For instance, according to the neurotrophic hypothesis of depression, levels of brain derived neurotrophic factor (BDNF, whose transcription is regulated by a CREB-dependent mechanism) are increased both by noradrenergic or/and serotonergic antidepressants, while exposure to stress is characterized by downregulation of BDNF expression in hippocampus12; this downregulation can be prevented by antidepressant treatment13,14. Here, CREB1 is linked to depressive disorder.