Sex differences in fear conditioning in posttraumatic stress disorder

Abstract

Background: Women are twice as likely as men to develop Posttraumatic Stress Disorder (PTSD). Abnormal acquisition of conditioned fear has been suggested as a mechanism for the development of PTSD. While some studies of healthy humans suggest that women are either no different or express less conditioned fear responses during conditioning relative to men, differences in the acquisition of conditioned fear between men and women diagnosed with PTSD has not been examined.

Methods: Thirty-one participants (18 men; 13 women) with full or subsyndromal PTSD completed a fear conditioning task. Participants were shown computer-generated colored circles that were paired (CS+) or unpaired (CS-) with an aversive electrical stimulus and skin conductance levels were assessed throughout the task.

Results: Repeated measures ANOVA indicated a significant sex by stimulus interaction during acquisition. Women had greater differential conditioned skin conductance responses (CS + trials compared to CS- trials) than did men, suggesting greater acquisition of conditioned fear in women with PTSD.

Conclusions: In contrast to studies of healthy individuals, we found enhanced acquisition of conditioned fear in women with PTSD. Greater fear conditioning in women may either be a pre-existing vulnerability trait or an acquired phenomenon that emerges in a sex-dependent manner after the development of PTSD. Characterizing the underlying mechanisms of these differences is needed to clarify sex-related differences in the pathophysiology of PTSD.

Published by Elsevier Ltd.

Figures

Fig. 1

A) Timeline of study procedures. Day 1: screening for psychiatric and medical history and setting US. Level ranged from .5 to 5.0 mA and self-determined to be “highly annoying but not painful”. Day 2: fear conditioning task: habituation (10 colored circles alone) was followed by acquisition (10 colored circles that were paired (CS+) or unpaired (CS−)) with US (US duration: 500 ms shock; CS duration: 8 s, intertrial interval (ITI) = 20 − 5 s). (B) Diagram to represent timing and measurement within the conditioned stimuli (CS+ and CS−) trial types during Acquisition. The SC response score for each CS interval was obtained by subtracting the mean level for the 2 s immediately preceding CS onset from the highest value among those recorded during the 8 s CS interval. The SC response score for the interval containing the UCR was obtained by subtracting the average SC level within 6–8 s following CS onset, from the maximum increase in SC level during the .5–6.5 s interval following CS offset (corresponding to the onset of the .5 s US).

Fig. 2

Men and women group mean skin conductance response scores for (A) the conditioned stimulus (CS) intervals of CS+ and CS− trials during habituation and acquisition and (B) the unconditioned stimulus intervals of CS+ and CS− trials during the acquisition phase. Data is square-root transformed. Error bars represent standard error.

Fig. 3

Differential scores (CS + minus CS−) for the conditioned stimulus (CS) intervals during the acquisition phase for men and women.