Our results verified the depression-like behaviors induced by CUMS and demonstrated that the protein expressions of BDNF, Copine 6, and synapsin I were significantly decreased in both the hippocampus and the PFC of CUMS rats, together with decreased hippocampal expression of synaptotagmin I. Moreover, the plasma levels of IL-6 and CRP were remarkably increased after 4 weeks of CUMS. This evidence concerns the gene CPNE6 and major depressive disorder.