed.
Cited by
- supports Depressed individuals show elevated levels of inflammatory markers like cytokines compared to healthy controls.