MAP2K7 and major depressive disorder: Hyperforin has been shown to improve synaptic plasticity via different pathways, including CaM-kinase IV (CaMKIV), PI3K/Akt, and Ras/MEK/ERK, enhancing the phosphorylation of cyclic adenosine monophosphate response element binding protein, associated with depression in primary hippocampal neurons and PC12 cells (Heiser et al., 2013).