Defensive Mobilization During Anticipation of Symptom Provocation: Association With Panic Pathology.

BACKGROUND: Anxious apprehension about feared body symptoms is thought to play a crucial role in the development, chronicity, and treatment of panic disorder (PD). In this study, we therefore aimed to elucidate the role of defensive reactivity to anticipated unpleasant symptoms in PD that can contribute to a better understanding of pathomechanisms of PD as well as identification of potential targets in PD-focused interventions. By measuring amygdala-dependent potentiation of the startle reflex, we aimed to investigate whether 1) patients with PD exhibit a specifically increased defensive reactivity to anticipated unpleasant body symptoms and 2) whether clinical severity of panic symptomatology varies with magnitude of defensive activation. METHODS: Defensive mobilization to anticipated threat was investigated in 73 patients with a primary diagnosis of PD with agoraphobia (PDA) and 52 healthy control subjects. Threat of symptom provocation was established by a standardized hyperventilation task and contrasted to threat of shock to the forearm of the participant. RESULTS: Patients with PDA and healthy control subjects did not differ in their defensive responses during anticipation of shock. In contrast, patients with severe PDA as compared with healthy control subjects exhibited increased defensive response mobilization and reported more anxiety and panic symptoms during anticipation of feared body symptoms. Moreover, startle potentiation during anticipation of hyperventilation covaried with the severity of panic symptomatology. CONCLUSIONS: The present findings suggest that increased defensive mobilization during anticipation of body symptoms is a neurobiological correlate of severe PDA that should be specifically targeted in PD interventions and might be used to monitor treatment success.

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.

Cue and context conditioning to respiratory threat: Effects of suffocation fear and implications for the etiology of panic disorder.

Interoceptive threats play a crucial role in the etiology of panic disorder (PD). While body sensations may become conditioned stimuli (CS) when paired with such interoceptive threats (cue conditioning), the environment in which such interoceptive threats occur may also be learned as a predictor of threat (context conditioning). Suffocation fear (SF) might facilitate these associative learning processes if threats of suffocation become relevant as unconditioned stimuli (US). To investigate whether SF affects associative learning during such respiratory threat, we used mild dyspnea as CS that predicted the occurrence of strong dyspnea (US) in one context (predictable), was not related to the occurrence of the US in another context (unpredictable) or was presented in a different context (safe) in which no US was delivered. Startle eyeblink responses and subjective reports were assessed in 34 participants during learning. Individuals reporting high SF showed a clear potentiation of the startle response during the interoceptive CS predicting the occurrence of interoceptive threat (US). Such startle potentiation was not observed when the CS remained unpaired (safe or unpredictable context). Moreover, high SF persons also showed a significant startle potentiation to the threatening context, when the CS did not predict the onset of the US. No such learning effects were observed for low SF individuals. The data support the view that defensive response mobilization can be triggered by cues but also by contexts that predict the occurrence of interoceptive threats if these threats are relevant for the individuals, supporting learning accounts for the development of PD.

Physiological and neural correlates of worry and rumination: Support for the contrast avoidance model of worry.

The current experiments tested neural and physiological correlates of worry and rumination in comparison to thinking about neutral events. According to the avoidance model-stating that worry is a strategy to reduce intense emotions-physiological and neurobiological activity during worried thinking should not differ from activation during neutral thinking. According to the contrast avoidance model-stating that worry is a strategy to reduce abrupt shifts of emotions-activity should be increased. To test these competing models, we induced worry and neutral thinking in healthy participants using personal topics. A rumination condition was added to investigate the specificity of changes induced by the mental process. Two experiments were conducted assessing the effects on different response levels: (1) neural activation using fMRI, and (2) physiological response mobilization using startle and autonomic measures. During worry, participants showed a potentiated startle response and BOLD activity indicative of emotional network activation. These data partly support the contrast avoidance model of worry. Both mental processes showed elevated activity in a common network referred to as default network indicating self-referential activity.

Anxiety sensitivity and expectation of arousal differentially affect the respiratory response to caffeine.

RATIONALE: This study aimed to test how expectations and anxiety sensitivity influence respiratory and autonomic responses to caffeine. OBJECTIVES: The current study investigated the effects of expected vs. unexpected caffeine ingestion in a group of persons prone to the anxiety-provoking effect of caffeine (high anxiety sensitive persons, that is, persons scoring at least one SD above the mean on the Anxiety Sensitivity Index (Peterson and Reiss 1992)) as compared to low-anxious controls. METHODS: Autonomic arousal (heart rate, skin conductance level), respiratory responding (expired CO2, minute ventilation), and subjective report were assessed in high and low anxiety sensitive participants immediately after beverage consumption and at absorption peak (30 min post-consumption) in four separate sessions during which either coffee (expectation of caffeine) or bitter lemon soda (no expectation of caffeine) was crossed with 4 mg/kg caffeine vs. no drug. RESULTS: High and low anxiety sensitive persons showed comparable autonomic arousal and symptom reports to caffeine which was modulated by expectation, i.e., greater for coffee. Respiratory responding (CO2 decrease, minute ventilation increase) was more accentuated when caffeine was both expected and administered in the low anxiety sensitive group but more accentuated when caffeine was unexpectedly administered in the high anxiety sensitive group. Autonomic arousal and respiratory effects were observable within a few minutes after caffeine administration and were most pronounced at maximum absorption. CONCLUSIONS: The results highlight the modulating role of expectancies in respiratory responding to caffeine in low vs. high anxiety sensitive persons and might have important implications for the better understanding of unexpected panic attacks.

Modulation of the blink reflex and P3 component of the startle response during an interoceptive challenge.

The blink reflex component of the startle response is potentiated during processing of exteroceptive unpleasant stimuli. In contrast, blink magnitudes are often inhibited during interoceptive challenges. We measured respiration, blink magnitudes, and the P3 component to the acoustic startle probes in 34 participants while breathing against a mild resistance (mask-with-tubing) compared to breathing with no mask. Breathing through a mask with tubing resulted in increased inspiratory resistance as indicated by increased flow rate and tidal volume, a compensatory breathing pattern. Blink magnitudes to probes presented during the mask-with-tubing condition were inhibited compared to no-mask. Likewise, the probe P3 component was smaller during breathing through a mild resistance. These data suggest that startle inhibition during interoceptive challenges might be due to a shift in attention towards the mildly unpleasant interoceptive stimuli.

Induction of dyspnea evokes increased anxiety and maladaptive breathing in individuals with high anxiety sensitivity and suffocation fear.

Although respiratory symptoms are relevant for diagnosis and etiology of panic disorder, anxiety responses and breathing behavior evoked by induction of dyspnea have rarely been studied. Therefore, dyspnea sensations and affective evaluations evoked by inspiratory resistive loads of different intensities were first assessed in 23 individuals with high versus 24 participants with low anxiety sensitivity (AS). High AS participants with high fear of suffocation rated loads of the same physical intensity as more unpleasant and reported more intense feelings of dyspnea and more respiratory and panic symptoms than low AS individuals. In the second experiment assessing physiological responses to physically comparable loads, high suffocation fear participants showed an increase in minute ventilation to compensate for fear-induced air hunger. This ventilation behavior results in increased frequency of dyspnea sensations, thus increasing fear of suffocation.