PTSD is characterized by excessive fear responding to trauma reminders that persist in the presence of safety reminders. Human neuroimaging studies suggest that this is, in part, due to the interplay of overactive, amygdala-driven excitatory circuits and deficient, higher-order inhibitory circuits.[17,50]
The objective of this study was to examine the psychophysiology of fear acquisition in a highly traumatized civilian population in order to shed light on the neural underpinnings of maladaptive fear in PTSD. Furthermore, the study aimed to compare FPS and SCRs during fear conditioning in their respective associations with specific PTSD symptom clusters.
A translational differential fear conditioning model was used to measure conditioned fear in PTSD and trauma-exposed control participants during both aversive (CS+) and safety (CS−) conditions. To address a discrepancy in findings from researchers that measured FPS versus SCR to assess fear discrimination in PTSD, these two fear measures were directly compared under the same experimental conditions. Based on previous findings and the differing neurobiology of these two fear measures,
it was predicted that FPS, but not SCR, would show group differences between PTSD and control participants.
Results showed that all participants displayed robust fear expression to the danger cue and significant discrimination between the danger and safety cue, which was captured in both measures, indicating successful fear conditioning. Furthermore, participants with PTSD expressed significantly greater fear to both the danger and safety cues than the trauma controls. This heightened fear was only captured with FPS, whereas SCR did not differ between groups. These findings replicate earlier studies showing exaggerated FPS to danger cues in PTSD subjects
and the validity of FPS as a measure of fear conditioning in human populations.[32,51]
They also replicate studies showing SCR to be a reliable measure of differential fear conditioning.[16,21,34]
Nevertheless, the current findings suggest that SCR may not be as sensitive a measure as FPS to diagnostic differences in fear expression.
To further explore this idea, independent contributions of FPS and SCR to PTSD variance were examined using regression analyses of re-experiencing symptoms and hyper-arousal symptoms measured from the PSS. Our previous studies demonstrated that FPS responses to danger cues (CS+) predicted re-experiencing symptoms,, 
whereas fear inhibition to safety cues predicted hyper-arousal symptoms of PTSD.
This may seem unexpected at first glance, given that exaggerated startle is indicated as part of the hyper-arousal cluster in DSM-IV. However, hyper-arousal in PTSD is also related to hyper-vigilance, irritability and difficulties in sleeping and concentration,
which speaks more to a lack of inhibitory control in general, and perhaps, more specifically, an inability to inhibit fear in safe situations. The re-experiencing cluster may be more related to a hyperactive amygdala response to trauma reminders,
which, in this study, is manifested as heightened FPS to CS+ (i.e., danger cue) in PTSD.
This study found a weak positive correlation between startle and SCR measures of fear. Although SCR is very frequently used as the sole measure of autonomic nervous system conditioning,
multiple physiological measures may be necessary for assessment of fear in clinical populations. Although previous research has used several psychophysiological measures to differentiate among anxiety disorder patients,[53,54]
only a small number of studies have examined these biomarkers along the symptom spectrum within symptom clusters. This study replicated our earlier findings showing that startle to danger cues significantly accounted for the variance in PTSD re-experiencing symptoms.
Unlike startle, SCR did not significantly contribute to re-experiencing symptoms. Similarly, impaired inhibition of FPS to safety cues significantly predicted hyper-arousal, whereas SCR to safety cues did not. It is important to note that several studies have found that decreased SCR habituation may be associated or even predictive of PTSD.[55,56]
It has been suggested that SCR is closely tied to contingency awareness that may involve activation of the hippocampus,
a structure that may be linked to vulnerability for PTSD.
On the other hand, the startle reflex is distinct from SCR in that it is directly modulated by the amygdala,
and associated with valence rather than arousal and novelty.
A recent study found that propranolol interrupted reconsolidation of fear memory when measured with FPS, but not SCR,
further suggesting the specificity of startle as a measure of amygdala dependent, cue-specific fear.
When using psychophysiological methods as translational tools to understand PTSD and develop objective measures that track treatment outcome, it may prove more effective to use methods that translate brain activity of the areas known to be involved in the neurobiology of PTSD symptoms. As such, FPS seems to provide an ideal translational tool for investigating the neurobiological underpinnings of PTSD symptom exacerbation, such as amygdala dysregulation, whereas SCR may not be as sensitive to these alterations. Another advantage of FPS is the availability of animal models, such as rodents[26,27]
and nonhuman primates,
which allow for basic investigation of neural underpinnings of fear expression and fear inhibition that can be used in development of fear inhibition-based therapeutic approaches for PTSD, such as exposure therapy.
The nature of this study sample provides both strengths and limitations. One limitation is the use of a self-report measure (PSS) to determine PTSD diagnosis. However, the PSS has good psychometric qualities, and strong validity with clinician-administered measures, such as the CAPS,
and has been well validated in our population.[38,39,42]
A strength of this study is statistically controlling for degree of trauma exposure between the PTSD and control participants. Although other studies have also used trauma-exposed control groups,
there appears to be a linear “dose response” association between trauma load and PTSD symptoms,
such that even trauma exposed individuals without PTSD may have significantly lower levels of trauma than individuals who meet DSM criteria for PTSD. Interestingly, the regression analyses indicate that heightened FPS is significantly related to PTSD symptoms beyond those accounted for by the trauma, thus underscoring its potential use as an objective measure of symptom severity. Finally, participants in this study were recruited from the primary care patient pool at Grady Hospital in Atlanta, which serves mainly an African-American, low-socioeconomic status, highly traumatized population. This population is significantly more susceptible to trauma-related stress disorders
and has been largely understudied in human clinical research. This study represents a much-needed effort toward understanding the psychological outcomes of similarly vulnerable populations.
In summary, we found that FPS provided a sensitive measure of heightened fear responses in PTSD, which were associated with specific clinical symptom presentations. Furthermore, the ability to translate FPS paradigms across species allows us to use genetics, biochemical and pharmacological research techniques. Given that the groundwork in fear neurocircuitry has been greatly developed in animal models, the field of PTSD research is well poised to discover novel approaches for prevention, intervention, and treatment of the disorder.