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Because there are conflicting results regarding the exact role of BDNF polymorphisms in MDD still, we set out to systematically review the current evidence regarding BDNF-related mutations in MDD.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270822000229_as2\"><jats:title>Methods:<\/jats:title><jats:p>We conducted a keyword-guided search of the PubMed and Embase databases, using \u2018BDNF\u2019 or \u2018brain-derived neurotrophic factor\u2019 and \u2018major depressive disorder\u2019 and \u2019single-nucleotide polymorphism\u2019. We included all publications in line with our exclusion and inclusion criteria that focused on BDNF-related mutations in the context of MDD.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270822000229_as3\"><jats:title>Results:<\/jats:title><jats:p>Our search yielded 427 records in total. After screening and application of our eligibility criteria, 71 studies were included in final analysis. According to present overall scientific data, there is a possibly major pathophysiological role for BDNF neurotrophic systems to play in MDD. However, on the one hand, the synthesis of evidence makes clear that likely no overall association of BDNF-related mutations with MDD exists. On the other hand, it can be appreciated that solidifying evidence emerged on specific significant sub-conditions and stratifications based on various demographic, clinico-phenotypical and neuromorphological variables.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270822000229_as4\"><jats:title>Conclusions:<\/jats:title><jats:p>Further research should elucidate specific BDNF-MDD associations based on demographic, clinico-phenotypical and neuromorphological variables. 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