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Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder

Family-based association study

Department of Psychiatry, University of Toronto, Canada, and Charité University of Berlin, Germany

VINCENZO DE LUCA, MD, TRICIA SICARD, BSc, NICOLE KING, BSc, JOHN STRAUSS, MD and JAMES L. KENNEDY, MD

Department of Psychiatry, University of Toronto, Canada

Correspondence: Dr James L. Kennedy, Neurogenetics Section, Centre for Addiction and Mental Health Department of Psychiatry, University of Toronto, 250 College Street R30, Toronto, ON, M5T1R8, Canada. Tel: +1 416 979 4987; fax +1 416 979 4666; email: James_Kennedy{at}camh.net

Declaration of interest None. Funding detailed in Acknowledgements.

Background We have previously reported the Val66Met and GT(n) repeat polymorphisms of the brain-derived neurotrophic factor (BDNF) gene to be associated with bipolar disorder. However, these findings have not been replicated consistently.

Aims To dissect the association of the BDNF gene with bipolar disorder by examining additional markers at the DNA level and by testing the illness categories of bipolar disorder I and II and rapid cycling.

Method We performed a family-based association study and haplotype analyses with 312 nuclear families using four single nucleotide polymorphisms (SNPs) and the Val66Met and GT(n) repeat polymorphisms.

Results The SNPs hCV11592756 and rs2049045, the Val66Met and GT(n) were significantly associated with bipolar disorder using transmission disequilibrium analyses (P=0.02, 0.009, 0.001 and 0.008 respectively). The effect atthese markers was mainly driven by the rapid-cycling patients.

Conclusions Within bipolar disorder, variation in the BDNF gene appears to predict risk for developing rapid cycling according to DSM–IV. Incorporating this clinical sub-phenotyping into other studies of the BDNF gene may help to resolve some of the inconsistencies reported thus far concerning BDNF and bipolar disorder.