Conclusions: These findings suggest that PTSD may be maintained by second-order conditioning where trauma-relevant cues come to serve as unconditioned stimuli, thus generalizing enhanced emotional responses to many previously neutral cues and impeding extinction. The extinction deficit in PTSD patients observed in this study underlines the need for therapies focusing on the extinction of learned responses, such as behavioral treatment, with or without the addition of pharmacological substances that enhance the extinction of a learned response.