SLC6A4 and major depressive disorder: In addition to PNN, the serotonin system plays a critical role in the pathogenesis of stress, but therapies that target the stress and depression associated genes such as Tph2 and Slc6a4 (SERT) to modulate serotonin reuptake and degradation have no obvious effect in clinical trials (Lalovic and Turecki, 2002; Bellivier et al., 2004; Oquendo et al., 2014).