Panic Disorder With Agoraphobia Research Articles

The moderating and mediating role of telepresence and cognitive change in cognitive behaviour therapy delivered via videoconference.

In this study, we combined the results of two controlled trials and examined the relationships between working alliance, telepresence, cognitive change and treatment outcome. Sixty-five participants with a primary diagnosis of generalized anxiety disorder (GAD) or panic disorder with agoraphobia (PDA) received cognitive behaviour therapy delivered via videoconference. Participants completed measures of working alliance and telepresence after three psychotherapy sessions. They also completed measures of treatment outcome and dysfunctional beliefs (cognitive change) specific to PDA and GAD at pretreatment and posttreatment. Results revealed that telepresence at the fifth session moderated the relationship between the working alliance at the first and fifth sessions. As telepresence increased, its impact on the working alliance diminished. Cognitive change mediated the relationship between the working alliance at the fifth session and treatment outcome.

Self-guided digital treatment with virtual reality for panic disorder and agoraphobia: a study protocol for a randomized controlled trial

BackgroundCognitive behavioral therapy is the first-line treatment for patients with panic disorder (PD) and agoraphobia (AG). Yet, many patients remain untreated due to limited treatment resources. Digital self-guided short-term treatment applications may help to overcome this issue. While some therapeutic applications are already supported by health insurance companies, data on their efficacy is limited. The current study investigates the effect of self-guided digital treatment comprising psychoeducation and virtual reality exposure therapy (VRET).MethodsThirty patients diagnosed with PD, AG, or panic disorder with agoraphobia (PDA) will be randomly assigned to either the experimental group (EG) or the control group (CG). Participants of both groups will undergo baseline diagnostics in the first two sessions. The subsequent treatment for the EG consists of a self-guided 6-week phase of application-based psychoeducation, one therapy session preparing for the VRET, and 4 weeks of application-based self-guided VRET. To control for the potential effects of the therapy session with the therapist, the CG will receive relaxation and stress-reduction training instead. All patients will then undergo a closing session which terminates with the post-assessment (~ 10 weeks after baseline assessment) and a follow-up assessment 6 weeks following the closing session. Symptom severity (primary outcome) will be assessed at baseline, interim, post-treatment, and follow-up. Additionally, remission status (secondary outcome) will be obtained at follow-up. Both measures will be compared between the groups.DiscussionThe current study aims at providing insights into the efficacy of short-term treatment applications including psychoeducation and self-guided VRET. If successful, this approach might be a feasible and promising way to ease the burden of PD, AG, and PDA on the public health system and contribute to a faster access to treatment.Trial registrationISRCTN ISRCTN10661970. Prospectively registered on 17 January 2022.

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

BackgroundAnxious 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. MethodsDefensive 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. ResultsPatients 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. ConclusionsThe 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.

Using 360-degree videos for virtual reality exposure in CBT for panic disorder with agoraphobia: a feasibility study.

Cognitive behavioural therapy (CBT) is an effective treatment for panic disorder with agoraphobia (PDA). However, implementation of some of the procedures involved, particularly in vivo exposure, can be time consuming and taxing for routine health care services. CBT with exposure taking place in virtual reality (VR-CBT) is a more time-efficient option and has shown promising results in the treatment of PDA. However, VR-CBT requires expensive equipment and appropriate virtual environments, which historically has been costly and cumbersome to produce. Thus, access to VR-CBT has been sparse in regular care environments. The aim of this study was to investigate whether VR-CBT using filmed virtual environments produced with a low-cost 360-degree film camera can be a feasible and acceptable treatment for PDA when implemented in a primary care context. This was an open feasibility trial with a within-group design, with assessments conducted at pre-test, post-test, and 6-month follow-up. Participants (n = 12) received a 10-12 week treatment programme of VR-CBT and PDA-related symptoms were assessed by the primary outcome measure The Mobility Inventory for Agoraphobia (MIA) and the Panic-Disorder Severity Scale-Self Rated (PDSS-SR). The results showed that treatment satisfaction was high and participants were significantly improved on PDA-related measures at post-treatment and at 6-month follow-up with large effect sizes (Cohen's d range = 1.46-2.82). All 12 participants completed the treatment. These findings suggest that VR-CBT with 360-degree video virtual environments delivered to primary care patients with PDA is feasible, acceptable, and potentially efficacious.

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.

