From adaptive to maladaptive fear: Heterogeneity in threat and safety learning across response systems in a representative sample.

Individual differences in fear learning are a crucial prerequisite for the translational value of the fear-conditioning model. In a representative sample (N = 936), we used latent class growth models to detect individual differences in associative fear learning. For a series of subsequent test phases varying in ambiguity (i.e., acquisition, extinction, generalization, reinstatement, and re-extinction), conditioned responding was assessed on three response domains (i.e., subjective distress, startle responding, and skin conductance). We also associated fear learning across the different test phases and response domains with selected personality traits related to risk and resilience for anxiety, namely Harm Avoidance, Stress Reaction, and Wellbeing (MPQ; Tellegen and Waller, 2008). Heterogeneity in fear learning was evident, with fit indices suggesting subgroups for each outcome measure. Identified subgroups showed adaptive, maladaptive, or limited-responding patterns. For subjective distress, fear and safety learning was more maladaptive in the subgroups high on Harm Avoidance, while more adaptive learning was observed in subgroups with medium Harm Avoidance and the limited- or non-responders were lowest in Harm Avoidance. Distress subgroups did not differ in Stress Reaction or Wellbeing. Startle and SCR subgroups did not differ on selected personality traits. The heterogeneity in fear-learning patterns resembled risk and resilient anxiety development observed in real life, which supports the associative fear-learning paradigm as a useful translational model for pathological fear development.

Deficient safety learning characterizes high trait anxious individuals.

Trait anxiety is a well-established risk factor for developing anxiety disorders, but evidence for abnormal associative fear learning in high trait anxious (HTA) individuals is inconclusive. In part, this may due to limitations in the scope and measures used to assess fear learning. The current study therefore assessed fear learning across multiple response domains and multiple test phases in a two-day discriminative fear-conditioning paradigm. We tested whether trait anxiety is associated with deficient safety learning, by comparing HTA individuals (N=20) and healthy Controls (N=22). HTA participants showed stronger fear on the startle response and distress ratings to the safety (CS(-)) but not to the threat stimulus (CS(+)) during acquisition, along with impaired extinction and re-extinction. Trait anxiety did not affect skin conductance responses and effects on UCS-expectancy were limited. We conclude that high trait anxiety may be characterized by deficient safety learning which in turn may promote persistent and generalized fear responses.

Worrying affects associative fear learning: a startle fear conditioning study.

A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS) and an anticipated disaster (Unconditioned Stimulus, UCS). Most anxiety disorders, however, do not evolve from a traumatic experience. Insights from neuroscience show that memory can be modified post-learning, which may elucidate how pathological fear can develop after relatively mild aversive events. Worrying--a process frequently observed in anxiety disorders--is a potential candidate to strengthen the formation of fear memory after learning. Here we tested in a discriminative fear conditioning procedure whether worry strengthens associative fear memory. Participants were randomly assigned to either a Worry (n = 23) or Control condition (n = 25). After fear acquisition, the participants in the Worry condition processed six worrisome questions regarding the personal aversive consequences of an electric stimulus (UCS), whereas the Control condition received difficult but neutral questions. Subsequently, extinction, reinstatement and re-extinction of fear were tested. Conditioned responding was measured by fear-potentiated startle (FPS), skin conductance (SCR) and UCS expectancy ratings. Our main results demonstrate that worrying resulted in increased fear responses (FPS) to both the feared stimulus (CS(+)) and the originally safe stimulus (CS(-)), whereas FPS remained unchanged in the Control condition. In addition, worrying impaired both extinction and re-extinction learning of UCS expectancy. The implication of our findings is that they show how worry may contribute to the development of anxiety disorders by affecting associative fear learning.