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[载脂蛋白E基因多态性对抑郁症易感性及抗抑郁药疗效的影响]

[Effects of apolipoprotein E genetic polymorphism on susceptibility of depression and efficacy of antidepressants].

作者信息

Zhang Jun, Shen Xin-hua, Qian Min-cai, Sun Ju-shui, Zhong Hua, Yang Jian-hong, Lin Min, Li Liang

机构信息

Department of Psychiatry,the Forth People's Hospital of Haining, Haining, Zhejiang, China.

出版信息

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2012 Dec;34(6):595-600. doi: 10.3881/j.issn.1000-503X.2012.06.011.

Abstract

OBJECTIVE

To assess the effects of apolipoprotein E (APOE) polymorphism on the susceptibility of depression and the efficacy of antidepressants.

METHODS

A total of 275 patients with depression, who met the diagnostic criteria of both CCMD-3 and DSM-4, were randomly assigned into venlafaxine group (n=136)and paroxetine group(n=139). Another 202 healthy subjects were enrolled as the control group. Hamilton Rating Scale for Depression (HAMD)-17 was adopted as the primary rating instrument to evaluate the severity of depression on the baseline and the end of the 1st, 2nd, 4th, 6th week after treatment, respectively. HAMD scores ≤7 was defined as remission, and the reduction of HAMD scores ≥50% was defined as response while <50% was defined as invalid. PCR-restriction fragment length polymorphisms (PCR-RFLP) was applied to detect the genetic polymorphism of the APOE in the case groups and control group.

RESULTS

In the venlafaxine group, the remission rate was 52.9%(n=72), the response rate was 26.5%(n=36), and the invalid rate was 20.6%(n=28), whereas the corresponding data in the paroxetine group wee 42.4%(n=59), 31.7%(n=44), and 25.9% (n=36), respectively. There were no significant differences in the efficacy between the two groups(p>0.05). In the venlafaxine group, there were no significant differences in the genotypes and the allele distribution frequency of APOEΕ2/Ε3/Ε4 between the remitters, nonremitters, and healthy controls at the end of the 6th week(p>0.05), but there was significant differences in the allele distribution frequency between the nonremitters and healthy controls(p=0.02). In paroxetine group, there were no significant differences in the genotypes and the allele distribution frequency of APOEΕ2/Ε3/Ε4 among the remitters, nonremitters and healthy controls at the end of the 6th week(p>0.05), but there were significant differences in the allele distribution frequency between the nonremitters and healthy controls (p=0.04); in addition, there were also significant differences in Ε2/Ε3 and Ε4 allele between the two groups (p=0.014).

CONCLUSIONS

The APOE gene may not play a major role in the pathogenesis of major depression. The efficacy of venlafaxine is same as paroxetine after treatment for six weeks. The APOE (Ε2+Ε3) allele may be an indicator of the bad efficacy of paroxetine treatment.

摘要

目的

评估载脂蛋白E(APOE)基因多态性对抑郁症易感性及抗抑郁药疗效的影响。

方法

将275例符合CCMD - 3和DSM - 4诊断标准的抑郁症患者随机分为文拉法辛组(n = 136)和帕罗西汀组(n = 139)。另选取202例健康受试者作为对照组。采用汉密尔顿抑郁量表(HAMD)-17作为主要评定工具,分别于治疗前及治疗第1、2、4、6周结束时评估抑郁严重程度。HAMD评分≤7分为临床痊愈,HAMD评分减分率≥50%为有效,<50%为无效。应用聚合酶链反应 - 限制性片段长度多态性(PCR - RFLP)技术检测病例组和对照组APOE基因多态性。

结果

文拉法辛组临床痊愈率为52.9%(n = 72),有效率为26.5%(n = 36),无效率为20.6%(n = 28);帕罗西汀组相应数据分别为42.4%(n = 59)、31.7%(n = 44)和25.9%(n = 36)。两组疗效差异无统计学意义(p>0.05)。文拉法辛组治疗6周后,临床痊愈者、未痊愈者及健康对照者的APOE Ε2/Ε3/Ε4基因型及等位基因分布频率差异无统计学意义(p>0.05),但未痊愈者与健康对照者的等位基因分布频率差异有统计学意义(p = 0.02)。帕罗西汀组治疗6周后,临床痊愈者、未痊愈者及健康对照者的APOE Ε2/Ε3/Ε4基因型及等位基因分布频率差异无统计学意义(p>0.05),但未痊愈者与健康对照者的等位基因分布频率差异有统计学意义(p = 0.04);此外,两组间Ε2/Ε3及Ε4等位基因差异也有统计学意义(p = 0.014)。

结论

APOE基因可能在重度抑郁症发病机制中不起主要作用。文拉法辛与帕罗西汀治疗6周疗效相当。APOE(Ε2 + Ε3)等位基因可能是帕罗西汀治疗效果不佳的一个指标。

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