Zai Clement C, Manchia Mirko, Sønderby Ida Elken, Yilmaz Zeynep, De Luca Vincenzo, Tiwari Arun K, Squassina Alessio, Zai Gwyneth C, Shaikh Sajid A, Strauss John, King Nicole, Le Foll Bernard, Kaplan Allan S, Finseth Per I, Vaaler Arne E, Djurovic Srdjan, Andreassen Ole A, Vincent John B, Kennedy James L
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH) , Toronto, Ontario , Canada.
World J Biol Psychiatry. 2015 Apr;16(3):171-9. doi: 10.3109/15622975.2014.953011. Epub 2014 Sep 29.
Suicide is a serious public health concern, and it is partly genetic. The brain-derived neurotrophic factor (BDNF) gene has been a strong candidate in genetic studies of suicide (Dwivedi et al., Arch Gen Psychiatry 2010;60:804-815; Zai et al., Prog Neuropsychopharmacol Biol Psychiatry 2012;34:1412-1418) and BDNF regulates the expression of the dopamine D3 receptor.
We examined the role of the BDNF and DRD3 genes in suicide.
We analysed four tag single-nucleotide polymorphisms (SNPs) in BDNF and 15 SNPs in the D3 receptor gene DRD3 for possible association with suicide attempt history in our Canadian sample of Schizophrenia (SCZ) patients of European ancestry (N = 188).
In this sample, we found a possible interaction between the BDNF Val66Met and DRD3 Ser9Gly SNPs in increasing the risk of suicide attempt(s) in our SCZ sample. Specifically, a larger proportion of SCZ patients who were carrying at least one copy of the minor allele at each of the Val66Met and Ser9Gly functional markers have attempted suicides compared to patients with other genotypes (Bonferroni P < 0.05). However, we could not replicate this finding in samples from other psychiatric populations.
Taken together, the results from the present study suggest that an interaction between BDNF and DRD3 may not play a major role in the risk for suicide attempt, though further studies, especially in SCZ, are required.
自杀是一个严重的公共卫生问题，且部分具有遗传性。脑源性神经营养因子（BDNF）基因一直是自杀遗传学研究中的有力候选基因（德维维迪等人，《美国医学会杂志·精神病学》2010年；60：804 - 815；扎伊等人，《神经精神药理学与生物学精神病学进展》2012年；34：1412 - 1418），且BDNF调节多巴胺D3受体的表达。
我们研究了BDNF和DRD3基因在自杀中的作用。
我们分析了BDNF中的四个标签单核苷酸多态性（SNP）以及D3受体基因DRD3中的15个SNP，以探讨它们与我们加拿大欧洲血统精神分裂症（SCZ）患者样本（N = 188）的自杀未遂史之间可能存在的关联。
在这个样本中，我们发现BDNF Val66Met和DRD3 Ser9Gly SNPs之间可能存在相互作用，会增加我们SCZ样本中自杀未遂的风险。具体而言，与其他基因型的患者相比，在Val66Met和Ser9Gly功能标记位点上至少携带一个次要等位基因拷贝的SCZ患者中有更大比例曾试图自杀（邦费罗尼校正P < 0.05）。然而，我们无法在其他精神科人群的样本中重复这一发现。
综上所述，本研究结果表明BDNF和DRD3之间的相互作用可能在自杀未遂风险中不发挥主要作用，不过仍需要进一步研究，尤其是针对SCZ患者的研究。
