Agoraphobic Cognitions Research Articles

Brief scales for the measurement of target variables and processes of change in cognitive behaviour therapy for major depression, panic disorder and social anxiety disorder.

The measurement of process variables derived from cognitive behavioural theory can aid treatment development and support the clinician in following treatment progress. Self-report process measures are ideally brief, which reduces the burden on patients and facilitates the implementation of repeated measurements. To develop 13 brief versions (3-6 items) of existing cognitive behavioural process scales for three common mental disorders: major depression, panic disorder, and social anxiety disorder. Using data from a real-world teaching clinic offering internet-delivered cognitive behavior therapy (n=370), we drafted brief process scales and then validated these scales in later cohorts (n=293). In the validation data, change in the brief process scales significantly mediated change in the corresponding domain outcomes, with standardized coefficient point estimates in the range of -0.53 to -0.21. Correlations with the original process scales were substantial (r=.83-.96), internal consistency was mostly adequate (α=0.65-0.86), and change scores were moderate to large (|d|=0.51-1.18). For depression, the brief Behavioral Activation for Depression Scale-Activation subscale was especially promising. For panic disorder, the brief Agoraphobic Cognitions Questionnaire-Physical Consequences subscale was especially promising. For social anxiety disorder, the Social Cognitions Questionnaire, the Social Probability and Cost Questionnaire, and the Social Behavior Questionnaire-Avoidance and Impression Management subscales were all promising. Several brief process scales showed promise as measures of treatment processes in cognitive behaviour therapy. There is a need for replication and further evaluation using experimental designs, in other clinical settings, and preferably in larger samples.

Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapeutic outcome in panic disorder-an exploratory study.

Patients with Panic Disorder (PD) show an abnormal stress-induced functioning of the Hypothalamic-Pituitary-adrenal (HPA)-axis. Different protocols for stress induction are of rather low relevance for the psychotherapeutic treatment. In practice, interoceptive exposure is often realized as Low Intensity Exercise (LIE), as compared to an incremental cycle exercise test to exhaustion. Currently, it is not known, whether LIE displays an effective interoceptive stressor 1.) leading to a significant anxiety induction; 2.) a comparable HPA- and Sympathetic-Adreno-Medullar (SAM)-axis response in both patients and healthy controls; 3.) stress responses under LIE are associated with treatment outcomes. N = 20 patients with PD and n = 20 healthy controls were exposed to ten minutes of LIE on an exercise bike. LIE was applied as part of the interoceptive exposure, during an intensive Cognitive-Behavioral Therapy (CBT) in a day clinic. Heart rate was monitored and salivary cortisol samples collected. Before and after the LIE, state anxiety/ arousal were assessed. In order to evaluate psychopathology, the Panic and Agoraphobia Scale, Mobility Inventory, Agoraphobic Cognitions Questionnaire and Body Sensations Questionnaire were applied, before (T1) and after five weeks (T2) of an intensive CBT. LIE led to a significant and similar heart rate increase in both groups. Cortisol decreased over time in both groups, especially in male patients. A higher psychopathology before, and after CBT, was associated with a significantly lower cortisol response under LIE. In the present study, LIE led to a divergent stress response: while there was a significant heart rate increase, cortisol decreased over time, particularly in male patients. A lower reactivity of the HPA-axis seems to be associated with a lower treatment outcome, which may affect extinction based learning. The findings suggest, that interoceptive stimuli should be designed carefully in order to be potent stressors.

Self-Reported Measures Have a Stronger Association With Dizziness-Related Handicap Compared With Physical Tests in Persons With Persistent Dizziness.

