Methylphenidate Effects on Brain Activity as a Function of SLC6A3 Genotype and Striatal Dopamine Transporter Availability
Methylphenidate Effects on Brain Activity as a Function of SLC6A3 Genotype and Striatal Dopamine Transporter Availability
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哌甲酯对大脑活动的影响与 SLC6A3 基因型和纹状体多巴胺转运蛋白可用性有关
DOI：
10.1038/npp.2014.240
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发表时间：
2015
影响因子：
7.6
通讯作者：
Ettinger U
中科院分区：
文献类型：
--
作者：
Kasparbauer AM;Rujescu D;Riedel M;Pogarell O;Costa A;Meindl T;la Fougère C;Ettinger U
我们使用醋甲酯对儿茶酚胺再摄取进行药理学挑战，以研究其在运动反应抑制任务中对大脑活动的影响，作为多巴胺转运体（DAT）基因（SLC6A3）的3 ' -UTR可变数串联重复序列（VNTR）多态性的功能以及纹状体中DAT的可用性。在40mg哌甲酯和安慰剂的影响下，我们使用3T功能磁共振成像测量了50名健康男性在Go/No-Go任务（一种认知控制措施）期间的脑血流动力学反应。根据SLC6A3 VNTR将受试者分为9重复（9R）携带者和10/10纯合子。在成功的不去试验中，与不去试验相比，哌醋甲酯诱导SLC6A3 9R等位基因携带者的血氧水平依赖（BOLD）信号增加，但丘脑皮质网络中10/10纯合子减少。当成功的不围棋实验与成功的围棋实验比较时，在尾状回和额下回也观察到相同的模式。我们还研究了35名参与者的基线纹状体数据可用性，通过123 I-FP-CIT单光子发射计算机断层扫描确定，是否预测哌甲酯引起的血流动力学反应或行为变化的量。与10/10纯合子相比，9R携带者的纹状体数据可用性名义上更高（d= 0.40），这与荟萃分析一致，但并不能预测MPH治疗后BOLD或行为变化。我们得出结论，急性MPH给药对脑激活的影响取决于DAT基因型，9R携带者在给药前多巴胺能化合物后表现出增强的BOLD。
We pharmacologically challenged catecholamine reuptake, using methylphenidate, to investigate its effects on brain activity during a motor response inhibition task as a function of the 3′-UTR variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) gene (SLC6A3) and the availability of DATs in the striatum. We measured the cerebral hemodynamic response of 50 healthy males during a Go/No-Go task, a measure of cognitive control, under the influence of 40 mg methylphenidate and placebo using 3T functional magnetic resonance imaging. Subjects were grouped into 9-repeat (9R) carriers and 10/10 homozygotes on the basis of the SLC6A3 VNTR. During successful no-go trials compared with oddball trials, methylphenidate induced an increase of blood oxygen level-dependent (BOLD) signal for carriers of the SLC6A3 9R allele but a decrease in 10/10 homozygotes in a thalamocortical network. The same pattern was observed in caudate and inferior frontal gyrus when successful no-go trials were compared with successful go trials. We additionally investigated in a subset of 35 participants whether baseline striatal DAT availability, ascertained with 123 I-FP-CIT single photon emission computed tomography, predicted the amount of methylphenidate-induced change in hemodynamic response or behavior. Striatal DAT availability was nominally greater in 9R carriers compared with 10/10 homozygotes (d= 0.40), in line with meta-analyses, but did not predict BOLD or behavioral changes following MPH administration. We conclude that the effects of acute MPH administration on brain activation are dependent on DAT genotype, with 9R carriers showing enhanced BOLD following administration of a prodopaminergic compound.
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影响因子：
11
作者：
Faraone, S. V.;Spencer, T. J.;Biederman, J.
通讯作者：
Biederman, J.
使用 [11C]FLB 457 PET 测量哌甲酯引起的纹状体外多巴胺浓度变化
影响因子：
6.3
作者：
A. Montgomery;M. Asselin;L. Farde;P. Grasby
通讯作者：
P. Grasby
基底神经节：解剖学、生理学和药理学。
影响因子：
1.7
作者：
S. Tisch;P. Silberstein;P. Limousin‐Dowsey;M. Jahanshahi
通讯作者：
M. Jahanshahi
影响因子：
2.3
作者：
Saba, Wadad;Valette, Heric;Bottlaender, Michel
通讯作者：
Bottlaender, Michel
哌醋甲酯、托莫西汀和西酞普兰对反应抑制神经网络的分离和常见影响
影响因子：
2.6
作者：
L. Nandam;R. Hester;M. Bellgrove
通讯作者：
M. Bellgrove