title: Homocysteine as a peripheral biomarker in bipolar disorder: A meta-analysis.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Australia; Bipolar Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain. Electronic address: esalagre@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Salagre
authors.affiliation: Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: A F
authors.initials: AF
authors.lastname: Vizuete
authors.affiliation: Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Leite
authors.affiliation: Monash University, Faculty of Medicine, Nursing and Health Sciences, Melbourne, Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Brownstein
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Australia.
authors.forename: A
authors.initials: A
authors.lastname: McGuinness
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Jacka
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, University of Melbourne, Parkville, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Dodd
authors.affiliation: Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK; Geriatrics Division, Department of Medicine-DIMED, University of Padova, Padova, Italy; Institute of clinical Research and Education in Medicine (IREM), Padova, Italy; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, SE5 8AZ London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Stubbs
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Köhler
authors.affiliation: Bipolar Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Vieta
authors.affiliation: Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, SE5 8AZ London, UK.
authors.forename: A F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, University of Melbourne, Parkville, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Berk
authors.affiliation: Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Australia; Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: brisasf@gmail.com.
authors.forename: B S
authors.initials: BS
authors.lastname: Fernandes
mesh_terms: D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000175:diagnosis*; D003430:Cross-Sectional Studies; D003527:Cyclothymic Disorder / Q000097:blood / Q000175:diagnosis*; D006710:Homocysteine / Q000097:blood*; D006801:Humans
chemical_list: D015415:Biomarkers; D006710:Homocysteine
keywords: Biomarker; Bipolar disorder; Homocysteine; Meta-analysis; Precision psychiatry; Systematic review