ESR1 and major depressive disorder: In conclusion, the novel described mechanisms of ESR that we propose to be protective against depression via tight control towards stress-induced IEGs transcription, together with the notion that in models of stress vulnerability IEGs are stably overexpressed (Bagot et al., 2015), clearly indicates an urgency to further elucidate ESR with the ultimate goal to understand the molecular basis of stress-induced depression, opening new avenues of interventions.