Cognitive state and connectivity effects of the genome-wide significant psychosis variant in ZNF804A
Cognitive state and connectivity effects of the genome-wide significant psychosis variant in ZNF804A
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DOI：
10.1016/j.neuroimage.2010.10.012
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发表时间：
2011-02-01
期刊：
影响因子：
5.7
通讯作者：
Meyer-Lindenberg, Andreas
中科院分区：
文献类型：
--
作者：
Esslinger, Christine;Kirsch, Peter;Meyer-Lindenberg, Andreas
连接性的改变是精神分裂症系统级病理生理学的核心。 ZNF804A 中的 rs1344706 单核苷酸多态性是这种高度遗传性疾病最确定的全基因组显着风险变异之一，最近被证明可以在工作记忆 (WM) 期间调节健康携带者的连接性，其模式与明显疾病中发现的模式相似。然而，尚不清楚这一发现是否特定于 WM，或者是否无论认知状态如何都存在。因此，我们检查了基因型对健康携带者在休息和没有 WM 成分的情绪处理任务中的连接性的影响。111 名健康的德国受试者执行了一系列功能成像任务。使用种子体素方法确定在休息和隐性情绪识别任务期间与右侧背外侧前额叶皮层的功能连接，并与 WM 期间的结果进行比较。在休息和情绪任务期间，可以看到随着 rs1344706 风险等位基因数量的增加，半球间前额叶连接减少的模式，该模式与 WM 期间几乎相同，表明遗传变异可能通过结构效应对半球间处理产生与状态无关的影响。相比之下，异常的前额叶-海马连接仅在 WM 任务期间出现，表明任务特异性一定程度与精神分裂症患者先前的结果一致。我们的研究结果证实了功能连接紊乱在精神分裂症遗传风险结构中的关键作用，并确定了与 WM 功能相关的认知状态依赖和独立成分。 (C) 2010 Elsevier Inc. 保留所有权利。
Alterations of connectivity are central to the systems-level pathophysiology of schizophrenia. One of the best-established genome-wide significant risk variants for this highly heritable disorder, the rs1344706 single nucleotide polymorphism in ZNF804A, was recently shown to modulate connectivity in healthy carriers during working memory (WM) in a pattern mirroring that which was found in overt disease. However, it was unclear whether this finding is specific to WM or if it is present regardless of cognitive state. Therefore, we examined genotype effects on connectivity in healthy carriers during rest and an emotion processing task without WM component.111 healthy German subjects performed a battery of functional imaging tasks. Functional connectivity with the right dorsolateral prefrontal cortex during rest and an implicit emotion recognition task was determined using the seed voxel method and compared to results during WM.During rest and during the emotional task, a pattern of reduced interhemispheric prefrontal connectivity with increasing number of rs1344706 risk alleles could be seen that was close to identical to that during WM, suggesting a state-independent influence of the genetic variant on interhemispheric processing, possibly through structural effects. By contrast, the abnormal prefronto-hippocampal connectivity was only seen during the WM task, indicating a degree of task specificity in agreement with prior results in patients with schizophrenia. Our findings confirm a key role for disturbed functional connectivity in the genetic risk architecture of schizophrenia and identify cognitive state-dependent and independent components with regard to WM function. (C) 2010 Elsevier Inc. All rights reserved.