Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People's Republic of China.
State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China.
BMC Psychiatry. 2019 Apr 5;19(1):108. doi: 10.1186/s12888-019-2088-5.
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.
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.
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.
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.
基于全基因组关联研究，NRGN 基因（rs12807809）中的单核苷酸多态性被认为与精神分裂症（SZ）有关。此外，海马功能障碍与 rs12807809 有关。此外，越来越多的证据表明，海马功能障碍与 SZ 病理生理学有关。然而，rs12807809、海马功能障碍和 SZ 病理生理学之间的关联尚不清楚。因此，本研究调查了 rs12807809 与 SZ 患者静息状态下海马功能连接的关系。
共有 158 名参与者参与了这项研究，包括携带非风险 C 等位基因的 C 携带者组（29 名 SZ 患者和 46 名健康对照者）和携带风险 T 等位基因的 TT 纯合子组（30 名 SZ 患者和 53 名健康对照者）。所有参与者均接受静息态功能磁共振成像扫描。计算并比较了 4 组之间的海马功能连接。
在海马与双侧梭状回、双侧舌回、左侧颞下回、左侧尾状核、双侧丘脑和双侧前扣带回之间的功能连接中，观察到诊断的显著主效应。相反，未发现基因型的显著主效应。此外，在海马与左侧前扣带回以及双侧中央扣带回之间的功能连接中，观察到基因型与诊断的显著交互作用，即与 SZ 患者相比，SZ 患者中的 TT 纯合子的功能连接减少，而健康对照组中的 TT 纯合子与 C 携带者相比。
这些发现首次表明 rs12807809 与 SZ 患者异常的 Papez 回路功能之间存在关联。本研究还提示 NRGN 变异与 SZ 病理生理学中的异常 Papez 回路功能有关。
