BDNF基因Val66Met功能多态性与抗抑郁剂疗效及血浆BDNF水平的关联研究

Research on association of BDNF gene Vai66Met polymorphism with efficacy of antidepressants and plasma BDNF level

目的分析BDNF基因Val66Met多态性与抗抑郁剂疗效及血浆BDNF水平的关联性。方法符合DSM—IV诊断标准的249例汉族抑郁症患者（研究组）用文拉法辛或帕罗西汀治疗。正常对照组202名。收集一般人口学资料，包括性别、年龄、受教育年限、职业、婚姻状况等。研究组临床疗效指标采用汉密尔顿抑郁量表（HAMDl7项），在基线及治疗后1、2、4及6周进行评定。按HAMD总分及减分率来衡量疗效。治疗前和治疗6周后分别抽血10mL和5mL，采用PCR-限制性片段长度多态性分析249例抑郁症患者和202名正常人的BDNF基因Val66Met功能多态性。采用夹层酶联免疫吸附剂测定法测定抑郁症患者抗抑郁药治疗前后及正常人的血浆BDNF水平。结果（1）研究组各基因型在基线、治疗后1、2、4及6周HAMD分值、减分率差异无统计学意义。（2）研究组6周末达痊愈者和非痊愈者、正常人之间Val66Met基因型和等位基因频率分布的差异无统计学意义。（3）研究组基线血浆BDNF水平较正常对照组低；经文拉法辛或帕罗西汀抗抑郁治疗6周后均较基线显著升高，但仍较正常组低；按照6周末是否达到痊愈来分组，文拉法辛组6周末痊愈患者BDNF水平和正常对照组相似，而帕罗西汀组较正常对照组仍低；非痊愈者BDNF水平均较正常对照组低。（4）研究组基线、6周末BDNF水平和Val66Met基因多态性无关联。结论BDNF基因Val66Met多态性和文拉法辛、帕罗西汀的6周疗效无关联；抑郁症患者基线BDNF水平较正常对照组低；抗抑郁治疗后均可上升，尤其是文拉法辛治疗痊愈患者，可达正常对照组水平。BNDF水平在抗抑郁治疗中有一定的疗效预测价值；BDNF水平和BDNF基因Val66Met多态性无关联。

Objective To assess the association of BDNF gene Va166Met polymorphism with efficacy of antidepressant treatment and plasma BDNF level. Methods Two hundred and forty-nine ethnic Han Chinese patients with depression（study group）, who have met the diagnostic criteria of DSM-IV, were prescribed with venlafaxine or paroxetine. Two hundred and two healthy individuals were recruited as the control group. General demographic information such as gender, age, educational status, occupation, and marriage status were collected. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th, 6th week of treatment. PCR-restriction fragment length polymorphism was applied to determine the Va166Met polymorphism of the BDNF gene in the two groups. Plasma BDNF concentration was measured with ELISA before and after 6 weeks of treatment. Results No significant differences have been found in HAMD scores and reduction of HAMD scores on the baseline and at the end of 1 st, 2nd, 4th, 6th weeks of treatment for each genotype. Nor were significant differences found in the Va166Met genotypes and allelic frequency between patients who achieved remission or not after 6 weeks＇ treatment as well as the healthy volunteers. The plasma BDNF level in depression patients was lower than that in healthy controls. The BDNF level has increased significantly after 6 weeks＇ treatment with both venlafaxine and paroxetine, but was still lower than the healthy controls. The BDNF level in the patients achieved remission who were treated with venlafaxine was similar to the normal controls, while those treated with paroxetine was still lower than normal controls. The BDNF level in patients who have not achieved remission was lower than normal controls. The BDNF level was not associated with the Va166Met polymorphism on the baseline and the end of 6th week. Conclusion No association has been found between the efficacy of venlafaxine or paroxetine and the BDNF Va166Met polymorphism. The BDNF level of patients with depression is significantly lower than healthy controls on the baseline, and can be enhanced with the treatment. Particularly, the BDNF level in patients who achieved remission after the treatment of venlafa.xine can rise to normal. The level of BDNF has certain value in the forecasting of efficacy in the anti-depression therapy. BDNF level is not associated with the Va166Met polymorphism of the BDNF gene.