Wray Naomi R, James Michael R, Handoko Herlina Y, Dumenil Troy, Lind Penelope A, Montgomery Grant W, Martin Nicholas G
Queensland Institute of Medical Research, Brisbane, Australia.
Psychiatr Genet. 2008 Oct;18(5):219-25. doi: 10.1097/YPG.0b013e3283050aee.
Association of the valine/methionine variant at codon 66 (Val66Met) of brain derived neurotrophic factor (BDNF) has been reported inconsistently across a spectrum of psychiatric disorders. Haplotypes of six tagging single nucleotide polymorphisms (SNPs) of a 37-kb region of dystrobrevin-binding protein 1 (DTNBP1) were found to be associated with schizophrenia. These haplotypes have not been studied extensively for other psychiatric disorders but are plausible candidates for anxiety and depression disorders. Here, association between variants of BDNF and DTNBP1, and multiple anxiety and depression phenotypes is explored.
Study participants were selected as sibling pairs that were either concordant or discordant for extreme neuroticism scores from a total sample of 18 742 Australian twin individuals and their siblings. All participants completed detailed Composite International Diagnostic Interview from which diagnoses of Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV depression and anxiety disorders were determined. Six hundred and seventy-four participants had a diagnosis of anxiety and/or depression from 492 families. The BDNF Val66Met and six DTNBP1 (rs3213207, rs1011313, rs2619528, rs760761, rs1018381, rs2619538) SNPs were genotyped on samples from study participants (n=2045 from 987 families) and, where possible, their parents (n=787). Family-based association tests were conducted between the individual SNPs and the DTNBP1 six SNP haplotypes and anxiety, depression, and neuroticism.
We found no convincing evidence for association between any of the variants studied and anxiety, depression, or neuroticism.
This study sample is relatively large but our results do not support an association between BDNF Val66Met and anxiety, depression, or neuroticisim. DTNBP1 haplotypes, which have been found to be risk factors for schizophrenia, are unlikely to be risk factors for anxiety and depression.
脑源性神经营养因子（BDNF）第66位密码子（Val66Met）处缬氨酸/甲硫氨酸变异与一系列精神疾病的关联报道并不一致。肌营养不良蛋白结合蛋白1（DTNBP1）一个37 kb区域的6个标签单核苷酸多态性（SNP）的单倍型被发现与精神分裂症有关。这些单倍型尚未针对其他精神疾病进行广泛研究，但可能是焦虑症和抑郁症的候选因素。在此，探讨BDNF和DTNBP1变异与多种焦虑和抑郁表型之间的关联。
研究参与者从18742名澳大利亚双胞胎个体及其兄弟姐妹的总样本中选取为神经质得分极高的同卵或异卵双胞胎对。所有参与者都完成了详细的复合国际诊断访谈，由此确定《精神疾病诊断与统计手册》（DSM）-IV抑郁症和焦虑症的诊断。674名参与者来自492个家庭，被诊断患有焦虑症和/或抑郁症。对研究参与者（来自987个家庭的2045名）以及尽可能多的他们的父母（787名）的样本进行BDNF Val66Met和6个DTNBP1（rs3213207、rs1011313、rs2619528、rs760761、rs1018381、rs2619538）SNP的基因分型。在个体SNP与DTNBP1的6个SNP单倍型以及焦虑症、抑郁症和神经质之间进行基于家系的关联测试。
我们没有发现所研究的任何变异与焦虑症、抑郁症或神经质之间存在令人信服的关联证据。
本研究样本相对较大，但我们的结果不支持BDNF Val66Met与焦虑症、抑郁症或神经质之间存在关联。已发现是精神分裂症风险因素的DTNBP1单倍型不太可能是焦虑症和抑郁症的风险因素。
