Serum C‑Reactive Protein (CRP) Titres in Bipolar Disorder: Systematic Review

Ebrahim, Marwa F.; Mikhael, Victor S.; El-Hamady, Mohamed M.; El-feky, Mohammed R.; Gebriel, Emad M.

doi:10.21608/bmfj.2025.410428.2595

Serum C‑Reactive Protein (CRP) Titres in Bipolar Disorder: Systematic Review

Articles in Press

Document Type : Review Article

Authors

¹ Lecturer of psychiatry Faculty of Medicine, Benha University

² Professor of Psychiatry Faculty of Medicine, Benha University

³ Professor of Psychiatry Faculty of Medicine - Benha University

⁴ Professor of Psychiatry Military Medical Academy

⁵ M.Sc. Degree in Neuropsychiatry Medicine

10.21608/bmfj.2025.410428.2595

Abstract

Bipolar disorder (BD) is a severe psychiatric illness linked to chronic inflammation, with elevated C-reactive protein (CRP) levels frequently reported, although findings across studies remain inconsistent. This systematic review synthesized evidence from 18 eligible studies, identified through a comprehensive search of Scopus, PubMed, and Web of Science (2010–2025), to evaluate CRP as a potential biomarker in BD and to explore its associations with disease phases, comorbidities, and other psychiatric disorders. The included cross-sectional, case-control, and cohort studies measured CRP in BD populations compared with healthy or psychiatric controls. Overall, CRP titres were consistently higher in BD than in healthy controls, with some studies indicating peak elevations during manic episodes. Comparisons with schizophrenia and depression yielded mixed findings, suggesting that inflammation may not be specific to BD. Methodological heterogeneity, inconsistent adjustment for confounding factors such as metabolic comorbidities and medication use, and a predominance of cross-sectional designs limited interpretability. Notably, only one large cohort study linked elevated CRP levels to subsequent BD onset, pointing to possible predictive value. These findings support the role of CRP in BD pathophysiology, yet its diagnostic or prognostic utility remains uncertain. Further longitudinal research using standardized methodologies is needed, and therapeutic strategies targeting inflammation may hold promise if confounding influences are adequately addressed.

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