Using unconditioned responses to predict fear acquisition, fear extinction learning, and extinction retention patterns: Sex hormone status matters

Abstract

Following a traumatic event, fear dysregulation can increase the likelihood of developing post-traumatic stress disorder (PTSD). This psychopathology is twice as prevalent in women than in men. High physiological reactivity following trauma may be an early risk indicator for the development of PTSD. Elevated physiological reactivity and low estradiol levels have individually been associated with higher fear acquisition and/or lower extinction retention. Thus, sex hormone status may also modulate fear regulation abilities. However, it is unknown whether these two vulnerability factors interact to modulate fear learning and regulation. Using a fear conditioning and extinction protocol, we examined whether physiological reactivity to the aversive stimulus during fear acquisition training predicted fear responses during fear learning, extinction learning, and extinction retention. We verified whether these associations differed according to sex hormone status. Seventy-seven non-clinical participants were recruited including oral contraceptive users (n = 18), early follicular women (n = 20, [low estradiol]), mid-cycle women (n = 20, [high estradiol]), and men (n = 19). Participants underwent a three-day fear conditioning and extinction protocol (day 1: fear acquisition training; day 2: extinction training; day 3: retention test). Skin conductance responses were recorded. In early follicular women, physiological reactivity predicted conditioned and extinguished stimulus fear responses during all phases. For the remaining women, this effect was only present during fear learning and extinction learning. These findings highlight the importance of considering physiological reactivity and sex hormone status following a traumatic event. This knowledge could aid in the early identification of those at higher risk of developing PTSD.