Tools for translational neuroscience: PTSD is associated with heightened fear responses using acoustic startle but not skin conductance measures.

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.

Cortisol suppression by dexamethasone reduces exaggerated fear responses in posttraumatic stress disorder.

PTSD symptoms are associated with heightened fear responses in laboratory fear conditioning paradigms. This study examined the effects of dexamethasone administration on hypothalamic-pituitary-adrenal (HPA) function and fear-potentiated startle (FPS) in trauma-exposed individuals with and without PTSD. We used an established fear discrimination procedure, in which one visual stimulus (CS+, danger cue) was paired with aversive airblasts to the throat (unconditioned stimulus, US), and another stimulus (CS-, safety cue) was presented without airblasts. In addition to FPS, the dexamethasone suppression test (DST) was performed. The study sample (N=100) was recruited from a highly traumatized civilian population in Atlanta, GA. Half of the subjects (n=54, 16 PTSD, 38 controls) underwent conditioning at baseline and the other half (n=46, 17 PTSD, 29 controls) after DST, in a cross-sectional design. We found a significant interaction effect of diagnostic group and dexamethasone treatment. Under baseline conditions, subjects with PTSD showed more than twice as much fear-potentiated startle to the danger cue compared to traumatized controls, F(1,53)=8.08, p=0.006. However, there was no group difference in subjects tested after dexamethasone suppression. Furthermore, there was a significant treatment effect in PTSD subjects but not in controls, with dexamethasone reducing fear-potentiated startle to the CS+, F(1,32)=4.00, p=0.05. There was also a positive correlation between PTSD subjects' FPS and cortisol levels, r=0.46, p=0.01. These results suggest that transient suppression of HPA function via dexamethasone suppression may reduce exaggerated fear in patients with PTSD.

Personality constellations in incarcerated psychopathic men.

Advances in the operationalization of psychopathy have led to an increased understanding of the boundaries, structure, and nomological network of this construct, although significant questions remain. The empirical identification of replicable and theoretically meaningful psychopathy subtypes may help to improve the classification and diagnosis of this condition. We conducted a classification study of 91 incarcerated men who met conventional criteria for high levels of psychopathy using the Psychopathy Checklist-Revised. We expanded on the methodology of previous research on psychopathy subtypes by utilizing a comprehensive personality assessment instrument and a prototype matching approach to classification. The analyses revealed a primary (narcissistic) subtype and a secondary (hostile and dysregulated) subtype that were broadly consistent with the previous literature. External validation analyses, statistical controls, and incremental validity analyses provided substantial support for the primary and secondary subtypes.

Fear potentiation is associated with hypothalamic-pituitary-adrenal axis function in PTSD.

A central problem in posttraumatic stress disorder (PTSD) is the inability to suppress fear under safe conditions. We have previously shown that PTSD patients cannot inhibit conditioned fear. Another relevant finding in PTSD is the hypersensitivity of the hypothalamic-pituitary-adrenal (HPA) axis feedback. Given their common neurobiological pathways, alterations in HPA function in PTSD may be associated with impaired fear inhibition. The present study examined the relationship between HPA axis function and fear-potentiated startle and inhibition of conditioned fear in trauma-exposed individuals. We used a conditional discrimination procedure (AX+/BX-), in which one set of shapes (AX+) was paired with aversive airblasts to the throat (danger signal), and the same X shape with a different shape (BX-) were presented without airblasts (safety signal). The paradigm also included a transfer of fear inhibition test (AB). In addition to fear-potentiated startle, blood was drawn for neuroendocrine analysis and the dexamethasone suppression test (DEX) was performed; cortisol and ACTH were assessed at baseline and post-DEX. Ninety highly traumatized individuals recruited from Grady Hospital in Atlanta, GA participated in the study. The sample was divided into those who met DSM-IV criteria for PTSD (n=29) and Non-PTSD controls (n=61) using the PTSD symptom scale (PSS). Both groups showed significant reduction in cortisol and ACTH levels after DEX. Subjects with PTSD had higher fear-potentiated startle to the safety signal, BX- (F(1,88)=4.44, p<0.05) and fear inhibition trials, AB (F(1,88)=5.20, p<0.05), both indicative of less fear inhibition in the presence of B, compared to control subjects. In addition, fear-potentiated startle to AX+, BX-, and AB was positively correlated with baseline and post-DEX ACTH in PTSD subjects. These results suggest that impaired fear inhibition and associated alterations in HPA feedback may reflect amygdala hyperactivity in subjects with PTSD.