The present study examined temporal dependencies of change of panic symptoms and two promising mechanisms of change (self-efficacy and anxiety sensitivity) during an 11-session course of ...cognitive-behavior therapy (CBT) for Panic Disorder (PD). 361 individuals with a principal diagnosis of PD completed measures of self-efficacy, anxiety sensitivity, and PD symptoms at each session during treatment. Effect size analyses indicated that the greatest changes in anxiety sensitivity occurred early in treatment, whereas the greatest changes in self-efficacy occurred later in treatment. Results of parallel process latent growth curve models indicated that changes in self-efficacy and anxiety sensitivity across treatment uniquely predicted changes in PD symptoms. Bivariate and multivariate latent difference score models indicated, as expected, that changes in anxiety sensitivity and self-efficacy temporally preceded changes in panic symptoms, and that intraindividual changes in anxiety sensitivity and self-efficacy independently predicted subsequent intraindividual changes in panic symptoms. These results provide strong evidence that changes in self-efficacy and anxiety sensitivity during CBT influence subsequent changes in panic symptoms, and that self-efficacy and anxiety sensitivity may therefore be two distinct mechanisms of change of CBT for PD that have their greatest impact at different stages of treatment.
•Mechanisms of change of cognitive behavior therapy for panic disorder were examined.•CBT produced large changes in both self-efficacy and anxiety sensitivity.•Self-efficacy and anxiety sensitivity uniquely predicted changes in panic symptoms.•Anxiety sensitivity changed early in treatment, whereas self-efficacy changed later.•Self-efficacy and anxiety sensitivity appear to be distinct mechanisms of change of CBT.
Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further ...elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn¹⁰⁷Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case-control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.
Objective:
There are numerous theories of panic disorder, each proposing a unique pathway of change leading to treatment success. However, little is known about whether improvements in proposed ...mediators are indeed associated with treatment outcomes and whether these mediators are specific to particular treatment modalities. Our purpose in this study was to analyze pathways of change in theoretically distinct interventions using longitudinal, moderated mediation analyses.
Method:
Forty-one patients with panic disorder and agoraphobia were randomly assigned to receive 4 weeks of training aimed at altering either respiration (capnometry-assisted respiratory training) or panic-related cognitions (cognitive training). Changes in respiration (PCO
2
, respiration rate), symptom appraisal, and a modality-nonspecific mediator (perceived control) were considered as possible mediators.
Results:
The reductions in panic symptom severity and panic-related cognitions and the improvements in perceived control were significant and comparable in both treatment groups. Capnometry-assisted respiratory training, but not cognitive training, led to corrections from initially hypocapnic to normocapnic levels. Moderated mediation and temporal analyses suggested that in capnometry-assisted respiratory training, PCO
2
unidirectionally mediated and preceded changes in symptom appraisal and perceived control and was unidirectionally associated with changes in panic symptom severity. In cognitive training, reductions in symptom appraisal were bidirectionally associated with perceived control and panic symptom severity. In addition, perceived control was bidirectionally related to panic symptom severity in both treatment conditions.
Conclusion:
The findings suggest that reductions in panic symptom severity can be achieved through different pathways, consistent with the underlying models.
Panic disorder with agoraphobia (PD/AG) is a prevalent mental disorder featuring a substantial complex genetic component. At present, only a few established risk genes exist. Among these, the gene ...encoding monoamine oxidase A (MAOA) is noteworthy given that genetic variation has been demonstrated to influence gene expression and monoamine levels. Long alleles of the MAOA-uVNTR promoter polymorphism are associated with PD/AG and correspond with increased enzyme activity. Here, we have thus investigated the impact of MAOA-uVNTR on therapy response, behavioral avoidance and brain activity in fear conditioning in a large controlled and randomized multicenter study on cognitive behavioral therapy (CBT) in PD/AG. The study consisted of 369 PD/AG patients, and genetic information was available for 283 patients. Carriers of the risk allele had significantly worse outcome as measured by the Hamilton Anxiety scale (46% responders vs 67%, P=0.017). This was accompanied by elevated heart rate and increased fear during an anxiety-provoking situation, that is, the behavioral avoidance task. All but one panic attack that happened during this task occurred in risk allele carriers and, furthermore, risk allele carriers did not habituate to the situation during repetitive exposure. Finally, functional neuroimaging during a classical fear conditioning paradigm evidenced that the protective allele is associated with increased activation of the anterior cingulate cortex upon presentation of the CS+ during acquisition of fear. Further differentiation between high- and low-risk subjects after treatment was observed in the inferior parietal lobes, suggesting differential brain activation patterns upon CBT. Taken together, we established that a genetic risk factor for PD/AG is associated with worse response to CBT and identify potential underlying neural mechanisms. These findings might govern how psychotherapy can include genetic information to tailor individualized treatment approaches.
