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DRD2/ANKK1和COMT基因多态性对精神分裂症注意力和认知功能的影响

Impact of DRD2/ANKK1 and COMT Polymorphisms on Attention and Cognitive Functions in Schizophrenia.

作者信息

Nkam Irene, Ramoz Nicolas, Breton Florence, Mallet Jasmina, Gorwood Philip, Dubertret Caroline

机构信息

INSERM U894, Center of Psychiatry and Neurosciences, Paris, France.

Pôle 1, Roger Prevot Hospital, Moisselles, France.

出版信息

PLoS One. 2017 Jan 13;12(1):e0170147. doi: 10.1371/journal.pone.0170147. eCollection 2017.

Abstract

BACKGROUND

Cognitive deficits such as poor selective attention and executive functions decline have been reported in patients with schizophrenia. Many studies have emphasized the role of dopamine in regulating cognitive functions in the general population as well as in schizophrenia. However, the relationship between cognitive processes, schizophrenia and dopaminergic candidate genes is an original approach given interesting results. The purpose of the current exploratory study was to examine the interaction of dopaminergic genes (coding for dopamine receptor D2, DRD2, and for Catecholamine-O-Methyl-Transferase, COMT) with the diagnostic of schizophrenia in (i) the executive control of attention, (ii) selective attention, and (iii) executive functions.

METHODS AND RESULTS

We recruited 52 patients with schizophrenia and 53 healthy controls who performed the Stroop Color-Word Test, the Attention Network Test and the Wisconsin Card Sorting test. Four single nucleotide polymorphisms (SNPs) in the DRD2 gene (rs6275, rs6277, rs2242592 and rs1800497) and two SNPs in the COMT gene (rs4680 and rs165599) have been genotyped. Patients with schizophrenia performed significantly worse than controls in all cognitive performance, taking into account demographic variables. A significant gene by disease interaction was found for the Stroop interference (p = 0.002) for rs6275 of the DRD2 gene. The COMT Val/Val genotype and schizophrenia were associated with increased number of perseverative errors (p = 0.01).

CONCLUSIONS

In our study, the DRD2 gene is involved in attention while the COMT gene is implicated in executive functions in patients with schizophrenia.

摘要

背景

已有报道称精神分裂症患者存在认知缺陷,如选择性注意力差和执行功能下降。许多研究强调了多巴胺在调节普通人群以及精神分裂症患者认知功能中的作用。然而,认知过程、精神分裂症与多巴胺能候选基因之间的关系是一种能得出有趣结果的新方法。当前这项探索性研究的目的是检验多巴胺能基因(编码多巴胺受体D2,即DRD2,以及儿茶酚-O-甲基转移酶,即COMT)与精神分裂症诊断在(i)注意力的执行控制、(ii)选择性注意力和(iii)执行功能方面的相互作用。

方法与结果

我们招募了52名精神分裂症患者和53名健康对照者,他们进行了斯特鲁普颜色-文字测试、注意力网络测试和威斯康星卡片分类测试。对DRD2基因中的四个单核苷酸多态性(SNP)(rs6275、rs6277、rs2242592和rs1800497)以及COMT基因中的两个SNP(rs4680和rs165599)进行了基因分型。考虑到人口统计学变量,精神分裂症患者在所有认知表现上均显著差于对照者。发现DRD2基因的rs6275在斯特鲁普干扰方面存在显著的基因与疾病相互作用(p = 0.002)。COMT Val/Val基因型与精神分裂症与持续性错误数量增加相关(p = 0.01)。

结论

在我们的研究中,DRD2基因参与精神分裂症患者的注意力调节,而COMT基因与执行功能有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce9b/5235377/954f5b294cad/pone.0170147.g001.jpg

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