Fear extinction in traumatized civilians with posttraumatic stress disorder: relation to symptom severity

Abstract

Background: The symptoms of posttraumatic stress disorder (PTSD) can be explained, at least in part, as an inability to inhibit learned fear during conditions of safety. Our group has shown that fear inhibition is impaired in both combat and civilian PTSD populations. On the basis of our earlier findings, we employed an established fear extinction paradigm to further explore fear dysregulation in a civilian traumatized population.

Methods: Fear-potentiated startle (FPS) was examined in 127 trauma-exposed individuals with and without PTSD. We used a protocol in which conditioned fear was first acquired through the presentation of one colored shape (reinforced conditioned stimulus, [CS+]) that was paired with an aversive air blast to the larynx (unconditioned stimulus) and a different colored shape that was not paired to the air blast (nonreinforced condition stimulus). Fear was extinguished 10 min later through repeated presentations of the CSs without reinforcement.

Results: Both groups demonstrated successful fear conditioning on the basis of startle and unconditioned stimulus-expectancy ratings; however, participants with PTSD displayed greater FPS responses to the CS+ and nonreinforced conditioned stimulus compared with the group without PTSD. During fear extinction, the PTSD group showed elevated FPS responses to the previously reinforced CS+ during the early and middle stages of extinction. During the acquisition and extinction phases, PTSD participants with higher levels of reexperiencing symptoms exhibited greater potentiated startle responses to the CS+ compared with PTSD participants with lower reexperiencing symptoms.

Conclusions: These results suggest that PTSD is associated with enhanced fear learning and a greater "fear load" to extinguish after conditioned fear is acquired.

Conflict of interest statement

Disclosure/Conflict of Interest

Dr. Norrholm has research support from the National Alliance for Research on Schizophrenia and Depression (NARSAD), the Department of Defense (DOD)/Congressionally Directed Medical Research Program (CDMRP, Award # W81XWH-08-2-0170), the Emory University Research Committee, and PHS Grant (UL1 RR025008) from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources. Dr. Jovanovic has research support from NIMH (F32 MH070129). Dr. Bradley has research support from the American Foundation for Suicide Prevention. Dr. Ressler has research support from NIMH (MH071537), National Centers for Research Resources (M01 RR00039), NARSAD, Burroughs Wellcome Foundation, and is co-founder of Extinction Pharmaceuticals for the development of NMDA-based therapeutics to enhance extinction. All other authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

(A) Schematic illustration of the experimental paradigm. (B) Representative breakout diagram of the conditioned stimuli (CS+ and CS−) trial types during the Acquisition Session. Note: The previously reinforced CS+ in the Extinction Session did not include the airblast (US).

Figure 2

Development of fear – potentiated startle and CS+/CS− discrimination during the Acquisition Session in (A) PTSD− and (B) PTSD+. Difference Score = [Mean startle response to the CS] – [Mean startle response to the noise probe alone (NA)]. Significant Block x Trial Type interaction (F(2,248)=8.60,p<0.001). CS HAB = Habituation phase consisting of 4 presentations each of the noise probe alone and the CS+ (without US pairing) and CS−. ACQ = Acquisition phase

Figure 3

(A) Using a fear-potentiated startle paradigm, traumatized individuals with PTSD showed greater potentiated startle responses to the reinforced conditioned stimulus (CS+) and the nonreinforced conditioned stimulus (CS−) compared to traumatized individuals without PTSD during late acquisition. Late acquisition was defined as the third block of the Fear Acquisition phase. Difference Score = [Mean startle response to the CS] – [Mean startle response to the noise probe alone (NA)]. * ANOVA, Between-Subjects Effect, F(1,124) =6.13,p<0.05. (B) Based on US-expectancy ratings, the groups with and without PTSD did not significantly differ in their discrimination between the CS+ and CS− during late acquisition. Responses of DANGER indicated that an individual expected the unconditioned stimulus (US) on a CS trial and were scored as +1. Responses of UNCERTAIN were scored as 0 and responses of SAFETY indicated that an individual did not expect the US on a CS trial and were scored as −1.

Figure 4

(A) During Early and Mid-Extinction, individuals with PTSD (dark bars) displayed higher fear-potentiated startle responses to the previously reinforced CS+ as compared to those without PTSD (open bars). * ANOVA, significant Between-Subjects Effect, F(1,114) = 4.06, p < 0.05. (B) Based on US-expectancy ratings, the groups with and without PTSD did not significantly differ in their expectancy of the US during the Fear Extinction phase. Both groups exhibited a reduction in their expectancy of the US as the Fear Extinction phase progressed (F(1,47) = 16.30, p < 0.001). Responses of DANGER indicated that an individual expected the unconditioned stimulus (US) on a CS trial and were scored as +1. Responses of UNCERTAIN were scored as 0 and responses of SAFETY indicated that an individual did not expect the US on a CS trial and were scored as −1.

Figure 5

A median split was performed based on the PTSD symptom cluster scores on the PTSD Symptom Scale (PSS). When comparing individuals with higher re-experiencing symptoms (SXS) to those with lower re-experiencing symptoms, potentiated startle responses to the reinforced CS+ were greater in the high sxs group *ANCOVA with Beck Depression Index, Childhood Trauma Questionnaire, and Traumatic Event Inventory scores as covariates, Early extinction: F(1, 109) = 5.67, p = 0.019) and Mid-extinction F(1, 109) = 5.96, p = 0.016. Early, mid-, and late extinction were defined as the mean difference scores to the CS+ for the first, middle, and last two blocks of the six blocks of extinction.