Fear reacquisition and symptoms of combat-related PTSD: Specificity and preliminary examination of the influence of the 5-HT3A receptor gene

Several studies have examined the acquisition and extinction of fear in PTSD in the context of Pavlovian conditioning. However, research examining reconditioning of fear following extinction, a form of post-extinction re-emergence of conditioned behavior is limited. Although the 5-HT3A receptor gene polymorphism has been linked to trauma responses, its influence on the re-emergence of conditioned fear among those exposed to trauma remain unclear. In the present study, combat-exposed veterans (N = 114) completed a differential fear conditioning task in which one colored rectangle (CS+) predicted a loud scream (US), whereas a different colored rectangle (CS-) predicted no US. Acquisition, extinction, and post-extinction reconditioning effects indexed by conditioned anxiety, US expectancy, and skin conductance response were examined. Associations with allelic variation in the serotonin 5-HT₃ gene, HTR3A (rs1062613) were also examined. Participants rated the CS+ as significantly more anxiety inducing and associated with greater US expectancy than the CS- during acquisition. The CS+ also elicited a stronger skin conductance response than the CS- during acquisition. A significant decrease in anxiety and US expectancy in response to the CS+ was observed after extinction and a re-emergence of conditioned responses to the CS+ was observed during reacquisition. Although a diagnosis of PTSD was characterized by greater anxiety to the CS + but not the CS- during acquisition and extinction, those with and without a PTSD diagnosis did not differ in the reacquisition of fear following extinction. Subsequent preliminary analysis did show that increased posttraumatic symptoms and cognitions were associated with increased US expectancy at reacquisition for the CS+ and CS- among CC carriers but not among T carriers of HTR3A (rs1062613). These findings suggest that posttraumatic symptoms among trauma exposed veterans with the CC polymorphism of the HTR3A gene may be associated with stronger reconditioning of fear following extinction.