School of Psychological Sciences, University of Melbourne, Australia.
Division of Psychology, School of Medicine, University of Tasmania, Australia; Department of Psychology, Swansea University, UK.
Psychoneuroendocrinology. 2018 May;91:142-148. doi: 10.1016/j.psyneuen.2018.03.002. Epub 2018 Mar 6.
The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val-Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val-Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val-Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy.
BDNF Val66Met 多态性的低表达 Met 等位基因与健康对照者的恐惧消退受损有关，并且与创伤后应激障碍（PTSD）患者的暴露疗法反应较差有关。鉴于恐惧消退是暴露疗法的基础，这就提出了 BDNFVal66Met 多态性对 PTSD 中恐惧消退的影响问题，但这一问题尚未得到检验。106 名参与者（22 名 PTSD、46 名创伤暴露对照者（TC）和 38 名非创伤暴露对照者（NTC））完成了恐惧条件反射和消退任务，并采集唾液样本进行 DNA 提取和 BDNF Val66Met 多态性基因分型。使用 PROCESS 进行的调节分析检查了 BDNF 基因型（Val-Val 与 Met 携带者）是否调节了 PTSD 症状严重程度（和诊断状况）与恐惧消退期间皮肤电传导反应（SCR）幅度之间的关系。与 TC 和 NTC 相比，PTSD 组在早期消退阶段显示出明显较慢的恐惧消退学习。BDNF Val66Met 多态性调节了 PTSD 与恐惧消退学习之间的关系，表现为携带低表达 Met 等位基因的个体的恐惧消退学习较差与 PTSD 症状严重程度（和 PTSD 诊断状况）相关，而 Val-Val 等位基因的个体则没有关系。这项研究表明，在携带低表达 BDNF Met 等位基因的 PTSD 个体中，恐惧消退学习受损尤为明显，而在携带 Val-Val 等位基因的个体中则没有。这为 BDNF 与 PTSD 中恐惧消退学习受损之间的联系提供了新的证据，这可能导致对暴露疗法的反应较差。
