Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Neuropharmacology. 2010 Jun;58(7):1168-73. doi: 10.1016/j.neuropharm.2010.02.013. Epub 2010 Feb 21.
Several investigations have suggested the possible involvement of sigma 1 non-opioid intracellular receptor 1 (sigma 1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma 1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma 1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline).
We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis.
In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples.
Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results.
多项研究表明，西格玛 1 型非阿片类细胞内受体 1（西格玛 1 受体）可能参与重度抑郁症（MDD）的病理生理学。西格玛 1 受体也是选择性 5-羟色胺再摄取抑制剂（SSRIs）的主要药理学治疗靶点之一。为了评估西格玛 1 受体基因（SIGMAR1）与 MDD 以及 SSRIs 治疗 MDD 反应的相关性，我们对日本样本（466 例 MDD 患者、516 例对照和 208 例 MDD 患者用氟伏沙明或舍曲林治疗）进行了病例对照研究。
我们将基线时 Structured Interview Guide for Hamilton Rating Scale for Depression（SIGH-D）评分减少 50%以上定义为临床反应，8 周时 SIGH-D 评分<7 定义为临床缓解。因此，我们选择了 SIGMAR1 中的 rs1800866 进行以下关联分析。
在逻辑回归分析中，我们检测到 rs1800866 基因型与表型（MDD 或对照）之间存在关联。然而，我们未检测到 rs1800866 与日本 MDD 患者 SSRIs 治疗反应之间的关联。此外，SSRIs 缓解与 rs1800866 无关。另外，我们在用 SSRIs 治疗的 MDD 样本进行突变搜索时未发现 SIGMAR1 的新多态性。
我们的结果表明，SIGMAR1 中的 rs1800866 可能在日本人群 MDD 的病理生理学中发挥作用。此外，SIGMAR1 不影响日本 MDD 患者对 SSRIs 的治疗反应。但是，由于我们的样本量较小，需要使用另一个人群和更大的样本进行复制研究以得出结论。
