Genetic variation in the tryptophan hydroxylase 2 gene moderates depressive symptom trajectories and remission over 8 weeks of escitalopram treatment
Genetic variation in the tryptophan hydroxylase 2 gene moderates depressive symptom trajectories and remission over 8 weeks of escitalopram treatment
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DOI：
10.1097/yic.0000000000000115
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发表时间：
2016-05
影响因子：
2.6
通讯作者：
Yun-Ai Su;Ji‐Tao Li;Wen Dai;Xuemei Liao;Li Dong;T. Lu;C. Bousman;T. Si
中科院分区：
文献类型：
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作者：
Yun-Ai Su;Ji‐Tao Li;Wen Dai;Xuemei Liao;Li Dong;T. Lu;C. Bousman;T. Si
5-羟色胺系统在重性抑郁症（MDD）的发病机制中起着重要作用，而抗抑郁药的疗效与5-羟色胺相关基因的遗传变异有关。本研究的目的是调查6个候选的多巴胺能基因（ADCY 9，HTR 1B，GNB 3，HTR 2A，TPH 2，SLC 6A 4）的基因型变异与抑郁和焦虑症状严重程度轨迹以及艾司西酞普兰治疗后缓解之间的关系。共166例中国MDD患者接受艾司西酞普兰（开放标签）治疗8周。与T等位基因携带者相比，TPH 2 rs 4570625 GG携带者更容易实现抑郁和焦虑症状缓解。在趋势水平（P校正=0.05），抑郁症状严重程度轨迹由TPH 2 rs 4570625调节。与TT基因型携带者相比，GT或GG基因型患者表现出更有利的抑郁症状严重程度轨迹。ADCY 9、HTR 1B和HTR 2A的多态性名义上与症状缓解相关，但不能经受多重比较的校正。HTTLPR多态性没有包括在我们的最终分析中，因为有很高比例的数据缺失。这些结果表明，TPH 2的基因型变异可能会调节中国MDD患者对艾司夏普仑的治疗反应。
The serotonin system plays an important role in the pathogenesis of major depressive disorder (MDD) and genetic variations in serotonin-related genes affect the efficacy of antidepressants. The aim of this study was to investigate the relationship between genotypic variation in six candidate serotonergic genes (ADCY9, HTR1B, GNB3, HTR2A, TPH2, SLC6A4) and depressive and anxiety symptom severity trajectories as well as remission following escitalopram treatment. A total of 166 Chinese patients with MDD were treated with escitalopram (open-label) for 8 weeks. TPH2 rs4570625 GG carriers were more likely to achieve depressive and anxiety symptom remission compared with T-allele carriers. At the trend level (Pcorrected=0.05), depressive symptom severity trajectories were moderated by TPH2 rs4570625. Patients with the GT or the GG genotype showed more favorable depressive symptom severity trajectories compared with TT genotype carriers. Polymorphisms in ADCY9, HTR1B, and HTR2A were nominally associated with symptom remission, but did not withstand correction for multiple comparisons. The HTTLPR polymorphism was not included in our final analysis because of a high percentage of missing data. These results suggested that genotypic variation in TPH2 may moderate the therapeutic response to esciatlopram among Chinese patients with MDD.