Differential activity of subgenual cingulate and brainstem in panic disorder and PTSD

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Abstract

Most functional neuroimaging studies of panic disorder (PD) have focused on the resting state, and have explored PD in relation to healthy controls rather than in relation to other anxiety disorders. Here, PD patients, posttraumatic stress disorder (PTSD) patients, and healthy control subjects were studied with functional magnetic resonance imaging utilizing an instructed fear conditioning paradigm incorporating both Threat and Safe conditions. Relative to PTSD and control subjects, PD patients demonstrated significantly less activation to the Threat condition and increased activity to the Safe condition in the subgenual cingulate, ventral striatum and extended amygdala, as well as in midbrain periaquaeductal grey, suggesting abnormal reactivity in this key region for fear expression. PTSD subjects failed to show the temporal pattern of activity decrease found in control subjects.

Research highlights

▶ Panic disorder (PD) and posttraumatic stress disorder (PTSD) share similar symptoms and both are thought of disorders of fear learning. ▶ Directly comparing neural correlates of fear learning of both disorders. ▶ PD patients show abnormal (inverse) activity in key fear regions. ▶ PTSD patients lack habituation in key fear regions.

Section snippets

Participants

Participants were 8 subjects meeting DSM-IV criteria for PD (mean age = 37 years, range = 24–50); 8 subjects meeting DSM-IV criteria for PTSD (mean age = 42 years, range = 37–50); and 8 healthy comparison subjects (mean age = 35 years, range = 24–49). PTSD and comparison subjects were a matched subset of larger groups. Each group consisted of 4 female and 4 male right-handed subjects. Among the patients, there were current secondary diagnoses of generalized anxiety disorder, social phobia, specific phobia,

Results

During debriefing all subjects indicated that they had expected to receive an electrodermal stimulation during the presentation of the Threat stimulus and that this expectation was associated with the feeling of fear which decreased with repeated presentations over time.

In healthy control subjects significant activation was exhibited in the contrast of Threat versus Safety in bilateral anterior insula, bilateral basal ganglia and thalamus, bilateral dorsal anterior cingulate and bilateral

Discussion

Using cognitively instructed fear, this study demonstrates significantly less activation to threat cues and increased activity to safety cues in the subgenual cingulate, ventral striatum, extended amygdala and midbrain periaquaeductal grey in PD patients, suggesting abnormal reactivity in these regions for fear expression. PTSD subjects, in comparison, failed to show the temporal pattern of activity decrease found in control subjects.

Considering the role of these regions in the regulation of

Conclusion

These findings contribute to the growing literature examining the potentially unique neurocircuitry subserving distinct anxiety disorders. Key findings in the present study may suggest a heightened sensitivity to internally generated, viscerosomatic threat in PD versus heightened sensitivity to external threat in PTSD, as well as to impaired discrimination learning in PD versus impaired extinction learning in PTSD on the behavioral level. Neuroimaging studies contributing to the

Acknowledgement

Funding for this study was provided by the NIMH Grant P50 MH58911-S1.

References (27)

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Both authors contributed equally to this work.

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