Fearfulness, neuroticism/anxiety, and COMT Val158Met in long-term fear conditioning and extinction

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Abstract

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.

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