Mental Health Research and Treatment Center, Ruhr-Universität Bochum, Germany.
Department of Genetic Psychology, Ruhr-Universität Bochum, Germany.
Behav Res Ther. 2018 Aug;107:117-126. doi: 10.1016/j.brat.2018.06.003. Epub 2018 Jun 22.
There is considerable interindividual variation in response to psychotherapeutical intervention. In order to realize the long-term goal of personalised treatment approaches, it is important to identify behavioural and biological moderators and mediators of treatment responses. Here, we tested the predictive value of experimental fear extinction efficacy as well as the role of genetic variation of the serotonin transporter gene for the outcome of a fear-exposure treatment. A discriminative fear conditioning paradigm was conducted in 159 adults highly fearful of spiders, dental surgeries or blood, injuries and injections. Participants were genotyped for the long (L) and short (S) allelic variant of the serotonin transporter gene linked polymorphic region (5HTTLPR) and treated with a highly standardized exposure-based one-session treatment. Participants' subjective fear was assessed during experimental fear conditioning and extinction. Furthermore, subjective phobic fear was assessed at pre-, post and at 7 months follow-up treatment assessment. A threat-biased contingency learning pattern characterized by exaggerated fear responses to the CS- was associated with larger initial subjective fear reduction immediately following the large-group treatment, p = .03. There were no learning pattern-associated differences in subjective fear at 7-month follow-up. The odds of homozygous s-allele carriers to display a threat-biased contingency learning pattern were 3.85 times larger compared to l-allele carriers, p = .01. Fear-recovery in homozygous S-allele carriers at follow-up assessment, p = .01, emerged regardless of the experimental fear acquisition pattern. Our results suggest the homozygous S-allele carriers are biologically biased towards ignoring safety signals in threat-related situations. Short-term, this response pattern might be positively related to the outcome of exposure treatments, potentially due to increased responding to safe context conditions or a stronger violation of threat expectancies. However, alterations in inhibiting the response to cues formerly signalling threat evidenced for S-allele carriers can have negative impact on exposure success.
个体对心理治疗干预的反应存在很大差异。为了实现个性化治疗方法的长期目标，识别治疗反应的行为和生物学调节因子和中介非常重要。在这里，我们测试了实验性恐惧消退效果的预测价值，以及 5-羟色胺转运体基因遗传变异对恐惧暴露治疗结果的作用。在 159 名非常害怕蜘蛛、牙科手术或血液、伤害和注射的成年人中进行了有区别的恐惧条件反射范式。参与者对 5-羟色胺转运体基因长（L）和短（S）等位基因变体的连接多态区（5HTTLPR）进行了基因分型，并接受了高度标准化的基于暴露的一次性治疗。在实验性恐惧条件反射和消退过程中评估了参与者的主观恐惧。此外，在治疗前、治疗后和 7 个月随访治疗评估时评估了主观恐惧症。以 CS 过度恐惧反应为特征的威胁偏向连续学习模式与大组治疗后立即出现的更大初始主观恐惧减轻有关，p=0.03。在 7 个月的随访中，没有与学习模式相关的恐惧差异。与 l-等位基因携带者相比，纯合 s-等位基因携带者表现出威胁偏向连续学习模式的可能性高 3.85 倍，p=0.01。在随访评估时，纯合 S-等位基因携带者的恐惧恢复，p=0.01，无论实验性恐惧习得模式如何，均会出现。我们的研究结果表明，纯合 S-等位基因携带者在生物学上偏向于忽略与威胁相关的情况下的安全信号。短期来看，这种反应模式可能与暴露治疗的结果呈正相关，这可能是由于对安全条件的反应增强，或者是对威胁预期的更强违反。然而，对以前表示威胁的线索的抑制反应的改变对 S-等位基因携带者的暴露成功可能产生负面影响。