BackgroundAssociations between dizziness-related handicap and a variety of self-reported measures have been reported. However, research regarding associations between dizziness-related handicap and aspects of functioning that includes both physical tests and self-reported measures is scarce.ObjectiveThe purpose of the study was to describe the variations in signs and symptoms in people with persistent dizziness using physical tests and self-reported outcomes across three severity levels of the Dizziness Handicap Inventory (DHI) and investigate their associations with the DHI.MethodParticipants with persistent dizziness (n = 107) were included in this cross-sectional study. The participants underwent (1) physical tests (gait tests, grip strength, body flexibility, and movement-induced dizziness) and completed questionnaires regarding (2) psychological measures (Mobility Inventory of Agoraphobia, Body Sensation Questionnaire, Agoraphobic Cognitions Questionnaire, and Hospital Depression and Anxiety Questionnaire), and (3) fatigue, dizziness severity, and quality of life (Chalders Fatigue Scale, Vertigo Symptom Scale-Short Form, and EQ visual analog scale), in addition to the DHI. Data were presented by descriptive statistics for three DHI severity levels (mild, moderate, and severe). A multiple linear backward regression analysis was conducted for each group of measures in relation to the DHI total score, with additional analyses adjusting for age and sex. Based on these results, significant associations were tested in a final regression model.ResultsWith increasing severity levels of DHI, the participants demonstrated worse performance on most of the physical tests (preferred and fast gait velocity, dizziness intensity after head movements), presented with worse scores on the self-reported measures (avoidance behavior, fear of bodily sensation, fear of fear itself, psychological distress, fatigue, dizziness severity, quality of life). After adjusting for age and sex, significant associations were found between total DHI and avoidance behavior, psychological distress, dizziness severity, and quality of life, but not with any of the physical tests, explaining almost 56% of the variance of the DHI total score.ConclusionThere was a trend toward worse scores on physical tests and self-reported measurements with increasing DHI severity level. The DHI seems to be a valuable tool in relation to several self-reported outcomes; however, several signs and symptoms may not be detected by the DHI, and thus, a combination of outcomes should be utilized when examining patients with persistent dizziness.

Correlations of plasma oxytocin with clinical and hormonal parameters in panic disorder

Aims The potential association between oxytocin (OXT) plasma levels and clinical and hormonal parameters in panic disorder (PD) especially in its acute phase – has not been investigated as yet. This was the aim of this article. Method Twenty-four consecutively-referred, acutely-ill, medication-free PD patients with (PDA, N = 21) or without agoraphobia, moreover without comorbidities, completed the following clinical measures: Hamilton Anxiety Rating Scale (HARS); Agoraphobic Cognitions Questionnaire (ACQ); Mobility Inventory-Alone subscale (MI-alone); and number of panic attacks during last 21 d (PA21d). Plasma levels of OXT, adrenocorticotropic hormone (ACTH) and cortisol were evaluated. Results OXT levels were significantly, negatively associated with the HARS scores (r= −0.59 p=.002) and weakly, negatively correlated with the ACQ scores (r = −0.403 p=.051). No significant correlations were traced between OXT levels and PA21d, MI-alone, ACTH, and cortisol. Conclusion In acutely-ill, medication-free PD patients, OXT plasma levels may be relevant to the severity of their ‘general’ anxiety symptoms, but not to the ‘specific’ panic psychopathology.

Emotional and personal characteristics of patients with benign paroxysmal positional vertigo and their influence on development of functional dizziness

Aim. To study the emotional and personal characteristics of patients with benign paroxysmal positional vertigo (BPPV) and their impact on the development of functional dizziness (FD).Materials and methods. 93 patients with BPPV were examined. Patients were twice examined (immediately after BPPV treatment and 1 month follow up) with scales: dizziness (DHI), depression (PHQ-9), anxiety (GAD-7), somatic symptoms scale (PHQ-15), Holmes – Rahe Stress Inventory, Leonhard – Schmishek personality accentuation test, Anxiety Sensitivity Index, and Agoraphobic Cognitions Scale.Results. Seventeen (18%) patients had FD1 month after BPPV treatment (FD+ group), 76 patients had no dizziness (FD– group). Immediately after BPPV treatment patients FD+ group had more hight results of DHI (57 [49; 68] vs 49 [33; 61], p = 0.035), GAD-7 (13 [7; 15] vs 4 [2; 7]), p < 0.001) and PHQ-9 (9 [6; 13] vs 5 [3; 11], p = 0.025). One month after BPPV treatment, the level of depression in the FD+ group was higher (4.5 [4; 11] vs 3 [1; 6], p = 0.049), but the level of anxiety decreased and became comparable with the FD– group (p = 0.2). In the FD+ group had found higher rates of anxious personal accentuation (15 [12; 18] vs 12 [9; 15]; p = 0.020), anxious sensitivity (55.5 [43; 68.5] vs 36.5 [22.5; 53.5]; p = 0.010), as well as agoraphobia (11 [9; 18] vs 6 [2; 9], p = 0.003). The level of psychosocial stress did not differ between the groups.Conclusion. Anxiety-depressive reaction is common in patients with BPPV. Anxiety and depression decrease after successful treatment with repositioning maneuvers. High levels of anxiety and depression, personal anxiety and anxiety sensitivity may be predictors of the development of functional dizziness.

