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精神分裂症中脑源性神经营养因子(BDNF)和多巴胺受体D3(DRD3)基因与酒精使用障碍的关联研究

Association study of BDNF and DRD3 genes with alcohol use disorder in Schizophrenia.

作者信息

Zai Clement C, Manchia Mirko, Zai Gwyneth C, Woo Julia, Tiwari Arun K, de Luca Vincenzo, Kennedy James L

机构信息

Neurogenetics Section, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Canada; Institute of Medical Science, University of Toronto, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Canada.

Section of Psychiatry, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy; Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.

出版信息

Neurosci Lett. 2018 Apr 3;671:1-6. doi: 10.1016/j.neulet.2018.01.033. Epub 2018 Jan 31.

Abstract

Alcohol use disorder (AUD) is a leading risk factor of disease burden in the world. It is also commonly comorbid with over 20% of schizophrenia patients. The brain-derived neurotrophic factor (BDNF) and dopamine D3 receptor (DRD3) have been implicated in alcohol drinking behaviour. Previous genetic studies of the BDNF and DRD3 genes produced mixed findings; however, only one study investigated two BDNF genetic markers with alcohol dependence in schizophrenia patients. We investigated 15 single-nucleotide polymorphisms (SNPs) in DRD3 and four SNPs in BDNF for possible association with alcohol abuse or dependence in schizophrenia patients of European ancestry (N = 195). The patients were assessed for the occurrence of alcohol abuse or alcohol dependence using the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-I/P). We found the BDNF Val66Met to be associated with alcohol dependence (p = 0.004). We also found haplotypes across BDNF to be nominally associated with alcohol dependence. Analyses of DRD3 markers and haplotypes yielded mostly negative findings. Our findings support a role of the BDNF gene in alcohol dependence in schizophrenia patients. Larger samples are required to confirm our findings, particularly those of BDNF haplotypes.

摘要

酒精使用障碍(AUD)是全球疾病负担的主要风险因素。它在超过20%的精神分裂症患者中也普遍存在共病情况。脑源性神经营养因子(BDNF)和多巴胺D3受体(DRD3)与饮酒行为有关。先前对BDNF和DRD3基因的遗传学研究结果不一;然而,仅有一项研究调查了精神分裂症患者中两个BDNF基因标记与酒精依赖的关系。我们研究了DRD3基因中的15个单核苷酸多态性(SNP)以及BDNF基因中的4个SNP,以探讨它们与欧洲血统精神分裂症患者(N = 195)酒精滥用或依赖的可能关联。使用《精神疾病诊断与统计手册》第四版轴I障碍患者版结构化临床访谈(SCID-I/P)评估患者酒精滥用或酒精依赖的发生情况。我们发现BDNF Val66Met与酒精依赖相关(p = 0.004)。我们还发现BDNF基因的单倍型与酒精依赖存在名义上的关联。对DRD3标记和单倍型的分析大多得出阴性结果。我们的研究结果支持BDNF基因在精神分裂症患者酒精依赖中所起的作用。需要更大规模的样本以证实我们的研究结果,尤其是BDNF单倍型的研究结果。

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