The Impact of MIR137 on Dorsolateral Prefrontal-Hippocampal Functional Connectivity in Healthy Subjects
The Impact of MIR137 on Dorsolateral Prefrontal-Hippocampal Functional Connectivity in Healthy Subjects
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MIR137 对健康受试者背外侧前额叶 - 海马功能连接的影响
DOI：
10.1038/npp.2014.63
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发表时间：
2014-08-01
影响因子：
7.6
通讯作者：
Jiang, Tianzi
中科院分区：
文献类型：
--
作者：
Liu, Bing;Zhang, Xiaolong;Jiang, Tianzi
最近一项综合全基因组关联研究数据的大规模分析显示，微小RNA 137（MIR137）的一个变体与精神分裂症具有最显著的关联。其他生物学证据也一致表明，MIR137可能在精神分裂症的发病机制中起关键作用。然而，潜在的神经机制仍不清楚。由于精神分裂症患者中广泛观察到背外侧前额叶皮质（DLPFC）与海马结构（HF）的连接中断，因此DLPFC - HF连接异常可被视为将精神疾病风险基因的遗传变异与精神分裂症联系起来的关键中间表型。本研究利用静息态功能磁共振成像，在290名年轻健康的汉族个体中检测MIR137变体（rs1625579）是否影响DLPFC - HF功能连接和认知表现。为了确定DLPFC和HF之间的功能连接，采用了基于种子点的功能连接分析。进一步在具有不同MIR137基因型的个体中检验了DLPFC - HF连接与工作记忆表现之间的关联。携带MIR137风险等位基因纯合子（TT）（赋予精神分裂症高风险）的个体与TG个体相比，表现出显著不同的DLPFC - HF功能连接。此外，DLPFC - HF连接能够预测MIR137 TG个体的工作记忆表现，但不能预测TT个体的工作记忆表现。在大量健康参与者样本中获得的当前研究结果，确定了通过DLPFC - HF连接这一中间表型将MIR137与患精神分裂症风险联系起来的潜在神经机制。
A recent mega-analysis combining genome-wide association study data revealed that a variant of microRNA 137 (MIR137) exhibits the most significant association with schizophrenia. Other biological evidence also consistently suggests that MIR137 may have a pivotal role in the pathogenesis of schizophrenia. However, the underlying neural mechanism remains unclear. As the disrupted dorsolateral prefrontal cortex (DLPFC) coupling with the hippocampal formation (HF) has been widely observed in schizophrenia patients, DLPFC-HF dysconnectivity can therefore be thought of as a pivotal intermediate phenotype that links genetic variants of psychiatric risk genes to schizophrenia. This study used resting-state functional magnetic resonance imaging to test whether the MIR137 variant (rs1625579) impacts DLPFC-HF functional connectivity and cognitive performance in 290 young, healthy Han Chinese individuals. To identify functional connectivity between DLPFC and HF, a seed-based functional connectivity analysis was used. The association between DLPFC-HF connectivity and working memory performance was further examined in individuals with different MIR137 genotypes. The individuals who are homozygous for the MIR137 risk allele (TT), which confers a high risk for schizophrenia, exhibited significantly different DLPFC-HF functional connectivity compared with TG individuals. Moreover, the DLPFC-HF connectivity could predict the working memory performance in MIR137 TG individuals, but not in TT individuals. The current findings obtained in a large sample of healthy participants identified potential neural mechanisms linking MIR137 with the risk of developing schizophrenia via the intermediate phenotype of DLPFC-HF connectivity.