European psychiatry : the journal of the Association of European Psychiatrists · 2026
Complete blood count-based inflammatory ratios in people with bipolar disorder: a systematic review and meta-analysis of neutrophil-to-lymphocyte, monocyte-to-lymphocyte, and platelet-to-lymphocyte ratios.
СтатьяСистематический обзорМетаанализНазвание и аннотация: Перевод в очереди
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Cavaleri Daniele, Cucchi Giorgio, Citton Martina, Monti Martina, Crocamo Cristina, Bartoli Francesco, Carrà Giuseppe
Аннотация
BACKGROUND: Bipolar disorder (BD) involves immune-inflammatory dysregulation. This systematic review and meta-analysis assessed complete blood count-based inflammatory indices - neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios - in BD versus healthy controls (HCs), major depressive disorder (MDD), and across BD mood states.
METHODS: Databases were searched through June 2025 for observational studies reporting at least one ratio in adults with BD and including as comparators either HCs, MDD, or within-BD mood-state contrasts (mania, bipolar depression, euthymia). Quality was appraised using BIOCROSS. Random-effects meta-analyses, sensitivity analyses, and meta-regressions were performed. GRADE was adapted to rate evidence certainty.
RESULTS: Fifty-one studies (38,309 participants) met the inclusion criteria. Compared to HCs, BD showed higher NLR (SMD = 0.44, p < 0.001) and MLR (SMD = 0.28, p < 0.001). In mania, NLR (SMD = 0.62, p < 0.001), MLR (SMD = 0.51, p < 0.001), and PLR (SMD = 0.18, p = 0.014) were all elevated versus HCs. Depression showed lower PLR (SMD = -0.14, p < 0.001) and euthymia higher NLR (SMD = 0.37, p = 0.002). Compared to MDD, BD had higher NLR (SMD = 0.21, p < 0.001) and MLR (SMD = 0.18, p < 0.001). Similarly, mania showed higher NLR (SMD = 0.53, p < 0.001) and MLR (SMD = 0.41, p < 0.001), while bipolar depression lower PLR (SMD = -0.15, p < 0.001). Mania had higher NLR (SMD = 0.32, p < 0.001), MLR (SMD = 0.32, p < 0.001), and PLR (SMD = 0.14, p = 0.028) than depression and higher MLR than euthymia (SMD = 0.44, p = 0.027), while depression had lower NLR (SMD = -0.28, p = 0.012) and PLR (SMD = -0.22, p < 0.001). Evidence certainty was mixed.
CONCLUSIONS: NLR, MLR, and PLR emerge as non-specific, group-level correlates of immune-inflammatory dysregulation in BD, however offering limited discrimination between bipolar and unipolar depression. Notwithstanding their potential role as trait- and state-related markers in BD, further studies are needed to support translation into clinically useful biomarkers.
METHODS: Databases were searched through June 2025 for observational studies reporting at least one ratio in adults with BD and including as comparators either HCs, MDD, or within-BD mood-state contrasts (mania, bipolar depression, euthymia). Quality was appraised using BIOCROSS. Random-effects meta-analyses, sensitivity analyses, and meta-regressions were performed. GRADE was adapted to rate evidence certainty.
RESULTS: Fifty-one studies (38,309 participants) met the inclusion criteria. Compared to HCs, BD showed higher NLR (SMD = 0.44, p < 0.001) and MLR (SMD = 0.28, p < 0.001). In mania, NLR (SMD = 0.62, p < 0.001), MLR (SMD = 0.51, p < 0.001), and PLR (SMD = 0.18, p = 0.014) were all elevated versus HCs. Depression showed lower PLR (SMD = -0.14, p < 0.001) and euthymia higher NLR (SMD = 0.37, p = 0.002). Compared to MDD, BD had higher NLR (SMD = 0.21, p < 0.001) and MLR (SMD = 0.18, p < 0.001). Similarly, mania showed higher NLR (SMD = 0.53, p < 0.001) and MLR (SMD = 0.41, p < 0.001), while bipolar depression lower PLR (SMD = -0.15, p < 0.001). Mania had higher NLR (SMD = 0.32, p < 0.001), MLR (SMD = 0.32, p < 0.001), and PLR (SMD = 0.14, p = 0.028) than depression and higher MLR than euthymia (SMD = 0.44, p = 0.027), while depression had lower NLR (SMD = -0.28, p = 0.012) and PLR (SMD = -0.22, p < 0.001). Evidence certainty was mixed.
CONCLUSIONS: NLR, MLR, and PLR emerge as non-specific, group-level correlates of immune-inflammatory dysregulation in BD, however offering limited discrimination between bipolar and unipolar depression. Notwithstanding their potential role as trait- and state-related markers in BD, further studies are needed to support translation into clinically useful biomarkers.