@phdthesis{Klinke2022,
  author    = {Klinke, Christopher Matthias},
  title     = {Experimental investigation of the effect of distal stress induction on threat conditioning in humans},
  doi       = {10.25972/OPUS-22556},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225562},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Stress constitutes a major risk factor for the development of psychiatric disorders, such as PTSD and anxiety disorders, by shifting the brain into a state of sensitization and makes it more vulnerable when being exposed to further aversive events. This was experimentally in-vestigated in rodents by examining the effect of a distal stress induction on threat conditioning, where stress impaired extinction learning and caused spontaneous recovery. However, this effect has never been experimentally investigated in humans, so far. Thus, the aim of this dissertation was to investigate the effect of distal stress on threat conditioning in humans. Therefore, two subsequent studies were conducted. For both studies, the threat conditioning paradigm comprised threat acquisition, extinction learning, and re-extinction. In the threat acquisition phase, two geometrical shapes were used as conditioned stimulus (CS), from which one (CS+) was paired with a painful electric stimulus (unconditioned stimulus, US), but not the other one (CS-). During extinction learning 24 h later and re-extinction seventeen days later, CSs were again presented but without any US delivery. In Study 1, 69 participants underwent either a stress (socially evaluated cold pressor test; SECPT) or sham protocol 10 days prior to threat conditioning. Furthermore, context effects were examined by placing the stress protocol in the same context (context-A stress, and sham group) or a different context (context-B stress group) than conditioning. Results revealed that the context-A, but not context-B, stress group displayed impaired safety learning (i.e. potenti-ation towards CS-) for startle response during threat acquisition. Moreover, the same stress group showed impaired threat extinction, evident in sustained CS discrimination in valence and arousal ratings during extinction learning, and memory recall. In sum, distal stress on the one hand impaired safety learning during threat conditioning on a level of startle response. On the other hand, stress impaired threat extinction on a level of ratings. Noteworthy, the effect of distal stress was only found when the stressor was placed in the same context as later threat learning. Hence, suggesting that the combination of stressor and stressor-associated context exerted the effect on threat extinction. In Study 2, it was examined if distal stress induction could also have an impact on threat and extinction processes without the necessity of context association. Therefore, the same stress (n = 45) or sham protocol (n = 44) as in Study 1 was conducted in a different context than and 24 h prior to a threat conditioning paradigm. Similar to Study 1, weakened extinction learning was found in fear ratings for the stress (vs. sham) group, which was indicated by persistent CS+/CS- differentiation after the first block of extinction trials. Alterations in safety learning towards the CS- during threat acquisition were only supported by significant correlations between stress measures on the stress day and conditioned startle response of the CS- during acquisition. Taken together, in two subsequent studies this dissertation provided first evidence of impaired threat extinction after distal stress induction in humans. Furthermore, impairments in safety learning, as can be observed in PTSD, were additionally demonstrated. Interestingly, the effects were boosted and more profound when associating the stressor to the later learning context. These results have clinical implications as they can be translated to the notion that prior stress exposure makes an individual more vulnerable for later aversive events.},
  subject      = {Stress},
  language  = {en}
}