CREB1 and major depressive disorder: In this study, BDNF was chosen as the downstream molecular target underlying the protecting effects of ARN-3236 against chronic stress, as BDNF is a very well-known member implicated in the pathogenesis of depression, and moreover, its biosynthesis is closely controlled by CRTC1 and CREB (Martinowich et al., 2007; Finsterwald et al., 2010; Esvald et al., 2020).