UC Berkeley Graduate Neuroscience Program, Helen Wills Neuroscience Institute, Berkeley, CA.
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC.
Schizophr Bull. 2018 Jun 6;44(4):844-853. doi: 10.1093/schbul/sbx140.
Recent work has begun to shed light on the neural correlates and possible mechanisms of polygenic risk for schizophrenia. Here, we map a schizophrenia polygenic risk profile score (PRS) based on genome-wide association study significant loci onto variability in the activity and functional connectivity of a frontoparietal network supporting the manipulation versus maintenance of information during a numerical working memory (WM) task in healthy young adults (n = 99, mean age = 19.8). Our analyses revealed that higher PRS was associated with hypoactivity of the dorsolateral prefrontal cortex (dlPFC) during the manipulation but not maintenance of information in WM (r2 = .0576, P = .018). Post hoc analyses revealed that PRS-modulated dlPFC hypoactivity correlated with faster reaction times during WM manipulation (r2 = .0967, P = .002), and faster processing speed (r2 = .0967, P = .003) on a separate behavioral task. These PRS-associated patterns recapitulate dlPFC hypoactivity observed in patients with schizophrenia during central executive manipulation of information in WM on this task.
最近的研究开始揭示精神分裂症多基因风险的神经相关性和可能的机制。在这里，我们基于全基因组关联研究显著位点，将精神分裂症多基因风险评分 (PRS) 映射到健康年轻成年人（n = 99，平均年龄 = 19.8 岁）在进行数字工作记忆 (WM) 任务时支持信息操作和维持的额顶网络的活动和功能连接的可变性上。我们的分析表明，较高的 PRS 与 WM 信息操作期间背外侧前额叶皮层 (dlPFC) 的活动减少有关（r2 =.0576，P =.018）。事后分析表明，PRS 调节的 dlPFC 活动减少与 WM 操作期间更快的反应时间相关（r2 =.0967，P =.002），并且在单独的行为任务中与更快的处理速度相关（r2 =.0967，P =.003）。这些与 PRS 相关的模式再现了在这项任务中精神分裂症患者在 WM 中进行中央执行信息操作期间观察到的 dlPFC 活动减少。
