Blocking promoter IV-driven BDNF expression (pIV-BDNF) in knock-in promoter IV (KIV) mice (Sakata et al. 2009) results in depression-related behaviors, such as decreased explorative activity and increased stress-induced despair, and cognitive inflexibility, such as reduced fear extinction and impaired response inhibition (Sakata et al. 2010; Sakata et al. 2013a). This evidence concerns the gene BDNF and major depressive disorder.