An umbrella review of inflammatory biomarkers and their relationship to treatment response in MDD.
Level 1 - systematic review of randomized trials
Umbrella review synthesizing systematic reviews and meta-analyses
PubMed 42252042 · doi:10.1016/j.neubiorev.2026.106806
What was done
This PRISMA-guided, PROSPERO-registered umbrella review evaluated meta-analytic evidence on inflammatory biomarkers as predictors of treatment response (antidepressants and electroconvulsive therapy [ECT]) in major depressive disorder (MDD). The authors searched PubMed, Embase, PsycINFO, and the Cochrane Database of Systematic Reviews for eligible meta-analyses. Methodological quality was evaluated using the JBI Critical Appraisal Checklist, and primary study overlap was measured via the Corrected Covered Area (CCA) method.
What was found
Eight meta-analyses met inclusion criteria. For antidepressants, lower baseline C-reactive protein (CRP) and interleukin-8 (IL-8), alongside treatment-related reductions in tumor necrosis factor-α (TNF-α), GM-CSF, and IL-5, were associated with better response across some meta-analyses, though findings were inconsistent and effect sizes were small (the abstract does not report specific numerical effect sizes or confidence intervals). For ECT, one meta-analysis found nominally significant links between greater symptom improvement and higher baseline CRP/IL-6 and lower kynurenine/tryptophan, but none remained significant after false discovery rate correction.
Why it matters
Despite widespread interest in inflammatory profiling to guide psychiatric care, current pooled evidence shows inconsistent links and minimal effect sizes, meaning inflammatory biomarkers cannot yet be recommended for clinical treatment selection in MDD.
Limits
The abstract notes a "very high" degree of primary study overlap across included meta-analyses, inflating redundancy. Findings across antidepressant meta-analyses were inconsistent with generally small effect sizes, ECT data relied on a single meta-analysis where nominal findings failed false discovery rate correction, and specific numeric values/subgroup details are not reported in the abstract.