Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology, and antidepressant response.

Preclinical studies have shown that brain-derived neurotrophic factor (BDNF) may be involved in both antidepressant action and the pathophysiology of major depressive disorder (MDD). The present study tested the hypothesis that the BDNF-gene Val66Met polymorphism is associated with MDD, its clinical manifestations, and antidepressant response. To elucidate a genetic predisposition of MDD, we studied BDNF-gene Val66Met polymorphism in 152 MDD patients in 255 normal controls. We also examined the association of this polymorphism and fluoxetine therapeutic response in 110 MDD patients who received a 4-week fluoxetine treatment. No significant differences were demonstrated for the genotype or allele frequency of the BDNF polymorphism comparing the MDD and control groups. Further, no significant differences were noted comparing the three-genotype groups for depressive-cluster symptoms. However, a trend (P = 0.086) to improved 4-week-fluoxetine antidepressant response was demonstrated for heterozygous patients in comparison to homozygous analogs. This finding suggests the BDNF polymorphism investigated plays no major role in the pathogenesis of MDD. Copyright 2003 Wiley-Liss, Inc.