Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children
Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children
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DOI：
10.1016/j.biopsych.2005.10.026
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发表时间：
2006-04-15
影响因子：
10.6
通讯作者：
Gelernter, J
中科院分区：
文献类型：
--
作者：
Kaufman, J;Yang, BZ;Gelernter, J
背景儿童虐待和基因型相互作用，有助于儿童抑郁症的风险。本研究探讨了基因与基因和基因与环境的相互作用。该研究包括196名儿童：109名受虐待儿童和87名未受虐待儿童。精神病学和社会支持的措施，获得使用标准的研究工具，和5-羟色胺转运蛋白（5-HTTLPR）（SLC 6A 4位点）和脑源性神经营养因子（BDNF）（变异val 66 met）基因型从唾液来源的DNA标本。人口结构控制的祖先的比例分数计算的基础上基因型的祖先信息标记在整个sample.Results：有一个显着的三向BDNF基因型，5-HTTLPR，和麦芽糖的历史之间的相互作用，在预测抑郁症。携带BDNF基因的met等位基因和5-HTTLPR的两个短等位基因的儿童抑郁评分最高，但与这两种基因型相关的易感性仅在受虐待儿童中明显。一个显着的四向互动也出现了，与社会支持，以进一步适度的风险depress.Conclusions：据我们所知，这是第一次调查，以证明一个基因的基因相互作用传递的脆弱性抑郁症。目前的数据还显示，社会支持在改善精神病理学的遗传和环境风险方面具有保护作用。
Background Child abuse and genotype interact to contribute to risk for depression in children. This study examined gene-by-gene and gene-by-environment interactions.Methods. The study included 196 children: 109 maltreated and 87 nonmaltreated comparison subjects. Measures of psychiatric symptomatology and social supports were obtained using standard research instruments, and serotonin transporter (5-HTTLPR) (locus SLC6A4) and brain-derived neurotrophic factor (BDNF) (variant val66met) genotypes were obtained from saliva-derived DNA specimens. Population structure was controlled by means of ancestral proportion scores computed based on genotypes of ancestry informative markers in the entire sample.Results: There was a significant three-way interaction between BDNF genotype, 5-HTTLPR, and maltrealment history in predicting depression. Children with the met allele of the BDNF, gene and two short alleles of 5-HTTLPR bad the highest depression scores, but The vulnerability associated with these two genotypes was only evident in the maltreated children. A significant four-way interaction also emerged, with, social supports found to further moderate risk for depression.Conclusions: To the best of our knowledge, this is the first investigation to demonstrate a gene-by-gene interaction conveying vulnerability to depression. The current data also show a protective effect of social supports in ameliorating genetic and environmental risk for psychopathology.