Zai Clement C, Manchia Mirko, Zai Gwyneth C, Woo Julia, Tiwari Arun K, de Luca Vincenzo, Kennedy James L
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.
Neurosci Lett. 2018 Apr 3;671:1-6. doi: 10.1016/j.neulet.2018.01.033. Epub 2018 Jan 31.
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.
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。