Personalized virtual reality exposure for panic disorder and agoraphobia: A preliminary neurophysiological study.

BACKGROUND: Personalization is considered an important principle in virtual reality (VR) exposure therapy. We aimed to identify whether personalized VR exposure could provoke increased anxiety in patients with panic disorder and agoraphobia as it is considered the first step in successful treatment for anxiety. METHODS: We performed a double-arm, one-day preliminary study among 28 patients with panic disorder and agoraphobia. Three sessions of VR exposure, including a theater, train, and elevator scenario, were conducted in two groups. In the personalized group (n = 14), the brightness and crowd density were customized based on a pre-assessment. In the control group (n = 14), these conditions were fully randomized. Self-reported anxiety, heart rate, skin conductance, and electroencephalography were measured before, during, and after the VR sessions. RESULTS: In the later VR sessions, higher self-reported anxiety levels measured by the Visual Analogue Scale were observed in the personalized exposure group. Increased heart rates during and after the VR sessions were observed in the personalized group. The changes in skin conductance peaks were not significantly different between the groups, but the increase in skin conductance was associated with the participants' perception of presence. The electroencephalogram showed widespread increases in alpha waves in the frontal and temporal areas of the brain in the personalized group than in the control group. CONCLUSION: Personalized VR exposure elicits stronger anxiogenic effects in patients with panic disorder and agoraphobia as suggested by self-report and neurophysiological data. Personalization of VR exposure has the potential for effective behavioral therapy.

Continuous positive airway pressure as an accurate marker for non-24-hour sleep-wake rhythm disorder.

Non-24-h sleep-wake rhythm disorder is quite rare in sighted patients and frequently associated with psychiatric disorders. We report the case of a 46-year-old man with autism spectrum disorder (ASD) and agoraphobia who had been referred for a suspicion of obstructive sleep apnea syndrome (OSAS). Polysomnography and arterial blood gas confirmed moderate OSAS associated with hypoventilation. Continuous positive airway pressure (CPAP) was started on fixed mode with excellent results. At follow-up, his CPAP report data revealed an irregular sleep-wake rhythm with a progressive offset of sleep schedule and wake time delayed from 1 h from day to day. Melatonin (or agonist) is efficacious and safe for long-term treatment in ASD and circadian rhythm sleep-wake disorder (CRSWD) with light therapy and wakefulness promoting medication. This case underlines the importance to sensitise psychiatrists to sleep and CRSWD, and also that CPAP data offer a possible objective alternative to sleep diary.

Agoraphobia and panic attacks complicated by primary aldosteronism improved by treatment with eplerenone: a case report.

BACKGROUND: Primary aldosteronism (PA) is an adrenal gland disease, that induces increased secretion of the mineralocorticoid, aldosterone, resulting in symptoms such as hypertension. This study reports a patient with agoraphobia and panic attacks, associated with PA. This patient's psychiatric symptoms improved after treatment with eplerenone, a mineralocorticoid receptor antagonist. CASE PRESENTATION: The patient was a 40-year-old female with agoraphobia, which refers to the irrational fear of situations that may cause anxiety, and panic attacks characterized by profuse sweating, palpitations, and generalized weakness. She was diagnosed with hypertension from PA. Subsequently, she received treatment with eplerenone, which improved her agoraphobia and panic attacks. CONCLUSIONS: There have been no previous reports on PA associated with agoraphobia and panic attacks that improved with pharmacotherapy. Patients with agoraphobia and panic attacks should be evaluated for PA. In patients with PA, pharmacotherapy with eplerenone should be considered.

Predicting the naturalistic course in anxiety disorders using clinical and biological markers: a machine learning approach.

