Search

Background: Theta-gamma coupling (TGC) describes the modulation of gamma oscillations by the theta phasic activity, which is crucial for processes such as the ordering of information during working memory (WM) performance. The mental arithmetic (MA), which involves performing calculations with numbers, is a crucial tool for evaluating and understanding the sensory processing and management abilities of WM. Evaluating TGC may provide greater insight into the neural mechanisms mediating WM deficits in panic disorder (PD)., Methods: Medical and electroencephalography (EEG) records of psychiatric outpatient clinic between 1 March 2020 and 30 September 2023 were retrospectively reviewed. A total of 34 PD patients and 34 age- and sex-matched healthy controls (HCs) underwent EEG to assess the overall functional interaction of the brain using multi-channel EEG analysis, focusing on specific brain regions including the frontal, temporal, parietal, and occipital lobes. EEG recordings were conducted during two sessions: a 5-min eyes-closed resting-state (RS) and a subsequent 5-min eyes-closed MA. The TGC and the spectral power of the theta and gamma frequency bands, which are well known to be associated with WM, were analysed., Results: Compared to those in HCs, TGC and theta power were significantly attenuated in PD patients. When analysing both HCs and PD patients together, RS TGC and relative theta power were negatively correlated with state anxiety and perceived stress scores, respectively. In contrast, TGC and relative theta power during the MA condition were positively correlated with the MA performance. Specifically, in PD patients, RS theta power across all electrodes was significantly negatively correlated with the Hamilton Anxiety Scale (HAMA) score. Linear regression analysis revealed that theta power in the T5 channel remained negatively correlated with pathological anxiety as measured by the HAMA score, even after controlling for other confounding factors., Conclusions: This study highlights significant alterations in TGC and theta power in PD patients. PD patients exhibit reduced TGC and theta power compared to HCs, indicating deficits in the neural mechanisms underlying anxiety and/or WM in PD. These insights contribute to a better understanding of the neural basis of WM deficits in PD and suggest potential avenues for targeted therapeutic interventions., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and was reviewed and approved by the Institutional Review Board of Yongin Severance Hospital, Yonsei University (approval number: 9-2022-0199; approval date: February 20, 2023). This study was exempted from the need for informed consent since it entailed a retrospective review of data. The study procedures were conducted in accordance with the applicable regulations governing research involving human participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The Bergen 4-Day Treatment (B4DT) is a concentrated cognitive behaviour therapy (CBT) approach that has shown promise in treating panic disorder (PD). However, the effectiveness of the B4DT, particularly regarding long-term outcomes in rural clinical settings, remains underexplored., Methods: A total of 58 patients were included using a naturalistic open-label trial design. Patients were assessed at 12-month follow-up. Measures included the Panic Disorder Severity Scale (PDSS), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 scale (GAD-7)., Results: The study revealed significant and lasting reductions in PD symptoms, with a high rate of remission maintained at 12-month follow-up (82.8%). Regarding the secondary outcomes, significant improvements in symptoms of depression and generalized anxiety were also shown., Conclusions: The B4DT represents a promising treatment approach for PD, demonstrating stable long-term outcomes in rural settings. This finding supports the potential of concentrated CBT formats in achieving sustained symptom improvement in patients with PD, warranting further investigation and broader implementation., Trial Registration: The study was reviewed by the Regional Committee for Medical Research Ethics Northern Norway, REK North (REK Nord2021/273145)., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the principles outlined in the Declaration of Helsinki and was reviewed by the Regional Committee for Medical Research Ethics Northern Norway, REK North (REK Nord-2021/273145). Informed written consent was obtained from all participants. The participants were informed that participation in the study was voluntary and that they had the right to withdraw from the study at any time without any negative effect on their treatment. All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Investigate the sleep characteristics of patients with obstructive sleep apnea syndrome (OSAS) comorbidity with panic disorder (PD), exploring its potential association with serum C-reactive protein (CRP) levels., Patients and Methods: Fifty-four patients (25 OSAS patients with PD and 29 without PD) and 25 healthy controls (HCs) were included. The Self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Pittsburgh sleep quality index (PSQI) were used to assess the mood and sleep quality of the subjects. All patients had circulating CRP levels and polysomnography was performed., Results: OSAS with PD had higher SAS, SDS, PSQI than the OSAS without PD. Compared to OSAS without PD, OSAS with PD had higher percentage of non- rapid eye movement sleep 1 and 2 (N1 and N2%), sleep latency, and a lower percentage of rapid eye movement sleep (REM%). Respiratory-related microarousal index, AHI, and time below 90% oxygen saturation (T90) were low, and the lowest oxygen saturation (LO2) was high. Serum CRP levels in OSAS patients with PD were lower than that in OSAS patients without PD, but higher than that in HCs. In OSAS patients with PD, serum CRP levels were negatively correlated with wake time after sleep onset and SAS scores but positively correlated with sleep efficiency and N2%. Serum CRP levels were positively correlated with T90 and negatively correlated with LO2., Conclusion: OSAS patients with PD had worse sleep quality, less severe OSAS, and low serum CRP levels. Serum CRP levels in OSAS patients with PD were associated with poorer sleep quality and duration of hypoxia rather than AHI., (© 2023. The Author(s).)

