BDNF and major depressive disorder: Since the neurotrophic factor Bdnf is a critical mediator of activity-dependent plasticity in the developing and mature brain, and since changes in neuronal plasticity and Bdnf signaling have been implicated both in the etiology of depression and antidepressant drug action15, the present study first examined whether increased acetylation of histone H4K12 also affects transcription of the Bdnf gene.