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

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, I-2 = 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, I-2 = 42 %; SMD = 0.31, 95 % CI: 0.15-0.48, p = 0.0001, I-2 = 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.