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一种单胺氧化酶B基因变体与短期抗抑郁治疗反应

A monoamine oxidase B gene variant and short-term antidepressant treatment response.

作者信息

Tadić André, Rujescu Dan, Müller Matthias J, Kohnen Ralf, Stassen Hans H, Dahmen Norbert, Szegedi Armin

机构信息

Department of Psychiatry, University of Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2007 Oct 1;31(7):1370-7. doi: 10.1016/j.pnpbp.2007.05.015. Epub 2007 Jun 7.

Abstract

Genetic differences among patients suffering from Major Depression are likely to contribute to interindividual differences in medication treatment response. Thus, the identification of gene variants affecting drug response is needed in order to be able to predict response to psychopharmacological drugs. This study analyzed a possible association of the common A644G single nucleotide polymorphism (SNP) within intron 13 of the monoamine oxidase B (MAOB) gene with antidepressant treatment response. The study population consisted of n = 102 patients with major depression (criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; DSM-IV) participating in a randomized double-blind controlled clinical trial, conducted at 50 centers in Germany, comparing the efficacy of mirtazapine and paroxetine during 6 weeks of treatment. Overall, female patients homozygous for the A-allele had a significantly faster and more pronounced antidepressant treatment response than AG/GG-carriers. In paroxetine-treated females these differences remained statistically significant. In mirtazapine-treated females homozygous for the A-allele compared to AG/GG-carriers, HAMD-17 scores during the study period were constantly and markedly lower, but not statistically different. In males, we found no association between the MAOB A644G intron 13 SNP and antidepressant treatment response. Our data provide first suggestive evidence that the MAOB A644G SNP is involved in the outcome of treatment with mirtazapine or paroxetine in females with major depression. To confirm the role of the MAOB A644G gene variant in antidepressant treatment response, independent replications are needed. If replicated, the MAOB A644G polymorphism could be considered useful for prospective confirmatory pharmacogenetic trials in patients with major depression.

摘要

重度抑郁症患者之间的基因差异可能导致药物治疗反应的个体差异。因此,为了能够预测对精神药物的反应,需要识别影响药物反应的基因变异。本研究分析了单胺氧化酶B(MAOB)基因第13内含子内常见的A644G单核苷酸多态性(SNP)与抗抑郁治疗反应之间的可能关联。研究人群包括102名重度抑郁症患者(符合《精神疾病诊断与统计手册》第4版;DSM-IV标准),他们参与了在德国50个中心进行的一项随机双盲对照临床试验,比较了米氮平和帕罗西汀在6周治疗期间的疗效。总体而言,A等位基因纯合的女性患者比AG/GG携带者具有明显更快、更显著的抗抑郁治疗反应。在接受帕罗西汀治疗的女性中,这些差异在统计学上仍然显著。在接受米氮平治疗的A等位基因纯合女性与AG/GG携带者相比,研究期间的汉密尔顿抑郁量表-17(HAMD-17)评分持续且显著较低,但无统计学差异。在男性中,我们未发现MAOB基因第13内含子A644G SNP与抗抑郁治疗反应之间存在关联。我们的数据提供了首个提示性证据,表明MAOB A644G SNP参与了重度抑郁症女性患者使用米氮平或帕罗西汀的治疗结果。为了证实MAOB A644G基因变异在抗抑郁治疗反应中的作用,需要进行独立重复研究。如果得到重复验证,MAOB A644G多态性可被认为对重度抑郁症患者的前瞻性验证性药物遗传学试验有用。

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