Fearfulness, neuroticism/anxiety, and COMT Val158Met in long-term fear conditioning and extinction
Fearfulness, neuroticism/anxiety, and COMT Val158Met in long-term fear conditioning and extinction
复制标题
DOI：
10.1016/j.nlm.2018.06.001
复制
发表时间：
2018-11-01
影响因子：
2.7
通讯作者：
Mueller, Erik M.
中科院分区：
文献类型：
--
作者：
Panitz, Christian;Sperl, Matthias F. J.;Mueller, Erik M.
恐惧记忆长期稳定性的个体差异可能与与威胁加工相关的稳定倾向有关，如神经质/焦虑和恐惧。以前的研究表明，多巴胺在保留条件性恐惧和消除恐惧方面起着重要作用，多巴胺能基因多态也可能与恐惧稳定性的个体差异有关。虽然COMT Val158Met多态导致前额叶多巴胺的个体差异，但它与人类长期恐惧消退的关联目前尚不清楚。在这里，健康男性Val/Val携带者、Val/Met携带者和Met/Met携带者分别接受了为期两天的差异条件反射范式，在第一天进行了恐惧获得和消除，并在第二天进行了回忆测试，记录了脑电和心电图。恐惧，而不是神经质/焦虑，可以预测第一天恐惧获得期间的恐惧心动过缓(即心跳减慢)，而不会影响消退或第二天的恐惧回忆。相比之下，COMT Val158Met显著调节了第二天的恐惧回忆，这在恐惧心动过缓和晚期正电位(LPP)幅度中很明显，而它不影响第一天的恐惧或灭绝学习。此外，探索性分析表明，在第二天的灭绝回忆中，恐惧心动过缓的个体差异取决于第一天的灭绝成功。重要的是，这种偶然性是(A)受COMT Val158 Met调节的，(B)在高神经质/焦虑与低神经质/焦虑的情况下显著减少。本研究表明：(A)多巴胺能基因分型的个体差异可能影响恐惧记忆的长期稳定性；(B)恐惧和神经质/焦虑在恐惧记忆的初始恐惧反应和长期稳定性中可能起着不同的作用。
Individual differences in long-term stability of fear memories are of potential relevance for stable dispositions related to threat processing, such as neuroticism/anxiety and fearfulness. As previous research suggests a prominent role of dopamine for the retention of conditioned and extinguished fear, dopaminergic gene polymorphisms may also relate to individual differences in fear stability. While the COMT Val158Met polymorphism causes individual differences in prefrontal dopamine, its associations with human long-term fear extinction are currently unknown. Here, n = 30/29/28 healthy male Val/Val, Val/Met and Met/Met carriers, respectively, underwent a two-day differential conditioning paradigm with fear acquisition and extinction on Day 1 and a recall test on Day 2 with recordings of EEG and ECG. Fearfulness but not neuroticism/anxiety predicted fear bradycardia (i.e., heart period slowing) during Day 1 fear acquisition while it did not affect extinction or Day 2 fear recall. In contrast, COMT Val158Met significantly modulated Day 2 fear recall as evident in fear bradycardia and Late Positive Potential (LPP) amplitudes while it did not affect Day 1 fear or extinction learning. Furthermore, exploratory analyses revealed that individual differences in fear bradycardia during Day 2 extinction recall depended on Day 1 extinction success. Importantly, this contingency was (a) modulated by COMT Val158Met and (b) significantly reduced in high vs. low neuroticism/anxiety. The present study indicates that (a) individual differences in dopaminergic genotypes may affect the long-term stability of fear memories and (b) fearfulness vs. neuroticism/anxiety might play distinct roles in initial fear reactions vs. long-term stability of fear memories, respectively.