Association between neutrophil-to-lymphocyte ratio and bipolar disorder: A systematic review and meta-analysis

Abstract

Objective

The neutrophil-to-lymphocyte ratio (NLR), a systemic indicator of inflammation and stress, shows inconsistent associations with bipolar disorder (BD). This meta-analysis will investigate NLR's diagnostic, prognostic, and therapeutic relevance in BD.

Methods

A systematic search across PubMed, Embase, Web of Science, PsycINFO, and Cochrane Library, using key terms ‘bipolar disorder’, ‘neutrophils’, ‘lymphocytes’, and ‘ratio’ yielded 31 studies assessed via Newcastle-Ottawa Scale. Sensitivity analyses, subgroup analyses and publication bias assessments were conducted to explore heterogeneity sources and result stability.

Results

The NLR values in BDs were significantly higher than those in healthy controls (HCs) (standardized mean difference [SMD] = 0.51, 95 % confidence interval [CI]: 0.40–0.62, p < 0.0001; odds ratio [OR] = 1.87, 95 % CI: 1.27–2.74, p = 0.001). The association was most pronounced between bipolar mania (BDM) and HC (SMD = 0.67, 95 % CI: 0.57–0.76, p < 0.0001, I² = 47 %). Additionally, BDM exhibited higher NLR than bipolar depression (BDD) and bipolar patients in euthymic episode (BDE) (SMD = 0.22, 95 % CI: 0.07–0.38, p = 0.04, I² = 42 %; SMD = 0.31, 95 % CI: 0.15–0.48, p = 0.0001, I² = 60 %, respectively). No significant differences were observed between BDD and HC (SMD = 0.30, 95 % CI: -0.05–0.64, p = 0.09). Subgroup analyses suggested that age may influence the association between NLR and BD.

Conclusion

An elevated NLR value is found in BD, particularly in BDM. However, the difference between BDD and HC is not statistically significant. NLR may be a potent biomarker for the identification and evaluation of BD.