What Predicts Improvement of Dizziness after Multimodal and Interdisciplinary Day Care Treatment?

Background: Vertigo and dizziness are common in community-dwelling people and can be treated in specialized multidisciplinary settings. To develop tailored interventions, however, we have to explore risk factors for favorable and unfavorable outcomes. Methods: We prospectively investigated patients with chronic vertigo and dizziness subjected to our 5-day multimodal and interdisciplinary day care treatment in the Center for Vertigo and Dizziness of Jena University Hospital, Germany. The Vertigo Severity Scale (VSS), the Body Sensations Questionnaire (BSQ), the Hospital Anxiety and Depression Scale (HADS), the Agoraphobic Cognitions Questionnaire (ACQ), the Mobility Inventory (MI), and the burden and intensity of dizziness (using a visual analogue scale) were assessed at baseline (n = 754) and after 6 months (n = 444). In addition, 14 Likert-scaled questions were used to quantify the change in personal attitude and behavior towards the complaints after 6 months. Results: Dizziness-related burden and intensity improved with a large effect size. The largest improvement was seen in the attitudes towards dizziness, the understanding of somatic causes, and the perceived ability to influence dizziness. However, the ability to work and to carry out professional activity was improved to a lesser extent. The overall improvement of dizziness was associated with the absence of a depressive mood, a short duration of vertigo, a lower VSS, a lower perceived intensity of vertigo, and distinct vertigo diagnoses, namely Meniere’s disease, vestibular migraine, vestibular neuritis, vestibular paroxysmia, and vestibular schwannoma. Worsening of dizziness/vertigo was associated with depressive symptoms, permanent vertigo, distinct vertigo diagnoses (central vertigo, multisensory deficit), and a higher perceived burden due to vertigo. Conclusion: The six-month outcome of patients with dizziness presented to a specialized outpatient clinic appears to be favorable. Nevertheless, people with the abovementioned risk factors at baseline have less benefit and probably need adapted and tailored vertigo interventions to improve long-term outcome.

How Healthcare Utilization Due to Dizziness and Vertigo Differs Between Older and Younger Adults

BackgroundVertigo and dizziness are common in older adults. We describe self-reported healthcare utilization because of dizziness and vertigo in older adults attending a tertiary care specialized vertigo center.MethodsData from 765 patients (45% were ≥60 years old) with chronic dizziness and vertigo who attended a daycare multimodal treatment program were recorded. Data included sociodemographic parameters, dizziness-related characteristics, the Body Sensations Questionnaire (BSQ), the Agoraphobic Cognitions Questionnaire (ACQ), and the Hospital Anxiety and Depression Scale (HADS). Also, healthcare utilization, including (1) physician and clinical services, (2) hospitalizations in the year before consulting the vertigo center, (3) prescription of drugs and other professional services were included. Descriptive statistics, exploratory data analysis, and regression models were used.ResultsIntensity of dizziness was similar in both age groups, however, distress due to dizziness was more severe in younger persons. Dizziness symptoms lasted longer in older adults than in younger persons. Older adults had a somatic diagnosis (74.6 vs. 35.0%) more frequently and reported more falls (37.2 vs. 28.5%) than younger individuals. Anxiety about bodily sensations was higher in younger patients (mean BSQ1 = 9.33 ± 5.6) than in older patients (mean BSQ1 = 6.72 ± 5.4). Older persons had fewer depressive symptoms (mean HADS depression = 5.8 ± 3.6 vs. 6.5 ± 4.1) and less anxiety (mean HADS anxiety = 5.7 ± 3.7 vs. 7.8 ± 4.1) than younger individuals. Younger people were more frequently hospitalized (24.4%) than older adults (16.3%) in the year before consulting the vertigo center. Also, younger patients and patients with non-somatic etiologies had considerably more consultations with healthcare providers than older patients. Older adults received less medication (50.3%), less physiotherapy (41%), and less psychological therapy (11.6%) for vertigo than younger people (59.7, 52.2, 20.4%, respectively).ConclusionAge-associated differences in healthcare utilization were defined in selected patients attending a specialized vertigo center. Since dizziness is frequently a heterogeneous disorder requiring interdisciplinary care, its diagnostic and therapeutic work-up must be improved for older patients with dizziness.