Panic attack provocation in panic disorder patients with a computer simulation

BackgroundComputer simulations (CS) and virtual reality exposure are promising techniques for research and treatment of panic disorder with agoraphobia (PDA). The objective of this study was to ascertain whether a given CS was a stimulus capable of producing panic attacks (PAs), anxiety and psychophysiological changes in patients with PDA. MethodsThirty PDA patients and 30 healthy subjects were recruited for this study. Subjects were exposed to a 3-min CS of a situation relevant to agoraphobic patients. Anxiety, panic symptoms, PAs, heart rate, skin conductance and respiration were recorded before, during and after the CS exposure. ResultsThe CS effectively induced anxiety, hyperventilation and electrodermal responses in PDA patients but not in healthy subjects. Forty percent of PDA patients had a PA while none of the control subjects had a PA. A subgroup of patients who were less sensitive to the CS than the other subgroup of PDA patients and did not present full-blown PAs still had more panic symptoms, higher anxiety levels and more respiratory irregularities than the controls. LimitationsLow immersion and low sense of presence, lack of interaction with the environment. ConclusionsExposure to the CS produced effects similar to in vivo exposure, respiratory and caffeine challenges. Subsequent studies should: make direct comparisons between CS and other challenges for PDA; investigate if CS can be a tool for predicting effects of medication; determine the potential of CS as a desensitization technique for situational PAs.

Reassurance seeking in the anxiety disorders and OCD: Construct validation, clinical correlates and CBT treatment response

BackgroundReassurance seeking has been hypothesized to be a key factor in the maintenance of anxiety and obsessive-compulsive disorders according to contemporary cognitive-behavioural therapy (CBT) approaches. The present study sought to examine the structure, clinical correlates, and malleability of reassurance seeking in the context of CBT treatment. MethodsTreatment-seeking participants (N = 738) with DSM-IV-TR (American Psychiatric Association, 2000) panic disorder with agoraphobia (PD/A), social anxiety disorder (SAD), generalized anxiety disorder (GAD), and obsessive compulsive disorder (OCD) completed the Reassurance Seeking Scale (RSS) with other symptom measures prior to and following CBT treatment. ResultsA confirmatory factor analysis supported a three factor solution: the need to seek excessive reassurance regarding decisions, attachment and the security of relationships, and perceived general threat and anxiety. The RSS was moderately correlated with general measures of anxiety and depression as well as disorder-specific symptom scales. Further, CBT was found to produce changes in reassurance seeking across CBT treatments and these reductions were significantly associated with disorder-specific clinical improvement. ConclusionReassurance seeking appears to be a common factor across anxiety disorders and its reduction in CBT treatment is associated with improved clinical outcomes.

Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls.

The neurobiological mechanisms behind panic disorder with agoraphobia (PD/AG) are not completely explored. The functional A/T single nucleotide polymorphism (SNP) rs324981 in the neuropeptide S receptor gene (NPSR1) has repeatedly been associated with panic disorder and might partly drive function respectively dysfunction of the neural "fear network". We aimed to investigate whether the NPSR1 T risk allele was associated with malfunctioning in a fronto-limbic network during the anticipation and perception of agoraphobia-specific stimuli. 121 patients with PD/AG and 77 healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) using the disorder specific "Westphal-Paradigm". It consists of neutral and agoraphobia-specific pictures, half of the pictures were cued to induce anticipatory anxiety. Risk allele carriers showed significantly higher amygdala activation during the perception of agoraphobia-specific stimuli than A/A homozygotes. A linear group x genotype interaction during the perception of agoraphobia-specific stimuli showed a strong trend towards significance. Patients with the one or two T alleles displayed the highest and HC with the A/A genotype the lowest activation in the inferior orbitofrontal cortex (iOFC). The study demonstrates an association of the NPSR1rs324981 genotype and the perception of agoraphobia-specific stimuli. These results support the assumption of a fronto-limbic dysfunction as an intermediate phenotype of PD/AG.

The role of therapist and patient in-session behavior for treatment outcome in exposure-based cognitive behavioral therapy for panic disorder with agoraphobia.

There is a very limited amount of research on the relationship between therapist and patient in-session behavior and treatment outcome in cognitive behavioral therapy (CBT) for panic disorder with agoraphobia (PD/AG). Additionally, the findings tend to be inconclusive. This study investigates the association between therapist competence, adherence, patient interpersonal behavior, and therapeutic alliance and outcome in a low-control CBT setting by using comprehensive measures. Twenty-six patients with PD/AG received 12 sessions of exposure-based CBT. With regard to the outcome, treatments were classified either as problematic or nonproblematic by means of distinct criteria. Two raters evaluated the in-session behavior. Patient interpersonal behavior was significantly associated with outcome at follow-up (r = 0.49). At posttreatment, the correlation did not reach significance ( r = 0.34). Competence, adherence, and alliance were not outcome associated. The findings emphasize the need for therapists to pay particular attention to patients' interpersonal behavior during treatment.

