HPA and startle data were collected on 90 subjects. Of these, 55 returned for the second, post-dexamethasone visit. One subject did not test positive for dexamethasone on the post-DEX day and their post-DEX data were not included in the analyses. The resulting sample had 90 subjects (29 PTSD and 61 Non-PTSD) with startle and baseline hormone data, and 54 subjects (18 PTSD and 36 Non-PTSD) with post-DEX data. We compared the subjects for the baseline sample and the subjects for the post-DEX sample on clinical data (PSS and BDI score), fear-potentiated startle data, and baseline cortisol and ACTH data—the two samples did not differ on any of these variables. All analyses of hormone data, including the correlations with startle were performed only on the 54 subjects who had both baseline and post-DEX data. All startle analyses were conducted on the 90 subjects who had baseline data. In the entire sample, the subjects’ age ranged from 18–63 years old and 61.3% were female. All subjects were African American. list the rates of traumas in the total sample. shows the demographic and clinical information of the subjects across the different groups, as well as trauma history.
Rates of traumatic experiences in the entire sample.
The table displays the demographic and clinical information across the two diagnostic groups.
As shown in , all subjects had approximately equivalent levels of childhood (F(1,73)=0.24, p=0.63) and adult (F(1,73)=2.36, p=0.13) trauma. However, the subjects that met current criteria for PTSD had significantly higher PSS scores, F(1,73)=105.18, p<0.0001, than traumatized controls without PTSD. Furthermore, the PTSD subjects had significantly greater current symptoms of depression compared to Non-PTSD controls (F(1,73)=7.25, p<0.01). Subjects were excluded from the study if they had schizophrenia. The prevalence of other current comorbid Axis I disorders, as assessed by the SCID, were as follows: major depression, 12.5% of sample (no difference in distribution between groups, χ2=0.20,p=0.67)—depression symptoms were also controlled statistically by covarying for BDI score; bipolar disorder, 1.3% of sample (only in Non-PTSD group, χ2=0.49,p=0.48); alcohol dependence, 6% of total sample (no difference in distribution between groups, χ2=2.57,p=0.11); drug dependence, 5% of sample (equally distributed between groups, χ2=0.08,p=0.78); panic disorder, 2.5% of sample (equally distributed between groups, χ2=0.34,p=0.56); social phobia, 3.9% of total sample (all of those were in the PTSD group, χ2=6.89,p<0.01); specific phobia, 8% of sample (equally distributed between groups, χ2=1.51,p=0.22); obsessive-compulsive disorder, 1.3% of sample (equally distributed between groups, χ2=2.10,p=0.15); and generalized anxiety disorder, 12.3% of sample (trend for higher likelihood in PTSD group, χ2=3.65,p=0.06).
shows baseline and post-DEX cortisol data, and shows baseline and post-DEX ACTH data in the diagnostic groups. Multivariate analyses of variance (MANOVA) were conducted on baseline and post-DEX levels of cortisol and ACTH, as well as change scores for the two variables, comparing PTSD and Non-PTSD subjects. Current depression was included as a covariate in these analyses. There were no group differences in baseline hormone levels, or change scores from baseline to post-DEX levels. However, there was a significant main effect of group on post-DEX cortisol levels, with PTSD subjects having lower cortisol levels after dexamethasone compared to Non-PTSD subjects (F(1,42)=3.86,p=0.05).
Baseline and post-dexamethasone (post-DEX) levels and change scores of HPA hormones across the two diagnostic groups
A RM ANOVA of dexamethasone effects showed a significant suppression of cortisol levels in both groups: PTSD, F(1,14)=17.67, p<0.001; Non-PTSD subjects, F(1,31)=53.94, p<0.01, see . ACTH levels were also significantly suppressed in the PTSD group, F(1,13)=5.36, p<0.05 and the Non-PTSD group (F(1,28)=10.13, p<0.01), see .
Startle magnitude was assessed during noise alone (NA) trials and in the presence of conditioned stimuli across 3 blocks of conditioning using a 3-way mixed ANOVA with block (3 levels) X trial type (NA, AX+, BX−) X group (PTSD, Non-PTSD) and BDI score as a covariate. Fear acquisition was assessed using a contrast between NA and the reinforced stimulus (AX+), while differential conditioning to the CS+ and CS− was assessed by contrasting AX+ to BX. There was a trend toward a three-way interaction for fear potentiation (F(1,79)=3.80, p=0.06) and differential conditioning (F(1,79)=3.26,p=0.08). There was no main effect of group on startle magnitude to the NA and CS trials.
The interactions were followed up by separate two-way RM ANOVAs of block X trial type within each group. shows startle magnitude to the CS+ and CS− across the conditioning blocks for each group. In Non-PTSD subjects there was a significant linear effect for block (F(1,53)=21.29, p<0.001), while the PTSD subjects did not show a significant effect of block (F(1,25)=2.55, p=0.13) indicating deficient habituation to the startle stimulus. Fear conditioning was significant in both groups, as startle magnitude to AX+ was greater than NA in PTSD subjects (F(1,25)=4.18, p=0.05) and Non-PTSD subjects (F(1,53)=15.41, p<0.001), see . Finally, startle magnitude was larger in the presence of AX+ than BX− in Non-PTSD (F(1,53)=5.03, p<0.05), but not in PTSD (F(1,25)=0.04, p=0.85) subjects. In order to determine that PTSD subjects were not simply slower at acquiring the discrimination, we compared startle magnitude on AX+ and BX− trials on the last block of conditioning in each group. Again, the Non-PTSD subjects had significant discrimination (F(1,53)=4.31, p<0.05), while the PTSD subjects did not (F(1,25)=0.22, p=0.65). The two-way RM ANOVAs within each group were also conducted without using BDI as a covariate, and the results were replicated, i.e., Non-PTSD subjects showed startle magnitude discrimination between AX+ and BX− (F(1,60)=4.17, p<0.05) and the PTSD subjects did not discriminate (F(1, 28)=0.39, p=0.54).
