Neurotrophic Tyrosine Kinase Polymorphism Impacts White Matter Connections in Patients with Major Depressive Disorder

Background: Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and its receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) have been implicated in mood disorders. The aim of this study was to examine whether the NTRK2 and BDNF polymorphisms impact brain white matter connections in major depressive disorder and whether they may also have an interactive effect with environmental stress in the form of early life adversity. Methods: The study group comprised 45 depressed patients and 45 age-and gender-matched control subjects. High angular resolution diffusion images were obtained and analyzed using tract-based spatial statistics. Analysis of a single nucleotide polymorphism in the BDNF (rs6265/Valine66Methionine) and NTRK2 (rs11140714) genes was performed. Results: An interactive effect was found between NTRK2 and depression diagnosis maximally affecting the cingulum. Depressed patients homozygous for the A allele of NTRK2 showed significantly reduced fractional anisotropy compared with depressed patients with at least one copy of the G allele or control subjects with either the A/A or G carrier genotypes in the left and right corona radiata, left uncinate fasciculus, left inferior fronto-occipital fasciculus, left cerebral peduncle, posterior thalamic radiation, and middle cerebral peduncle. Significantly smaller gray matter volume was seen in frontal lobe regions in patients homozygous for the A allele. Conclusions: Polymorphisms in NTRK2 gene increase risk of architectural changes in several brain regions involved in emotional regulation.