Abdolhosseinzadeh Setareh, Sina Marzie, Ahmadiani Abolhassan, Asadi Sareh, Shams Jamal
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Clin Pharm Ther. 2019 Feb;44(1):39-48. doi: 10.1111/jcpt.12766. Epub 2018 Oct 12.
Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric disorder. Selective serotonin reuptake inhibitors (SSRIs) are the first line of medication for OCD treatment; however, 40%-60% of patients with OCD do not respond to SSRIs adequately. There are growing pieces of evidence which suggest a significant role for the glutamatergic system in the genesis of OCD and its consequent treatment. In the present study, we aimed to assess the association of SLC1A1 polymorphisms (rs301430, rs2228622 and rs3780413) with OCD and its clinical characteristics, as well as the importance of these SNPs in the response of OCD patients to SSRI pharmacotherapy.
Sample study consisted of 243 OCD cases and 221 control subjects. Patients were treated 12 weeks with fluvoxamine (daily dose: 150-300 mg). Based on the reduction in obsessive and compulsive severity scores using Y-BOCS severity scale, patients were classified as responders, non-responders and refractory. A total of 239, 228 and 215 patients were genotyped for rs301430, rs2228622 and rs3780413, respectively, by the means of PCR-RFLP.
No association was detected between SLC1A1 SNPs and OCD, except an association between the familial form of the disease in males with rs2228622 (P = 0.033). The results of pharmacogenetic studies revealed the associations of two SLC1A1 SNPs, rs2228622 (P = 0.031) and rs3780413 (P = 0.008), with treatment response.
Results of the current study suggest a role for the glutamate transporter in OCD treatment response with SSRIs which should encourage researchers to further investigate the importance of glutamate transporter in OCD pharmacogenetics.
强迫症（OCD）是一种慢性神经精神疾病。选择性5-羟色胺再摄取抑制剂（SSRIs）是治疗强迫症的一线用药；然而，40%-60%的强迫症患者对SSRIs反应欠佳。越来越多的证据表明，谷氨酸能系统在强迫症的发病机制及其后续治疗中发挥着重要作用。在本研究中，我们旨在评估溶质载体家族1成员1（SLC1A1）基因多态性（rs301430、rs2228622和rs3780413）与强迫症及其临床特征之间的关联，以及这些单核苷酸多态性（SNPs）在强迫症患者对SSRI药物治疗反应中的重要性。
样本研究包括243例强迫症患者和221例对照受试者。患者接受12周的氟伏沙明治疗（日剂量：150-300mg）。根据使用耶鲁布朗强迫症量表（Y-BOCS）严重程度量表得出的强迫观念和强迫行为严重程度评分的降低情况，将患者分为反应者、无反应者和难治者。分别通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对239例、228例和215例患者进行rs301430、rs2228622和rs3780413基因分型。
未检测到SLC1A1基因单核苷酸多态性与强迫症之间的关联，但男性家族性强迫症形式与rs2228622之间存在关联（P = 0.033）。药物遗传学研究结果显示，两个SLC1A1基因单核苷酸多态性，rs2228622（P = 0.031）和rs3780413（P = 0.008）与治疗反应有关。
本研究结果表明谷氨酸转运体在强迫症患者对SSRIs的治疗反应中发挥作用，这应促使研究人员进一步探究谷氨酸转运体在强迫症药物遗传学中的重要性。