The impact of depressive comorbidity on neural plasticity following cognitive-behavioral therapy in panic disorder with agoraphobia

Background: Depressive disorders are a frequent comorbidity of panic disorder with agoraphobia (PD/AG). Cognitive-behavioral therapy (CBT) for PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbidities. However, as depressive comorbidities can confound fear circuitry activation (i.e. amygdalae, insulae, anterior cingulate cortex) in PD/AG, we investigated whether comorbid depressive disorders alter neural plasticity following CBT. Methods: Within a randomized, controlled clinical trial on exposure-based CBT, forty-two PD/AG patients including fifteen (35.7%) with a comorbid depressive disorder (PD/AG + DEP) participated in a longitudinal functional magnetic resonance imaging (fMRI) study. A differential fear conditioning task was used as probe of interest. A generalized psycho-physiological interaction analysis (gPPI) served to study functional connectivity patterns. Results: After CBT, only PD/AG patients without comorbid depressive disorders (PD/AG-DEP) showed reduced activation in the left inferior frontal gyrus (IFG) extending to the insula. While PD/AG-DEP patients showed enhanced functional connectivity (FC) between the left IFG and subcortical structures (anterior cingulate cortex, thalamus and midbrain), PD/AG + DEP patients exhibited increased FC between the left IFG and cortical structures (prefrontal, parietal regions). In both groups, FC decreased following CBT. Limitations: Primary depressed and medicated patients were excluded. Major depression and dysthymia were collapsed. Conclusions: Reduced activation in the left IFG, as previously shown in PD/AG, appears to be a specific substrate of CBT effects in PD/AG-DEP patients only. Differential patterns of FC pertaining to fear circuitry networks in patients without depression vs. cognitive networks in patients with comorbid depression may point towards different pathways recruited by CBT as a function of comorbidity.

Emotion Regulation Strategies in Cognitive Behavioral Therapy for Panic Disorder

Emotion regulation (ER) has been incorporated into many models of psychopathology, but it has not been examined directly in cognitive behavioral therapy (CBT) for panic disorder with agoraphobia (PD/A). In this study, a preliminary model of ER in CBT for PD/A is proposed based on existing theories, and several propositions of the model are tested. We hypothesized that increases in cognitive reappraisal would precede decreases in biased cognitions, decreases in expressive suppression would follow decreases in biased cognitions, and a reduction in symptom severity would follow decreases in expressive suppression. Twenty-nine patients who received CBT for PD/A completed weekly self-report measures of symptom severity, anxiety sensitivity, reappraisal and expressive suppression. In addition, patients were compared to a matched normal sample. Cross-lagged analyses partially supported the hypotheses. Reappraisal did not change until late stages of therapy and was generally not associated with treatment outcome. Suppression decreased significantly and exhibited a reciprocal relationship with biased cognitions. Symptom reduction followed decreases in suppression as hypothesized. However, patients did not differ in ER from matched controls at either pre- or posttreatment. Results suggest the important distinction between reappraisal and appraisal, and stress the role of session-by-session decreases in suppression as a predictor of symptom reduction.

Improvement in adult anxious and avoidant attachment during cognitive behavioral therapy for panic disorder

Objective: This study examined attachment within the framework of cognitive behavioral therapy (CBT) for panic disorder with agoraphobia (PDA) by measuring the changes in avoidant and anxious attachment in a session-by-session analysis. Method: Thirty-one patients with PDA were treated using CBT. Pre-session data on attachment style (ECR), avoidance behaviors (MI-alone: MI-al; MI-accompanied: MI-ac), anxiety sensitivity (ASI), emotion regulation (ERQ), and working alliance (WAI) were collected. Mixed model analyses were conducted to estimate relationship between changes in attachment, PDA symptoms, and related measures. Results: Variables improved during therapy. Changes in ASI were positively related to changes in avoidant and anxious attachment. Changes in MI-al, but not MI-ac, were related to changes in ECR. Changes in ASI and MI-al predicted changes in ECR-anxiety in the following session, but not vice versa. Similarly, changes in avoidance behaviors and ERQ-suppression, preceded changes in ECR-avoidance unidirectionally. Whereas WAI significantly improved, its variability was related only to simultaneous changes in ECR-anxiety. Conclusions: Overall, avoidant and anxious attachment improved during CBT for PDA. This change was related to and preceded by improved anxiety sensitivity, avoidance behaviors, and emotion regulation. These findings suggest that CBT for panic probably has downstream effects on attachment representations.Clinical or methodological significance of this article: This is the first report of changes in attachment via cognitive behavioral therapy for panic disorder. Data were examined using repeated measures session by session, allowing for examination of temporal precedence of changes. Results revealed that anxiety sensitivity, avoidance, and suppression preceded changes in attachment. Results are discussed in the framework of modern attachment theory models.

