Smits K M, Smits L J M, Schouten J S A G, Stelma F F, Nelemans P, Prins M H
Department of Epidemiology, Maastricht University, Maastricht, The Netherlands.
Mol Psychiatry. 2004 May;9(5):433-41. doi: 10.1038/sj.mp.4001488.
Large differences in clinical response to selective serotonin reuptake inhibitors (SSRIs) are observed in depressive patients with different genotypes. Quantification of these differences is needed to decide if genetic testing prior to antidepressant treatment is useful. We conducted a systematic review of the literature on the influence of polymorphisms in the serotonin transporter gene (SERTPR (or 5-HTTLPR) and STin2) on SSRI response. Studies were identified by the use of MEDLINE, EmBase and PsycINFO, references of articles, reviews and information from pharmaceutical companies. Nine studies assessing the influence of SERTPR or STin2 on treatment response were included. Outcome was expressed as the percentage of decrease in depression score (HAM-D or MADRS) or as the percentage of responders (> or =50% reduction on the depression scale). Both study methodologies and study outcomes showed large heterogeneity. Weighted mean decreases in depression score for patients with the s/s, s/l and l/l genotypes were 35.4, 46.3 and 48.0% at week 4, respectively, and 53.9, 54.6 and 48.3% at week 6. Among Caucasian patients, both mean decrease in depression score and response rate were lowest in the s/s group, while among Asian patients, results were inconsistent. Weighted response rates were 36.1% for the 10/12 genotype of the STin2 polymorphism and 80.7% for the 12/12 genotype (chi2=27.8, P<0.001) (only Asians). The available evidence points to a less favourable response to SSRI treatment among Caucasian patients with the SERTPR s/s genotype and among (Asian) patients with the STin2 10/12 genotype. In view of the scarcity and heterogeneity of the studies, however, current information is insufficiently reliable as a basis for implementing genetic testing in the diagnostic work-up of the depressive patient.
在具有不同基因型的抑郁症患者中，观察到对选择性5-羟色胺再摄取抑制剂（SSRI）的临床反应存在很大差异。需要对这些差异进行量化，以确定在抗抑郁治疗前进行基因检测是否有用。我们对血清素转运体基因（SERTPR（或5-HTTLPR）和STin2）多态性对SSRI反应影响的文献进行了系统综述。通过使用MEDLINE、EmBase和PsycINFO、文章参考文献、综述以及制药公司提供的信息来识别研究。纳入了9项评估SERTPR或STin2对治疗反应影响的研究。结果以抑郁评分降低的百分比（汉密尔顿抑郁量表（HAM-D）或蒙哥马利-艾森伯格抑郁量表（MADRS））或反应者的百分比（抑郁量表降低≥50%）来表示。研究方法和研究结果均显示出很大的异质性。s/s、s/l和l/l基因型患者在第4周时抑郁评分的加权平均降低分别为35.4%、46.3%和48.0%，在第6周时分别为53.9%、54.6%和48.3%。在白种人患者中，s/s组的抑郁评分平均降低和反应率均最低，而在亚洲患者中，结果不一致。STin2多态性的10/12基因型的加权反应率为36.1%，12/12基因型的加权反应率为80.7%（χ2 = 27.8，P < 0.001）（仅亚洲人）。现有证据表明，具有SERTPR s/s基因型的白种人患者以及具有STin2 10/12基因型的（亚洲）患者对SSRI治疗的反应较差。然而，鉴于研究的稀缺性和异质性，目前的信息作为在抑郁症患者诊断检查中实施基因检测的基础，可靠性不足。