BACKGROUND: Disease trajectories of patients with anxiety disorders are highly diverse and approximately 60% remain chronically ill. The ability to predict disease course in individual patients would enable personalized management of these patients. This study aimed to predict recovery from anxiety disorders within 2 years applying a machine learning approach. METHODS: In total, 887 patients with anxiety disorders (panic disorder, generalized anxiety disorder, agoraphobia, or social phobia) were selected from a naturalistic cohort study. A wide array of baseline predictors (N = 569) from five domains (clinical, psychological, sociodemographic, biological, lifestyle) were used to predict recovery from anxiety disorders and recovery from all common mental disorders (CMDs: anxiety disorders, major depressive disorder, dysthymia, or alcohol dependency) at 2-year follow-up using random forest classifiers (RFCs). RESULTS: At follow-up, 484 patients (54.6%) had recovered from anxiety disorders. RFCs achieved a cross-validated area-under-the-receiving-operator-characteristic-curve (AUC) of 0.67 when using the combination of all predictor domains (sensitivity: 62.0%, specificity 62.8%) for predicting recovery from anxiety disorders. Classification of recovery from CMDs yielded an AUC of 0.70 (sensitivity: 64.6%, specificity: 62.3%) when using all domains. In both cases, the clinical domain alone provided comparable performances. Feature analysis showed that prediction of recovery from anxiety disorders was primarily driven by anxiety features, whereas recovery from CMDs was primarily driven by depression features. CONCLUSIONS: The current study showed moderate performance in predicting recovery from anxiety disorders over a 2-year follow-up for individual patients and indicates that anxiety features are most indicative for anxiety improvement and depression features for improvement in general.

French adaptation and validation of the Panic Disorder Severity Scale-self-report.

BACKGROUND: The aims of this study were to conduct a cross-cultural validation of the Panic Disorder Severity Scale - Self-Report (PDSS-SR) and to examine psychometric properties of the French-Canadian version. METHODS: A sample of 256 adults were included in the validation study based on data from the baseline interview of a clinical trial on transdiagnostic cognitive-behavioral therapy for mixed anxiety disorders. Participants completed the Anxiety and Related Disorders Interview Schedule (ADIS-5), and self-report instruments including the PDSS-SR, Beck Anxiety Inventory (BAI), Mobility Inventory for Agoraphobia (MIA), Sheehan Disability Scale (SDS), Patient Health Questionnaire (PHQ-9), Social Phobia Inventory (SPIN), Insomnia Severity Index (ISI) and Penn State Worry Questionnaire (PSWQ). The cross-cultural adaptation in French of the PDSS-SR included a rigorous back-translation process, with an expert committee review. Sensitivity to change was also examined with a subgroup of patients (n = 72) enrolled in the trial. RESULTS: The French version of the PDSS-SR demonstrated good psychometric properties. The exploratory factor analysis supported a one factor structure with an eigenvalue > 1 that explained 64.9% of the total variability. The confirmatory factor analysis (CFA) corroborated a one-factor model with a good model fit. Internal consistency analysis showed a .91 Cronbach's alpha. The convergent validity was adequate with the ADIS-5 clinical severity ratings for panic disorder (r = .56) and agoraphobia (r = .39), as well as for self-report instruments [BAI (r = .63), MIA (accompanied: r = .50; alone: r = .47) and SDS (r = .37)]. With respect to discriminant validity, lower correlations were found with the SPIN (r = .17), PSWQ (r = .11), ISI (r = .19) and PHQ-9 (r = .28). The optimal threshold for probable diagnosis was 9 for the PDSS-SR and 4 for the very brief 2-item version. The French version showed good sensitivity to change. CONCLUSIONS: The French version of the PDSS-SR has psychometric properties consistent with the original version and constitutes a valid brief scale to assess the severity of panic disorder and change in severity over time, both in research and clinical practice.

Face-to-face versus Video Teleconference Group Cognitive Behavioural Therapy for Anxiety and Related Disorders: A Preliminary Comparison.