Purpose
Posttraumatic stress disorder (PTSD) often co-occurs with panic disorder (PD), with some etiological models positing a causal role of panic reactivity in PTSD onset; however, data addressing ...the temporal ordering of these conditions are lacking. The aim of this study was to examine the bi-directional associations between PD and PTSD in a nationally representative, epidemiologic sample of trauma-exposed adults.
Methods
Participants were community-dwelling adults (62.6% women;
M
age
= 48.9, SD 16.3) with lifetime DSM-IV PTSD criterion A trauma exposure drawn from the 2001/2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and re-interviewed in 2004/5 (
N
= 12,467). Cox discrete-time proportional hazards models with time-varying covariates were used to investigate the bi-directional associations between lifetime PD and PTSD, accounting for demographic characteristics, trauma load, and lifetime history of major depression, generalized anxiety disorder, and social anxiety disorder.
Results
PD was significantly associated with subsequent onset of PTSD (HR 1.210, 95%CI = 1.207–1.214,
p
< .001), and PTSD was significantly associated with onset of PD (HR 1.601, 95% CI 1.597–1.604,
p
< .001). The association between PTSD and subsequent PD was stronger in magnitude than that between PD and subsequent PTSD (
Z
= − 275.21,
p
< .01). Men evidenced stronger associations between PD and PTSD compared to women.
Conclusions
Results were consistent with a bidirectional pathway of risk, whereby PD significantly increased risk for the development of PTSD, and PTSD significantly increased risk for PD. Given the association between PTSD and subsequent PD, particularly among men, clinicians may consider supplementing PTSD treatment with panic-specific interventions, such as interoceptive exposure, to prevent or treat this disabling comorbidity.
Objective: Cognitive-behavioral therapy (CBT) is a first-line treatment for panic disorder with agoraphobia (PD/AG). Nevertheless, an understanding of its mechanisms and particularly the role of ...therapist-guided exposure is lacking. This study was aimed to evaluate whether therapist-guided exposure in situ is associated with more pervasive and long-lasting effects than therapist-prescribed exposure in situ. Method: A multicenter randomized controlled trial, in which 369 PD/AG patients were treated and followed up for 6 months. Patients were randomized to 2 manual-based variants of CBT (T+/T−) or a wait-list control group (WL; n = 68) and were treated twice weekly for 12 sessions. CBT variants were identical in content, structure, and length, except for implementation of exposure in situ: In the T+ variant (n = 163), therapists planned and supervised exposure in situ exercises outside the therapy room; in the T− group (n = 138), therapists planned and discussed patients' in situ exposure exercises but did not accompany them. Primary outcome measures were (a) Hamilton Anxiety Scale, (b) Clinical Global Impression, (c) number of panic attacks, and (d) agoraphobic avoidance (Mobility Inventory). Results: For T+ and T− compared with WL, all outcome measures improved significantly with large effect sizes from baseline to post (range = −0.5 to −2.5) and from post to follow-up (range = −0.02 to −1.0). T+ improved more than T− on the Clinical Global Impression and Mobility Inventory at post and follow-up and had greater reduction in panic attacks during the follow-up period. Reduction in agoraphobic avoidance accelerated after exposure was introduced. A dose-response relation was found for Time × Frequency of Exposure and reduction in agoraphobic avoidance. Conclusions: Therapist-guided exposure is more effective for agoraphobic avoidance, overall functioning, and panic attacks in the follow-up period than is CBT without therapist-guided exposure. Therapist-guided exposure promotes additional therapeutic improvement-possibly mediated by increased physical engagement in feared situations-beyond the effects of a CBT treatment in which exposure is simply instructed.
