CREB1 and major depressive disorder: Therapeutic effects arising from changes in PKA may be mediated by the downstream phosphorylation and activation of CREB, and subsequent transcription of BDNF, both of which have been associated with depression and the antidepressant response (Chen et al., 2001; Khundakar and Zetterström, 2006; Dwivedi and Pandey, 2011).