This is the author accepted manuscript. The final version is available from Elsevier at http://www.jad-journal.com/article/S0165-0327%2815%2900383-3/abstract. ; Background: Rs6265 single nucleotide polymorphism, which influences brain-derived neurotrophic factor (BDNF) levels in the cortical and subcortical brain structures, may result in distinguished patterns of neural activation during a major depressive disorder (MDD) episode. Valine homozygotes with high levels of BDNF and methionine carriers with lower levels of BDNF may present specific neural correlates of MDD. In our study we have tested differences in blood oxygen level dependent (BOLD) signal between individuals with MDD and healthy controls for both allelic variants. Methods: Individuals with MDD (N=37) and healthy controls (N=39) were genotyped for rs6265 and compared separately in each allelic variant for BOLD response in a functional magnetic resonance imaging experiment examining appraisal of emotional scenes. The two allelic variants were also compared separately for both individuals with MDD and healthy controls. Results: In the homozygous valine group MDD was associated with decreased neural activation in areas responsible for cognitive appraisal of emotional scenes. In the methionine group MDD was related to increased activation in subcortical regions responsible for visceral reaction to emotional stimuli. During an MDD episode methionine carriers showed more activation in areas associated with cognitive appraisal of emotional information in comparison to valine homozygotes. Limitations: Small sample size of healthy controls carrying methionine (N=8). Conclusion: Our results suggest that allelic variations in the rs6265 gene lead to specific neural correlates of MDD which may be associated with different mechanisms of MDD in the two allelic groups. This may have potential importance for screening and treatment of patients. ; Funding for this study was provided by the Science Foundation Ireland (Grant Number: SFI/07SK/B1214C). Health Research Board (HRB) Ireland provided funding for magnetic resonance imaging infrastructure at the Centre of Advanced Medical Imaging (CAMI) at St. James?s Hospital in Dublin.