Support Vector Machine Analysis of Functional Magnetic Resonance Imaging of Interoception Does Not Reliably Predict Individual Outcomes of Cognitive Behavioral Therapy in Panic Disorder with Agoraphobia.

The approach to apply multivariate pattern analyses based on neuro imaging data for outcome prediction holds out the prospect to improve therapeutic decisions in mental disorders. Patients suffering from panic disorder with agoraphobia (PD/AG) often exhibit an increased perception of bodily sensations. The purpose of this investigation was to assess whether multivariate classification applied to a functional magnetic resonance imaging (fMRI) interoception paradigm can predict individual responses to cognitive behavioral therapy (CBT) in PD/AG. This analysis is based on pretreatment fMRI data during an interoceptive challenge from a multicenter trial of the German PANIC-NET. Patients with DSM-IV PD/AG were dichotomized as responders (n = 30) or non-responders (n = 29) based on the primary outcome (Hamilton Anxiety Scale Reduction ≥50%) after 6 weeks of CBT (2 h/week). fMRI parametric maps were used as features for response classification with linear support vector machines (SVM) with or without automated feature selection. Predictive accuracies were assessed using cross validation and permutation testing. The influence of methodological parameters and the predictive ability for specific interoception-related symptom reduction were further evaluated. SVM did not reach sufficient overall predictive accuracies (38.0-54.2%) for anxiety reduction in the primary outcome. In the exploratory analyses, better accuracies (66.7%) were achieved for predicting interoception-specific symptom relief as an alternative outcome domain. Subtle information regarding this alternative response criterion but not the primary outcome was revealed by post hoc univariate comparisons. In contrast to reports on other neurofunctional probes, SVM based on an interoception paradigm was not able to reliably predict individual response to CBT. Results speak against the clinical applicability of this technique.

Long-term disability in anxiety disorders.

BackgroundThis longitudinal study aims to investigate differences in long-term disability between social anxiety disorder (SAD), panic disorder with agoraphobia (PDA), panic disorder without agoraphobia (PD), generalized anxiety disorder (GAD) and multiple anxiety disorders (multiple AD), focusing on the effects of different course trajectories (remission, recurrence and chronic course) and specific symptom dimensions (anxiety arousal and avoidance behaviour).MethodsData were used from participants with no psychiatric diagnosis (healthy controls, n = 647) or with a current anxiety disorder (SAD, n = 191; PDA, n = 90; PD, n = 84; GAD, n = 110; multiple AD, n = 480). Severity of anxiety arousal and avoidance behaviour symptoms was measured using the Beck Anxiety Inventory and the Fear Questionnaire. The World Health Organization Disability Assessment Schedule II was used to measure disability.ResultsLong-term disability was most prevalent in participants with SAD and multiple AD, and lowest in PDA and PD. GAD had an intermediate position. Anxiety arousal and avoidance behaviour were associated with more long-term disability in anxiety disorders than course trajectories.ConclusionsVarious anxiety disorders have different disability levels over 4 years of time, therefore diagnostic distinction is important for treatment focus. Anxiety arousal and avoidance behaviour are major predictors for long-term disability in anxiety disorders.

