Decreased defensive reactivity to interoceptive threat after successful exposure-based psychotherapy in patients with panic disorder

Panic disorder (PD) is characterized by a dysfunctional defensive responding to panic-related body symptoms that is assumed to contribute to the persistence of panic symptomatology. The present study aimed at examining whether this dysfunctional defensive reactivity to panic-related body symptoms would no longer be present following successful cognitive behavior therapy (CBT) but would persist when patients show insufficient symptom improvement. Therefore, in the present study, effects of CBT on reported symptoms and defensive response mobilization during interoceptive challenge were investigated using hyperventilation as a respiratory symptom provocation procedure. Changes in defensive mobilization to body symptoms in the course of CBT were investigated in patients with a primary diagnosis of PD with or without agoraphobia by applying a highly standardized hyperventilation task prior to and after a manual-based CBT (n = 38) or a waiting period (wait-list controls: n = 20). Defensive activation was indexed by the potentiation of the amygdala-dependent startle eyeblink response. All patients showed a pronounced defensive response mobilization to body symptoms at baseline. After treatment, no startle reflex potentiation was found in those patients who showed a clinically significant improvement. However, wait-list controls and treatment non-responders continued to show increased defensive responses to actually innocuous body symptoms after the treatment/waiting period. The present results indicate that the elimination of defensive reactivity to actually innocuous body symptoms might be a neurobiological correlate and indicator of successful CBT in patients with PD, which may help to monitor and optimize CBT outcomes.

The role of startle fluctuation and non-response startle reflex in tracking amygdala dynamics

ABSTRACTThe startle reflex is considered a sensitive defensive reaction to potential threats that manifests as a unique eye blink-like pattern in the EMG. Eye blink EMG has a bell-shaped potential when startle probes are elicited, that strongly corresponds to amygdala activity. Considering how amygdala activity fluctuates over time in response to emotional and self-threatening stimuli, observing startle eyeblink size fluctuation over time could provide a cost-effective, convenient, and less resource intensive means for examining amygdala activity over time. Yet based on current standards in the literature, often startle evoked eye blink EMG values do not exhibit activity 3SDs from the mean eyeblink response, thus these trials are typically excluded from startle analyses. It stands to reason, however, that these trials may still index amygdala activity in a meaningful way. Through investigating the association between startle eyeblink amplitude, corresponding ERP amplitude, and underlying neural activity, the current study provides evidence that startle amplitudes exhibit a linear relationship with proxies for amygdala activity, e.g., N100 amplitudes and regions heavily interconnected with the amygdala. Specifically, the startle reflex correlates to large amount of brain regions in N100 time window in addition to the N100 amplitude. Thus, both valid and otherwise traditionally non-valid startle reflex responses appear to index amygdala activity and should be included accordingly. This approach could help salvage large amounts of meaningful data traditionally excluded from studies interested in amygdala responses to various stimuli over time.

Effect of Comorbid Post-Traumatic Stress Disorder and Panic Disorder on Defensive Responding

Although panic disorder (PD) and post-traumatic stress disorder (PTSD) are characterized by heightened sensitivity to threat, no study to date has examined the effect of comorbid PD and PTSD on defensive responding. The present study probed startle eyeblink response to an acoustic probe in three groups of participants recruited from the community: (1) healthy individuals (n = 63), (2) individuals with PD without PTSD (n = 62), and (3) individuals with comorbid PD and PTSD (n = 24). Results indicated that PD individuals without PTSD exhibited greater sensitivity to threat relative to controls, and comorbid individuals displayed attenuated sensitivity to threat relative to PD individuals without PTSD (both ps < .05). The results are discussed in the context of the anxiety disorder spectrum, which postulates that anxiety disorders exist on a continuum spanning from specific/simple fear to broad distress, with defensive responding decreasing as distress increases.

Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders

BackgroundHeightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT).MethodsParticipants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding.ResultsAcross both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable.ConclusionsTogether, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.