Neuroimaging Center, Department of Neuroscience, University of Groningen, University Medical Center Groningen, PO Box 196, 9700, AD, Groningen, the Netherlands.
MRC Cognition and Brain Sciences Unit, University of Cambridge, 15 Chaucer Road, Cambridge, CB2 7EF, UK.
Brain Imaging Behav. 2017 Dec;11(6):1581-1591. doi: 10.1007/s11682-016-9626-2.
Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on neuroticism. The aim of the current study was to investigate how genetic risk factors impact functional network organization and whether genetic risk factors moderate the association between neuroticism and functional network organization. We applied graph theory analysis on resting-state fMRI data in a sample of 120 women selected based on their neuroticism score, and genotyped two polymorphisms: 5-HTTLPR (S-carriers and L-homozygotes) and COMT (rs4680-rs165599; COMT risk group and COMT non-risk group). For the 5-HTTLPR polymorphism, we found that subnetworks related to cognitive control show less connections with other subnetworks in S-carriers compared to L-homozygotes. The COMT polymorphism moderated the association between neuroticism and functional network organization. We found that neuroticism was associated with lower efficiency coefficients in visual and somatosensory-motor subnetworks in the COMT risk group compared to the COMT non-risk group. The findings of altered topology of specific subnetworks point to different cognitive-emotional processes that may be affected in relation to the genetic risk factors, concerning emotion regulation in S-carriers (5-HTTLPR) and emotional salience processing in COMT risk carriers.
神经质和 5-羟色胺转运体（SLC6A4）和儿茶酚-O-甲基转移酶（COMT）基因的遗传变异是精神病理学的危险因素。最近发现，神经质得分较高的个体的神经回路功能整合和分离发生了改变。本研究的目的是探讨遗传风险因素如何影响功能网络组织，以及遗传风险因素是否调节神经质与功能网络组织之间的关联。我们应用图论分析方法对 120 名女性的静息态 fMRI 数据进行了研究，这些女性是根据其神经质评分选择的，并对两种多态性进行了基因分型：5-HTTLPR（S 携带者和 L 纯合子）和 COMT（rs4680-rs165599；COMT 风险组和 COMT 非风险组）。对于 5-HTTLPR 多态性，我们发现与认知控制相关的子网与其他子网的连接较少 S 携带者比 L 纯合子。COMT 多态性调节了神经质与功能网络组织之间的关联。我们发现，与 COMT 非风险组相比，COMT 风险组的神经质与视觉和躯体感觉运动子网中的效率系数较低有关。特定子网拓扑结构改变的发现表明，与遗传风险因素有关的可能受到影响的不同认知-情绪过程，涉及 S 携带者的情绪调节（5-HTTLPR）和 COMT 风险携带者的情绪显著处理。
