Val66Met polymorphism and serum brain-derived neurotrophic factor in bipolar disorder: an open-label trial.

Brain-derived neurotrophic factor (BDNF) is consistently associated with acute mood episodes in bipolar disorder, but there is a lack of longitudinal data to support this hypothesis. In this 16-week open-label clinical trial, we tested the predictive role of BDNF Val66Met polymorphism on serum BDNF levels and the relationship of serum BDNF and clinical response in people with bipolar disorder during an acute illness episode.Sixty-four people with bipolar disorder who were medication-free at baseline and in an acute mood episode were recruited. They were matched with 64 healthy controls. Clinical evaluation, serum BDNF, and BDNF Val66Met polymorphism were determined at baseline, and change in serum BDNF was assessed in patients at weeks 2, 4, 8 and 16.There were no differences between patients and controls in serum BDNF or in frequencies of the BDNF Val66Met polymorphism genotype at baseline. The multivariable model showed that Met carriers had a significantly different change in BDNF levels compared with Val homozygotes. Not achieving a complete remission was also associated with lower prospectively assessed BDNF levels.This study provides the first longitudinal evidence that both the BDNF Val66Met polymorphism and remission status predict change in circulating BDNF levels.