The psychological mechanisms of action of Xiao-Yao-San and its modifications have been investigated. It has been reported that the formula may act on psychological symptoms by upregulating central neurotransmitters such as serotonin. Bao et al. [79] reported that Xiao-Yao-San produced antidepressant effects in a mouse model of depression by ameliorating brain cortex 5-HT and 5-HIAA content. Other mechanisms of the formula have also been reported. Yue et al. [80] reported that Xiao-Yao-San suppressed chronic stress in a rat model by up-regulating GluR2/3, the AMPA receptor subunit 2/3, which mediates the postsynaptic depolarization that initiates neuronal firing [81] , and by downregulating PICK1, a protein that interacts with C-kinase 1, which may lead to AMPA receptor anchorage [82] in hippocampal regions CA1 and CA3. Similar findings, that Xiao-Yao-San upregulates AMPA receptor subunit mRNA expression in hippocampal region CA1 and the amygdala, were reported [83] . Furthermore, Xiao-Yao-San and its modifications were reported to suppress chronic stress by maintaining the stability of hippocampal neurons [84] , inhibiting hypothalamic-pituitary-adrenocortical axis negative feedback regulation [85] , and counteracting increase of Ca 2+ concentration in hippocampal synaptosomes [86] . Based on TCM theory, seven drugs were added in our modification, mainly from another classic TCM formula, Er-Chen-Tang. According to our previous preclinical study, this modification may 8 Evidence-Based Complementary and Alternative Medicine suppress depression by up-regulating the 5-HT 1A receptor in the hippocampus in a rat model of chronic stress [87] . However, because Xiao-Yao-San and its modifications contain multiple ingredients, specific active ingredients have not been identified, and the herbal interactions within the formula have not been systematically investigated. Further investigation to elucidate the mechanisms of action of this formula is warranted.