Evidence for impaired extinction learning in humans after distal stress exposure

Stressful or traumatic events can be risk factors for anxiety or trauma- and stressor-related disorders. In this regard, it has been shown that stress affects aversive learning and memory processes. In rodents, stress exposure 10 days prior to fear acquisition impairs fear extinction. However, in humans the effect of distal stress on fear conditioning is sparse. Therefore, we examined the influence of distal stress on fear memory in humans in two studies. In Study 1, participants underwent either socially evaluated cold-pressor test (SECPT) or sham procedure 10 days or 40 min before a fear conditioning paradigm (four groups, N = 78). In Study 2, context effects were examined by conducting SECPT and sham procedures 10 days prior conditioning either in the later fear conditioning context or in another context (three groups, N = 69). During acquisition phase, one geometrical shape (conditioned stimulus, CS+) was paired with painful electric shocks (unconditioned stimulus, US), but never a second shape (CS-). Extinction phase was identical to acquisition, but without US delivery. Importantly, for Study 1 these phases were conducted on one day, while for Study 2 on two separated days. Successful fear acquisition was indicated by aversive ratings and startle potentiation to CS+ versus CS- in both studies. Interestingly, participants stressed 10 days earlier showed impaired extinction on the implicit level (startle potentiation to CS+ vs. CS-) in Study 1 and only in the acquisition context on the explicit level (aversive ratings for CS+ vs. CS-) in Study 2. In sum, distal stress may strengthen later acquired fear memories and thereby impair fear extinction. This finding could have clinical implications, showing that prior stress exposure sensitizes later aversive processing and impairs therapy.