Objective: Autism spectrum disorder (ASD) is characterized by high rates of comorbidity with other mental disorders, including anxiety disorders and obsessive-compulsive disorder. Beyond a mere concept of comorbidity, recent literature is speculating the existence of a neurodevelopmental nature of such mental disorders. The aim of the study is to investigate the distribution of social-phobic, obsessive-compulsive and panic-agoraphobic traits within a sample of individuals with ASD, social anxiety disorder (SAD), obsessive-compulsive disorder (OCD) and panic disorder (PD)., Methods: 40 participants with ASD, 40 with SAD, 40 with OCD, 40 with PD and 50 HC were assessed with the Social Anxiety Spectrum-Short Version (SHY-SV) questionnaire, the Obsessive-Compulsive Spectrum-Short Version (OBS-SV) questionnaire and the Panic Agoraphobic Spectrum-Short Version (PAS-SV) questionnaire. Statistical analyses included Kruskal-Wallis test and Chi-square test., Results: When analyzing SHY-SV scores, the SAD group obtained the highest scores, with individuals with ASD following closely, significantly surpassing the scores of the remaining diagnostic groups. In the examination of OBS-SV questionnaire scores, individuals with ASD once again secured the second-highest scores, trailing only the OCD group. These scores were notably higher than those of both the PD group and healthy controls. In the analysis of PAS-SV scores, the ASD group once again achieved the highest scores after the PD individuals, although this time the difference was not statistically significant compared to the other diagnostic groups., Discussion: These findings highlight the central role of the autism spectrum in SAD and OCD diagnoses. They provide support for the hypotheses of a neurodevelopmental basis for social anxiety and OCD, contributing to the growing body of evidence supporting a dimensional and interconnected view of mental health conditions., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the declaration of Helsinki, and approved by the Institutional Ethics Committee of Azienda Ospedaliero Universitaria Pisana. A written informed consent was signed by the participants after receiving an accurate description of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Bergen 4-day treatment (B4DT) is a concentrated exposure-based treatment (cET), where the patient receives concentrated, individually tailored cognitive behavioral therapy (CBT) during four consecutive days. Previous findings have indicated that B4DT could be a promising treatment for panic disorder (PD)., Aim: The aim of the present study was to evaluate the implementation of B4DT for panic disorder with- and without agoraphobia, at a new clinic. This is the first replication study for B4DT on panic disorder., Method: Thirty consecutively recruited patients with PD were included in an open trial design. Assessment of symptoms of panic disorder were measured with Panic Disorder Severity Scale (PDSS), while symptoms of generalized anxiety were assessed by Generalized Anxiety Disorder-7 (GAD-7) and depressive symptoms by Patient Health Questionnaire (PHQ-9) pre-treatment, post-treatment and at 3-month follow-up. Treatment satisfaction was measured with Client Satisfaction Questionnaire (CSQ-8) post-treatment., Results: The results showed a significant reduction in symptom severity from pre-treatment to post-treatment (d = 4.32), and at 3-month follow-up (d = 4.91). The proportion of patients classified as fulfilling the criteria for remission was 80.0% at post-treatment and 86.7% at follow up. There was a significant reduction in symptoms of depression and generalized anxiety. Treatment satisfaction was high and none of the patients dropped out., Conclusion: The current study replicated the results from the original study and indicate that the treatment can be successfully implemented at new clinics. B4DT may be a promising treatment for panic disorder and comorbid symptoms of generalized anxiety and depression. Larger and more controlled studies are needed to establish the efficacy of B4DT for panic disorder., (© 2022. The Author(s).)

Abstract Background Panic disorder (PD) is often undiagnosed, misdiagnosed, or untreated in non-psychiatric clinical settings. Therefore, a cost-effective, accurate and easy-to-administer instrument for PD assessment is still needed. For that reason, the self-report version of the Panic Disorder Severity Scale (PDSS-SR) has been developed and suggested to be a reliable and useful tool in clinical and research settings. The current study aims to evaluate the reliability and validity of the Chinese version of the PDSS-SR and determine the cut-off score of the PDSS-SR. Methods A total of 133 patients with PD in Shanghai were assessed by the PDSS-SR, PDSS and Hamilton Anxiety Rating Scale (HAMA). Moreover, 117 patients with non-PD anxiety and 51 healthy subjects also completed the PDSS-SR to construct a receiver operating characteristic (ROC) curve with the scores of PD patients. Results The internal consistency (Cronbach’s α) of the PDSS-SR was 0.72–0.80, and the interrater correlation coefficient was 0.78. The results of principal component analysis and varimax rotation indicated that the PDSS-SR had a two-factor structure, with all seven items having salient loadings. The cut-off score was 4, which was associated with high sensitivity (96.03%) and specificity (61.31%). Conclusions The findings demonstrate that these items and the total score of the PDSS-SR have acceptable reliability and validity in patients with PD and that the PDSS-SR can be used by general doctors for clinical screening in China.

Background: A number of studies have shown that genetic factor plays an important role in etiology of panic disorder (PD). The aim of the present study was to examine the association of serotonin-related gene polymorphisms with PD risk. Then, we analyzed the correlation between these gene polymorphisms and response to sertraline drug., Methods: Two hundred thirty-three patients with PD and 231 healthy controls were enrolled in the study. Panic Disorder Severity Scale (PDSS) were administered to all subjects, and all patients in the study were also assessed after 4 weeks of treatment. The SLC6A4(rs140701, rs3813034, 5-HTTLPR and STin2), 5-HTR1A rs6295, 5-HTR2A rs6313 and COMT rs4680 gene polymorphisms were genotyped and assessed for the potential association., Results: The allelic model showed that the SLC6A4 rs140701 polymorphism variant was significantly associated with increased risk of PD (OR = 0.624, 95% CI 0.450-0.864, p < 0.05), and a significant result was found in the dominant model (OR = 0.546; 95% CI, 0.371-0.804, p < 0.05). There was a significant difference in allele and genotype frequency between responders and nonresponders in the 5-HTTLPR polymorphism (OR = 0.205, 95% CI 0.128-0.328; OR = 0.249, 95% CI 0.155-0.401, both p < 0.001), indicating the PD patients with S-allele had a poorer response to sertraline than L-allele carriers., Conclusions: The present study suggests that the SLC6A4 rs140701 polymorphism variant may be associated with susceptibility to PD, and 5-HTTLPR polymorphism may be a predictor of response to sertraline in the treatment of PD.

