BDNF and depressive disorder: This therapeutic effect is mediated through up-regulation of p-ERK1/2 and enhanced BDNF expression in the prefrontal cortex, suggesting a crucial role for ERK-BDNF signaling in acupuncture’s mechanism of action.[155,164,215–217] Substantial evidence indicates that acupuncture stimulation activates the MAPK/ERK signaling cascade, subsequently triggering CREB pathway activation, which collectively contributes to the amelioration of depressive states.[218,219] The most frequently selected acupoints for depressive disorders are GV20 and GV29, with supplementary use of GB34 and PC6.