OBJECTIVE: Telehealth is being increasingly incorporated into the delivery of mental health care and has received widespread attention during the COVID-19 pandemic for its ability to facilitate care during physical distancing restrictions. Videoconferencing is a common telehealth modality for delivering psychotherapy and has demonstrated similar outcomes to those of face-to-face therapy. Cognitive behavioural therapy (CBT) is the most common psychotherapy evaluated across various telehealth modalities; however, studies on CBT delivered via videoconference, particularly in a group therapy format, are lacking. Further, little research exists on videoconference group CBT for anxiety disorders. Accordingly, the present study compared the outcomes of group CBT for anxiety and related disorders delivered via videoconference versus face-to-face. METHOD: Using a non-randomized design, data on attendance, dropout, clinical outcomes, and functional impairment were collected from 413 adult outpatients of a tertiary care anxiety disorders clinic who attended a CBT group for panic disorder/agoraphobia, social anxiety disorder, generalized anxiety disorder (GAD), or obsessive-compulsive disorder delivered either face-to-face (pre-COVID-19 pandemic) or via videoconference (since the onset of COVID-19 pandemic). Outcomes were assessed using well-validated self-report measures. Data were collected pre-treatment, across 12 weekly sessions, and post-treatment. Intent-to-treat analyses were applied to symptom outcome measures. RESULTS: Face-to-face CBT conferred only a slight benefit over videoconference CBT for symptom outcomes across all groups, but when assessed individually, only the GAD group showed greater symptom improvement in the face-to-face format. Effect sizes for significant differences between the delivery formats were small. Participants in videoconference groups tended to have slightly higher attendance rates in some instances, whereas functional improvement and treatment dropout were comparable across the delivery formats. CONCLUSIONS: Results provide preliminary evidence that videoconference group CBT for anxiety and related disorders may be a promising and effective alternative to face-to-face CBT. Additional research is needed to establish equivalence between these delivery formats.

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

BACKGROUND: 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. AIMS: 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. METHOD: 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). RESULTS: 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. CONCLUSIONS: 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.

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.

BACKGROUND: Prompt 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. METHODS: Randomized 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. RESULTS: The 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. CONCLUSION: PMHC 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.

Co-morbidity between mood and anxiety disorders: A systematic review and meta-analysis.

There is consistent evidence that mood disorders often co-occur with anxiety disorders, however, the strength of the association of these two broad groups of disorders has been challenging to summarize across different studies. The aim was to conduct a meta-analysis of publications reporting on the pairwise comorbidity between mood and anxiety disorders after sorting into comparable study types. We searched MEDLINE, Embase, CINAHL, Web of Science, and the grey literature for publications between 1980 and 2017 regardless of geographical locations and languages. We meta-analyzed estimates from original articles after sorting by: (a) broad or narrow diagnostic criteria, (b) study time-frame, and (c) estimates with or without covariate adjustments. Over 43 000 unique studies were identified through electronic searches, of which 391 were selected for full-text review. Finally, 171 studies were eligible for inclusion, including 53 articles from additional snowball searching. In general, regardless of variations in diagnosis type, study time-frame, temporal order, or use of adjustments, there was substantial comorbidity between mood and anxiety disorders. Based on the entire 90 separate meta-analyses, the median OR was 6.1 (range 1.5-18.7). Of these estimates, all 90 were above 1, and 87 were significantly greater than 1 (i.e., the 95% confidence intervals did not include 1). Fourteen of the 90 pooled estimates had ORs that were greater than 10. This systematic review found robust and consistent evidence of comorbidity between broadly defined mood and anxiety disorders. Clinicians should be vigilant for the prompt identification and treatment of this common type of comorbidity.

Elevated costly avoidance in anxiety disorders: Patients show little downregulation of acquired avoidance in face of competing rewards for approach.

