Polymorphism in schizophrenia risk gene MIR137 is associated with the posterior cingulate Cortex's activation and functional and structural connectivity in healthy controls.
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ABSTRACT:
SUBMITTER: Zhang Z
PROVIDER: S-EPMC6051762 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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Polymorphism in schizophrenia risk gene <i>MIR137</i> is associated with the posterior cingulate Cortex's activation and functional and structural connectivity in healthy controls.
Zhang Zhifang Z Yan Tongjun T Wang Yanyan Y Zhang Qiumei Q Zhao Wan W Chen Xiongying X Zhai Jinguo J Chen Min M Du Boqi B Deng Xiaoxiang X Ji Feng F Xiang Yutao Y Wu Hongjie H Song Jie J Dong Qi Q Chen Chuansheng C Li Jun J
NeuroImage. Clinical 20180403
<i>MIR137</i> gene has been repeatedly reported as a schizophrenia risk gene in genome-wide association studies (GWAS). A polymorphism (rs1625579) at the <i>MIR137</i> gene has been associated with both neural activation and behavioral performance during a working memory task. This study examined <i>MIR137</i>'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 ri ...[more]
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Project description:The SNP rs2958182 was reported to be significantly associated with schizophrenia (SCZ) in Han Chinese. This study examined this SNP's associations with cognitive functions in 580 SCZ patients and 498 controls. Cognitive functions were assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-RC), the Attention Network Task (ANT), the Stroop task, the dot pattern expectancy (DPX), task and the N-back working memory task. Results showed significant or marginally significant interaction effects between genotype and diagnosis status on IQ (P=0.011) and attention-related tasks (ie, the forward digit span of WAIS-RC, P=0.005; the ANT conflict effect; P=0.020, and its ratios over mean reaction time (RT), P=0.036; the Stroop conflict effect, P=0.032, and its ratios over mean RT, P=0.062; and the DPX task's error rate under the BX condition, P<0.001, and the error rate of BX minus the error rate of AY (BX-AY), P=0.002). There were no such interaction effects on the measures of working memory (all P-values >0.05). Further analysis of the significant genotype-by-diagnosis interactions showed that the risk (T) allele was associated with better performance on cognitive tasks in patients but with worse performance in controls. These results seem to indicate that the association between this SNP and selected cognitive functions may be of an inverted U-shaped pattern. Future research is needed to replicate these results and to explore the biochemical mechanisms behind this association.
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Project description:BackgroundThe underlying neurobiological mechanism for abnormal functional connectivity in schizophrenia (SCZ) remains unknown. This project investigated whether glutamate and GABA, 2 metabolites that contribute to excitatory and inhibitory functions, may influence functional connectivity in SCZ.MethodsResting-state functional magnetic resonance imaging and proton magnetic resonance spectroscopy were acquired from 58 SCZ patients and 61 healthy controls (HC). Seed-based connectivity maps were extracted between the anterior cingulate cortex (ACC) spectroscopic voxel and all other brain voxels. Magnetic resonance spectroscopy (MRS) spectra were processed to quantify glutamate and GABA levels. Regression analysis was performed to describe relationships between functional connectivity and glutamate and GABA levels.ResultsReduced ACC functional connectivity in SCZ was found in regions associated with several neural networks including the default mode network (DMN) compared to HC. In the HC, positive correlations were found between glutamate and both ACC-right inferior frontal gyrus functional connectivity and ACC-bilateral superior temporal gyrus functional connectivity. A negative correlation between GABA and ACC-left posterior cingulate functional connectivity was also observed in HC. These same relationships were not statistically significant in SCZ.ConclusionsThe present investigation is one of the first studies to examine links between functional connectivity and glutamate and GABA levels in SCZ. Results indicate that glutamate and GABA play an important role in the functional connectivity modulation in the healthy brain. The absence of glutamate and GABA correlations in areas where SCZ showed significantly reduced functional connectivity may suggest that this chemical-functional relationship is disrupted in SCZ.
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