ARC and major depressive disorder: Interestingly, electroconvulsive stimulation (ECS), which remains one of the most effective treatments against severe depression (Berton and Nestler, 2006), strongly induces Arc at 1 and 4 ​h post exposure (Lyford et al., 1995), and causes a significant increase in DNA methylation of the Arc gene promoter at 24 ​h suggesting repression of Arc expression for a long period post-ECS (Dyrvig et al., 2012).