Further, support of BDNF's involvement stems from the decreased antidepressant-like effectiveness of ketamine in genetically engineered mice carrying at least one allele with methionine substituted for valine of the BDNF Val66Met polymorphism (Liu et al., 2012), which has also been confirmed in a small sample of human MDD patients (Laje et al., 2012). This evidence concerns the gene BDNF and major depressive disorder.