School of Psychology, Nanjing Normal University, Nanjing 210097, Jiangsu, PR China.
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, PR China; School of Public Health, Jining Medical University, Jining 272013, Shandong, PR China.
Schizophr Res. 2022 Oct;248:173-179. doi: 10.1016/j.schres.2022.08.014. Epub 2022 Sep 5.
A recent Chinese genome-wide association study found evidence for 58 out of the 128 schizophrenia-associated variants previously discovered in Western samples by the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC). However, the functional impact of these trans-ancestry genome-wide single-nucleotide polymorphisms (SNPs) is not clear. In the current study, we examined the roles of trans-ancestry SNPs in cognitive and neural plasticity. We first performed a behavioral study of 547 healthy volunteers, who received month-long working memory training, and working memory capability assessment both before and after the training. A separate sample of 101 subjects received the same training and received fMRI scans during a working memory task, both before and after the training. The behavioral study found a significant association between the polygenic risk score (PRS) and behavioral plasticity, with higher schizophrenia risk scores being linked to less plasticity. At the SNP level, rs36068923 showed a significant signal, with the risk allele being associated with less plasticity. The fMRI study further found that the PRS and rs36068923 polymorphism were associated with training-induced changes in striatal activation, with higher PRS and the risk allele of rs36068923 being linked to less brain plasticity. In sum, this study found that a high genetic risk for schizophrenia was associated with less plasticity at both behavioral and neural levels. These results provide new insights into the neural and cognitive mechanisms linking genes to schizophrenia.
最近一项中国全基因组关联研究发现，精神分裂症协作基因组学研究组（PGC）在西方样本中发现的 128 个与精神分裂症相关的变异中有 58 个在中国人中存在证据。然而，这些跨种族全基因组单核苷酸多态性（SNP）的功能影响尚不清楚。在当前的研究中，我们研究了跨种族 SNP 在认知和神经可塑性中的作用。我们首先对 547 名健康志愿者进行了一项行为研究，这些志愿者接受了为期一个月的工作记忆训练，并在训练前后进行了工作记忆能力评估。另一组 101 名受试者接受了相同的训练，并在工作记忆任务前后进行了 fMRI 扫描。行为研究发现，多基因风险评分（PRS）与行为可塑性之间存在显著关联，较高的精神分裂症风险评分与较低的可塑性相关。在 SNP 水平上，rs36068923 显示出显著的信号，风险等位基因与较低的可塑性相关。fMRI 研究进一步发现，PRS 和 rs36068923 多态性与纹状体激活的训练诱导变化有关，较高的 PRS 和 rs36068923 的风险等位基因与较低的大脑可塑性有关。总之，这项研究发现，精神分裂症的高遗传风险与行为和神经水平的较低可塑性有关。这些结果为基因与精神分裂症之间的神经和认知机制提供了新的见解。
