Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder: family-based association study.

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.