Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jan 10;40:273-80. doi: 10.1016/j.pnpbp.2012.10.011. Epub 2012 Oct 26.
We evaluated the role that selected variants in serotonin transporter (5-HTT), dopamine receptor 2 (DRD2) and brain-derived neurotrophic factor (BDNF) genes play in PTSD symptom severity in an at-risk population. We also investigated the interaction between the genetic variants to determine whether these variables and the interactions between the variables influenced the severity of PTSD symptoms.
PTSD symptoms were quantitatively assessed using the Davidson Trauma Scale (DTS) in 150 participants from an at-risk South African population. All participants were genotyped for the 5-HTTLPR, DRD2 Taq1A and BDNF Val66Met polymorphisms. Gene-gene interactions were investigated using various linear models. All analyses were adjusted for age, gender, major depressive disorder diagnosis, level of resilience, level of social support and alcohol dependence.
A significant interaction effect between DRD2 Taq1A and BDNF Val66Met variants on DTS score was observed. On the background of the BDNF Val66Val genotype, DTS score increased significantly with the addition of a DRD2 Taq1A A1 allele. However, on the BDNF Met66 allele background, the addition of an A1 allele was found to reduce total DTS score.
This study provides preliminary evidence for an epistatic interaction between BDNF Val66Met and DRD2 Taq1A polymorphisms on the severity of PTSD symptoms, where both too little and too much dopamine can result in increased PTSD symptom severity.
我们评估了在高危人群中,5-羟色胺转运体(5-HTT)、多巴胺受体 2(DRD2)和脑源性神经营养因子(BDNF)基因的某些变体在 PTSD 症状严重程度中所起的作用。我们还研究了基因变异之间的相互作用,以确定这些变量以及变量之间的相互作用是否会影响 PTSD 症状的严重程度。
使用 Davidson 创伤量表(DTS)对来自南非高危人群的 150 名参与者进行 PTSD 症状的定量评估。所有参与者均进行了 5-HTTLPR、DRD2 Taq1A 和 BDNF Val66Met 多态性的基因分型。使用各种线性模型研究基因-基因相互作用。所有分析均针对年龄、性别、重度抑郁障碍诊断、韧性水平、社会支持水平和酒精依赖进行了调整。
在 DTS 评分中观察到 DRD2 Taq1A 和 BDNF Val66Met 变体之间存在显著的交互作用效应。在 BDNF Val66Val 基因型的背景下,随着 DRD2 Taq1A A1 等位基因的增加,DTS 评分显著增加。然而,在 BDNF Met66 等位基因背景下,发现添加 A1 等位基因可降低总 DTS 评分。
本研究初步提供了 BDNF Val66Met 和 DRD2 Taq1A 多态性在 PTSD 症状严重程度上的上位性相互作用的证据,其中多巴胺过少和过多都会导致 PTSD 症状严重程度增加。