A survey of depression and anxiety disorders in urban and rural Suriname

BackgroundSuriname is a Low-middle income country consisting of diverse population groups. Epidemiological studies concerning mental disorders like depression and anxiety had not been conducted until 2015. The treatment gap for mental disorders in Low and middle-income countries (LMICs) may reach 76-80% as treatment is not always readily available. In this study, we estimate and compare the prevalence of potential cases of depression and anxiety, as well as the size of the treatment gap in a rural (Nickerie) and urban (Paramaribo) region of Suriname, a lower middle-income country.MethodsSubjects were selected by a specific sampling method of the national census bureau. The Center for Epidemiological Studies-Depression (CES-D) was used to assess depression. Generalized anxiety disorder was assessed with the Generalized Anxiety Disorder 7 (GAD-7) and The Agoraphobic Cognitions Questionnaire (ACQ), the Body Sensations Questionnaire (BSQ) were used to assess Panic disorder. The treatment gap was calculated by estimating the percentage of subjects with depression or anxiety that did not seek out professional help.ResultsAbout 18% of the respondents from Nickerie and 16% from Paramaribo were at risk of depression and the established cut-off values of the instruments used indicate that about 3-4% in both regions may suffer from Generalized Anxiety Disorder. Women in both samples were most at risk of high anxiety about body sensations and maladaptive thoughts about panic. The treatment gap varies between 78 and 100% for the two disorders.ConclusionsA high depression rate has been found in both areas, especially among young females. In addition, a high treatment gap is noted which insinuates that more therapeutic strategies are required to tackle depression and anxiety in Suriname.

Stress Hormones as Predictors of Response to Cognitive Behavior Therapy in Panic Disorder

Objective: Data regarding the potential association between the outcome of psychotherapy of panic disorder (PD) and biological parameters are few. In 21 (16 females) consecutively referred, medication-free, acutely ill PD outpatients, without comorbidities, except agoraphobia, we systematically explored for potential neuroendocrine and clinical correlates of response to a brief cognitive behavior therapy (CBT). Methods: Cortisol and adrenocorticotropic hormone (ACTH) basal plasma levels were measured. Measures of psychopathology: (a) Symptom Checklist–90-Revised (SCL-90-R), (b) Clinical Global Impressions-Improvement (CGI-I) Scale, (c) Agoraphobic Cognitions Questionnaire (ACQ), and (d) Mobility Inventory (MI)-alone subscale. Results: Nonresponders to CBT (CGI-I >2; N = 6) – as compared to the responders (CGI-I ≤2; N = 15) – demonstrated significantly higher cortisol and ACTH basal plasma concentrations. These differences were much stronger when only female patients (nonresponders = 4; responders = 12) were taken into consideration. Regarding psychopathology, nonresponders to CBT suffered from more severe agoraphobia (MI-alone) at baseline. On the contrary, more intense manifestations of anger (SCL-90-R) at baseline were associated with a better treatment outcome. Response to CBT was associated with significant reductions in all SCL-90-R subscales, more pronounced for “phobic anxiety” and “anxiety” subscales. Conclusions: This study suggests that in acutely ill, medication-free PD patients, response to CBT may be associated with certain hormonal and clinical parameters at baseline.

Social anxiety and agoraphobia symptoms effectively treated by Prompt Mental Health Care versus TAU at 6- and 12-month follow-up: Secondary analysis from a randomized controlled trial.

BackgroundPrompt Mental Health Care (PMHC, Norwegian adaption of Improving Access to Psychological Therapies) has shown effects on symptoms of anxiety and depression compared to treatment as usual (TAU). In this secondary analysis, we examine the effectiveness of PMHC among clients presenting with symptoms of social anxiety disorder (SAD) and/or agoraphobia on core symptoms at 6‐ and 12‐month follow‐up.MethodsRandomized controlled trial in two PMHC sites (70:30 ratio PMHC:TAU). Of participants, 61.3% (n = 472) scored at caseness for SAD and 47.7% (n = 367) for agoraphobia (40% both). Effects on SAD avoidance and physiological discomfort (SPIN‐9), SAD cognitions (ATQ‐SA), agoraphobic avoidance (MIA‐8), and agoraphobic cognitions (ATQ‐AP) were examined in piecewise growth models.ResultsThe PMHC group showed substantially greater symptom reduction than the TAU group for all outcomes: At 6‐month follow‐up, the between‐group effect sizes were d −0.60 (95% CI: −0.94 to −0.26) for SPIN‐9, −0.45 (95% CI: −0.70 to −0.20) for ATQ‐SA, −0.50 (95% CI: −0.87 to −0.13) for MIA‐8, and −0.61 (95% CI: −0.92 to −0.31) for ATQ‐AP. All effects were sustained at similar level at a 12‐month follow‐up.ConclusionPMHC effectively alleviated SAD and agoraphobia symptoms, and individuals struggling with such symptoms constituted a large proportion of clients. Although results should be interpreted with caution due to risk of attrition bias, they lend further support for a scale‐up of PMHC and similar initiatives. Individuals struggling with SAD and/or agoraphobia stood out as relatively high burdened, whereas only one of five had sought help the last 12 months, underscoring the need for the PMHC service.

