BDNF and major depressive disorder: In addition, plasma level of BDNF in patients with major depression was significantly lower than healthy participants (Gonul et al., 2005; Karege et al., 2005; Brunoni et al., 2008), and chronic antidepressant treatment significantly relieved the clinical symptoms by increasing BDNF (Shimizu et al., 2003) and activation of TrkB in the brain (Castren et al., 2007; Monteggia et al., 2007; B. H. Lee and Kim, 2010).