Abstract 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

Abstract Background Suicidal ideation is common in patients suffering from panic disorder. The present study investigated rates of suicidal ideation and risk factors for suicidal ideation in a sample of primary care patients suffering from panic disorder with or without agoraphobia. Methods A total of N = 296 patients [n = 215 (72.6%) women; age: M = 43.99, SD = 13.44] were investigated. Anxiety severity, anxiety symptoms, avoidance behavior, comorbid depression diagnosis, severity of depression, age, sex, employment status, living situation and frequency of visits at the general practitioner were considered as risk factors of suicidal ideation. Results Suicidal ideation was experienced by 25% of the respondents. In a logistic regression analysis, depression diagnosis and depression severity emerged as significant risk factors for suicidal ideation. Anxiety measures were not associated with suicidal ideation. Conclusion Suicidal ideation is common in primary care patients suffering from panic disorder with or without agoraphobia. Individuals with greater burden of mental illness in terms of mood disorder comorbidity and depressive symptomatology are especially likely to suffer from suicidal ideation.

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., (© 2023. The Author(s).)

Background: Sarcoidosis is a systemic disease of unknown etiology, in which granulomas develop in various organs, including the skin, lungs, eyes, or heart. It has been reported that patients with sarcoidosis are more likely to develop panic disorder than members of the general population. However, there are many unknown factors concerning the causal relationship between these conditions., Case Presentation: We present the case of a 57-year-old woman who appeared to have panic disorder, as she experienced repeated panic attacks induced by transient complete atrioventricular block, associated with cardiac sarcoidosis. Psychotherapy and pharmacotherapy were not effective in the treatment of her panic attacks. However, when we implanted a permanent pacemaker and initiated steroid treatment for cardiac sarcoidosis, panic attacks were ameliorated. Based on these findings, we diagnosed the patient's symptoms as an anxiety disorder associated with cardiac sarcoidosis, rather than panic disorder., Conclusions: This report highlights the importance of considering cardiac sarcoidosis in the differential diagnosis of panic disorder. This cardiac disease should be considered especially in patients have a history of cardiac disease (e.g., arrhythmia) and atypical presentations of panic symptoms. Panic disorder is a psychiatric condition that is typically diagnosed after other medical conditions have been excluded. Because the diagnosis of sarcoidosis is difficult in some patients, caution is required. The palpitations and symptoms of heart failure associated with cardiac sarcoidosis can be misdiagnosed as psychiatric symptoms of panic disorder. The condition described in the current case study appears to constitute a physical disease, the diagnosis of which requires significant consideration and caution.

Background: Approximately 40% of Emergency Department (ED) patients with chest pain meet diagnostic criteria for panic-related anxiety, but only 1-2% are correctly diagnosed and appropriately managed in the ED. A stepped-care model, which focuses on providing evidence-based interventions in a resource-efficient manner, is the state-of-the art for treating panic disorder patients in medical settings such as primary care. Stepped-care has yet to be tested in the ED setting, which is the first point of contact with the healthcare system for most patients with panic symptoms., Methods: This multi-site randomized controlled trial (RCT) aims to evaluate the clinical, patient-centred, and economic effectiveness of a stepped-care intervention in a sample of 212 patients with panic-related anxiety presenting to the ED of Singapore's largest public healthcare group. Participants will be randomly assigned to either: 1) an enhanced care arm consisting of a stepped-care intervention for panic-related anxiety; or 2) a control arm consisting of screening for panic attacks and panic disorder. Screening will be followed by baseline assessments and blocked randomization in a 1:1 ratio. Masked follow-up assessments will be conducted at 1, 3, 6, and 12 months. Clinical outcomes will be panic symptom severity and rates of panic disorder. Patient-centred outcomes will be health-related quality of life, daily functioning, psychiatric comorbidity, and health services utilization. Economic effectiveness outcomes will be the incremental cost-effectiveness ratio of the stepped-care intervention relative to screening alone., Discussion: This trial will examine the impact of early intervention for patients with panic-related anxiety in the ED setting. The results will be used to propose a clinically-meaningful and cost-effective model of care for ED patients with panic-related anxiety., Trial Registration: ClinicalTrials.gov NCT03632356. Retrospectively registered 15 August 2018., (© 2022. The Author(s).)

Background Observational studies have suggested a link between panic disorder (PD) and Alzheimer disease (AD). This study aimed to identify the underlying association of PD with the risk of AD using Mendelian randomization. Methods Genetic instrumental variables (IVs) were retrieved in the genome-wide association study between PD and AD. Then, five different models, namely inverse variance weighting (IVW), weighted median, weighted mode, MR-Egger and MR-robust adjusted profile scores (MR-RAPS), were used for MR Analysis. Finally, the heterogeneity and pleiotropy of identified IVs were verified by multiple sensitivity tests. Results The Cochran’s Q test based on MR Egger and IVW showed that no evidence of heterogeneity was found in the effects of instrumental variables, so a fixed-effect model was used. IVW analysis (OR 1.000479, 95% CI [1.000147056, 1.000811539], p=0.005) indicated that PD was associated with an increased risk of AD, and a causal association existed between them. Meanwhile, weighted median (OR 1.000513373, 95% CI [1.000052145, 1.000974814], p=0.029) and MR-RAPS (OR 1.000510118, 95% CI [1.000148046, 1.00087232], p=0.006) also showed the similar findings. In addition, extensive sensitivity analyses confirmed the robustness and accuracy of these results. Conclusion This investigation provides evidence of a potential causal relationship between PD and the increased risk of AD. Based on our MR results, when diagnosing and treating patients with PD, clinicians should pay more attention to their AD-related symptoms to choose therapeutic measures or minimize comorbidities. Furthermore, the development of drugs that improve both PD and AD may better treat patients with these comorbidities. [ABSTRACT FROM AUTHOR]

