BDNF基因多态性与西酞普兰抗抑郁疗效的关联研究  

The association study between the polymorphisms of BDNF gene and the response of citalopram anti- depressant treatment

作　　者：陈志璐[1,2] 刘莎[1,2] 何小婷[1,2] 李素萍[2] 张克让[1,2] 

机构地区：[1]山西医科大学第一临床医学院,太原030001 [2]山西医科大学第一医院精神卫生科,太原030001

出　　处：《中华行为医学与脑科学杂志》2017年第10期877-882,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目（81471379;81601192）

摘　　要：目的探讨脑源性神经营养因子（brain—derived neurotrophic factor，BDNF）基因多态性位点rs7124442、rs6265与西酞普兰抗抑郁疗效的关联性。方法采用聚合酶连反应技术（polymerase chain reaction，PCR）对280例完成6周抗抑郁治疗的抑郁障碍（major depressive disorder，MDD）患者进行BDNF基因型分型，运用汉密顿抑郁量表（HAMD）评估其基线和1，2，4，6周末严重程度，收集患者各时间点的一般资料和临床资料，对BDNF基因rs7124442、rs6265与西酞普兰抗抑郁疗效进行关联分析。结果（1）以患者6周末HAMD分值作为结局指标，有效组（HAMD总分减分率≥50％，n=242）与无效组（HAMD总分减分率〈50％，n=38）、缓解组（HAMD≤7分，n=175）与未缓解组（HAMD〉7分，n=105）MDD患者间BDNFrs7124442、rs6265基因型及等位基因的分布差异无统计学意义（均P〉0．05）。（2）将不同时间点HAMD分值纳入重复测量方差分析后发现，BDNF基因rs6265位点的三种基因型患者在治疗的5个时间点间HAMD分值变化差异无统计学意义（P=0．075），对其进行合并发现在治疗后的第2、4、6周末GA＋AA基因型患者分值[2，4，6周末HAMD分别为（9．98±4．97）分，（8．02±4．50）分，（5．83±3．49）分]显著低于GG基因型患者[2，4，6周末HAMD分别为（11．90±6．55）分，（9．34±4．71）分，（7．07±4．28）分]，差异有统计学意义（P=0．031）。结论BDNFrs6265可能与中国汉族MDD患者西酞普兰抗抑郁药物疗效相关。Objective To investigate the relevance of brain-derived neurotrophic factor （BDNF） gene polymorphisms and the effects of citalopram antidepressant.Methods The subjects comprised 280 patients according to the diagnostic and statistical manual of mental disorders in the fourth edition （DSM-IV） criterion for major depressive disorder （MDD）.Severity of depression were assessed by 17 Hamilton depres- sion scale （HAMD） at the baseline and 1,2,4,6 weekend. Citalopram were selected for treatment.Polymerase chain reaction （PCR） and DNA sequencing analysis were used to detect the genotype of SNPs rs7124442 and rs6265 of BDNF.SPSS17.0 software was used for statistical analysis.Results （ 1 ） There were 280 patients （242 responders and 38 nonresponders; 175 remissioners and 105 nonremissioners） accomplished 6 weeks of treatment.No association was found between the polymorphisms and antidepressant drug response or remission （the reduction rate of HAMD score I〉50% was defined as response, conversely, defined as nonresponse; HAMD score more than 7 was named as remission,in contrast,named as nonremission） （P〉0.05）. （2） Repeated measures analysis of variance was adopted to compare the change of HAMD scores among the genotypes at different time points.There was a significant difference in rs6265 polymorphism between the GA ＋AA genotype （ the scores of HAMD at 2,4,6 weeks were（ 9.98±4.97）, （ 8.02±4.50）, （5.83±3.49） respec- tively） and the GG genotype groups （ the scores of HAMD at 2,4,6 weeks were （ 11.90± 6.55 ）, （ 9.34±4.71） , （7.07±4.28） respectively） （P= 0.031）.Conclusion The results suggest that BDNF rs6265 polymorphisms in part determine the antidepressant response to citalopram.

关 键 词：抑郁障碍 脑源性神经营养因子 基因多态性 西酞普兰 抗抑郁治疗 

分 类 号：R749.4[医药卫生—神经病学与精神病学]