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融合的遗传和功能脑成像证据将神经元兴奋性与工作记忆、精神疾病和大脑活动联系起来。

Converging genetic and functional brain imaging evidence links neuronal excitability to working memory, psychiatric disease, and brain activity.

机构信息

Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Psychiatric University Clinics, University of Basel, CH-4055 Basel, Switzerland.

Division of Molecular Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland; Division of Cognitive Neuroscience, Department of Psychology, University of Basel, CH-4055 Basel, Switzerland.

出版信息

Neuron. 2014 Mar 5;81(5):1203-1213. doi: 10.1016/j.neuron.2014.01.010. Epub 2014 Feb 13.

Abstract

Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n = 2,824) and in a large schizophrenia case-control sample (n = 32,143). The voltage-gated cation channel activity gene set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages and to schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set also to working memory-related activity in the parietal cortex and the cerebellum. Gene set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity, and psychopathology.

摘要

工作记忆是指在认知任务期间主动维持与任务相关信息的能力,是一种可遗传的特征。工作记忆缺陷是许多精神疾病的特征。我们在多个独立的年轻和老年认知健康受试者数据集(n=2824)和一个大型精神分裂症病例对照样本(n=32143)中进行了全基因组基因集富集分析。电压门控阳离子通道活性基因集由与神经元兴奋性相关的基因组成,该基因集与不同年龄段的工作记忆相关任务的表现以及精神分裂症显著相关。在 707 名健康参与者的功能性脑成像研究中,该基因集也与顶叶皮层和小脑的工作记忆相关活动相关。基因集分析可能有助于剖析认知维度、大脑活动和精神病理学的分子基础。

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