Allelic variation in the serotonin transporter promoter affects neuromodulatory effects of a selective serotonin transporter reuptake inhibitor (SSRI)
Allelic variation in the serotonin transporter promoter affects neuromodulatory effects of a selective serotonin transporter reuptake inhibitor (SSRI)
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DOI：
10.1007/s00213-002-1370-1
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发表时间：
2003-03-01
影响因子：
3.4
通讯作者：
Hajak, G
中科院分区：
文献类型：
--
作者：
Eichhammer, P;Langguth, B;Hajak, G
理论基础：选择性5-羟色胺再摄取抑制剂(SSRIs)的抗抑郁效果已被证明依赖于5-HTTLPR基因启动子区域的功能多态。该基因产生一种双等位基因多态，命名为长(1)和短(S)。与S/L或S/s型相比，长变异体(11-基因型)的纯合与2倍的5-羟色胺摄取效率相关。双脉冲经颅磁刺激是检测SSRIs引起的运动皮质兴奋性改变的一种可行工具。目的：本研究旨在探讨SSRIs对具有不同5-HTTLPR基因特征的健康志愿者皮层兴奋性的神经调节作用。方法：测定8名具有遗传特征的受试者服用60 mg西酞普兰前后皮质兴奋性的变化。结果：携带11个5-HTTLPR等位基因的受试者与不携带11个等位基因的受试者相比，运动皮质兴奋性的一个特定成分(皮质内抑制)显著增强。结论：基于5-HTTLPR的等位基因变异，服用西酞普兰后具有明显的神经调节作用，这可能解释了SSRIs治疗患者的不同反应。
Rationale: Antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) has been shown to depend on functional polymorphisms within the promoter region of the serotonin transporter gene (5-HTTLPR). This gene gives rise to a biallelic polymorphism designated long (1) and short (s). Homozygosity for the long variant (11-genotype) is associated with a two times more efficient 5-HT uptake compared to the s/l- or s/sgenotype. Paired pulse transcranial magnetic stimulation is a feasible tool in detecting changes of motor cortex excitability induced by SSRIs. Objective: Our study aimed to measure neuromodulatory effects of SSRIs on cortical excitability in healthy volunteers characterized by distinct genotypes of the 5-HTTLPR. Methods: Cortical excitability was determined in eight genetically defined subjects pre- and post-ingestion of 60 mg citalopram.Results: Subjects with the 11-genotype of the 5-HTTLPR showed a significant enhancement of a particular component of motor cortex excitability (intracortical inhibition) as compared to volunteers without the 11-genotype.Conclusion: Distinct neuromodulatory effects after intake of citalopram based on allelic variations of the 5-HTTLPR may explain variable response of patients treated with SSRIs.