Brain-derived neurotrophic factor as a potential risk locus for bipolar disorder: evidence, limitations, and implications.

Brain-derived neurotrophic factor (BDNF) plays an important role in promoting and modifying growth, development, and survival of neuronal populations, and, in the mature nervous system, is involved in activity-dependent neuronal plasticity. Based on several lines of evidence, BDNF has been hypothesized to play an important role in the pathogenesis of mood disorder and the therapeutic action of at least some effective treatments. The gene encoding BDNF lies on the short arm of chromosome 11 in a region where some linkage studies of bipolar disorder have reported evidence for a susceptibility gene. BDNF can, thus, be considered as an attractive candidate gene for involvement in the pathogenesis of bipolar disorder, and two recent family-based association studies have provided evidence that one or more sequence variants within or near the BDNF gene show an association with disease susceptibility. These findings are of great interest and may open up a new chapter in the understanding of the causation and treatment of bipolar disorder. However, it is still early in the genetic investigation of BDNF in bipolar disorder, and it is important that these findings are replicated in large independent samples and that functional studies can confirm and characterize the pathogenic relevance of this genetic variation.