Abstract
Identifying individual differences in the ability to discriminate signals of threat and safety holds great potential to elucidate etiological mechanisms of pathological anxiety and resilience and may ultimately foster the development of targeted prevention and clinical intervention programs. Constructs that can be subsumed under the umbrella term of negative affect such as trait-anxiety (STAI-T), neuroticism (N), and intolerance of uncertainty (IU) have been suggested to contribute to aberrant fear learning in different studies. However, collinearity between and individual contributions of these constructs in relation to fear learning, as well as the neurobiological mechanisms remain unclear. Here, we apply a multivariate and dimensional approach (structural equation modeling) across multiple units of analyses (ratings, skin conductance, fear potentiated startle, fMRI) in a differential fear conditioning paradigm in two independent samples (Nbehavioral study 1=288; NfMRI study 2=116). Trait-anxiety was identified as the unique facet of negative affect predicting differences in discriminating signals of threat and safety in skin conductance responses beyond other measures of negative affect (N, IU). This was replicated in a second independent sample and extended by showing that the association between trait-anxiety and skin conductance responding is mediated by differential amygdala activation. These findings elucidate an intriguing mechanism (discrimination deficits) by which the individual's disposition to experience anxiety-relevant emotions may confer a predisposition to the development of pathological anxiety and hence suggest a possible mechanistic target (i.e. discrimination training) for clinical intervention and prevention.