BACKGROUND: Pathological avoidance is a transdiagnostic characteristic of anxiety disorders. Avoidance conditioning re-emerged as a translational model to examine mechanisms and treatment of avoidance. However, its validity for anxiety disorders remains unclear. METHODS: This study tested for altered avoidance in patients with anxiety disorders compared to matched controls (n = 40/group) using instrumental conditioning assessing low-cost avoidance (avoiding a single aversive outcome) and costly avoidance (avoidance conflicted with gaining rewards). Autonomic arousal and threat expectancy were assessed as indicators of conditioned fear. Associations with dimensional symptom severity were examined. RESULTS: Patients and controls showed frequent low-cost avoidance without group differences. Controls subsequently inhibited avoidance to gain rewards, which was amplified when aversive outcomes discontinued. In contrast, patients failed to reduce avoidance when aversive and positive outcomes competed (elevated costly avoidance) and showed limited reduction when aversive outcomes discontinued (persistent costly avoidance). Interestingly, elevated costly avoidance was not linked to higher conditioned fear in patients. Moreover, individual data revealed a bimodal distribution of costly avoidance: Some patients showed persistent avoidance, others showed little to no avoidance. Persistent versus low avoiders did not differ in other task-related variables, response to gains and losses in absence of threat, sociodemographic data, or clinical characteristics. CONCLUSIONS: Findings suggest that anxious psychopathology is associated with a deficit to inhibit avoidance in presence of competing positive outcomes. This offers novel perspectives for research on mechanisms and treatment of anxiety disorders.

Association of Serotonin Transporter Gene (5-HTTLPR/rs25531) Polymorphism with Comorbidities of Panic Disorder.

INTRODUCTION: Panic disorder (PD) has many comorbidities such as depression, bipolar disorder (BPD), and agoraphobia (AG). PD is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Recently, a tri-allelic serotonin transporter (5-HTTLPR/rs25531) polymorphism was reported to be more sensitive to personality traits compared to the bi-allelic 5-HTTLPR polymorphism. We hypothesized that the 5-HTTLPR/rs25531 polymorphism may lead to a pathological anxious state depending on the presence or absence of a comorbidity in PD. METHODS: In this study, we investigated the relationship between comorbidities in PD and tri-allelic 5-HTTLPR polymorphisms. A total of 515 patients with PD (148 males, 367 females) were genotyped, and the Revised NEO Personality Inventory as well as anxiety-related psychological tests were administered. Depression, BPD, and AG were diagnosed as comorbidities. RESULTS: For the tri-allele 5-HTTLPR genotype, a significant interaction effect was found between openness to experience and comorbid depression. Examination of the interaction between AG and the tri-allelic 5-HTTLPR genotype revealed that L' allele carriers are associated with higher trait anxiety than the S'S' genotype group in PD without AG. CONCLUSION: Some anxiety and personality traits can be characterized by the tri-allelic gene effect of 5-HTTLPR. These results suggest that tri-allelic 5-HTTLPR genotypes have genetic effects on the presence of comorbidities of PD.

Evaluating a Hybrid Web-Based Training Program for Panic Disorder and Agoraphobia: Randomized Controlled Trial.

BACKGROUND: Previous studies provide evidence for the effectiveness of web-based interventions for panic disorder with and without agoraphobia. Smartphone-based technologies hold significant potential for further enhancing the accessibility and efficacy of such interventions. OBJECTIVE: This randomized controlled trial aims to evaluate the efficacy of a guided, hybrid web-based training program based on cognitive behavioral therapy for adults with symptoms of panic disorder. METHODS: Participants (N=92) with total scores in the Panic and Agoraphobia Scale ranging from 9 to 28 were recruited from the general population and allocated either to a hybrid intervention (GET.ON Panic) or to a wait-list control group. The primary outcome was the reduction in panic symptoms, as self-assessed using a web-based version of the Panic and Agoraphobia Scale. RESULTS: Analysis of covariance-based intention-to-treat analyses revealed a significantly stronger decrease in panic symptoms posttreatment (F=9.77; P=.002; Cohen d=0.66; 95% CI 0.24-1.08) in the intervention group than in the wait-list control group. Comparisons between groups of the follow-up measures at 3 and 6 months yielded even stronger effects (3-month follow-up: F=17.40, P<.001, Cohen d=0.89, 95% CI 0.46-1.31; 6-month follow-up: F=14.63, P<.001, Cohen d=0.81, 95% CI 0.38-1.24). CONCLUSIONS: Hybrid web-based training programs may help reduce the symptoms of panic disorder and hence play an important role in improving health care for patients with this debilitating disorder. TRIAL REGISTRATION: German Clinical Trial Register DRKS00005223; https://tinyurl.com/f4zt5ran. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1745-6215-15-427.

