Relationship between a BDNF gene polymorphism and the brain volume in treatment-naive patients with major depressive disorder: A VBM analysis of brain MRI

The brain-derived neurotrophic factor (BDNF) relates to basic neuronal functions, such as cell survival, axonal outgrowth, and dendritic growth. The Val66Met polymorphism of the BDNF gene may affect genetic susceptibility to major depressive disorder (MDD). We prospectively investigated the relationship between the Val66Met BDNF genotype and voxel-based morphometry (VBM) findings for first episode and drug-naïve MDD patients and healthy subjects (HS). Participants comprised 38 MDD patients and 42 age- and sex-matched HS were divided into groups based on their BDNF genotype. The effects of diagnosis and genotype, as well as the genotype-diagnosis interaction, in relation to brain morphology were evaluated using a voxel-by-voxel statistical analysis of high-resolution magnetic resonance imaging (MRI) findings. Among the Met-carriers, the volume of the left middle frontal gyrus (composition of the prefrontal cortex [PFC]) was significantly smaller for MDD patients than for the HS, i.e., there was a significant genotype-diagnosis interaction effect on brain morphology noted in the left PFC. The BDNF polymorphism was associated with atrophy of the PFC in MDD patients, which suggests that the BDNF Val66Met polymorphism may play an important role in the pathogenesis of early stages of MDD.