Staeker Julia, Leucht Stefan, Laika Barbara, Steimer Werner
1 Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München , München, Germany .
Genet Test Mol Biomarkers. 2014 Jan;18(1):20-31. doi: 10.1089/gtmb.2013.0217. Epub 2013 Nov 5.
Serotonergic pathways are known to play an essential role in the effects generated by antidepressants. Polymorphisms in serotonin receptor and transporter genes have been identified as an important factor. To investigate which of these polymorphisms may be useful to predict clinical outcome, we assessed their effect in a naturalistic clinical study. We studied the influence of the 5-hydroxytryptamine transporter (5-HTT) variable number of tandem repeats (VNTR), 5-HTTLPR/rs25531 and a 5-HTR2A intron 2 SNP with regard to response and side effects in 273 psychiatric inpatients. Main clinical assessments included Clinical Global Impressions ratings, paranoid depression scale self-rating scale and Dosage Record, and Treatment Emergent Symptoms (DOTES) Scale. We found significant associations between 5-HTTLPR/rs25531 S/L(G) alleles and response and side effects in 100 patients with selective serotonin reuptake inhibitor (SSRI) treatment (p = 0.037, CGI-I ≤ 2: 0% vs. 19% and p = 0.0005, DOTES cluster c: 0.76 vs. 0.19). 5-HTT VNTR and 5-HTR2A intron 2 polymorphisms were associated significantly with adverse effects in patients with selective and nonselective SRI (5-HTT VNTR 12/12: n = 170, p = 0.0001, side effect rates: 51% vs. 19% and rs7997012 [A/A]: n = 50, p = 0.020, side effects rates: 43% vs. 11%). No impact of the polymorphisms on mirtazapine treatment was found. Our study confirms the influence of serotonergic polymorphisms at the receptor and transporter level on SSRI response and side effects, supporting previous reports based on various study designs. The effects were strong enough to be noticed clinically in this naturalistic setting. However, randomized controlled trials are warranted to provide unequivocal evidence of the clinical usefulness of pretherapeutic screening for these polymorphisms.
已知血清素能通路在抗抑郁药产生的效应中起重要作用。血清素受体和转运体基因的多态性已被确定为一个重要因素。为了研究这些多态性中哪些可能有助于预测临床结果，我们在一项自然主义临床研究中评估了它们的作用。我们研究了5-羟色胺转运体（5-HTT）可变串联重复序列（VNTR）、5-HTTLPR/rs25531以及5-HTR2A内含子2单核苷酸多态性对273名精神科住院患者反应和副作用的影响。主要临床评估包括临床总体印象评分、偏执抑郁量表自评量表和剂量记录，以及治疗中出现的症状（DOTES）量表。我们发现，在100名接受选择性5-羟色胺再摄取抑制剂（SSRI）治疗的患者中，5-HTTLPR/rs25531 S/L（G）等位基因与反应和副作用之间存在显著关联（p = 0.037，临床总体印象改善量表-I≤2：0%对19%；p = 0.0005，DOTES聚类c：0.76对0.19）。5-HTT VNTR和5-HTR2A内含子2多态性与选择性和非选择性5-羟色胺再摄取抑制剂（SRI）患者的不良反应显著相关（5-HTT VNTR 12/12：n = 170，p = 0.0001，副作用发生率：51%对19%；rs7997012 [A/A]：n = 50，p = 0.020，副作用发生率：43%对11%）。未发现这些多态性对米氮平治疗有影响。我们的研究证实了血清素能多态性在受体和转运体水平对SSRI反应和副作用的影响，支持了基于各种研究设计的先前报告。在这种自然主义环境中，这些效应强大到足以在临床上被注意到。然而，需要进行随机对照试验，以提供关于这些多态性治疗前筛查临床实用性的确切证据。
