Dataset Information

Association between NRGN gene polymorphism and resting-state hippocampal functional connectivity in schizophrenia.

ABSTRACT: BACKGROUND:Based on genome-wide association studies, a single-nucleotide polymorphism in the NRGN gene (rs12807809) is considered associated with schizophrenia (SZ). Moreover, hippocampal dysfunction is associated with rs12807809. In addition, converging evidence suggests that hippocampal dysfunction is involved in SZ pathophysiology. However, the association among rs12807809, hippocampal dysfunction and SZ pathophysiology is unknown. Therefore, this study investigated the association between rs12807809 and hippocampal functional connectivity at rest in SZ. METHODS:In total, 158 participants were studied, including a C-carrier group carrying the non-risk C allele (29 SZ patients and 46 healthy controls) and a TT homozygous group carrying the risk T allele (30 SZ patients and 53 healthy controls). All participants were scanned using resting-state functional magnetic resonance imaging. Hippocampal functional connectivity was computed and compared among the 4 groups. RESULTS:Significant main effects of diagnosis were observed in the functional connectivity between the hippocampus and bilateral fusiform gyrus, bilateral lingual gyrus, left inferior temporal gyrus, left caudate nucleus, bilateral thalamus and bilateral anterior cingulate gyri. In contrast, no significant main effect of genotype was found. In addition, a significant genotype by diagnosis interaction in the functional connectivity between the hippocampus and left anterior cingulate gyrus, as well as bilateral middle cingulate gyri, was observed, with TT homozygotes with SZ showing less functional connectivity than C-carriers with SZ and healthy control TT homozygotes. CONCLUSIONS:These findings are the first to suggest an association between rs12807809 and abnormal Papez circuit function in patients with SZ. This study also implicates NRGN variation and abnormal Papez circuit function in SZ pathophysiology.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6451258 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Association between NRGN gene polymorphism and resting-state hippocampal functional connectivity in schizophrenia.

Zhang Yifan Y Gong Xiaohong X Yin Zhiyang Z Cui Lingling L Yang Jian J Wang Pengshuo P Zhou Yifang Y Jiang Xiaowei X Wei Shengnan S Wang Fei F Tang Yanqing Y

BMC psychiatry 20190405 1

<h4>Background</h4>Based on genome-wide association studies, a single-nucleotide polymorphism in the NRGN gene (rs12807809) is considered associated with schizophrenia (SZ). Moreover, hippocampal dysfunction is associated with rs12807809. In addition, converging evidence suggests that hippocampal dysfunction is involved in SZ pathophysiology. However, the association among rs12807809, hippocampal dysfunction and SZ pathophysiology is unknown. Therefore, this study investigated the association be ...[more]

PMID: 30953482

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Project description:The reliability of magnetoencephalography (MEG) resting-state functional connectivity in schizophrenia (SZ) is unknown as previous research has focused on healthy controls (HC). Here, we examined reliability in 26 participants (13-SZ, 13-HC). Eyes opened and eyes closed resting-state data were collected on 4 separate occasions during 2 visits, 1 week apart. For source modeling, we used minimum norm software to apply dynamic statistical parametric mapping. Source analyses compared the following functional connectivity metrics from each data run: coherence (coh), imaginary coherence (imcoh), pairwise phase consistency (ppc), phase-locking value (plv), phase lag index (pli), weighted phase lag index (wpli), and weighted phase lag index debiased (wpli2). Intraclass correlation coefficients (ICCs) were calculated for whole brain, network, and network pair averages. For reliability, ICCs above 0.75 = excellent, above 0.60 = good, above 0.40 = fair, and below 0.40 = poor reliability. We found the reliability of these metrics varied greatly depending on frequency band, network, network pair, and participant group examined. Broadband (1-58 Hz) whole brain averages in both HC and SZ showed excellent reliability for wpli2, and good to fair reliability for ppc, plv, and coh. Broadband network averages showed excellent to good reliability across 1 hour and 1 week for coh, imcoh, ppc, plv, wpli within default mode, cognitive control, and visual networks in HC, while the same metrics had excellent to fair reliability in SZ. Regional network pair averages showed good to fair reliability for coh, ppc, plv within default mode, cognitive control and visual network pairs in HC and SZ. In general, HC had higher reliability compared to SZ, and the default mode, cognitive control, and visual networks had higher reliability compared to somatosensory and auditory networks. Similar reliability levels occurred for both eyes opened and eyes closed resting-states for most metrics. The functional connectivity metrics of coh, ppc, and plv performed best across 1 hour and 1 week in HC and SZ. We also found that SZ had reduced coh, plv, and ppc in the dmn average and pair values indicating dysconnectivity in SZ. These findings encourage collecting both eyes opened and eyes closed resting-state MEG, while demonstrating that clinical populations may differ in reliability.

Dataset Information

Association between NRGN gene polymorphism and resting-state hippocampal functional connectivity in schizophrenia.

Publications

Association between NRGN gene polymorphism and resting-state hippocampal functional connectivity in schizophrenia.

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