Impaired discriminative fear-conditioning resulting from elevated fear responding to learned safety cues among individuals with panic disorder

Classical fear-conditioning is central to many etiologic accounts of panic disorder (PD), but few lab-based conditioning studies in PD have been conducted. One conditioning perspective proposes associative-learning deficits characterized by deficient safety learning among PD patients. The current study of PD assesses acquisition and retention of discriminative aversive conditioning using a fear-potentiated startle paradigm. This paradigm was chosen for its specific capacity to independently assess safety- and danger learning in the service of characterizing putative anomalies in each type of learning among those with PD. Though no group difference in fear-potentiated startle was found at retention, acquisition results demonstrate impaired discriminative learning among PD patients as indexed by measures of conditioned startle-potentiation to learned safety and danger cues. Importantly, this discrimination deficit was driven by enhanced startle-potentiation to the learned safety cue rather than aberrant reactivity to the danger cue. Consistent with this finding, PD patients relative to healthy individuals reported higher expectancies of dangerous outcomes in the presence of the safety cue, but equal danger expectancies during exposure to the danger cue. Such results link PD to impaired discrimination learning, reflecting elevated fear responding to learned safety cues.     

Fear conditioning in panic disorder: Enhanced resistance to extinction

Enhanced conditionability has been proposed as a crucial factor in the etiology and maintenance of panic disorder (PD). To test this assumption, the authors of the current study examined the acquisition and extinction of conditioned responses to aversive stimuli in PD. Thirty-nine PD patients and 33 healthy control participants took part in a differential aversive conditioning experiment. A highly annoying but not painful electrical stimulus served as the unconditioned stimulus (US), and two neutral pictures were used as either the paired conditioned stimulus (CS+) or the unpaired conditioned stimulus (CS-). Results indicate that PD patients do not show larger conditioned responses during acquisition than control participants. However, in contrast to control participants, PD patients exhibited larger skin conductance responses to CS+ stimuli during extinction and maintained a more negative evaluation of them, as indicated by valence ratings obtained several times throughout the experiment. This suggests that PD patients show enhanced conditionability with respect to extinction.     

Attentional control moderates fearful responding to a 35% CO(2) challenge

Attentional control (AC) is an individual difference variable indexing the ability to voluntarily focus attention and shift attention when desired. AC is thought to impact the experience of fear by facilitating the disengagement of attention from threat and promoting the deployment of attentional resources toward regulatory or coping strategies. Whereas previous research has focused on visual threat cues, in the current study we examined whether this model also applies to interoceptive threat by evaluating the extent to which individual differences in AC moderated the relationship between trait anxiety and self-reported fear in response to a single vital capacity inhalation of a 35% CO(2), 65% balanced O(2) gas mixture. The sample comprised a large nonclinical group of young adults (N=128). Results indicated that AC moderated the relationship between trait anxiety and fearful responding to the challenge. Findings suggest that AC plays a significant and clinically important role in modulating self-reported fear.     

Cognitive flexibility mediates the relation between intolerance of uncertainty and safety signal responding in those with panic disorder

There is a growing literature associating anxiety disorders with an inability to inhibit defensive responding during safety conditions of threatening tasks. However, investigations on the relation between panic disorder (PD) and defensive responding to safety have yielded mixed results. A recent study from our laboratory revealed that intolerance of uncertainty (IU) moderates this association, such that only individuals with PD and a high IU exhibit heightened startle potentiation during safety. The mechanism underlying this relationship is unknown. Given that safety conditions typically alternate with periods of threat, cognitive flexibility (i.e., the ability to adjust one's habitual responding to a situation, given the input of new information) may be involved in the ongoing reappraisal of danger and adjustment of defensive responding. Thus, the present study sought to investigate whether deficits in cognitive flexibility mediate the association between IU and defensive responding to safety among a sample of 71 adults diagnosed with PD. As hypothesised, cognitive flexibility mediated the relationship between IU and heightened startle potentiation during safety conditions. This finding suggests that within this subgroup, a failure to inhibit defensive responding during safety conditions may be due to deficits in cognitive flexibility.     

Effects of anxiety sensitivity on anxiety and pain during a cold pressor challenge in patients with panic disorder

Fear of anxiety symptoms, or anxiety sensitivity (AS), has been extensively studied in anxiety disorders and more recently has been linked to other psychopathological conditions including pain. Asmundson and colleagues have suggested that AS may act as a risk factor for chronic pain and several studies have demonstrated an association between AS, avoidance behaviors and pain. The present study assessed whether AS levels would be predictive of pain and anxiety during a brief pain induction task. Clinical participants meeting DSM-IV criteria for panic disorder (n = 22) were age and sex matched with nonclinical controls (n = 22) and exposed to a 2-min cold pressor challenge. Diagnostic status and AS were significantly predictive of pain and anxiety during the cold pressor task. Moreover, AS appears to mediate the relationship between diagnostic status and pain. However, AS appears to be only indirectly associated with pain through its contribution to anxiety.     

