Kato Masaki, Fukuda Tsuyoshi, Wakeno Masataka, Fukuda Kazuhiro, Okugawa Gaku, Ikenaga Yuka, Yamashita Megumi, Takekita Yoshiteru, Nobuhara Kenji, Azuma Junichi, Kinoshita Toshihiko
Department of Neuropsychiatry, Kansai Medical University, Moriguchi, Japan.
Neuropsychobiology. 2006;53(4):186-95. doi: 10.1159/000094727. Epub 2006 Jul 26.
In this study, we tested the influence of the serotonin type 2A, 3A and 3B receptor genes (HTR2A, HTR3A, HTR3B) in addition to a polymorphism in the promoter region of the serotonin transporter (SERTPR), and investigated the different characteristics of clinical responses to paroxetine and fluvoxamine. A total of 100 Japanese patients affected by major recurrent depression were enrolled in a randomized 6-week study. The clinical response was evaluated using the Hamilton Rating Scale for Depression (HAM-D), and adverse drug reactions were assessed at each visit. Patients with the l allele of SERTPR showed a better response to SSRIs than s/s genotype carriers (p = 0.015-0.042), more significantly to fluvoxamine. The -1438G/G genotype of HTR2A was associated with a good response to SSRIs (p = 0.010-0.039), especially to fluvoxamine, and significantly with severe nausea in paroxetine-treated patients (p = 0.013). The 178C/C genotype of the HTR3A was associated with an antidepressant response (p = 0.022-0.042), and more significantly in paroxetine-treated patients (p = 0.002-0.042). These effects were independent of one another. We replicated the finding that the SERPTR polymorphism was associated with a response to SSRIs. We additionally found that HTR2A and HTR3A polymorphisms are associated with the efficacy, and the HTR2A polymorphism is also associated with adverse drug reactions. Furthermore, the effects of these polymorphisms varied from one SSRI to another and thus may depend on the characteristics of each SSRI.
在本研究中，我们除了检测血清素转运体（SERTPR）启动子区域的多态性外，还测试了血清素2A、3A和3B受体基因（HTR2A、HTR3A、HTR3B）的影响，并研究了对帕罗西汀和氟伏沙明临床反应的不同特征。共有100名患有复发性重度抑郁症的日本患者参加了一项为期6周的随机研究。使用汉密尔顿抑郁评定量表（HAM-D）评估临床反应，并在每次就诊时评估药物不良反应。携带SERTPR基因l等位基因的患者对选择性5-羟色胺再摄取抑制剂（SSRI）的反应优于s/s基因型携带者（p = 0.015 - 0.042），对氟伏沙明的反应更显著。HTR2A基因的-1438G/G基因型与对SSRI的良好反应相关（p = 0.010 - 0.039），尤其是对氟伏沙明，并且与帕罗西汀治疗患者的严重恶心显著相关（p = 0.013）。HTR3A基因的178C/C基因型与抗抑郁反应相关（p = 0.022 - 0.042），在帕罗西汀治疗的患者中更显著（p = 0.002 - 0.042）。这些效应相互独立。我们重复了SERPTR多态性与对SSRI反应相关的这一发现。我们还发现HTR2A和HTR3A多态性与疗效相关，并且HTR2A多态性也与药物不良反应相关。此外，这些多态性的效应因不同的SSRI而异，因此可能取决于每种SSRI的特性。