Pituitary-adrenal axis hormones in early-onset versus late-onset panic disorder

Objective It has been hypothesised that early-onset panic disorder (PD) may constitute a biologically distinct subtype of PD, but the few relevant data are inconclusive. We systematically explored for potential psychopathological and hormonal differences between early-onset (age at onset ≤ 27 years) versus late-onset PD, in consecutively-referred, medication-free, acutely-ill PD outpatients, moreover without comorbid mental disorders except agoraphobia (N = 54; age = 32.3 ± 7.5 years; early-onset = 27; females = 38). Methods Hormones assessed (plasma levels) included adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS). Psychopathological measures included panic attacks’ number during last three weeks, the Agoraphobic Cognitions and the Body Sensations Questionnaires and the Hamilton Anxiety Rating Scale. Results Early-onset PD patients – compared to their late-onset counterparts – had longer duration of the disease. The two onset-groups demonstrated similar panic and anxiety symptoms and similar ratios of smokers/never-smokers. However, early-onset patients demonstrated significantly greater ACTH and DHEAS levels and higher (marginally significant) cortisol levels than the late-onset patients. Moreover, in the early-onset patients only, significant positive correlations emerged between ACTH levels and the severity of both panic and anxiety symptomatology. Conclusions These findings suggest that the two onset-groups demonstrate significant differences in the hypothalamic-pituitary-adrenal axis functioning, at least when acutely-ill. Key points Early-onset panic disorder (EOPD) may differ biologically from late-onset PD (LOPD). EOPD was correlated with greater adrenocorticotropic hormone (ACTH) plasma levels. EOPD was correlated with greater dehydroepiandrosterone sulphate plasma levels. In EOPD only, ACTH levels were positively correlated with panic and anxiety symptoms.

An investigation of genetic variability of DNA methyltransferases DNMT3A and 3B does not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes.

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

The Impact of Personality Pathology on Treatment Outcome in Late-life Panic Disorder.

Comorbid personality disorders are assumed to negatively interfere with the treatment outcome of affective disorders. Data on late-life panic disorder remain unknown. We examined the association of personality pathology and treatment outcome related to age and treatment modality. An observational study on the effectiveness of cognitive-behavioral therapy (CBT) for panic disorder with agoraphobia among patients 18 to 74 years of age and randomized controlled comparison of paroxetine and CBT in older patients (60 y of age or older) were performed. The diagnosis of panic disorder was confirmed by the Anxiety Disorder Interview Schedule-Revised (ADIS-IV) and personality features were assessed with the Personality Diagnostic Questionnaire. The impact of personality features on either agoraphobic cognitions (Agoraphobic Cognitions Questionnaire) or avoidance behavior (Mobility Inventory Avoidance Scale) was examined by multiple linear regression analyses adjusted for sex, level of education, duration of illness, comorbid psychopathology, and baseline severity. The interaction between personality and age was examined among those treated with CBT (n=90); the interaction between personality and treatment modality was examined among the older subgroup (n=34). Cluster B personality pathology (evaluated on the basis of either Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria depending on the date of assessment) was negatively associated with outcomes of CBT in both younger and older adults with panic disorder and agoraphobia. Older adults with a higher number of features of any personality pathology or cluster A pathology had worse treatment outcomes when treated with paroxetine compared with CBT. Cluster B pathology had a detrimental effect on CBT treatment outcome for panic disorder in both age groups. In late-life panic disorder with comorbid personality pathology, CBT may be preferred over treatment with paroxetine.