Facing the fear – clinical and neural effects of cognitive behavioural and pharmacotherapy in panic disorder with agoraphobia

Introduction: Cognitive behavioural therapy (CBT) and pharmacological treatment with selective serotonin or serotonin-noradrenalin reuptake inhibitors (SSRI/SSNRI) are regarded as efficacious treatments for panic disorder with agoraphobia (PD/AG). However, little is known about treatment-specific effects on symptoms and neurofunctional correlates. Experimental procedures: We used a comparative design with PD/AG patients receiving either two types of CBT (therapist-guided (n=29) or non-guided exposure (n=22)) or pharmacological treatment (SSRI/SSNRI; n=28) as well as a wait-list control group (WL; n=15) to investigate differential treatment effects in general aspects of fear and depression (Hamilton Anxiety Rating Scale HAM-A and Beck Depression Inventory BDI), disorder-specific symptoms (Mobility Inventory MI, Panic and Agoraphobia Scale subscale panic attacks PAS-panic, Anxiety Sensitivity Index ASI, rating of agoraphobic stimuli) and neurofunctional substrates during symptom provocation (Westphal-Paradigm) using functional magnetic resonance imaging (fMRI). Comparisons of neural activation patterns also included healthy controls (n=29). Results: Both treatments led to a significantly greater reduction in panic attacks, depression and general anxiety than the WL group. The CBT groups, in particular, the therapist-guided arm, had a significantly greater decrease in avoidance, fear of phobic situations and anxiety symptoms and reduction in bilateral amygdala activation while the processing of agoraphobia-related pictures compared to the SSRI/SSNRI and WL groups. Discussion: This study demonstrates that therapist-guided CBT leads to a more pronounced short-term impact on agoraphobic psychopathology and supports the assumption of the amygdala as a central structure in a complex fear processing system as well as the amygdala׳s involvement in the fear system׳s sensitivity to treatment.

Cognitive models for panic disorder with agoraphobia: A study of disaggregated within-person effects.

The purpose of this study was to test 2 cognitive models of panic disorder with agoraphobia (PDA)-a catastrophic cognitions model and a low self-efficacy model-by examining the within-person effects of model-derived cognitive variables on subsequent anxiety symptoms. Participants were 46 PDA patients with agoraphobic avoidance of moderate to severe degree who were randomly allocated to 6 weeks of either cognitive therapy, based on the catastrophic cognitions model of PDA, or guided mastery (guided exposure) therapy, based on the self-efficacy model of PDA. Cognitions and anxiety were measured weekly over the course of treatment. The data were analyzed with mixed models, using person-mean centering to disaggregate within- and between-person effects. All of the studied variables changed in the expected way over the course of therapy. There was a within-person effect of physical fears, loss of control fears, social fears, and self-efficacy when alone on subsequent state anxiety. On the other hand, within-person changes in anxiety did not predict subsequent cognitions. Loss of control and social fears both predicted subsequent self-efficacy, whereas self-efficacy did not predict catastrophic cognitions. In a multipredictor analysis, within-person catastrophic cognitions still predicted subsequent anxiety, but self-efficacy when alone did not. Overall, the findings indicate that anxiety in PDA, at least in severe and long-standing cases, is driven by catastrophic cognitions. Thus, these cognitions seem to be useful therapeutic targets. (PsycINFO Database Record

Functional MRI activation in response to panic-specific, non-panic aversive, and neutral pictures in patients with panic disorder and healthy controls.

There is evidence that besides limbic brain structures, prefrontal and insular cortical activations and deactivations are involved in the pathophysiology of panic disorder. This study investigated activation response patterns to stimulation with individually selected panic-specific pictures in patients with panic disorder with agoraphobia (PDA) and healthy control subjects using functional magnetic resonance imaging (fMRI). Structures of interest were the prefrontal, cingulate, and insular cortex, and the amygdalo-hippocampal complex. Nineteen PDA subjects (10 females, 9 males) and 21 healthy matched controls were investigated using a Siemens 3-Tesla scanner. First, PDA subjects gave Self-Assessment Manikin (SAM) ratings on 120 pictures showing characteristic panic/agoraphobia situations, of which 20 pictures with the individually highest SAM ratings were selected. Twenty matched pictures showing aversive but not panic-specific stimuli and 80 neutral pictures from the International Affective Picture System were chosen for each subject as controls. Each picture was shown twice in each of four subsequent blocks. Anxiety and depression ratings were recorded before and after the experiment. Group comparisons revealed a significantly greater activation in PDA patients than control subjects in the insular cortices, left inferior frontal gyrus, dorsomedial prefrontal cortex, the left hippocampal formation, and left caudatum, when PA and N responses were compared. Comparisons for stimulation with unspecific aversive pictures showed activation of similar brain regions in both groups. Results indicate region-specific activations to panic-specific picture stimulation in PDA patients. They also imply dysfunctionality in the processing of interoceptive cues in PDA and the regulation of negative emotionality. Therefore, differences in the functional networks between PDA patients and control subjects should be further investigated.

