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Biofluid Biomarkers of Cognitive Functioning in Bipolar Disorder: A Systematic Review by the Targeting Cognition and Older-Age Bipolar Disorder ISBD Task Forces

Beunders AJM, Schouws SNTM, Olagunju AT, Balanzá-Martínez V, Korten NCM, Kupka RW, Burdick KE, Carvalho AF et al.

Bipolar disorders, 2026

59 participants

Abstract

Background: Cognitive impairment is common in bipolar disorder (BD), but the underlying pathophysiology remains unclear. This systematic review aimed to (1) summarize all literature describing relationships of biofluid biomarkers and cognition in BD and (2) identify which biofluid biomarkers correlate most consistently with cognition in BD.

Methods: This systematic review followed procedures of the PRISMA statement. PubMed, EMBASE, and PsycINFO were searched from inception until July 2023. Original studies assessing the relationships between biofluid biomarkers and cognitive functioning in adults with BD were included. Studies on neuroimaging markers and genetic biomarkers were excluded.

Results: We identified 60 studies, together describing 184 biofluid biomarkers that were measured in relation to cognitive functioning in BD. Biomarkers were organized into ten categories: oxidative stress markers (n = 14); growth factors (n = 13); neurotransmitters (n = 14); neuropeptides and hormones (n = 14); neurodegenerative markers (n = 11); inflammatory/immune markers (n = 59); serostatus to infectious agents (n = 11); amino acids, vitamins, and minerals (n = 7); metabolic factors (n = 23); hemogram, coagulation, and fibrinolysis markers (n = 18). Preliminary evidence for a significant relationship with cognition appeared for HSV-1 IgG, CRP, and homocysteine (Hcy); higher biomarker levels were associated with worse cognition.

Discussion: Included studies were heterogeneous and many…

How strong is the evidence?

Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 59 participants or records.

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