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.
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