Role of panic appraisal in predicting the severity of panic and agoraphobic symptoms.

OBJECTIVE: The present study examined the contribution of panic appraisal (PA) dimensions to the prediction of panic and agoraphobic symptoms, above and beyond anxiety sensitivity (AS), among patients with panic disorder. PA dimensions consist of anticipated panic, perceived panic consequences, and panic coping efficacy. METHOD: Panic disorder patients (N = 84, 60.7% female, M = 38 years) completed self-report measures of panic and agoraphobic symptoms, three dimensions of PA, AS, anxiety, and depression symptoms. RESULTS: PA dimensions significantly contributed to the prediction of overall and all facets of panic and agoraphobic symptoms, as well as anxiety symptoms, but not depressive symptoms, above and beyond AS. Of the three PA dimensions, both anticipated panic and panic coping efficacy uniquely contributed to agoraphobic avoidance after controlling for AS and the other dimensions of PA. CONCLUSION: PA dimensions may emerge as an important predictor of panic and agoraphobic or anxiety symptoms.

Separating From the Mothership: A Coordinated Individual and Parent-Based Approach to Severe Agoraphobia in a Young Adult.

Families are invested in an older adolescent gradually separating from the family to live independently as an adult, but for many families, adolescent psychopathology makes this transition difficult. Addressing such psychopathology is critical in preventing "failure to launch," a breakdown in gaining age-appropriate independence from parents. This case study illustrates a promising approach directed at helping an 18-year-old female with agoraphobia and panic disorder who, upon intake, was at risk for long-lasting, prohibitive dependence on her parents. The clinical approach entails the convergence of two psychological treatments conducted in the same treatment center. One provider, working directly with the patient, delivered traditional cognitive-behavioral therapy (CBT) for anxiety. A second provider, working with the parents, delivered Supportive Parenting for Anxious Childhood Emotions (SPACE) a parent-based treatment focused on reducing family accommodation of the patient's anxiety. Behavioral indices and self-report scores indicated clinically significant improvement following the combined intervention. Attention is drawn to the convergence of those treatments and the utility and special considerations in taking this kind of approach. Overall, the combined treatment may have been more successful than the sum of its parts at preventing failure to launch. This case study, the first to describe the integration of CBT and SPACE, can provide useful guidance for clinicians helping families of adult children to transition to independence.

Affective Temperaments, Panic Disorder and Their Bipolar Connections.

Background and Objectives: The role of affective temperament in the genesis and outcome of major mood disorders is well studied, but there are only a few reports on the relationship between panic disorder (PD) and affective temperaments. Accordingly, we aimed to study the distribution of affective temperaments (depressive (DE); cyclothymic (CT); irritable (IRR); hyperthymic (HT) and anxious (ANX)) among outpatients with PD. Materials and Methods: Affective temperaments of 118 PD outpatients (80 females and 38 males) with or without agoraphobia but without any other psychiatric disorder at the time of inclusion were evaluated using the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) and compared with the affective temperament scores of control subjects. All patients were followed up for at least 1.5 years in order to detect the onset of any major affective disorders, substance use disorders and suicide attempts. Results: Among females, the dominant ANX and DE temperaments were four and three times as common as in a large normative Hungarian sample (for both cases p < 0.01). Among male PD patients, only the dominant DE temperament was slightly overrepresented in a non-significant manner. Females with PD obtained significantly higher scores on ANX, DE and CT subscales of the TEMPS-A, whereas males with PD showed significantly higher scores on ANX, DE and HT temperament subscales compared with the members of a large normative Hungarian sample and also with a gender- and age-matched control group. During the follow-up, newly developed unipolar major depression and bipolar spectrum (bipolar I or II and cyclothymic) disorders appeared in 64% and 22% of subjects, respectively. Conclusions: Our preliminary findings suggest that a specific, ANX-DE-CT affective temperament profile is characteristic primarily for female patients, and an ANX-DE-HT affective temperament profile is characteristic for male patients with PD, respectively. These findings are in line with expectations because PD is an anxiety disorder par excellence on the one hand, whereas, on the other hand, it is quite frequently comorbid with mood (including bipolar) disorders.

