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重度抑郁症中的dysbindin基因(DTNBP1):与选择性5-羟色胺再摄取抑制剂的临床反应的关联

Dysbindin gene (DTNBP1) in major depression: association with clinical response to selective serotonin reuptake inhibitors.

作者信息

Arias Bárbara, Serretti Alessandro, Mandelli Laura, Gastó Cristóbal, Catalán Rosa, Ronchi Diana De, Fañanás Lourdes

机构信息

Unitat d'Antropologia (Dep de Biologia Animal) Facultat de Biologia and Institut de Biomedicina, Universitat de Barcelona Barcelona, Spain.

出版信息

Pharmacogenet Genomics. 2009 Feb;19(2):121-8. doi: 10.1097/FPC.0b013e32831ebb4b.

Abstract

BACKGROUND

Dysbindin gene (dystrobrevin-binding-protein 1, DTNBP1) variants have been associated with several psychiatric conditions including mood disorders and antidepressant efficacy. We investigated dysbindin gene (DTNBP1) variants in major depression and clinical response to selective serotonin reuptake inhibitors.

METHODS

In this study we investigated the role of DTNBP1 gene (rs3213207, rs2005976, rs760761 and rs2619522) in 313 major depressive outpatients and 149 healthy individuals. One hundred and forty-seven depressive patients were treated with citalopram and evaluated for response (4th week) and remission (12th week) by the 1-item Hamilton Depression Rating Scale. Single nucleotide polymorphisms (SNPs) were assayed by using Applied Biosystems TaqMan technology.

RESULTS

Genotype and haplotype frequencies for four SNPs within DTNBP1 gene did not significantly differ between patients and controls. Allele distribution of SNP rs760761, however, showed a trend of difference between responders and nonresponders (4th week). Haplotype analyses produced a significant association with response to treatment at week 4. No differences were found in remission (12th week).

DISCUSSION

DTNBP seems to have an effect on short-term clinical response to citalopram. New studies focused on other genes involved in glutamatergic neurotransmission and related proteins could help to elucidate the complex mechanism of clinical response to antidepressants.

摘要

背景

联结蛋白基因(肌营养不良蛋白结合蛋白1,DTNBP1)变异与包括情绪障碍和抗抑郁药疗效在内的多种精神疾病有关。我们研究了重度抑郁症中联结蛋白基因(DTNBP1)变异以及对选择性5-羟色胺再摄取抑制剂的临床反应。

方法

在本研究中,我们调查了DTNBP1基因(rs3213207、rs2005976、rs760761和rs2619522)在313例重度抑郁门诊患者和149名健康个体中的作用。147例抑郁患者接受西酞普兰治疗,并通过1项汉密尔顿抑郁评定量表评估第4周的反应和第12周的缓解情况。使用应用生物系统公司的TaqMan技术检测单核苷酸多态性(SNP)。

结果

DTNBP1基因内4个SNP的基因型和单倍型频率在患者和对照组之间无显著差异。然而,SNP rs760761的等位基因分布在第4周时显示出反应者与无反应者之间存在差异趋势。单倍型分析显示与第4周的治疗反应有显著关联。第12周时未发现差异。

讨论

联结蛋白似乎对西酞普兰的短期临床反应有影响。聚焦于参与谷氨酸能神经传递的其他基因及相关蛋白的新研究可能有助于阐明抗抑郁药临床反应的复杂机制。

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