Dong Zai-Quan, Li Xi-Rong, He Lin, He Guang, Yu Tao, Sun Xue-Li
Psychological Center, West China Hospital, Sichuan University, Chengdu, Sichuan.
Mental Health Center, First Affiliated Hospital, Chongqing Medical University, Chongqing.
Neuropsychiatr Dis Treat. 2016 Jul 4;12:1623-9. doi: 10.2147/NDT.S93562. eCollection 2016.
Genetic variabilities within the serotoninergic system may predict response or remission to antidepressant drugs. Several serotonin receptor (5-HTR) gene polymorphisms have been associated with susceptibility to psychiatric diseases. In this study, we analyzed the correlation between 5-HTR1A and 5-HTR2A polymorphisms and response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs.
Two hundred and ninety patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder were involved in this study. SSRIs (fluoxetine, paroxetine, citalopram, or sertraline) were selected randomly for treatment. The Hamilton Rating Scale for Depression was used to evaluate the antidepressant effect. To assess 5-HTR gene variabilities, two single-nucleotide polymorphisms in 5-HTR1A (rs1364043 and rs10042486) and three in 5-HTR2A (rs6311, rs6313, and rs17289304) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the Sequenom MassARRAY Analyzer 4 system.
There were 220 responders and 70 nonresponders (120 remissioners and 170 nonremissioners) after 6 weeks of treatment. We found no association between any of the five 5-HTR1A and 5-HTR2A gene polymorphisms and antidepressant drug response or remission (P>0.05). It is worth mentioning that TT genotype frequency of rs10042486 was significantly different from the CT genotype frequency between responders and nonresponders, although the significance was not maintained after correcting for multiple testing.
Thus, 5-HTR1A and 5-HTR2A gene polymorphisms may not play an important role in antidepressant drug response or remission.
血清素能系统内的基因变异性可能预测对抗抑郁药物的反应或缓解情况。几种血清素受体（5-HTR）基因多态性与精神疾病易感性相关。在本研究中，我们分析了5-HTR1A和5-HTR2A多态性与选择性血清素再摄取抑制剂（SSRI）药物反应或缓解之间的相关性。
290例符合《精神障碍诊断与统计手册》第四版重性抑郁障碍标准的患者参与本研究。随机选择SSRI（氟西汀、帕罗西汀、西酞普兰或舍曲林）进行治疗。采用汉密尔顿抑郁量表评估抗抑郁效果。为评估5-HTR基因变异性，使用Sequenom MassARRAY Analyzer 4系统通过基质辅助激光解吸/电离飞行时间质谱对5-HTR1A中的两个单核苷酸多态性（rs1364043和rs10042486）以及5-HTR2A中的三个单核苷酸多态性（rs6311、rs6313和rs17289304）进行基因分型。
治疗6周后，有220例反应者和70例无反应者（120例缓解者和170例未缓解者）。我们发现5-HTR1A和5-HTR2A的五个基因多态性中的任何一个与抗抑郁药物反应或缓解之间均无关联（P>0.05）。值得一提的是，尽管在多重检验校正后显著性未保持，但rs10042486的TT基因型频率在反应者和无反应者之间与CT基因型频率存在显著差异。
因此，5-HTR1A和5-HTR2A基因多态性可能在抗抑郁药物反应或缓解中不发挥重要作用。
