Homocysteine as a potential biomarker in bipolar disorders: a critical review and suggestions for improved studies

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords:

• biomarker
• bipolar disorder
• folic acid
• homocysteine
• one-carbon
• oxidative stress

Declaration of interest

M Berk is a co-inventor of two provisional patents regarding the use of NAC and related compounds for psychiatric indications. He has received support from Stanley Medical Research Foundation, MBF, NHMRC, NHMRC Senior Principal Research Fellowship 1059660, Cooperative Research Centre, Simons Autism Foundation Cancer Council of Victoria, MBF, Rotary Health, Meat and Livestock Board, Woolworths, BeyondBlue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma and Servier. He is a consultant at AstraZeneca, Bristol Myers Squibb, Eli Lilly, Bioadvantex, Merck, Glaxo SmithKline, Lundbeck, Janssen Cilag, Servier. He is a speaker at Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Lundbeck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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