Agorafobinin eslik ettigi ve etmedigi panik bozukluk ile agorafobinin bilissel ozellikler acisindan karsilastirilmasi

Panic disorder (PD) and Agoraphobia (AG) exhibit both similar and distinct cognitive features. The aim of this study was to compare patients with PD, AG and panic disorder with agoraphobia (PBA) in terms of agoraphobic cognitions, body sensations, catastrophic cognitions, and meta-cognitions. 64 PDA, 52 AG, and 36 PD patients were included in the study. The Structural Clinical Interview for Axis-I (SCID-I), Agoraphobic Cognitions Questionnaire (ACQ), Body Sensations Questionnaire (BSQ), Catastrophic Cognitions Questionnaire (CCQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Meta-Cognitions Questionnaire (MCQ) were administered to the participants. Chi-square test and Kruskal Wallis analysis were used to compare sociodemographic data and scale scores between the three groups. The results showed that ACQ total scores of the PDA group were significantly higher compared to the other groups. There were no statistically significant differences between PD, AG and PDA groups in terms of BSQ, CCQ, and MCQ total scores. BDI total scores of PD group were significantly lower than AG and PDA groups. BAI total scores of PDA group were significantly higher compared to the other groups. Studies on cognitive features among patients with PD, AG or PDA will contribute to cognitive behavioral models and treatment process of these disorders.

Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes

Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.

Five-sessions of cognitive behavioral group therapy in patients with panic disorder: a preliminary study

Background: The present study was designed to examine the relationship between panic severity and symptomatic outcome following brief cognitive-behavioral group therapy (CBGT). Method: The sample consisted of 15 outpatients suffering from Panic Disorder who underwent CBGT. Panic severity was assessed by the Panic Disorder Severity Scale (PDSS), and Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Body Sensations Questionnaire (BSQ), Agoraphobic Cognitions Questionnaire (ACQ) and Health Anxiety Inventory (HAI) were administered to the patients by the study team at baseline, after the second and 5th session,post-treatment and first month. Results: At the end of 5 sessions, a significant decrease was observed in the severity of panic disorder, depression and anxiety values, body sensations and health anxiety levels and this decrease was maintained at 1 month. Conclusions: According to our results, our 5-session protocol seems to be a fast and effective option in the treatment of panic disorder.

Associations of plasma testosterone with clinical manifestations in acute panic disorder

The probable implication of testosterone in the neurobiology of anxiety disorders, and particularly panic disorder (PD), is poorly studied. We explored for potential differences concerning testosterone (T) plasma levels and the ratio testosterone/cortisol (T/C) between medication-free, consecutively-referred patients with acute exacerbation of PD comorbid with agoraphobia (PDA) (N = 40; females = 24; age = 31.4 ± 7.1 years) and healthy controls (N = 80; females = 48; matched for age). Moreover, we investigated for potential associations of T levels and T/C ratio with the severity of acute PDA psychopathology in the patients of the sample. Psychometric measures included panic attacks’ number during last three weeks (PA-21days), the Agoraphobic Cognitions Questionnaire (ACQ) and the Hamilton Anxiety Rating Scale (HARS). Male patients –but not female ones- demonstrated significantly lower T levels compared to controls. Moreover, in male patients, a significant inverse association emerged between T/C ratio and PA-21days, so that lower T/C ratio is associated with significantly more panic attacks. On the contrary, female patients demonstrated significant positive associations: (a) between T levels and PDA-related pathological cognitions (ACQ); (b) between the T/C ratio and both PA-21days and anxiety symptoms’ severity (HARS). The results of the study suggest that testosterone is significantly associated to the severity of clinical manifestations of acute panic disorder, although in a different fashion concerning the two genders.

Running for extinction? Aerobic exercise as an augmentation of exposure therapy in panic disorder with agoraphobia

