Background: Posttraumatic stress disorder (PTSD) patients show heightened fear responses to trauma reminders and an inability to inhibit fear in the presence of safety reminders. Brain imaging studies suggest that this is in part due to amygdala over-reactivity as well as deficient top-down cortical inhibition of the amygdala. Consistent with these findings, previous studies, using fear-potentiated startle (FPS), have shown exaggerated startle and deficits in fear inhibition in PTSD participants. However, many PTSD studies using the skin conductance response (SCR) report no group differences in fear acquisition.
Method: The study included 41 participants with PTSD and 70 without PTSD. The fear conditioning session included a reinforced conditioned stimulus (CS+, danger cue) paired with an aversive airblast, and a nonreinforced conditioned stimulus (CS-, safety cue). Acoustic startle responses and SCR were acquired during the presentation of each CS.
Results: The results showed that fear conditioned responses were captured in both the FPS and SCR measures. Furthermore, PTSD participants had higher FPS to the danger cue and safety cue compared to trauma controls. However, SCR did not differ between groups. Finally, we found that FPS to the danger cue predicted re-experiencing symptoms, whereas FPS to the safety cue predicted hyper-arousal symptoms. However, SCR did not contribute to PTSD symptom variance.
Conclusions: Replicating earlier studies, we showed increased FPS in PTSD participants. However, although SCR was a good measure of differential conditioning, it did not differentiate between PTSD groups. These data suggest that FPS may be a useful tool for translational research.
The neural circuitry underlying the fear response is extremely well conserved across mammalian species, which has allowed for the rapid translation of research findings in rodent models of fear to therapeutic interventions in human populations. Many aspects of exposure-based psychotherapy treatments in humans, which are widely used in the treatment of PTSD, panic disorder, phobias, and other anxiety disorders, are closely paralleled by extinction training in rodent fear conditioning models. Here, we discuss how the neural circuitry of fear learning and extinction in rodent animal models may be used to understand the underlying neural circuitry of fear-related disorders, such as PTSD in humans. We examine the factors that contribute to the pathology and development of PTSD. Next, we will review how fear is measured in animal models using classical Pavlovian fear conditioning paradigms, as well as brain regions such as the amygdala, which are involved in the fear response across species. Finally, we highlight the following three systems involved in the extinction of fear, all of which represent promising avenues for therapeutic interventions in the clinic: (1) the role of the glutamatergic N-methyl-d-aspartate (NMDA) receptor, (2) the role of the brain-derived neurotrophic factor (BDNF)–tyrosine kinase B (TrkB) induced signaling pathway, and (3) the role of the renin-angiotensin system. The modulation of pathways underlying fear learning and extinction, such as the ones presented in this review, in combination with extinction-based exposure therapy, represents promising avenues for therapeutic intervention in the treatment of human fear related disorders.