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  • Meanwhile high levels of extraversion have been associated w

    2019-07-15

    Meanwhile, high levels of extraversion have been associated with weaker conditioning and faster Metabolism Compound Library for learning (Eysenck, 1970). Similar to neuroticism/anxiety, the role of extraversion for fear conditioning and extinction has found only limited empirical support (Rauch et al., 2005) with several studies reporting mixed (Pineles et al., 2009) or null effects (Guimarães et al., 1991, Martínez et al., 2012, Otto et al., 2007). In the study of long-term fear extinction, however, the agency facet of extraversion (describing the disposition to be active, assertive, achievement-oriented) might be more predictive than general extraversion due to its putative dopaminergic basis (Depue and Collins, 1999, Wacker et al., 2006, Wacker et al., 2012). The present study investigated if and in which manner (a) the COMT Val158Met polymorphism as well as (b) neuroticism/anxiety, (c) fearfulness and (d) agentic extraversion modulate fear and extinction retention in a delayed recall test. We employed an established two-day fear conditioning and extinction paradigm (Mueller, Panitz, Hermann, & Pizzagalli, 2014). On Day 1, two reinforced CS+ and two CS− were presented during an initial fear acquisition phase. In a subsequent extinction phase, one of the two CS+ and one of the two CS− were presented without a US. One day later, all four CS were presented again in a recall test to assess long-term recall of conditioned and extinguished fear. We assessed the Late Positive Potential (LPP) and fear bradycardia as cortical and autonomic components of the conditioned fear response, respectively. The LPP is a sustained positivity in the posterior event-related potential and is sensitive to motivational stimulus significance (Keil et al., 2002, Lang and Bradley, 2010). It has been used in previous fear conditioning studies on acquisition (Nelson, Weinberg, Pawluk, Gawlowska, & Proudfit, 2015) and extinction recall (Panitz, Hermann, & Mueller, 2015). Fear bradycardia describes cardiac slowing between 2 and 5 s after detection of a threat cue (Vila et al., 2007) and indicates focused attention as part of a freezing response (Lang et al., 2000, Löw et al., 2008, Löw et al., 2015). It has been used to investigate fear acquisition (Bradley et al., 2005, Panitz et al., 2015, Sperl et al., 2016), extinction (Notterman, 1952, Panitz et al., 2015, Sperl et al., 2016) and long-term recall of conditioned fear (Panitz et al., 2015). In addition, we assessed skin conductance responses (SCR) and affective CS ratings as additional, widely used measures of conditioned fear (Lonsdorf et al., 2017).
    Method
    Results
    Discussion The present study investigated the roles of personality and a dopaminergic gene polymorphism in long-term fear extinction. Previously genotyped participants were recruited based on their dopaminergic COMT Val158Met polymorphism and performed a two-day differential fear conditioning paradigm with acquisition and extinction phases on Day 1 and a recall test on Day 2. With regard to genetics, we found that COMT Val158Met predicted successful fear and extinction recall on Day 2 as measured with fear bradycardia and the LPP. At the beginning of the recall test, one day after conditioning and extinction, Val homozygotes but not Met carriers showed significantly enhanced LPP amplitudes and enhanced cardiac slowing to the non-extinguished vs. extinguished CS+. Meanwhile, Met homozygotes initially showed enhanced LPP amplitudes to both, previously extinguished and non-extinguished CS+. These results are consistent with previous rodent data, where Met homozygotes showed more freezing to an extinguished CS+ in the first four trials of an extinction recall test compared to Val homozygotes (Risbrough et al., 2014) and suggest an advantage for the Val allele in long-term fear Metabolism Compound Library for extinction. When comparing genotype groups, differences in fear and extinction recall were mainly qualified by (a) reduced non-extinguished fear responses (but comparably low extinguished fear responses) in Met carriers relative to Val homozygotes and (b) failed reduction in extinguished fear bradycardia in Val/Met compared to Val/Val carriers. Taken together, Val homozygotes showed the most adaptive response pattern, reflecting actual Day 1 CS-US contingencies in their responses while Met carriers showed patterns inconsistent with previous CS-US contingencies. Exploratory analyses revealed that failure of Met carriers to produce a reduced fear bradycardia to previously extinguished fear stimuli was particularly driven by those Met carriers who already failed to reduce fear during Day 1 extinction. As stated above, this Day-1-Day-2 transfer was also compromised in individuals with high neuroticism/anxiety such that emotionally instable individuals showed high Day-1-Day-2 fluctuations. While COMT Val158Met modulated long-term learning, there was no direct relation to within-session/short-term fear acquisition or extinction. This pattern of findings indicates that the COMT Val158Met polymorphism contributes to individual differences in long-term fear learning (Bellander et al., 2015).