Objective: Cognitive models of panic disorder suggest that change in catastrophic misinterpretations of bodily sensations will predict symptom reduction. To examine change processes, we used a ...repeated measures design to evaluate whether the trajectory of change in misinterpretations over the course of 12-week cognitive behavior therapy is related to the trajectory of change in a variety of panic-relevant outcomes. Method: Participants had a primary diagnosis of panic disorder (N = 43; 70% female; mean age = 40.14 years). Race or ethnicity was reported as 91% Caucasian, 5% African American, 2.3% biracial, and 2.3% "other." Change in catastrophic misinterpretations (assessed with the Brief Body Sensations Interpretation Questionnaire; Clark et al., 1997) was used to predict a variety of treatment outcomes, including overall panic symptom severity (assessed with the Panic Disorder Severity Scale PDSS; Shear et al., 1997), panic attack frequency (assessed with the relevant PDSS item), panic-related distress/apprehension (assessed by a latent factor, including peak anxiety in response to a panic-relevant stressor-a straw breathing task), and avoidance (assessed by a latent factor, which included the Fear Questionnaire-Agoraphobic Avoidance subscale; Marks & Mathews, 1979). Results: Bivariate latent difference score modeling indicated that, as expected, change in catastrophic misinterpretations predicted subsequent reductions in overall symptom severity, panic attack frequency, distress/apprehension, and avoidance behavior. However, change in the various symptom domains was not typically a significant predictor of later interpretation change (except for the distress/apprehension factor). Conclusions: These results provide considerable support for the cognitive model of panic and speak to the temporal sequence of change processes during therapy.
The amygdala has been known to play a pivotal role in mediating fear-related responses including panic attacks. Given the functionally distinct role of the amygdalar subregions, morphometric ...measurements of the amygdala may point to the pathophysiological mechanisms underlying panic disorder. The current study aimed to determine the global and local morphometric alterations of the amygdala related to panic disorder.
Volumetric and surface-based morphometric approach to high-resolution three-dimensional T1-weighted images was used to examine the structural variations of the amygdala, with respect to extent and location, in 23 patients with panic disorder and 31 matched healthy individuals.
There were no significant differences in bilateral amygdalar volumes between patients with panic disorder and healthy individuals despite a trend-level right amygdalar volume reduction related to panic disorder (right, β = -0.23, p = 0.09, Cohen's d = 0.51; left, β = -0.18, p = 0.19, Cohen's d = 0.45). Amygdalar subregions were localized into three groups including the superficial, centromedial, and laterobasal groups based on the cytoarchitectonically defined probability map. Surface-based morphometric analysis revealed shape alterations in the laterobasal and centromedial groups of the right amygdala in patients with panic disorder (false discovery rate corrected p < 0.05).
The current findings suggest that subregion-specific shape alterations in the right amygdala may be involved in the development and maintenance of panic disorder, which may be attributed to the cause or effects of amygdalar hyperactivation.
Despite the scientific consensus on the efficacy of psychotherapy for the treatment of psychological disorders, the evidence of treatment-related changes towards normalization of abnormal brain ...functions in patients is mixed. In the present experiment, we investigated whether treatment can affect early information processing, by testing abnormal event-related potentials (ERPs) evoked by internal and external signals in panic disorder. Sixteen patients with panic disorder and comorbid personality disorder and sixteen control participants performed a response-choice task and a passive viewing task in two testing sessions, separated by around 14 months. During this period, patients received psychological treatment. In agreement with previous studies of performance monitoring, the abnormal amplitude of the Ne/ERN-an index of error processing based on internal signals-did not change between the first and second testing session. However, treatment-related changes were evident for the abnormal vertex positive potential (VPP) evoked by external signals in the response-choice task and the passive viewing task. In patients, the VPP was smaller in the second session compared to the first session, whereas no significant changes occurred in controls. This result supplies evidence of treatment-related changes towards normalization in the early information processing of external visual stimuli in panic disorder.
Emerging evidence suggests that anxiety sensitivity (AS) predicts subsequent development of anxiety symptoms and panic attacks. However, evidence regarding whether AS serves as a premorbid risk ...factor for the development of clinical syndromes is lacking. The primary aim of the present study was to determine whether AS acts as a vulnerability factor in the pathogenesis of psychiatric diagnoses. A large nonclinical sample of young adults (
N
=
404) was prospectively followed over two years. The Anxiety Sensitivity Index (ASI: Reiss S, Peterson RA, Gursky DM, McNally RJ. Anxiety sensitivity, anxiety frequency, and the prediction of fearfulness. Behaviour Research and Therapy 1986; 24: 1–8.) and trait anxiety served as predictors. Consistent with prior reports, AS predicted the development of spontaneous panic attacks in those with no history of panic. Importantly, AS was found to predict the incidence of anxiety disorder diagnoses and overall Axis I diagnoses in those with no history of Axis I diagnoses at study entry. These are the first data to provide strong prospective evidence for AS as a risk factor in the development of anxiety disorders.
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