Interactions of genetic variants reveal inverse modulation patterns of dopamine system on brain gray matter volume and resting-state functional connectivity in healthy young adults.
Interactions of genetic variants reveal inverse modulation patterns of dopamine system on brain gray matter volume and resting-state functional connectivity in healthy young adults.
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遗传变异的相互作用揭示了多巴胺系统对健康年轻人大脑灰质体积和静息态功能连接的反向调节模式
DOI：
10.1007/s00429-015-1134-4
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发表时间：
2016-11
影响因子：
3.1
通讯作者：
Yu C
中科院分区：
文献类型：
--
作者：
Xu J;Qin W;Liu B;Jiang T;Yu C
COMT和DRD 2的不同基因型组合可以产生具有不同水平多巴胺信号传导的多个亚组。通过分析COMT和DRD 2的联合基因效应可以研究其对脑特性的调节作用。然而，多巴胺系统对大脑结构和功能特性的调制模式之间的内在关联仍然未知。在294名健康年轻人中，我们使用基于体素的分析研究了COMT和DRD 2对灰质体积（GMV）和静息状态功能连接（rsFC）的加性和非加性相互作用。在右侧背侧前扣带皮层（dACC）中发现了一个显著的非加性COMT × DRD 2相互作用，表现出多巴胺信号的倒U形调制。在右侧dACC和楔前叶之间的rsFC中，我们还发现了显著的非加和性COMT × DRD 2相互作用，显示出多巴胺信号的U形调节。此外，该rsFC与右侧dACC的GMV呈负相关。虽然添加剂的相互作用没有通过多重比较的校正，我们也发现了一个趋势，朝着逆调制模式和右额下回的GMV和rsFC之间的负相关。在认知、情绪和人格的任何评估中均未检测到基因型差异。这些研究结果表明，没有最佳多巴胺信号的健康年轻人可能会通过功能性补偿机制来维持他们正常的行为表现，以应对遗传变异引起的结构性缺陷。
Different genotypic combinations ofCOMTandDRD2can generate multiple subgroups with different levels of dopamine signaling. Its modulations on brain properties can be investigated by analyzing the combined gene effects ofCOMTandDRD2. However, the inherent association between modulation patterns of the dopamine system on structural and functional properties of the brain remains unknown. In 294 healthy young adults, we investigated both additive and non-additive interactions ofCOMTandDRD2on gray matter volume (GMV) and resting-state functional connectivity (rsFC) using a voxel-based analysis. We found a significant non-additiveCOMT×DRD2interaction in the right dorsal anterior cingulate cortex (dACC), exhibiting an inverted U-shape modulation by dopamine signaling. We also found a significant non-additiveCOMT×DRD2interaction in the rsFC between the right dACC and precuneus, displaying a U-shape modulation by dopamine signaling. Moreover, this rsFC was negatively correlated with the GMV of the right dACC. Although the additive interaction did not pass corrections for multiple comparisons, we also found a trend towards an inverse modulation pattern and a negative correlation between the GMV and rsFC of the right inferior frontal gyrus. No genotypic differences were detected in any assessments of the cognition, mood and personality. These findings suggest that healthy young adults without optimal dopamine signaling may maintain their normal behavioral performance via a functional compensatory mechanism in response to structural deficit due to genetic variation.
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DOI：
10.1073/pnas.111134598
发表时间：
2001-06-05
影响因子：
11.1
作者：
Egan, MF;Goldberg, TE;Weinberger, DR
通讯作者：
Weinberger, DR
DOI：
10.1523/jneurosci.4858-08.2009
发表时间：
2009-01-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bertolino A;Fazio L;Di Giorgio A;Blasi G;Romano R;Taurisano P;Caforio G;Sinibaldi L;Ursini G;Popolizio T;Tirotta E;Papp A;Dallapiccola B;Borrelli E;Sadee W
通讯作者：
Sadee W
影响因子：
3.4
作者：
Henseler, I.;Falkai, P.;Gruber, O.
通讯作者：
Gruber, O.
影响因子：
56.9
作者：
Contreras, Marco;Ceric, Francisco;Torrealba, Fernando
通讯作者：
Torrealba, Fernando
影响因子：
10.6
作者：
Bruder, GE;Keilp, JG;Gilliam, TC
通讯作者：
Gilliam, TC