Figure 3 Startle magnitude to Noise alone (NA), AX+ trials (danger signal), and BX− trials (safety signal) during the conditioning phase for the two groups. * denotes p<0.05 for trial type (NA vs. AX+, p<0.05; AX+ vs. BX−, ns); (more ...)
The degree of differential conditioning to AX+ and BX−, and fear inhibition on AB trials was assessed with a MANOVA comparing the groups on average percent startle potentiation to AX+, BX−, and AB. Computing percent potentiation from noise alone in each block accounted for individual variability in startle magnitude as well as habituation to the startle stimulus. This analysis showed a significant main effect of group on BX− trials (F(1,88)=4.44, p<0.05) and AB trials (F(1,88)=5.20, p<0.05), with higher fear potentiation in PTSD compared to Non-PTSD subjects, indicative of less fear inhibition, see . In order to examine the reduction in the percent fear potentiation to BX− and AB relative to AX+ in PTSD and Non-PTSD subjects, a RM ANOVA of CS trial type was performed within each group. We found significant discrimination between AX+ and BX− in the controls, F(1,60)=14.52, p<0.001 while PTSD subjects did not show differential conditioning (F(1,28)=1.86,p=0.18), replicating the finding in startle magnitude. The contrast between AB and AX+ indicated that controls had significant fear inhibition on the AB trials, F(1,60)=7.14, p=0.01, while PTSD subjects did not (F(1,28)=0.05, p=0.82), .
Percent fear-potentiated startle to AX+ (danger signal), BX− (safety signal), and AB (safety transfer) across the two diagnostic groups. * denotes p<0.05; ** denotes p<0.01.
We also examined the correlation between percent fear potentiation on AX+, BX−, and AB with PTSD symptom severity in the three major symptom clusters: re-experiencing, avoidance and hyper-arousal symptoms. Percent potentiation to the nonreinforced cue, BX−, was positively correlated with avoidance symptoms (r(77)=0.23,p<0.05) and hyper-arousal symptoms (r(77)=0.23,p<0.05) on the PSS. Percent potentiation to the fear inhibition test trials, AB, was positively correlated with avoidance symptoms (r(77)=0.23,p<0.05). However, there were no significant correlations with startle to the danger signal, AX+.
The results of the response keypad data showed that, across both groups, subjects understood the experimental contingencies. Four subjects (2 PTSD and 2 Non-PTSD) had missing response pad data. A mixed ANOVA in the two groups showed a main effect of CS type, with higher US expectancy for AX+ than BX−: PTSD (F(1, 26)=13.93, p<0.001), Non-PTSD (F(1, 58)=52.44, p<0.001). However, there were no between-group differences in US expectancy to either trial type and there were no CS type by group interactions. We used the response keypad data to categorize individuals as to their awareness of the reinforcement contingencies in the experiment. Individuals were considered aware if they had two consecutive correct responses on the keypad. In this sample, 20.9% of the subjects were classified as unaware; however, the distribution of aware and unaware subjects did not vary in the two diagnostic groups (χ2 (86)=0.59, p=0.44).
In order to eliminate the effect of unawareness on discrimination, we re-analyzed the differential conditioning data by restricting the dataset to only the aware subjects. We compared startle on the last conditioning block of AX+ to BX−, with BDI again as a covariate. These analyses replicated the earlier findings: Non-PTSD subjects had significantly higher startle magnitude in the presence of AX+ than BX− (F(1,40)=11.51,p<0.01), while PTSD subjects did not (F(1,16)=1.05, p=0.32). Similarly, percent startle potentiation on AX+ trials was significantly higher than percent potentiation on BX− trials in the controls (F(1,40)=6.81,p=0.01) but not the PTSD subjects (F(1,16)=0.004, p=0.95).
HPA and Fear-Potentiated Startle Correlations
We performed partial correlations on the HPA and startle data separately for each group, with depression as a covariate. shows the correlations for all variables. We found that the PTSD group had a positive correlation between ACTH levels and fear-potentiated startle. This finding was true of baseline ACTH levels and post-DEX ACTH levels, and the relationship held for each trial type, see . shows the scatter diagram of startle to AX+ and BX− with baseline ACTH, and shows the scatter diagram of startle to AX+ and BX− with post-DEX ACTH. Cortisol levels were negatively associated with fear-potentiated startle in PTSD; however, the level of significance did not meet the criterion for multiple comparisons.
Correlations between HPA variables and fear-potentiated startle variables (square root) in PTSD and Non-PTSD subjects.
Scatter diagram of the percent fear-potentiated startle (square root) to AX+ (danger signal) and BX− (safety signal) and adenocorticotropin hormones (ACTH) in PTSD subjects