Emotion-Abstraction Patterns and Cognitive Interventions in a Single Case of Standard Cognitive-Behavioral Therapy

Cognitive-behavioral therapy (CBT) assumes that therapeutic change de-pends mainly on change of cognitive content, while, from a theoretical viewpoint, other processes are excluded. This study aims to explore standard CBT interventions using a model of therapeutic change that includes both emotional and cognitive processes, i.e., the therapeutic cycle model (TCM; Mergenthaler, 1985; 1996), which describes the pro-cesses of therapeutic change in terms of cycles involving both emotional arousal and ab-stract thinking activation. We classified standard CBT interventions in three main are-as: assessing, disputing, and reframing biased beliefs. In 10 individual cognitive therapy sessions with a 30-year-old patient affected by a panic disorder with agoraphobia (PDA), this study aimed to explore whether cognitive interventions are not only related to abstract thinking but also to the emotional activation phases of TCM. Three inde-pendent judges assessed the presence of cognitive therapeutic interventions using the Comprehensive Psychotherapeutic Interventions Rating Scale (CPIRS; Trijsburg et al., 2002). A software program measured the TCM cognitive and emotional variables. The measures revealed significant correlations between cognitive therapeutic interventions and phases of abstract thinking activation during the therapeutic process. The results clarified the role of cognitive interventions in the therapeutic process as a useful instru-ment aimed to increase reality testing.

5HTT is associated with the phenotype psychological flexibility: results from a randomized clinical trial.

Adaption to changing environments is evolutionarily advantageous. Studies that link genetic and phenotypic expression of flexible adjustment to one's context are largely lacking. In this study, we tested the importance of psychological flexibility, or goal-related context sensitivity, in an interaction between psychotherapy outcome for panic disorder with agoraphobia (PD/AG) and a genetic polymorphism. Given the established role of the 5HTT-LPR polymorphism in behavioral flexibility, we tested whether this polymorphism (short group vs. long group) impacted therapy response as a function of various endophenotypes (i.e., psychological flexibility, panic, agoraphobic avoidance, and anxiety sensitivity). Patients with PD/AG were recruited from a large multicenter randomized controlled clinical trial on cognitive-behavioral therapy. Pre- to post-treatment changes by 5HTT polymorphism were analyzed. 5HTT polymorphism status differentiated pre- to post-treatment changes in the endophenotype psychological flexibility (effect size difference d = 0.4, p < 0.05), but none of the specific symptom-related endophenotypes consistently for both the intent-to-treat sample (n = 228) and the treatment completers (n = 194). Based on the consistency of these findings with existing theory on behavioral flexibility, the specificity of the results across phenotypes, and the consistency of results across analyses (i.e., completer and intent to treat), we conclude that 5HTT polymorphism and the endophenotype psychological flexibility are important variables for the treatment of PD/AG. The endophenotype psychological flexibility may help bridge genetic and psychological literatures. Despite the limitation of the post hoc nature of these analyses, further study is clearly warranted.

Therapygenetics: anterior cingulate cortex-amygdala coupling is associated with 5-HTTLPR and treatment response in panic disorder with agoraphobia.

Variation in the 5'-flanking promoter region of the serotonin transporter gene SLC6A4, the 5-HTT-linked polymorphic region (5-HTTLPR) has been inconclusively associated with response to cognitive-behavioural therapy (CBT). As genomic functions are stronger related to neural than to behavioural markers, we investigated the association of treatment response, 5-HTTLPR and functional brain connectivity in patients with panic disorder with agoraphobia (PD/AG). Within the national research network PANIC-NET 231 PD/AG patients who provided genetic information underwent a manualized exposure-based CBT. A subset of 41 patients participated in a functional magnetic resonance imaging (fMRI) add-on study prior to treatment applying a differential fear conditioning task. Neither the treatment nor the reduced fMRI sample showed a direct effect of 5-HTTLPR on treatment response as defined by a reduction in the Hamilton Anxiety Scale score ≥50% from baseline to post assessment. On a neural level, inhibitory anterior cingulate cortex (ACC)-amygdala coupling during fear conditioning that had previously been shown to characterize treatment response in this sample was driven by responders with the L/L genotype. Building upon conclusive evidence from basic and preclinical findings on the association of the 5-HTTLPR polymorphism with emotion regulation and related brain connectivity patterns, present findings translate these to a clinical sample of PD/AG patients and point towards a potential intermediate connectivity phenotype modulating response to exposure-based CBT.