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Meta-analysis reveals no association of the Val66Met polymorphism of brain-derived neurotrophic factor with either schizophrenia or bipolar disorder

Kanazawa, Tetsufumia e; Glatt, Stephen J.a b f; Kia-Keating, Bretta; Yoneda, Hiroshie; Tsuang, Ming T.a b d c

doi: 10.1097/YPG.0b013e32801da2e2

Background A long-term controversy exists on whether or not major psychotic disorders can be discretely divided into two groups, for example, schizophrenia and bipolar disorder. Many genes and polymorphisms have been studied for a role in both disorders, including the Val66Met (also known as rs 6265 or G196A) variant of brain-derived neurotrophic factor (BDNF). Many case–control association studies have been performed to see if BDNF could serve as a useful clinical diagnostic biomarker for schizophrenia or bipolar disorder, but results have been equivocal.

Objective To determine, by meta-analysis, if the Val66Met polymorphism of BDNF influences risk for either schizophrenia, bipolar disorder, or both.

Methods We searched Pubmed, Medline, and PsycInfo using keywords including Val66Met, Rs6265, G196A, BDNF, schizophrenia, and bipolar disorder. A total of 13 studies for schizophrenia and 11 studies for bipolar disorder were combined by random-effects meta-analysis.

Main results The pooled results from the schizophrenia sample (2955 patients; 4035 controls) and the bipolar disorder sample (3143 patients; 6347 controls) indicated lack of significance with either of the two psychoses, with pooled odds ratios of 1.00 (P=0.944) and 0.95 (P=0.161), respectively.

Conclusion Although there are some limitations on the study, our results indicate there is a lack of association between the Val66Met polymorphism and either of the two psychoses. A larger sample size, and evaluation of more single-nucleotide polymorphisms are needed to obtain more robust and conclusive findings regarding the relationship between the BDNF gene and psychosis.

aDepartment of Psychiatry, Center for Behavioral Genomics, University of California

bVeterans Medical Research Foundation

cVeterans Affairs San Diego Healthcare System, San Diego, California

dHarvard Departments of Epidemiology and Psychiatry, Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, Massachusetts, USA

eDepartment of Neuropsychiatry, Osaka Medical College, Takatsuki-city, Osaka, Japan

fDepartment of Psychiatry and Behavioral Sciences and Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York, USA

Correspondence to Tetsufumi Kanazawa, MD, Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, Mail Code 0603, La Jolla, CA 92093, USA

Tel: +1 858 534 0206; fax: +1 858 822 2469;


Received 24 May 2006 Accepted 6 November 2006

© 2007 Lippincott Williams & Wilkins, Inc.