Homocysteine as a peripheral biomarker in bipolar disorder: A meta-analysis

E. Salagre, A. F. Vizuete, M. Leite, D. J. Brownstein, A. McGuinness, Felice N Jacka, S Dodd, Brendon Stubbs, C. A. Köhler, Eduard Vieta, André F. Carvalho, M. Berk, B. S. Fernandes

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31 Citations (Scopus)


Background Bipolar disorder (BD) is a psychiatric disorder with an uncertain aetiology. Recently, special attention has been given to homocysteine (Hcy), as it has been suggested that alterations in 1-carbon metabolism might be implicated in diverse psychiatric disorders. However, there is uncertainty regarding possible alterations in peripheral Hcy levels in BD. Methods This study comprises a meta-analysis comparing serum and plasma Hcy levels in persons with BD and healthy controls. We conducted a systematic search for all eligible English and non-English peer-reviewed articles. Results Nine cross-sectional studies were included in the meta-analyses, providing data on 1547 participants. Random-effects meta-analysis showed that serum and plasma levels of Hcy were increased in subjects with BD in either mania or euthymia when compared to healthy controls, with a large effect size in the mania group (g = 0.98, 95% CI: 0.8–1.17, P < 0.001, n = 495) and a small effect in the euthymia group (g = 0.3, 95% CI: 0.11–0.48, P = 0.002, n = 1052). Conclusions Our meta-analysis provides evidence that Hcy levels are elevated in persons with BD during mania and euthymia. Peripheral Hcy could be considered as a potential biomarker in BD, both of trait (since it is increased in euthymia), and also of state (since its increase is more accentuated in mania). Longitudinal studies are needed to clarify the relationship between bipolar disorder and Hcy, as well as the usefulness of peripheral Hcy as both a trait and state biomarker in BD.

Original languageEnglish
Pages (from-to)81-91
Number of pages11
JournalEuropean Psychiatry
Publication statusPublished - 1 Jun 2017
Externally publishedYes


  • Biomarker
  • Bipolar disorder
  • Homocysteine
  • Meta-analysis
  • Precision psychiatry
  • Systematic review

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