Department of Psychiatry and Psychotherapy, University of Greifswald, Germany.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Mar 30;36(2):264-70. doi: 10.1016/j.pnpbp.2011.09.010. Epub 2011 Oct 2.
Based on biological interactions between the serotonergic system and the brain-derived neurotrophic factor (BDNF), BDNF is a plausible candidate for a gene-gene-environment interaction moderating the interaction between the s/l- promoter polymorphism of the serotonin transporter (5-HTTLPR) and childhood abuse. We tested the hypothesis of a three-way interaction with respect to depressive symptoms.
2035 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and the Childhood Trauma Questionnaire. All subjects were genotyped for the BDNF Val66Met (rs6265) and the s/l 5-HTTLPR polymorphisms.
Tobit regression analyses revealed a three-way-interaction between the three genotypes of 5-HTTLPR and the BDNF genotypes and overall childhood abuse for the BDI-II score (p=0.02). Emotional abuse carried the main effect of the interaction (p=0.008). The s/s genotype of the 5-HTTLPR exerted its negative impact on mental health after childhood abuse only in the presence of the BDNF Val/Val genotype but not in the presence of the BDNF Met allele. In contrast, the l allele of the 5-HTTLPR also emerged as a genetic risk factor for depression in carriers of one or two Met alleles.
Our results point to a gene-gene-environment interaction that relevantly impacts on the role of the s/s genotype of the 5-HTTLPR in childhood abuse: Depending on the BDNF background (Val/Val versus Met allele) the s/s genotype showed either protective or risk properties with regard to depressive symptoms.
基于血清素能系统和脑源性神经营养因子（BDNF）之间的生物学相互作用，BDNF 是基因-基因-环境相互作用的一个合理候选者，可以调节血清素转运体（5-HTTLPR）的 s/l-启动子多态性与儿童期虐待之间的相互作用。我们测试了关于抑郁症状的三向相互作用假设。
来自波罗的海健康研究（德国普通人群）的 2035 名白种人受试者完成了贝克抑郁量表（BDI-II）和儿童期创伤问卷。所有受试者均进行了 BDNF Val66Met（rs6265）和 s/l 5-HTTLPR 多态性的基因分型。
Tobit 回归分析显示，5-HTTLPR 的三种基因型与 BDNF 基因型以及整体儿童虐待对 BDI-II 评分存在三向相互作用（p=0.02）。情感虐待对相互作用具有主要影响（p=0.008）。只有在 BDNF Val/Val 基因型存在的情况下，5-HTTLPR 的 s/s 基因型才会对心理健康产生负面影响，而在 BDNF Met 等位基因存在的情况下则不会。相反，5-HTTLPR 的 l 等位基因也成为携带一个或两个 Met 等位基因的个体抑郁的遗传风险因素。
我们的结果表明存在基因-基因-环境相互作用，这对 5-HTTLPR 的 s/s 基因型在儿童期虐待中的作用具有重要影响：根据 BDNF 背景（Val/Val 与 Met 等位基因），s/s 基因型在抑郁症状方面表现出保护或风险特征。