Influence of Comorbid Psychiatric Disorders on the Risk of Development of Alcohol Dependence by Genetic Variations of ALDH2 and ADH1B.

BACKGROUND: Inactive aldehyde dehydrogenase-2 (ALDH2) is a well-known deterrent to the development of alcohol use disorder (AUD), and however, some individuals with inactive ALDH2 do go on to develop AUD. These alcoholics are likely to have strong risk factors for the development of this disorder. Using a model of alcoholics with inactive ALDH2 (the AIA model), we investigated the unique characteristics of alcoholics with inactive ALDH2 in an attempt to identify the risk factors for AUD. In this study, we focused on comorbid psychiatric and personality disorders as potential risk factors for AUD. METHODS: The subjects were 103 male alcoholics with inactive ALDH2 (AIAs), 87 age- and ADH1B genotype-matched alcoholics with active ALDH2 (AAAs) and 200 age-matched healthy men. The alcoholics were divided into 4 subgroups according to their ALDH2 and ADH1B genotypes (inactive ALDH2 vs. active ALDH2, usual ADH1B vs. superactive ADH1B). To assess the participants' comorbid psychiatric disorders, we conducted semi-structured interviews using the Japanese translation of SSAGA version 2. We compared the prevalence of comorbid psychiatric and personality disorders among groups with different combinations of the ALDH2 and ADH1B genotypes. RESULTS: The prevalence of attention-deficit/hyperactivity disorder (ADHD) was significantly higher in the AIAs with usual ADH1B than in the other 3 subgroups of alcoholics. In contrast, the prevalence rates of agoraphobia and panic disorder were significantly lower in the AIAs with superactive ADH1B than in the other 3 subgroups of alcoholics. CONCLUSIONS: This study suggested that (i) ADHD is a risk factor for AUD, consistent with previous reports; (ii) agoraphobia and panic disorder may have deterrent effects against the development of AUD in individuals with inactive ALDH2, probably attributable to the similarity between the symptoms of agoraphobia and panic disorder and the adverse reactions to consumption of alcohol in subjects with inactive ALDH2.

Pessimistically biased perception in panic disorder during risk learning.

BACKGROUND: Despite the well-known association between anxiety and risk-avoidant decision making, it is unclear how pathological anxiety biases risk learning. We propose a Bayesian inference model with bias parameters of prior, learning, and perception during risk learning in individuals with pathological anxiety. METHODS: Patients with panic disorder (PD, n = 40) and healthy control subjects (n = 84) completed the balloon analog risk task (BART). By fitting our computational model of three bias parameters (prior belief, learning rate, and perceptual bias) to the participants' behavior, we estimated the degree of bias in risk learning and its relationship with anxiety symptoms. RESULTS: Relative to the healthy control subjects, the pathologically anxious participants exhibited a biased underestimation of perceptual evidence rather than differences in priors and learning rates. The degree of perceptual bias was correlated with the anxiety and depression symptom severity in the patients with PD. Furthermore, our proposed model was the winning model for BART data in an external data set from different patient groups. CONCLUSIONS: Our results showed that individuals with pathological anxiety demonstrate perceptual bias in evidence accumulation, which may explain why patients with anxiety overestimate risk in their daily lives. This clarification highlights the importance of interventions focusing on perceptual bias, such as enhancing the clarity of favorable outcome probabilities.

Cognitive behavioral group therapy for panic disorder in a general clinical setting: a prospective cohort study with 12 to 31-years follow-up.