Background: Cognitive behavioral therapy (CBT) represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. We have recently demonstrated that the ability to extinguish learned fear responses is associated with a functional genetic polymorphism (COMTval158met) in the COMT gene and this study was aimed at transferring the experimental results on the COMTval158met polymorphism on extinction into a clinical setting., Methods: We tested a possible effect of the COMTval158met polymorphism on the efficacy of CBT, in particular exposure-based treatment modules, in a sample of 69 panic disorder patients., Results: We present evidence that panic patients with the COMTval158met met/met genotype may profit less from (exposure-based) CBT treatment methods as compared to patients carrying at least one val-allele. No association was found with the 5-HTTLPR/rs25531 genotypes which is presented as additional material., Conclusions: We were thus able to transfer findings on the effect of the COMTval158met polymorphism from an experimental extinction study obtained using healthy subjects to a clinical setting. Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype. Limitations of the study as well as possible clinical implications are discussed., Trial Registration: Clinical Trial Registry name: Internet-Versus Group-Administered Cognitive Behavior Therapy for Panic Disorder (IP2). Registration Identification number: NCT00845260, http://www.clinicaltrials.gov/ct2/show/NCT00845260.

Background: Internet administered cognitive behaviour therapy (CBT) is a promising new way to deliver psychological treatment, but its effectiveness in regular care settings and in relation to more traditional CBT group treatment has not yet been determined. The primary aim of this study was to compare the effectiveness of Internet-and group administered CBT for panic disorder (with or without agoraphobia) in a randomised trial within a regular psychiatric care setting. The second aim of the study was to establish the cost-effectiveness of these interventions., Methods: Patients referred for treatment by their physician, or self-referred, were telephone-screened by a psychiatric nurse. Patients fulfilling screening criteria underwent an in-person structured clinical interview carried out by a psychiatrist. A total of 113 consecutive patients were then randomly assigned to 10 weeks of either guided Internet delivered CBT (n = 53) or group CBT (n = 60). After treatment, and at a 6-month follow-up, patients were again assessed by the psychiatrist, blind to treatment condition., Results: Immediately after randomization 9 patients dropped out, leaving 104 patients who started treatment. Patients in both treatment conditions showed significant improvement on the main outcome measure, the Panic Disorder Severity Scale (PDSS) after treatment. For the Internet treatment the within-group effect size (pre-post) on the PDSS was Cohen's d = 1.73, and for the group treatment it was d = 1.63. Between group effect sizes were low and treatment effects were maintained at 6-months follow-up. We found no statistically significant differences between the two treatment conditions using a mixed models approach to account for missing data. Group CBT utilised considerably more therapist time than did Internet CBT. Defining effect as proportion of PDSS responders, the cost-effectiveness analysis concerning therapist time showed that Internet treatment had superior cost-effectiveness ratios in relation to group treatment both at post-treatment and follow-up., Conclusions: This study provides support for the effectiveness of Internet CBT in a psychiatric setting for patients with panic disorder, and suggests that it is equally effective as the more widely used group administered CBT in reducing panic-and agoraphobic symptoms, as well as being more cost effective with respect to therapist time., Trial Registration: ClinicalTrials.gov NCT00845260.

Background: A better understanding is needed of factors behind the long-term outcome of dysthymic and panic disorders. Combining patients' perceptions of factors that help and hind remission with objective assessments of outcome may give greater insight into mechanisms for maintaining recovery., Methods: Twenty-three dysthymic and 15 panic disorder patients participated in a 9-year follow-up investigation of a naturalistic study with psychotherapy and antidepressants. Degree of remission was determined by reassessments with SCID-I & II interviews, self-reported symptoms and life-charting (aided by case records). Qualitative content analysis of in-depth interviews with all 38 patients was done to examine the phenomenon of enduring remission by exploring: 1) perceived helpful and hindering factors, 2) factors common to and specific for the diagnostic groups, 3) convergence between patients' subjective views on remission with objective diagnostic assessments., Results: About 50% of the patients were in full or partial remission. Subjective and objective views on degree of remission generally converged, and remission was perceived as receiving 'Tools to handle life'. Common helpful factors were self-understanding, enhanced flexibility of thinking, and antidepressant medication, as well as confidence in the therapist and social support. The perceived main obstacle was difficulty in negotiating treatments. Remitted had overcome the obstacles, whereas many non-remitted had problems expressing their needs. Patients with dysthymia and panic disorder described specific helpful relationships with the therapist: 'As a parent' versus 'As a coach', and specific central areas for change: self-acceptance and resolution of relational problems versus awareness and handling of feelings., Conclusion: A general model for recovery from dysthymic and panic disorders is proposed, involving: 1) understanding self and illness mechanisms, 2) enhanced flexibility of thinking, and 3) change from avoidance coping to approach coping; and recognising that a vehicle for this change is a helpful relationship to the health care provider. The perceived needs of specific treatment ingredients suggest that it is essential to differentiate between early-onset dysthymia and secondary depressions. The perceived access problems will be further investigated.

