Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China; and Brain Function Research Section, The First Affiliated Hospital of China Medical University, PR China.
Department of Psychiatry, The First Affiliated Hospital of China Medical University, PR China; Brain Function Research Section, The First Affiliated Hospital of China Medical University, PR China; and Department of Psychology, Weifang Medical University, PR China.
Br J Psychiatry. 2021 Jul;219(1):392-400. doi: 10.1192/bjp.2021.47.
Schizophrenia is considered a polygenic disorder. People with schizophrenia and those with genetic high risk of schizophrenia (GHR) have presented with similar neurodevelopmental deficits in hemispheric asymmetry. The potential associations between neurodevelopmental abnormalities and schizophrenia-related risk genes in both schizophrenia and those with GHR remains unclear.
To investigate the shared and specific alternations to the structural network in people with schizophrenia and those with GHR. And to identify an association between vulnerable structural network alternation and schizophrenia-related risk genes.
A total of 97 participants with schizophrenia, 79 participants with GHR and 192 healthy controls, underwent diffusion tensor imaging (DTI) scans at a single site. We used graph theory to characterise hemispheric and whole-brain structural network topological metrics. For 26 people in the schizophrenia group and 48 in the GHR group with DTI scans we also calculated their schizophrenia-related polygenic risk scores (SZ-PRSs). The correlations between alterations to the structural network and SZ-PRSs were calculated. Based on the identified genetic-neural association, bioinformatics enrichment was explored.
There were significant hemispheric asymmetric deficits of nodal efficiency, global and local efficiency in the schizophrenia and GHR groups. Hemispheric asymmetric deficit of local efficiency was significantly positively correlated with SZ-PRSs in the schizophrenia and GHR groups. Bioinformatics enrichment analysis showed that these risk genes may be linked to signal transduction, neural development and neuron structure. The schizophrenia group showed a significant decrease in the whole-brain structural network.
The shared asymmetric deficits in people with schizophrenia and those with GHR, and the association between anomalous asymmetry and SZ-PRSs suggested a vulnerability imaging marker regulated by schizophrenia-related risk genes. Our findings provide new insights into asymmetry regulated by risk genes and provides a better understanding of the genetic-neural pathological underpinnings of schizophrenia.
精神分裂症被认为是一种多基因疾病。精神分裂症患者和遗传高风险精神分裂症（GHR）患者在大脑半球不对称的神经发育缺陷方面表现出相似的特征。精神分裂症患者和 GHR 患者的神经发育异常与精神分裂症相关风险基因之间的潜在关联尚不清楚。
探讨精神分裂症患者和 GHR 患者的结构网络的共享和特定改变。并确定易损结构网络改变与精神分裂症相关风险基因之间的关联。
共有 97 名精神分裂症患者、79 名 GHR 患者和 192 名健康对照者在一个地点接受弥散张量成像（DTI）扫描。我们使用图论来描述大脑半球和全脑结构网络拓扑度量。对于精神分裂症组的 26 人和 GHR 组的 48 人，我们还计算了他们的精神分裂症相关多基因风险评分（SZ-PRS）。计算结构网络改变与 SZ-PRS 之间的相关性。基于所确定的遗传-神经关联，进行了生物信息学富集分析。
精神分裂症和 GHR 组患者存在明显的半球不对称性节点效率、全局效率和局部效率降低。精神分裂症和 GHR 组患者的局部效率半球不对称性缺陷与 SZ-PRS 呈显著正相关。生物信息学富集分析表明，这些风险基因可能与信号转导、神经发育和神经元结构有关。精神分裂症组患者的全脑结构网络明显下降。
精神分裂症患者和 GHR 患者存在共享的不对称性缺陷，以及异常不对称性与 SZ-PRS 之间的关联表明，精神分裂症相关风险基因调控的易损性成像标志物。我们的研究结果为风险基因调控的不对称性提供了新的见解，并为精神分裂症的遗传-神经病理基础提供了更好的理解。
