{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:18:43Z","timestamp":1793092723043,"version":"4.5.0"},"reference-count":106,"publisher":"Royal College of Psychiatrists","issue":"1","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"unspecified","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur. Psychiatr."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S0924933826101746_sec1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bipolar disorder (BD) involves immune-inflammatory dysregulation. This systematic review and meta-analysis assessed complete blood count-based inflammatory indices \u2013 neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios \u2013 in BD versus healthy controls (HCs), major depressive disorder (MDD), and across BD mood states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0924933826101746_sec2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0924933826101746_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty-one studies (38,309 participants) met the inclusion criteria. Compared to HCs, BD showed higher NLR (SMD\u00a0=\u00a00.44,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) and MLR (SMD\u00a0=\u00a00.28,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). In mania, NLR (SMD\u00a0=\u00a00.62,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), MLR (SMD\u00a0=\u00a00.51,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), and PLR (SMD\u00a0=\u00a00.18,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.014) were all elevated versus HCs. Depression showed lower PLR (SMD\u00a0=\u00a0\u20130.14,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) and euthymia higher NLR (SMD\u00a0=\u00a00.37,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.002). Compared to MDD, BD had higher NLR (SMD\u00a0=\u00a00.21,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) and MLR (SMD\u00a0=\u00a00.18,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Similarly, mania showed higher NLR (SMD\u00a0=\u00a00.53,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) and MLR (SMD\u00a0=\u00a00.41,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), while bipolar depression lower PLR (SMD\u00a0=\u00a0\u20130.15,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Mania had higher NLR (SMD\u00a0=\u00a00.32,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), MLR (SMD\u00a0=\u00a00.32,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), and PLR (SMD\u00a0=\u00a00.14,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.028) than depression and higher MLR than euthymia (SMD\u00a0=\u00a00.44,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.027), while depression had lower NLR (SMD\u00a0=\u00a0\u20130.28,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.012) and PLR (SMD\u00a0=\u00a0\u20130.22,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Evidence certainty was mixed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0924933826101746_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1192\/j.eurpsy.2026.10174","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T10:46:21Z","timestamp":1771411581000},"source":"Crossref","is-referenced-by-count":7,"title":["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"],"prefix":"10.1192","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5342-9394","authenticated-orcid":false,"given":"Daniele","family":"Cavaleri","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ynf4891","id-type":"ROR","asserted-by":"publisher"}],"name":"University of 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