Background: Cognitive model of panic disorder have proposed that panic attacks result from the catastrophic misinterpretation of certain bodily sensations. Cognitive-Behavioral Therapy (CBT) for panic disorder aims to change these catastrophic cognitions. CBT intervention successfully caused reduction of catastrophic cognitions and symptomatic improvement in the majority of cases. However there are some patients who fail to modify their catastrophic cognitions or rather experience an increase in them during CBT treatment. It is clinically and theoretically important to understand about cognitive sensitization of panic disorder during CBT sessions. The purpose of the present study is 1) to clarify the baseline characteristics of panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment, and 2) to examine the course of symptomatic changes for them., Methods: Of ninety-five outpatients with panic disorder started the group CBT program for treatment of panic disorder, seventy-nine completer were classified as "cognitively sensitized (CS)" or "cognitive responding (CR)" or "no-responder" according to the difference of the Agoraphobic Cognitions Questionnaire score across treatment. We compared the CS and CR patients in terms of their baseline clinical characteristics. Then we assessed the symptomatic and functional changes for both groups., Results: At the start of the CBT program, despite of the same degree of panic disorder severity, CS scored significantly lower on ACQ score than CR. CS also showed significantly lower score on anticipatory anxiety compared to CR. At the end of treatment CS showed significant improvement in severity of panic disorder, although the degree of improvement was smaller than that for CR. Then CS would progressively reduce their agoraphobic fear and avoidance, and would improve their functional impairment up to three month of follow-up., Conclusion: Panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment could nonetheless gradually improve. They showed a relatively low level of catastrophic cognition and anticipatory anxiety before starting the CBT program. We might conclude that temporary sensitization of catastrophic cognition may be necessary before improvement especially among those with initially low catastrophic body sensation fears and that we need not be concerned too much with temporary increase in catastrophic cognition in the process of CBT for panic disorder.

Background: This naturalistic open label follow-up study had three objectives: 1) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment, 2) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia, 3) To observe paroxetine's tolerability over a 24 month period., Methods: 143 patients with panic disorder (PD), with or without agoraphobia, successfully finished a short-term (ie 12 week) trial of paroxetine treatment. All patients then continued to receive paroxetine maintenance therapy for a total of 12 months. At the end of this period, 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase. The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored, as in the first group, for another year while medication-free. The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a randomized manner., Results: Only 21 of 143 patients (14%) relapsed during the one year medication discontinuation follow-up phase. There were no significant differences in relapse rates between the patients who received intermediate-term (up to 12 months) paroxetine and those who chose the long-term course (24 month paroxetine treatment). 43 patients (30.1%) reported sexual dysfunction. The patients exhibited an average weight gain of 5.06 kg. All patients who eventually relapsed demonstrated significantly greater weight increase (7.3 kg) during the treatment phase., Conclusions: The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation. Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment.

Background: In a number of drug and psychotherapy comparative trials, psychotherapy-placebo combination has been assumed to represent psychotherapy. Whether psychotherapy plus pill placebo is the same as psychotherapy alone is an empirical question which however has to date never been examined systematically., Methods: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) that directly compared cognitive-behavior therapy (CBT) alone against CBT plus pill placebo in the treatment of panic disorder., Results: Extensive literature search was able to identify three relevant RCTs. At the end of the acute phase treatment, patients who received CBT plus placebo had 26% (95%CI: 2 to 55%) increased chances of responding than those who received CBT alone. At follow-up the difference was no longer statistically significant (22%, 95%CI: -10% to 64%)., Conclusion: The act of taking a pill placebo may enhance the placebo effect already contained in the effective psychotherapeutic intervention during the acute phase treatment. Theoretically this is an argument against the recently claimed null hypothesis of placebo effect in general and clinically it may point to some further room for enhancing the psychotherapeutic approach for panic disorder.

Background: Interoceptive exposure has been validated as an effective component of cognitive behavioral therapy (CBT) for the treatment of panic disorder but has hitherto received little research attention. We examined the effectiveness of various interoceptive exposure exercises using the Body Sensations Questionnaire (BSQ) (Chambless et al., 1984)., Methods: We first performed an exploratory principal factor analysis of all the items contained in the BSQ to obtain meaningful dimensions of interoceptive fears. Next, we examined the correlations between each interoceptive exposure task's degree of similarity to panic attacks and each BSQ factor and then examined whether the BSQ factor scores decreased in comparison with the baseline values when the corresponding exposure tasks were successfully completed by the subjects., Results: The factor analyses revealed four factors, which we named "pseudoneurological fears", "gastrointestinal fears", "cardiorespiratory fears" and "fears of dissociative feelings." Among the nine interoceptive exposure tasks, 'hyperventilation', 'shaking head', 'holding breath' and 'chest breathing' were considered to reproduce pseudoneurological symptoms, 'breathing through a straw' was considered to reproduce gastrointestinal symptoms, and 'spinning' was considered to reproduce both pseudoneurological and dissociative symptoms; none of the interoceptive exercises were found to reproduce cardiorespiratory symptoms. Among each group of patients for whom 'hyperventilation', 'holding breath', 'spinning' or 'chest breathing' was effective, a significant improvement in the BSQ pseudoneurological fears factor scores was observed. On the other hand, no significant difference between the baseline and endpoint values of the BSQ gastrointestinal fears or the BSQ fears of dissociative feelings factor scores were observed among the patients for whom 'spinning' or 'breathing through a straw' was effective., Conclusion: Several interoceptive exposure tasks were particularly effective in reducing pseudoneurological fears. New interoceptive tasks, especially tasks related to cardiorespiratory and dissociative feelings, are needed.

