Brain Volume-Related Polymorphisms of the Glycogen Synthase Kinase-3β Gene and Their Effect on Antidepressant Treatment in Major Depressive Disorder
Brain Volume-Related Polymorphisms of the Glycogen Synthase Kinase-3β Gene and Their Effect on Antidepressant Treatment in Major Depressive Disorder
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糖原合成酶激酶 3β 基因的脑容量相关多态性及其对重度抑郁症抗抑郁治疗的影响
DOI：
10.1159/000500614
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发表时间：
2019
影响因子：
3.2
通讯作者：
Kato Masaki
中科院分区：
文献类型：
--
作者：
Sunada Naotaka;Takekita Yoshiteru;Nonen Shinpei;Wakeno Masataka;Koshikawa Yosuke;Ogata Haruhiko;Kinoshita Toshihiko;Kato Masaki
背景：糖原合成酶-3β(GSK-3β)基因多态性可影响重度抑郁障碍患者的海马脑组织体积。目的：在本研究中，我们研究了GSK-3β基因单核苷酸多态(SNPs)与MDD患者抗抑郁疗效的关系。方法：对14 3例日本MDD患者应用帕罗西汀、氟伏沙明或米那普兰治疗。对影响海马区脑体积的两个GSK-3β基因SNP(rs6438552和rs12630592)进行了基因分型。对于主要结果，检验了SNPs的遗传变异与第6周汉密尔顿抑郁量表(HAM-D)评分变化百分比之间的关系。结果：这两个SNPs与HAM-D评分的变化有显著相关性(rs6438552A/A与A/G+G/G：P=0.016；rs12630592G/G与G/T+T/T：P=0.016)。Rs6438552和rs12630592 SNPs之间存在高度连锁不平衡。随着时间的推移，高疗效与两个β的相关性也得到了证实(rs6438552A/A与其他：P=0.031；rs12630592G/G与其他：P=0.031)。结论：我们的结果表明，影响脑体积的两个GSK-3 SNP变异与6周时HAM-D评分的变化有关。
Background:Glycogen synthase kinase-3β (GSK-3β) polymorphisms are known to influence hippocampal brain tissue volume in individuals with major depressive disorder (MDD). However, the effects of the GSK-3β gene single nucleotide polymorphisms (SNPs) in those receiving antidepressant therapy are unknown.Objectives:In the present study, we examined the relationship between brain volume-related SNPs of the GSK-3β gene and antidepressant treatment effects in patients with MDD.Methods:Paroxetine, fluvoxamine, or milnacipran was administered to 143 Japanese patients with MDD. Two SNPs of the GSK-3β gene (rs6438552 and rs12630592) that influence brain volume in the hippocampus were genotyped. For the primary outcome, the relationship between genetic variations in the SNPs and the percent change in the Hamilton Rating Scale for Depression (HAM-D) score at week 6 was examined. In addition, rs334558, which has been reported repeatedly, was also genotyped.Results:There was a significant correlation between the two SNPs and the percent change in the HAM-D scores at week 6 (rs6438552 A/A vs. A/G + G/G:p= 0.016; rs12630592 G/G vs. G/T + T/T:p= 0.016). There was high linkage disequilibrium between the rs6438552 and rs12630592 SNPs. The correlation between high therapeutic response over time and the two SNPs were also confirmed (rs6438552 A/A vs. others:p= 0.031; rs12630592 G/G vs. others:p= 0.031).Conclusions:Our results suggest that two GSK-3β variants that influence brain volume were associated with changes in the HAM-D scores at week 6 in patients with MDD.
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杜塞尔多夫
DOI：
10.1007/s42354-018-0139-6
发表时间：
2018
期刊：
Digitale Welt
影响因子：
--
作者：
Claudia Linnhoff
通讯作者：
Claudia Linnhoff
根据跨诊断类别的灰质体积预测抗抑郁治疗反应
影响因子：
5.6
作者：
P. Sämann;D. Höhn;N. Chechko;S. Kloiber;S. Lucae;M. Ising;F. Holsboer;M. Czisch
通讯作者：
M. Czisch
影响因子：
13.5
作者：
Beurel, Eleonore;Grieco, Steven F.;Jope, Richard S.
通讯作者：
Jope, Richard S.
影响因子：
2.1
作者：
Higgins, Gerald A.;Allyn-Feuer, Ari;Athey, Brian D.
通讯作者：
Athey, Brian D.
影响因子：
3.2
作者：
Kato, Masaki;Fukuda, Tsuyoshi;Kinoshita, Toshihiko
通讯作者：
Kinoshita, Toshihiko