BACKGROUND: The long-term prognosis after cognitive behavioral therapy (CBT) in outpatient groups for panic disorder and agoraphobia is not well known. The purpose of this study was to assess long-term outcomes in terms of psychological health, health-related quality of life (HRQoL), quality of life (QoL) and treatment satisfaction after CBT for panic disorder and agoraphobia. METHODS: The sample consisted of 68 patients (61% response rate), who were assessed at pretreatment; at the start and end of treatment; and after 3 months, after 1 year, and over the long term (M = 24 years; SD = 5.3; range: 12 to 31 years). The main outcome was the total score on the Phobic Avoidance Rating Scale (PARS-total). At long-term follow-up, HRQoL was measured with the RAND-12 questionnaire, and QoL was measured with two questions from the "Study on European Union Statistics on Income and Living Conditions". Patient experiences and treatment satisfaction were assessed by the Generic Short Patient Experiences Questionnaire. A marginal longitudinal model was applied to study the main outcome. RESULTS: The effect size of the long-term change (mean change/ pooled SD) in the PARS-total score was (- 1.6, p < 0.001) and was stable over time. A PARS-total score reduction of 50% was found in 98% of patients at the long-term follow-up. The patients' HRQoL and QoL were similar to the expected scores for the general Norwegian population. Of the patients, 95% reported high to very high satisfaction with the CBT, and 93% reported large treatment benefits. CONCLUSIONS: To the best of our knowledge, this study has the longest follow-up after group CBT for panic disorder and agoraphobia, showing a good prognosis in ≥93% of the participating patients.

Internet-delivered cognitive behavioral therapy for panic disorder with or without agoraphobia: a systematic review and meta-analysis.

The current systematic review and meta-analysis examined the efficacy and effectiveness of internet-delivered cognitive behavioral therapy (iCBT) on panic disorder and agoraphobia symptom severity. Twenty-seven studies were identified. Results from nine randomised controlled trials (RCTs) showed that iCBT outperformed waiting list and information controls for panic (g = 1.22) and agoraphobia (g = .91) symptoms, but the quality of RCTs varied and heterogeneity was high. Results from three RCTs suggested iCBT may have similar outcomes to face-to-face CBT in reducing panic and agoraphobia symptoms. Within-group effect sizes between baseline and post-treatment were large for panic (n = 29, g = 1.16) and medium for agoraphobia symptom severity (n = 18, g = .73). Subgroup analyses of within-group pre/post treatment effect sizes showed larger within-group effect sizes for efficacy studies (n = 15) compared to effectiveness studies (n = 14) for panic severity (g = 1.38 vs. g = .98) but not agoraphobia severity. There was no impact of program length, inclusion or arousal reduction techniques, or degree of clinician support. Within-group effects of iCBT suggest the reduction in panic and agoraphobia symptom severity is maintained at 3-6 month follow-up (n = 12).

Neuroinflammation-Associated Alterations of the Brain as Potential Neural Biomarkers in Anxiety Disorders.

Stress-induced changes in the immune system, which lead to neuroinflammation and consequent brain alterations, have been suggested as possible neurobiological substrates of anxiety disorders, with previous literature predominantly focusing on panic disorder, agoraphobia, and generalized anxiety disorder, among the anxiety disorders. Anxiety disorders have frequently been associated with chronic stress, with chronically stressful situations being reported to precipitate the onset of anxiety disorders. Also, chronic stress has been reported to lead to hypothalamic-pituitary-adrenal axis and autonomic nervous system disruption, which may in turn induce systemic proinflammatory conditions. Preliminary evidence suggests anxiety disorders are also associated with increased inflammation. Systemic inflammation can access the brain, and enhance pro-inflammatory cytokine levels that have been shown to precipitate direct and indirect neurotoxic effects. Prefrontal and limbic structures are widely reported to be influenced by neuroinflammatory conditions. In concordance with these findings, various imaging studies on panic disorder, agoraphobia, and generalized anxiety disorder have reported alterations in structure, function, and connectivity of prefrontal and limbic structures. Further research is needed on the use of inflammatory markers and brain imaging in the early diagnosis of anxiety disorders, along with the possible efficacy of anti-inflammatory interventions on the prevention and treatment of anxiety disorders.