Wang C, Liu B, Long H, Fan L, Li J, Zhang X, Qiu C, Yu C, Jiang T
Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
Neuroscience. 2015 Jul 9;298:380-8. doi: 10.1016/j.neuroscience.2015.04.014. Epub 2015 Apr 18.
The frontostriatal system plays a critical role in emotional and cognitive control. Brain-derived neurotrophic factor (BDNF) influences the release of dopamine (DA) in the ventral striatum (VST), while catechol-O-methyltransferase (COMT) impacts DA availability in the prefrontal cortex (PFC). Behavioral studies have already shown a genetic interaction of BDNF Val66Met and COMT Val158Met, but the interaction on the DA-related neural circuit has not been previously studied. Here we show, using functional magnetic resonance imaging in a sample of healthy human subjects, that BDNF and COMT epistatically interacted on the functional connectivity between the bilateral VST and the anterior cingulate cortex. Specifically, BDNF Val66Met impacted the VST-PFC functional connectivity in an inverted U-shaped in COMT Met carriers, while COMT Val homozygotes displayed a U-shaped. These data may be helpful elucidating the mechanism of the interaction between BDNF and COMT on the cognitive functions that are based in the frontostriatal system.
额前叶纹状体系统在情绪和认知控制中起关键作用。脑源性神经营养因子（BDNF）影响腹侧纹状体（VST）中多巴胺（DA）的释放，而儿茶酚-O-甲基转移酶（COMT）影响前额叶皮质（PFC）中DA的可用性。行为学研究已经表明BDNF Val66Met和COMT Val158Met存在基因相互作用，但此前尚未研究过它们在与DA相关的神经回路上的相互作用。在此，我们通过对健康人类受试者样本进行功能磁共振成像研究发现，BDNF和COMT在上双侧VST与前扣带回皮质之间的功能连接上存在上位性相互作用。具体而言，在携带COMT Met的个体中，BDNF Val66Met对VST-PFC功能连接的影响呈倒U形，而COMT Val纯合子则呈U形。这些数据可能有助于阐明BDNF和COMT在基于额前叶纹状体系统的认知功能上相互作用的机制。
