Association between serum inflammatory cytokines levels and post-stroke depression among stroke patients: A meta-analysis and systematic review

Abstract

Background

Post-stroke depression (PSD) is a common neuropsychiatric complication after stroke. Neuroinflammation triggered by the stroke event may be its predisposing factor.

Methods

We systematically searched all electronic databases up to December 22, 2024. Observational studies comparing cytokine levels between PSD and non-PSD patients were included. Sensitivity analysis, subgroup analysis, and meta-regression were conducted to assess robustness, explore heterogeneity, and identify effect modifiers.

Results

A total of 26 studies with 6573 acute stroke patients were included, of whom 2453 developed PSD. PSD patients were older (63.7 vs. 62.8 years) and included more females (36.4 % vs. 35.1 %) than non-PSD patients. PSD patients had significantly higher serum levels of IL-1β (SMD = 0.35, 95 % CI = [0.07, 0.63], p = 0.02), IL-6 (SMD = 0.74, 95 % CI = [0.50, 0.97], p < 0.001), IL-18 (SMD = 0.49, 95% CI = [0.13, 0.86], p = 0.007), TNF-α (SMD = 0.44, 95 % CI = [0.15, 0.72], p = 0.003) and IFN-γ (SMD = 0.11, 95 % CI = [0.02, 0.19], p = 0.01), while IL-10 levels showed no significant difference (p = 0.06). IL-6 levels remained associated with PSD diagnosis at 1, 3 and 6 months. Meta-regression identified female proportion (IL-6: p = 0.043; IL-10: p = 0.024), mean age (IL-18: p = 0.015; TNF-α: p = 0.040), BMI (IL-18: p = 0.019), and diabetes proportion (IL-6: p = 0.009; TNF-α: p = 0.033) as significant moderators.

Conclusions

Inflammatory cytokines may serve as biomarkers for PSD, offering insights into its pathophysiology and potential diagnostic tools.

Prospero registration number: CRD42024548753.