Background: The integration of a personal recovery-oriented practice in mental health services is an emerging principle in policy planning. Self-management support (SMS) is an intervention promoting recovery that aims at educating patients on the nature of their mental disorder, improving their strategies to manage their day-to-day symptoms, fostering self-efficacy and empowerment, preventing relapse, and promoting well-being. While SMS is well established for chronic physical conditions, there is a lack of evidence to support the implementation of structured SMS programs for common mental disorders, and particularly for anxiety disorders. This study aims to examine the effectiveness of a group-based self-management support program for anxiety disorders as an add-on to treatment-as-usual in community-based care settings., Methods/design: We will conduct a multicentre pragmatic randomized controlled trial with a pre-treatment, post-treatment (4-month post-randomization), and follow-ups at 8, 12 and 24-months. TREATMENT AND CONTROL GROUPS: a) group self-management support (10 weekly 2.5-h group web-based sessions with 10-15 patients with two trained facilitators); b) treatment-as-usual. Participants will include adults meeting DSM-5 criteria for Panic Disorder, Agoraphobia, Social Anxiety Disorder, and/or Generalized Anxiety Disorder. The primary outcome measure will be the Beck Anxiety Inventory; secondary outcome measures will comprise self-reported instruments for anxiety and depressive symptoms, recovery, self-management, quality of life, and service utilisation., Statistical Analysis: Data will be analysed based on intention-to-treat with a mixed effects regression model accounting for between and within-subject variations in the effects of the intervention., Discussion: This study will contribute to the limited knowledge base regarding the effectiveness of structured group self-management support for anxiety disorders. It is expected that changes in patients' self-management behaviour will lead to better anxiety management and, consequently, to improved patient outcomes., Trial Registration: ClinicalTrials.gov: NCT05124639 . Prospectively registered 18 November 2021., (© 2022. The Author(s).)

Background: Transdiagnostic Cognitive Behavior Therapy (TCBT) manuals delivered in individual format have been reported to be just as effective as traditional diagnosis specific CBT manuals. We have translated and modified the "The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders" (UP-CBT) for group delivery in Mental Health Service (MHS), and shown effects comparable to traditional CBT in a naturalistic study. As the use of one manual instead of several diagnosis-specific manuals could simplify logistics, reduce waiting time, and increase therapist expertise compared to diagnosis specific CBT, we aim to test the relative efficacy of group UP-CBT and diagnosis specific group CBT., Methods/design: The study is a partially blinded, pragmatic, non-inferiority, parallel, multi-center randomized controlled trial (RCT) of UP-CBT vs diagnosis specific CBT for Unipolar Depression, Social Anxiety Disorder and Agoraphobia/Panic Disorder. In total, 248 patients are recruited from three regional MHS centers across Denmark and included in two intervention arms. The primary outcome is patient-ratings of well-being (WHO Well-being Index, WHO-5), secondary outcomes include level of depressive and anxious symptoms, personality variables, emotion regulation, reflective functioning, and social adjustment. Assessments are conducted before and after therapy and at 6 months follow-up. Weekly patient-rated outcomes and group evaluations are collected for every session. Outcome assessors, blind to treatment allocation, will perform the observer-based symptom ratings, and fidelity assessors will monitor manual adherence., Discussion: The current study will be the first RCT investigating the dissemination of the UP in a MHS setting, the UP delivered in groups, and with depressive patients included. Hence the results are expected to add substantially to the evidence base for rational group psychotherapy in MHS. The planned moderator and mediator analyses could spur new hypotheses about mechanisms of change in psychotherapy and the association between patient characteristics and treatment effect., Trial Registration: Clinicaltrials.gov NCT02954731 . Registered 25 October 2016.

Background: There is concern that rates of mental disorders may be increasing although findings disagree. Using an innovative design with a daughter-mother data set we assess whether there has been a generational increase in lifetime ever rates of major depressive disorder, generalised anxiety disorder, panic disorder, and post-traumatic stress disorder (PTSD) experienced prior to 30 years of age., Methods: Pregnant women were recruited during 1981-1983 and administered the Composite International Diagnostic Interview (CIDI) at the 27-year follow-up (2008-11). Offspring were administered the CIDI at the 30-year follow-up (2010-2014). Comparisons for onset of diagnosis are restricted to daughter and mother dyads up to 30 years of age. To address recall bias, disorders were stratified into more (≥12 months duration) and less persistent episodes (< 12 months duration) for the purposes of comparison. Sensitivity analyses with inflation were used to account for possible maternal failure to differentially recall past episodes., Results: When comparing life time ever diagnoses before 30 years, daughters had higher rates of persistent generalised anxiety disorder, and less persistent major depressive disorder, generalised anxiety disorder and PTSD., Conclusions: In the context of conflicting findings concerning generational changes in mental disorders we find an increase in generational rates of persistent generalised anxiety disorders and a range of less persistent disorders. It is not clear whether this finding reflects actual changes in symptom levels over a generation or whether there has been a generational change in recognition of and willingness to report symptoms of mental illness., (© 2021. The Author(s).)

