抑郁症发病率和药物疗效存在明显性别差异，女性发病高于男性2-3倍，其机制研究国内外报道尚少。基于“女子以肝为先天”理论，研究大鼠脑5-HT介导“AC-cAMP-PKA-CREB”信号转导差异与上下游蛋白酶活性变化、基因多态性变异与性别发病关系。采用RTFQ-PCR和RFLP-PCR等技术，检测AC、PKA、CREB蛋白表达以及ACmRNA、PKAmRNA、CREBmRNA基因表达变化，再进行上游靶点5-HT1A受体、5-HT2A受体与下游靶蛋白BDNF与受体TrkB基因上单核苷酸多态性基因分型分析，最后借助ETDT系统对每个位点进行传递/不平衡分析检验。揭示5-HT介导“AC-cAMP-PKA-CREB”信号转导差异与性别差异的关系，发现抑郁症雌性易感基因位点与发病性别差异机制，阐明“女子以肝为先天”理论的物质载体，为补充抑郁症发病理论和性别差异化治疗提供新理论新思路。

A large clinic and experimental evidences have suggested that the female patient with depression has been higher more than the male by 2-3 times,which means that prevelence and morbidity of depression have been obviously differences among the sex.Based on the theory "Woman with liver as a congenital",the present research would aim to duplicate human depression using CUMS,and determine the changes of hippocanpus intracellular signal conduction pathway, AC-cAMP-PKA-CREB pathway and related gene polymorphism.Using the RTFQ-PCR,RFLP-PCR and so on ,it would has been determined that gene expression level of ACmRNA/PKAmRNA/CREBmRNA ,and the variations of single nucleotide polymorphism(SNP) in uptargets 5-HT1A & 2A Receptor gene,and downtargets BDNF & Trk Receptor gene.Therefore,the software ETDT would been used to analyze the transmission disequelibrium test(TDT) in SNPs of them.It would been found that the vulnerable gene of the female and pathophysiological mechanism and the variations in gene polumorphism of gender differences in prelevence and morbidity of the depression, meanwhile compleined the cellular substances of the theory "Woman with liver as a congenital" and discovered the gender defferences of clinical usage by the antidepressant Xiaoyaosan.