title: Homocysteine as a potential biomarker in bipolar disorders: a critical review and suggestions for improved studies.
abstract: BACKGROUND
  Homocysteine levels have been associated with major depression, but associations with bipolar disorder remain less clear. Some data suggest homocysteine levels have potential as a biomarker of treatment response; however the literature is mixed.
  
  
  METHODS
  Oxidized forms of homocysteine can be potentially neurotoxic leading to glutamate toxicity, apoptotic transformation and neurodegenerative processes. High homocysteine may be a risk biomarker for bipolar disorders, but the empirical base remains too weak for firm conclusions. This review discusses the current literature for homocysteine levels as a biomarker.
  
  
  CONCLUSIONS
  It is premature to foreclose the utility of homocysteine levels as a biomarker for bipolar disorder due the methodological inadequacies in the existing literature. These methodological design issues include lack of control for the confounding variables of concurrent medication, phase of bipolar disorder, gender, age, nutritional status, thyroid, liver and renal function, smoking or lean body mass. Well-powered association studies with confounder control could help shed more light on the important clinical question of homocysteine's utility as a biomarker in bipolar disorder. Future experiments are needed to examine the outcome of interventions modulating homocysteine for treating bipolar disorder. Only prospective randomized control trials will provide definitive evidence of the utility of homocysteine as a biomarker or therapeutic target.
authors.affiliation: Shiraz University of Medical Sciences, School of Medicine, Research Center for Psychiatry and Behavioral Sciences, Department of Psychiatry , Shiraz , Iran +00987116273070 ; ghanizad@sina.tums.ac.ir.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Ghanizadeh
authors.forename: Ajeet B
authors.initials: AB
authors.lastname: Singh
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Mohammad
authors.initials: M
authors.lastname: Torabi-Nami
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000188:drug therapy / Q000503:physiopathology*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D012107:Research Design
chemical_list: D015415:Biomarkers; D006710:Homocysteine
keywords: biomarker; bipolar disorder; folic acid; homocysteine; one-carbon; oxidative stress