Background: Efficacy of self-help internet-based cognitive behavior therapy (ICBT) for anxiety disorders has been confirmed in several randomized controlled trials. However, the amount and type of therapist guidance needed in ICBT are still under debate. Previous studies have shown divergent results regarding the role of therapist guidance and its impact on treatment outcome. This issue is central to the development of ICBT programs and needs to be addressed directly. The present study aims to compare the benefits of regular therapist guidance via online real-time audio-video communication (i.e. Skype) to no therapist guidance during a 12-week Romanian self-help ICBT program for Panic Disorder. Both treatments are compared to a waiting-list control group., Methods/design: A parallel group randomized controlled trial is proposed. The participants, 192 Romanian adults fulfilling diagnostic criteria for panic disorder according to a diagnostic interview, conducted via secured Skype or telephone, are randomly assigned to one of the three conditions: independent use of the internet-based self-help program PAXonline, the same self-help treatment with regular therapist support via secured Skype, and waiting-list control group. The primary outcomes are severity of self-report panic symptoms (PDSS-SR) and diagnostic status (assessors are blind to group assignment), at the end of the intervention (12 weeks) and at follow-up (months 3 and 6). The secondary measures address symptoms of comorbid anxiety disorders, depression, quality of life, adherence and satisfaction with ICBT. Additional measures of socio-demographic characteristics, personality traits, treatment expectancies, catastrophic cognitions, body vigilance and working alliance are considered as potential moderators and/ or mediators of treatment outcome., Discussion: To the best of our knowledge, the present study is the first effort to investigate the efficacy of a self-help internet-based intervention with therapist guidance via real-time video communication. A direct comparison between therapist guided versus unguided self-directed intervention for panic disorder will also be addressed for the first time. Findings from this study will inform researchers and practitioners about the added value of online video-therapy guidance sessions and the type of patients who may benefit the most from guided and unguided ICBT for Panic disorder., Trial Registration: ACTRN12614000547640 (Australian New Zealand Clinical Trials Registry). Registered 22/05/2014.

Background: The efficacy of combined psychotherapy and benzodiazepine treatment for panic disorder is still unclear despite its widespread use. The present systematic review aims to examine its efficacy compared with either monotherapy alone., Methods: All randomised trials comparing combined psychotherapy and benzodiazepine for panic disorder with either therapy alone were identified by comprehensive electronic search on the Cochrane Registers, by checking references of relevant studies and of other reviews, and by contacting experts in the field. Two reviewers independently checked eligibility of trials, assessed quality of trials and extracted data from eligible trials using a standardized data extraction form. Our primary outcome was "response" defined by global judgement. Authors of the original trials were contacted for further unpublished data. Meta-analyses were undertaken synthesizing data from all relevant trials., Results: Only two studies, which compared the combination with behaviour (exposure) therapy, met our eligibility criteria. Both studies had a 16-week intervention. Unpublished data were retrieved for one study. The relative risk for response for the combination was 1.25 (95%CI: 0.78 to 2.03) during acute phase treatment, 0.78 (0.45 to 1.35) at the end of treatment, and 0.62 (0.36 to 1.07) at 6-12 months follow-up. Some secondary outcomes hinted at superiority of the combination during acute phase treatment. One study was identified comparing the combination to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98), 3.39 (1.03 to 11.21, statistically significant) and 2.31 (0.79 to 6.74) respectively. The superiority of the combination was observed on secondary outcomes at all the time points. No sub-group analyses were conducted due to the limited number of included trials., Conclusion: Unlike some narrative reviews in the literature, our systematic search established the paucity of high quality evidence for or against the combined psychotherapy plus benzodiazepine therapy for panic disorder. Based on limited available published and unpublished data, however, the combined therapy is probably to be recommended over benzodiazepine alone for panic disorder with agoraphobia. The combination might be superior to behaviour therapy alone during the acute phase, but afterwards this trend may be reversed. We know little from these trials about their adverse effects.

Background: This 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)., Methods: Data 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., Results: Long-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., Conclusions: Various 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.

Abstract Background During the COVID-19 pandemic, internet-delivered psychotherapeutic interventions (IPI) move increasingly into the focus of attention. Method We reviewed 39 randomized controlled studies of IPIs with 97 study arms (n = 4122 patients) for anxiety disorders (panic disorder/agoraphobia, generalized anxiety disorder, and social anxiety disorder) and performed a meta-analysis. Most studies were conducted with cognitive behavioural approaches (iCBT). Results were compared with a previous meta-analysis examining medications and face-to-face (F2F) psychotherapy. Results In direct comparisons, IPIs were as effective as F2F-CBT and superior to waitlist controls. Programs with more intensive therapist contact yielded higher effect sizes (ES). We compared the obtained ES with a previous comprehensive meta-analysis of 234 studies. In this comparison, iCBT was less effective than individual F2F-CBT and medications, not different from pill placebos, and more effective than psychological placebo and waitlist (p > .0001 for all comparisons). ES of IPIs may be overestimated. Treatments were only compared to waitlist, which is not a sufficient control condition. 97% of the studies were not blinded with regard to the main outcome measure. 32% of the participants received antianxiety drugs during the trials. In 89%, participants were recruited by advertisements rather than from clinical settings, and 63% of the participants had an academic background (students or university employees) which might affect the generalizability of the findings. Remote diagnoses were often made by students without completed training in psychotherapy. In only 15% of the studies, diagnoses were made in personal contact with a psychiatrist or psychologist. In 44% of the studies, the ‘therapists’ maintaining remote contact with the participants were mostly students without completed psychotherapy education. Conclusions IPIs may be a useful tool when face-to-face psychotherapy is not easily available, or as an add-on to standard psychotherapeutic or psychopharmacological treatments but should perhaps not be used as monotherapy. We have suggested standards for future research and the practical use of IPIs.

