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抗精神病药物治疗八周后精神分裂症和分裂情感性障碍中NEUROD2基因多态性与认知功能障碍变化的关联

Associations of NEUROD2 polymorphisms and change of cognitive dysfunctions in schizophrenia and schizoaffective disorder after eight weeks of antipsychotic treatment.

作者信息

Spellmann Ilja, Riedel Michael, Städtler Julia, Zill Peter, Obermeier Michael, Cerovecki Anja, Dehning Sandra, Schennach Rebecca, Epple Maria, Opgen-Rhein Markus, Müller Norbert, Bondy Brigitta, Möller Hans-Jürgen, Musil Richard

机构信息

a Department of Psychiatry and Psychotherapy , Ludwig-Maximilians-University Munich , Munich , Germany.

出版信息

Cogn Neuropsychiatry. 2017 Jul;22(4):280-297. doi: 10.1080/13546805.2017.1322502. Epub 2017 May 4.

Abstract

INTRODUCTION

NEUROD2 is a neurospecific helix-loop-helix transcription factor which has an impact on the regulation of glutamatergic and GABAergic genes. We investigated an association of NEUROD2 with neurocognitive dysfunctions in schizophrenia and schizoaffective disorder patients before and during treatment with different second-generation antipsychotics.

METHODS

Patients were genotyped for four different polymorphisms of the NEUROD2 gene ((rs9889354(A/G), rs1877032(C/T), rs12453682(C/T) and rs11078918(C/G)). Cognitive function was assessed at baseline and week 8. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index.

RESULTS

167 patients were included in the study. The NEUROD2 exonic polymorphism rs11078918 showed significant associations with verbal memory and executive functions, whereas the NEUROD2 polymorphism rs12453682 was significantly associated with working and verbal memory, executive functions and with a cognitive index. Significant associations were found at baseline and after eight weeks. Moreover, significant associations between the change in neuropsychological test results during antipsychotic treatment and the NEUROD2 polymorphisms rs11078918 and rs12453682 were observed.

CONCLUSIONS

Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

摘要

引言

NEUROD2是一种神经特异性螺旋-环-螺旋转录因子,对谷氨酸能和γ-氨基丁酸能基因的调控有影响。我们研究了精神分裂症和分裂情感性障碍患者在使用不同第二代抗精神病药物治疗之前和治疗期间NEUROD2与神经认知功能障碍之间的关联。

方法

对患者进行NEUROD2基因四种不同多态性(rs9889354(A/G)、rs1877032(C/T)、rs12453682(C/T)和rs11078918(C/G))的基因分型。在基线和第8周评估认知功能。将个体神经心理学测试结果分为六个认知领域(反应时间和质量;执行功能;工作记忆、言语记忆和视觉记忆)以及一个总体认知指数。

结果

167名患者纳入研究。NEUROD2外显子多态性rs11078918与言语记忆和执行功能显著相关,而NEUROD2多态性rs12453682与工作记忆、言语记忆、执行功能以及认知指数显著相关。在基线和八周后均发现显著关联。此外,观察到抗精神病治疗期间神经心理学测试结果的变化与NEUROD2多态性rs11078918和rs12453682之间存在显著关联。

结论

我们的研究结果表明,NEUROD2基因可能在精神分裂症和分裂情感性障碍的神经认知功能障碍的病理生理学以及抗精神病治疗下认知症状的变化中起作用。

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