State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, PR China.
The PLA 102nd Hospital and Mental Health Center of Military, Changzhou 213003, PR China.
Neuroimage Clin. 2018 Apr 3;19:160-166. doi: 10.1016/j.nicl.2018.03.039. eCollection 2018.
gene has been repeatedly reported as a schizophrenia risk gene in genome-wide association studies (GWAS). A polymorphism (rs1625579) at the gene has been associated with both neural activation and behavioral performance during a working memory task. This study examined 's associations with task-related (N-back working memory) fMRI, resting state fMRI, and diffusion tensor images (DTI) data in 177 healthy adults. We found less deactivation of the PCC in risk allele homozygotes (TT) as compared to the GT heterozygotes (cluster size = 630 voxels, cluster level < 0.001) during the N-back task, which replicated previous findings. Using the identified cluster within the PCC as the seed, we further found decreased functional connectivity between the PCC and the anterior cingulate cortex and its adjacent medial prefrontal cortex (ACC/MPFC) in risk allele homozygotes during both resting state (cluster size = 427 voxels, cluster level = 0.001) and the N-back task (cluster size = 73 voxels, cluster level = 0.05). Finally, an analysis of our DTI data showed decreased white matter integrity of the posterior cingulum in risk allele homozygotes (cluster size = 214 voxels, cluster level = 0.03). Taken together, rs1625579 seems to play an important role in both functional and structural connectivity between the PCC and the ACC/MPFC, which may serve as the brain mechanisms for the link between rs1625579 and schizophrenia.
基因已被多次报道为全基因组关联研究 (GWAS) 中的精神分裂症风险基因。 基因的一个多态性 (rs1625579) 与工作记忆任务期间的神经激活和行为表现都有关联。 本研究在 177 名健康成年人中检查了基因与任务相关的 (N-back 工作记忆) fMRI、静息状态 fMRI 和弥散张量成像 (DTI) 数据之间的关联。 我们发现，在 N-back 任务中，风险等位基因纯合子 (TT) 的 PCC 去激活程度低于 GT 杂合子 (簇大小=630 个体素，簇水平<0.001)，这与先前的发现一致。 使用 PCC 内鉴定的簇作为种子，我们还发现风险等位基因纯合子在静息状态 (簇大小=427 个体素，簇水平=0.001) 和 N-back 任务 (簇大小=73 个体素，簇水平=0.05) 期间，PCC 与前扣带皮层及其相邻的前额叶皮层 (ACC/MPFC) 之间的功能连接减少。 最后，我们对 DTI 数据的分析表明，风险等位基因纯合子的后扣带白质完整性降低 (簇大小=214 个体素，簇水平=0.03)。 总之，rs1625579 似乎在 PCC 和 ACC/MPFC 之间的功能和结构连接中都起着重要作用，这可能是 rs1625579 与精神分裂症之间联系的大脑机制。
