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神经调节蛋白 1 与全基因组关联研究时代的精神分裂症。

Neuregulin-1 and schizophrenia in the genome-wide association study era.

机构信息

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.

Schizophrenia Research Institute, Sydney, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Barker Street, Sydney, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.

出版信息

Neurosci Biobehav Rev. 2016 Sep;68:387-409. doi: 10.1016/j.neubiorev.2016.06.001. Epub 2016 Jun 6.

Abstract

Clinical and pre-clinical evidence has implicated neuregulin 1 (NRG1) as a critical component in the pathophysiology of schizophrenia. However, the arrival of the genome-wide association study (GWAS) era has yielded results that challenge the relevance of NRG1 in schizophrenia due to the absence of a genome-wide significant NRG1 variant associated with schizophrenia. To assess NRG1's relevance to schizophrenia in the GWAS era, we provide a targeted review of recent preclinical evidence on NRG1's role in regulating several aspects of excitatory/inhibitory neurotransmission and in turn schizophrenia risk. We also present a systematic review of the last decade of clinical research examining NRG1 in the context of schizophrenia. We include concise summaries of genotypic variation, gene-expression, protein expression, structural and functional neuroimaging as well as cognitive studies conducted during this time period. We conclude with recommendations for future clinical and preclinical work that we hope will help prioritize a strategy forward to further advance our understanding of the relationship between NRG1 and schizophrenia.

摘要

临床前和临床证据表明,神经调节蛋白 1(NRG1)是精神分裂症病理生理学的关键组成部分。然而,全基因组关联研究(GWAS)时代的到来产生的结果挑战了 NRG1 在精神分裂症中的相关性,因为没有与精神分裂症相关的全基因组显著的 NRG1 变体。为了评估 NRG1 在 GWAS 时代与精神分裂症的相关性,我们提供了对 NRG1 在调节兴奋性/抑制性神经递质传递几个方面的作用的最新临床前证据的针对性综述,进而评估其与精神分裂症风险的相关性。我们还对过去十年中在精神分裂症背景下研究 NRG1 的临床研究进行了系统回顾。我们包括在此期间进行的基因型变异、基因表达、蛋白质表达、结构和功能神经影像学以及认知研究的简明总结。最后,我们提出了未来临床前和临床工作的建议,希望这将有助于制定一项策略,进一步推进我们对 NRG1 与精神分裂症之间关系的理解。

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