Bertolino Alessandro, Blasi Giuseppe, Latorre Valeria, Rubino Valeria, Rampino Antonio, Sinibaldi Lorenzo, Caforio Grazia, Petruzzella Vittoria, Pizzuti Antonio, Scarabino Tommaso, Nardini Marcello, Weinberger Daniel R, Dallapiccola Bruno
Psychiatric Neuroscience Group, Department of Neurological and Psychiatric Sciences, University of Bari, 70124 Bari, Italy.
J Neurosci. 2006 Apr 12;26(15):3918-22. doi: 10.1523/JNEUROSCI.4975-05.2006.
Functional polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) genes modulate dopamine inactivation, which is crucial for determining neuronal signal-to-noise ratios in prefrontal cortex during working memory. We show that the COMT Met158 allele and the DAT 3' variable number of tandem repeat 10-repeat allele are independently associated in healthy humans with more focused neuronal activity (as measured with blood oxygen level-dependent functional magnetic resonance imaging) in the working memory cortical network, including the prefrontal cortex. Moreover, subjects homozygous for the COMT Met allele and the DAT 10-repeat allele have the most focused response, whereas the COMT Val and the DAT 9-repeat alleles have the least. These results demonstrate additive genetic effects of genes regulating dopamine signaling on specific neuronal networks subserving working memory.
儿茶酚-O-甲基转移酶（COMT）基因和多巴胺转运体（DAT）基因中的功能多态性可调节多巴胺失活，这对于在工作记忆期间确定前额叶皮质中的神经元信噪比至关重要。我们发现，在健康人群中，COMT基因的Met158等位基因和DAT基因3'端可变串联重复序列的10次重复等位基因与工作记忆皮质网络（包括前额叶皮质）中更集中的神经元活动（通过血氧水平依赖性功能磁共振成像测量）独立相关。此外，COMT基因Met等位基因和DAT基因10次重复等位基因的纯合子受试者具有最集中的反应，而COMT基因Val等位基因和DAT基因9次重复等位基因的反应最不集中。这些结果证明了调节多巴胺信号的基因对支持工作记忆的特定神经元网络具有累加遗传效应。
