No Time-Dependent Effects of Psychosocial Stress on Fear Contextualization and Generalization: A Randomized-Controlled Study With Healthy Participants

Abstract

The formation of context-dependent fear memories (fear contextualization) can aid the recognition of danger in new, similar, situations. Overgeneralization of fear is often seen as hallmark of anxiety and trauma-related disorders. In this randomizedcontrolled study, we investigated whether exposure to a psychosocial stressor influences retention of fear contextualization and generalization in a time-dependent manner. The Trier Social Stress Test was used to induce psychosocial stress. Healthy male participants (n ¼ 117) were randomly divided into three experimental groups that were subjected to the acquisition phase of the Fear Generalization Task: (1) without stress, (2) immediately after acute stress, or (3) 2 h after acute stress. In this task, a male with neutral facial expression (conditioned stimuli) was depicted in two different contexts that modulated the conditioned stimuli-unconditioned stimuli (¼shock) association (threat, safe). Salivary alpha-amylase and cortisol levels were measured throughout the experiment. After a 24-h delay, context-dependency of fear memory was investigated with an unannounced memory test consisting of the threat and safe contexts alternated with a novel context (the generalization context). Multilevel analyses revealed that participants showed increased fear-potentiated startle responses to the conditioned stimuli in the threat compared to the safe context, at the end of the acquisition phase, indicating adequate fear contextualization. Directly after acquisition, there were no time-dependent effects of psychosocial stress on fear contextualization. Context-dependency of fear memories was retained 24 h later, as fear-potentiated startle responding was modulated by context (threat > safe or novel). At that time, the context-dependency of fear memories was also not influenced by the early or late effects of the endogenous stress response during acquisition. These results with experimental stress deviate in some aspects from those earlier obtained with exogenous hydrocortisone administration, suggesting a distinct role for stress mediators other than cortisol.

Fear and Trembling of Cruise Ship Employees: Psychological Effects of the COVID-19 Pandemic

“…Fear is a mind killer [ 75 ], and being afraid of something suppresses the ability to think straight [ 74 ]. As a consequence, Sep et al [ 76 ] conclude how extrapolation of fear is a frequent indication of anxiety and trauma-related disorders. During the discussion, participants clearly outlined how they feel agitated due to the uncertainty of what the future holds.…”

Pre-trauma memory contextualization as predictor for PTSD-like behavior in male rats

“…In our design we followed the earlier human studies (Sep et al, 2019b(Sep et al, , 2019a as closely as possible. For example, we made use of an acute stressor in rats -the resident-intruder situation with a partition between the two rats-which translated the human situation of the Trier Social Stress Test to an ecologically relevant version in rodents, maintaining important elements of social evaluation in the absence of a physical stressor, although there are of course also important differences between the two situations.…”

“…Methodological RI details are provided in appendix A1. This social stressor and timepoint were selected to align with earlier experiments in humans, where the time-dependent effects of social stress on memory contextualization were investigated using the Trier Social Stress Test (Joëls et al, 2018(Joëls et al, , 2012Sep et al, 2019aSep et al, , 2019b. Plasma corticosterone increase from baseline, as proxy for HPA-axis activation, in SD rats by the RI procedure was confirmed in two separate pilot experiments (Appendix 6: Pilot I and IV).…”

Postural freezing relates to startle potentiation in a human fear‐conditioning paradigm

“…Further, the number of startle probes are described per condition: noise alone (NA) probes that are presented during habituation and the ITIs, Cxt probes that are presented during either of the three contexts, and the probes that are presented during the CS in any of these conditions processing may pose an important vulnerability for the development of anxiety (Maren et al, 2013), likely caused by alterations in hippocampal functioning contributing to exacerbated fear generalization. The paradigm was based on previous studies using a similar design (Mühlberger et al, 2013;Schmajuk & Buhusi, 1997;Sep et al, 2019;Van Ast et al, 2012). For the threat condition, presentation of the CS in one specific context (background picture) predicted the occurrence of the unconditioned stimulus (US; shock).…”

“…In other words, the paradigm can be considered a mixed cued/contextual fear‐conditioning paradigm. Critically, during the following generalization phase, the CS is presented without the US in a third novel and ambiguous context (the generalization context, Van Ast et al, 2012; Mühlberger et al, 2013; Sep et al, 2019). We hypothesized that postural freezing responses can be conditioned in humans, just as they can in other species.…”