Exposure-based Cognitive Behavioral Therapy (eb-CBT) represents the most evidence-based psychotherapeutic approach in anxiety disorders. However, its efficacy may be limited by a delay in onset of action and a substantial number of patients does not respond sufficiently to treatment. In this context, aerobic exercise was found to be effective in reducing clinical anxiety as well as to improve (elements of) disorder-specific CBT in some mental disorders. We therefore investigated the effect of aerobic exercise supplementary to an eb-CBT in panic disorder and agoraphobia (PD/AG). 77 patients with PD/AG performed a 30 min treadmill task with moderate or low intensity (70% or 30% of the maximal oxygen uptake [VO2max]) prior to five exposure sessions within a standardized seven-week CBT. At baseline, after completing the treatment period (post) and six month after post (follow-up), several measures of (un)specific psychopathology (Hamilton Anxiety Rating Scale [Ham-A], Mobility Inventory [MI], Panic and Agoraphobia Scale [PAS], Agoraphobic Cognitions Questionnaire [ACQ], Body Sensations Questionnaire [BSQ]) were established to assess for clinical changes. All patients experienced a significant improvement of symptoms from baseline to post (for all measures p < .001) but repeated-measures analyses of variance found a trend towards a significant time × group interaction in the Ham-A in favor for the moderate intense exercise group (f[1, 74] = 4.15, p = .045, α=.025). This trend, however, disappeared at follow-up since the low-intense exercise group further improved significantly in Ham-A after post. Our findings therefore might point to an accelerating effect of moderate-intense exercise within an exposure-based CBT for AG/PD.

Stress hormone response to the DEX\u2013CRH test and its relation to psychotherapy outcome in panic disorder patients with and without agoraphobia

This study tested whether the hormonal stress response to the DEX–CRH test may be predictive of the psychotherapy success for panic disorder (PD). Thirty-four patients diagnosed either with agoraphobia with PD or PD without agoraphobia were subjected to cognitive behavioural therapy (CBT). Patients (pre-therapy) and healthy volunteers were exposed to the DEX–CRH test. Blood samples were taken for cortisol and adrenocorticotropic hormone (ACTH) assessment. Established panic-specific questionnaires were handed out for the pre-therapy and post-therapy evaluation of disease severity (with reference to panic beliefs and agoraphobic cognitions, fear of bodily sensations, agoraphobic avoidance behaviour). Repeated measures ANCOVA were conducted for the analysis of the pre-therapy hormonal response, and Pearson’s correlation analysis to test for associations with the psychotherapy outcome. Data analyses revealed large effect sizes for CBT in the clinical measures (η2 ≥ 0.321), main effects of time for cortisol and ACTH with no differences between both groups, and significant associations between cortisol release and agoraphobic cognitions for the patients. PD diagnosis had no impact on the hormonal response. However, those patients with higher cortisol release showed less improvement after CBT (significantly for agoraphobic cognitions). Clinical implications of these findings are the prediction of the therapy success from a potential endocrine correlate whose persistency (if assessed repeatedly) during the treatment may predict (non-)response to the current treatment, possibly representing a decision support for a change in treatment to avoid the continuation of an inefficient treatment.

Cognitive Behavioral Therapy vs. Eye Movement Desensitization and Reprocessing for Treating Panic Disorder: A Randomized Controlled Trial.

Objective: Cognitive Behavioral Therapy (CBT) is an effective intervention for patients with panic disorder (PD). From a theoretical perspective, Eye Movement Desensitization and Reprocessing (EMDR) therapy could also be useful in the treatment of PD because: (1) panic attacks can be experienced as life threatening; (2) panic memories specific to PD resemble traumatic memories as seen in posttraumatic stress disorder (PTSD); and (3) PD often develops following a distressing life event. The primary objective of this Randomized Controlled Trial (RCT), was to compare EMDR therapy with CBT for PD and determine whether EMDR is not worse than CBT in reducing panic symptoms and improving Quality Of Life (QOL).Methods: Two-arm (CBT and EMDR) parallel RCT in patients with PD (N = 84). Patients were measured at baseline (T1), directly after the last therapy session (T2), and 3 months after ending therapy (T3). Non-inferiority testing (linear mixed model with intention-to-treat analysis) was applied. Patients were randomly assigned to 13 weekly 60-min sessions of CBT (N = 42) or EMDR therapy (N = 42). Standard protocols were used. The primary outcome measure was severity of PD at T3, as measured with the Agoraphobic Cognitions Questionnaire (ACQ), the Body Sensations Questionnaire (BSQ), and the Mobility Inventory (MI). The secondary outcome measure was QOL, as measured with the World Health Organization Quality of Life short version (WHOQOL-Bref), at T3.Results: The severity of PD variables ACQ and BSQ showed non-inferiority of EMDR to CBT, while MI was inconclusive (adjusted analyses). Overall QOL and general health, Psychological health, Social relationships, and Environment showed non-inferiority of EMDR to CBT, while Physical health was inconclusive.Conclusion: EMDR therapy proved to be as effective as CBT for treating PD patients.Trial Registration: Dutch Trial Register, Nr. 3134 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3134