Avoidant coping in panic disorder: a yohimbine biological challenge study

Abstract

Few studies have addressed whether the use of avoidance-oriented coping strategies is related to the development of panic in patients with panic disorder(PD). Self-report, clinician-rated, and physiological data were collected from 42 individuals who participated in a yohimbine biological challenge study, performed under double-blind, placebo-controlled conditions. Participants included 20 healthy controls and 22 currently symptomatic patients who met DSM-IV-TR diagnostic criteria for PD. Consistent with prediction, patients with PD who had higher perceived efficacy of avoidance-oriented strategies in reducing anxiety-related thoughts reported increased severity in panic symptoms during the yohimbine challenge condition as compared to the placebo. Further, patients with PD who had more fear of cognitive dyscontrol, cardiovascular symptoms, and publicly observable anxiety also reported increased severity in panic symptoms during the challenge. Healthy controls who had more fear of cardiovascular symptoms similarly reported increased severity in panic symptoms during the challenge. No effects were found for heart rate response to the challenge agent. These results provide support for the role of avoidance-oriented coping strategies and fear of anxiety-related symptoms as risk and maintenance factors in the development of panic symptoms, particularly within a biological challenge model.     

Avoidant coping in panic disorder: a yohimbine biological challenge study

Few studies have addressed whether the use of avoidance-oriented coping strategies is related to the development of panic in patients with panic disorder(PD). Self-report, clinician-rated, and physiological data were collected from 42 individuals who participated in a yohimbine biological challenge study, performed under double-blind, placebo-controlled conditions. Participants included 20 healthy controls and 22 currently symptomatic patients who met DSM-IV-TR diagnostic criteria for PD. Consistent with prediction, patients with PD who had higher perceived efficacy of avoidance-oriented strategies in reducing anxiety-related thoughts reported increased severity in panic symptoms during the yohimbine challenge condition as compared to the placebo. Further, patients with PD who had more fear of cognitive dyscontrol, cardiovascular symptoms, and publicly observable anxiety also reported increased severity in panic symptoms during the challenge. Healthy controls who had more fear of cardiovascular symptoms similarly reported increased severity in panic symptoms during the challenge. No effects were found for heart rate response to the challenge agent. These results provide support for the role of avoidance-oriented coping strategies and fear of anxiety-related symptoms as risk and maintenance factors in the development of panic symptoms, particularly within a biological challenge model.     

Psychological and physiological predictors of response to carbon dioxide challenge in individuals with panic disorder

Past studies in nonclinical samples have found that suffocation fear, but not a behavioral index of carbon dioxide (CO2) sensitivity (i.e., breath-holding duration), predicts anxious response to CO2 challenge. These associations were examined in individuals with panic disorder while adding more sensitive indices of CO2 sensitivity. Consistent with the earlier studies, the authors found that suffocation fear predicted anxious responding to CO2 challenge but breath-holding duration did not. However, highly precise measures of CO2 sensitivity, not included in earlier studies, did predict anxious challenge responding. These findings support the predictive value and possible etiological relevance of both specific psychological variables and physiological CO2 sensitivity in panic vulnerability. Further work is still needed to determine whether the findings are specific to panic disorder.     

Differential effects of safety behaviour subtypes in social anxiety disorder

Clinical observations indicate that individuals with Social Anxiety Disorder (SAD) use a variety of safety behaviours; however, virtually no research has examined the functional effect of different safety-seeking strategies. Accordingly, we conducted two studies to address this issue. Study 1 measured global patterns of safety behaviour use in a large analogue sample. Factor analysis revealed two primary safety behaviour categories, avoidance and impression management. Study 2 assessed situational use of safety behaviours during a controlled social interaction in a clinical sample of 93 patients with Generalised SAD. Factor analysis again revealed support for avoidance and impression-management subtypes. Notably, the two types of safety behaviours were associated with different social outcomes. Avoidance safety behaviours were associated with higher state anxiety during the interaction and negative reactions from participants’ interaction partners. Impression-management strategies appeared to impede corrections in negative predictions about subsequent interactions. These findings suggest that it may be beneficial to consider the unique effects of different safety-seeking strategies when assessing and treating SAD.     

Exaggerated anxiety is not unique to CO2 in panic disorder: a comparison of hypercapnic and hypoxic challenges.

Current biological models of panic disorder (PD) assert that this disorder is maintained by hypersensitivity to carbon dioxide (CO2) and related asphyxia cues, which is manifested as an exaggerated suffocation alarm (D. Klein, 1993). Because suffocation can result from both increased CO2 (hypercapnia) and decreased oxygen (O2; hypoxia), this study examined respiratory responding and anxiety during 5% CO2 (a hypercapnic challenge) and 12% O2 (a hypoxic challenge) in 14 PD patients and 14 matched controls (MC). Results demonstrate that irrespective of the source of suffocation, PD patients respond with increased anxiety relative to MC participants. Significant group differences were observed in respiratory functioning, with the PD patients showing higher respiratory rates in response to both challenges. The MC sample demonstrated the expected respiratory responses to both hypercapnia and hypoxia. The findings indicate that PD patients are hypersensitive to alterations in breathing and that this reactivity is not specific to CO2.     

Anxiety sensitivity in first-degree relatives of patients with panic disorder

Anxiety sensitivity (AS) has been proposed as a risk factor for the development of panic disorder. Strong familial-genetic influences in panic disorder (PD) have been reported. AS may be familial too. The current study therefore examined whether first-degree relatives of PD patients are more anxiety-sensitive than normals. Twenty-three first-degree relatives of PD patients, 38 PD patients and 30 normals were given the Anxiety Sensitive Index and the Body Sensations Questionnaire. It was found that the first-degree relatives were, indeed, more anxiety-sensitive than the normals, but less so than the PD patients, suggesting that AS runs in families.