Abstract Background Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive–compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of exposure-based therapy. Growing evidence links orexin system activity to deficits in fear extinction and we have demonstrated that reactivity to an inhaled carbon dioxide (CO2) challenge—a safe, affordable, and easy-to-implement procedure—can serve as a proxy for orexin system activity and predicts fear extinction deficits in rodents. Building upon this basic research, the goal for the proposed study is to validate CO2 reactivity as a biomarker of exposure-based therapy non-response. Methods We will assess CO2 reactivity in 600 adults meeting criteria for one or more fear- or anxiety-related disorders prior to providing open exposure-based therapy. By incorporating CO2 reactivity into a multivariate model predicting treatment non-response that also includes reactivity to hyperventilation as well as a number of related predictor variables, we will establish the mechanistic specificity and the additive predictive utility of the potential CO2 reactivity biomarker. By developing models independently within two study sites (University of Texas at Austin and Boston University) and predicting the other site’s data, we will validate that the results are likely to generalize to future clinical samples. Discussion Representing a necessary stage in translating basic research, this investigation addresses an important public health issue by testing an accessible clinical assessment strategy that may lead to a more effective treatment selection (personalized medicine) for patients with anxiety- and fear-related disorders, and enhanced understanding of the mechanisms governing exposure-based therapy. Trial registration ClinicalTrials.gov Identifier: NCT05467683 (20/07/2022).

Background: Sarcoidosis is a systemic disease of unknown etiology, in which granulomas develop in various organs, including the skin, lungs, eyes, or heart. It has been reported that patients with sarcoidosis are more likely to develop panic disorder than members of the general population. However, there are many unknown factors concerning the causal relationship between these conditions. Case presentation: We present the case of a 57-year-old woman who appeared to have panic disorder, as she experienced repeated panic attacks induced by transient complete atrioventricular block, associated with cardiac sarcoidosis. Psychotherapy and pharmacotherapy were not effective in the treatment of her panic attacks. However, when we implanted a permanent pacemaker and initiated steroid treatment for cardiac sarcoidosis, panic attacks were ameliorated. Based on these findings, we diagnosed the patient's symptoms as an anxiety disorder associated with cardiac sarcoidosis, rather than panic disorder. Conclusions: This report highlights the importance of considering cardiac sarcoidosis in the differential diagnosis of panic disorder. This cardiac disease should be considered especially in patients have a history of cardiac disease (e.g., arrhythmia) and atypical presentations of panic symptoms. Panic disorder is a psychiatric condition that is typically diagnosed after other medical conditions have been excluded. Because the diagnosis of sarcoidosis is difficult in some patients, caution is required. The palpitations and symptoms of heart failure associated with cardiac sarcoidosis can be misdiagnosed as psychiatric symptoms of panic disorder. The condition described in the current case study appears to constitute a physical disease, the diagnosis of which requires significant consideration and caution. [ABSTRACT FROM AUTHOR]

Background: Cognitive model of panic disorder have proposed that panic attacks result from the catastrophic misinterpretation of certain bodily sensations. Cognitive-Behavioral Therapy (CBT) for panic disorder aims to change these catastrophic cognitions. CBT intervention successfully caused reduction of catastrophic cognitions and symptomatic improvement in the majority of cases. However there are some patients who fail to modify their catastrophic cognitions or rather experience an increase in them during CBT treatment. It is clinically and theoretically important to understand about cognitive sensitization of panic disorder during CBT sessions. The purpose of the present study is 1) to clarify the baseline characteristics of panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment, and 2) to examine the course of symptomatic changes for them. Methods: Of ninety-five outpatients with panic disorder started the group CBT program for treatment of panic disorder, seventy-nine completer were classified as "cognitively sensitized (CS)" or "cognitive responding (CR)" or "no-responder" according to the difference of the Agoraphobic Cognitions Questionnaire score across treatment. We compared the CS and CR patients in terms of their baseline clinical characteristics. Then we assessed the symptomatic and functional changes for both groups. Results: At the start of the CBT program, despite of the same degree of panic disorder severity, CS scored significantly lower on ACQ score than CR. CS also showed significantly lower score on anticipatory anxiety compared to CR. At the end of treatment CS showed significant improvement in severity of panic disorder, although the degree of improvement was smaller than that for CR.Then CS would progressively reduce their agoraphobic fear and avoidance, and would improve their functional impairment up to three month of follow-up. Conclusion: Panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment could nonetheless gradually improve. They showed a relatively low level of catastrophic cognition and anticipatory anxiety before starting the CBT program. We might conclude that temporary sensitization of catastrophic cognition may be necessary before improvement especially among those with initially low catastrophic body sensation fears and that we need not be concerned too much with temporary increase in catastrophic cognition in the process of CBT for panic disorder. [ABSTRACT FROM AUTHOR]

Abstract Background Many studies have previously compared the prevalence or sample means of distress and mental health problems from before to during the COVID-19 pandemic, while results on changes at the individual-level, and regarding multiple outcome measures are demanded. Methods This online study investigated individual changes in stress and mental health from before the COVID-19 pandemic to the first lockdown in adults from Southeastern Germany. This region was selected as it was where SARS-CoV-2 was first documented in Germany, and also due to the implementation of strict stay-at-home orders and social contact prohibitions. From April 10–27, 2020, we collected state measures and their clinical relevance for the subareas of perceived stress: worries, tension, joy, and demands. We also collected information regarding the following mental health problems: depression, anxiety, pathological worry, posttraumatic stress disorder (PTSD), and health anxiety; as well as retrospective measures of how participants felt they have changed in comparison to before the pandemic, ranging from worse to better. Results The analytical sample comprised 396 adult participants. On average, participants experienced increases in worries, tension, and lack of joy, and increases in mental health problems, but a decrease in demands. Perceived increases in symptoms of depression (26.0%) and PTSD (25.5%) were significantly more frequent than in symptoms of anxiety (particularly acute fear and panic) (5.6%), pathological worry (9.8%), and health anxiety (7.3%) (ps