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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 effects of panic disorder (PD) and pharmacotherapy on brain functional hubs in drug-free patients, and the utility of their degree centrality (DC) in diagnosing and predicting treatment response (TR) for PD, remained unclear., Aims: This study aimed to assess the effects of PD and paroxetine on brain functional hubs in drug-free patients and to identify neuroimaging biomarkers for diagnosing and predicting TR in patients with PD., Methods: Imaging data from 54 medication-free PD patients and 54 matched healthy controls (HCs) underwent DC and functional connectivity (FC) analyses before and after a 4-week paroxetine treatment. Diagnosis and prediction of TR models for PD were constructed using support vector machine (SVM) and support vector regression (SVR), with DC as features., Results: Patients with PD showed aberrant DC and FC in the anterior cingulum, temporal, and occipital areas compared with HCs at baseline. After treatment, DC of the patients increased in the calcarine cortex, lingual gyrus, and cerebellum IV/V, along with improved clinical symptoms. Utilizing voxel-wise DC values at baseline, the SVM effectively distinguished patients with PD from HCs with an accuracy of 83.33%. In SVR, the predicted TR significantly correlated with the observed TR (correlation coefficient ( r ) = 0.893, Mean Squared Error = 0.009)., Conclusion: Patients with PD exhibited abnormal DC and FC, notably in the limbic network, temporal, and occipital regions. Paroxetine ameliorated patients' symptoms while altering their brain FC. SVM and SVR models, utilizing baseline DC, effectively distinguished the patients from HCs and accurately predicted TR., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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).)

Panic disorder (PD) is a debilitating mental health condition, characterized by a preoccupation with the occurrence of panic attacks. Previous research has found that PD patients display increased fear generalization, which entails inflated fear responses to ambiguous stimuli (e.g., intermediate size circles) following fear conditioning wherein a neutral stimulus (e.g., large circle) gets paired with an aversive stimulus (e.g., electric shocks), whereas another neutral stimulus (e.g., small circle) is not paired with this aversive stimulus. The overgeneralization of fear to ambiguous stimuli may be a causal mechanism in the development of panic symptoms. However, this finding requires replication, particularly among subclinical groups to establish temporal priority of fear overgeneralization prior to the development of PD symptoms. This study examines whether fear generalization levels differ between individuals with high and low levels of some PD symptoms. Participants (N = 110) underwent fear conditioning and generalization, measuring physiological and self-report fear responses. Successful fear acquisition and generalization were observed. However, fear generalization did not significantly differ between groups with high and low PD symptomatology. These findings suggest that generalization observed in clinical populations might result from psychopathology rather than causing it. Using both clinical and subclinical samples in experimental psychopathology research is therefore important., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Panic disorder is a common disabling condition with limited biomarkers. We aimed to explore the diagnostic and treatment response prediction value of functional temporal variability in people with panic disorder., Methods: Patients with panic disorder and healthy controls received resting-state functional magnetic resonance imaging scans and assessments. After 2 weeks of treatment, the patients with panic disorder were divided into remitted (RPD; n = 39) or nonremitted (NRPD; n = 43) subgroups. Baseline temporal variability was analyzed between the panic disorder and control groups as well as between RPD and NRPD subgroups., Results: Our sample included 82 patients with panic disorder (39 RPD, 43 NRPD) and 105 controls. The panic disorder group showed decreased temporal variability in the left posterior cingulate gyrus (PCG), right lingual gyrus, right fusiform gyrus, and right thalamus (all p < 0.05, Bonferroni-corrected). A combination of variability in the lingual gyrus, PCG, and thalamus had optimal predictive value for distinguishing between the panic disorder and control groups (area under the curve = 0.776, sensitivity = 0.781, specificity = 0.732). In addition, the RPD subgroup showed significantly lower temporal variability in the left insula, right PCG, and bilateral lingual gyrus than the NRPD subgroup and control group (all p < 0.05, Bonferroni-corrected). Variability in the left insula and left lingual gyrus negatively correlated with the reduction rate of panic symptoms (all p < 0.05, Bonferroni-corrected)., Limitations: Functional brain images were collected only at baseline and may have been affected by medication use. Also, the follow-up period was only 2 weeks; sustained clinical remission may require longer follow-up., Conclusion: Combining lingual gyrus, PCG, and thalamus temporal variability alterations helped distinguish patients with panic disorder from healthy controls. The temporal variability in the insula and lingual gyrus are potential biomarkers for the treatment of panic disorder., Competing Interests: Competing interests:: None declared., (© 2024 CMA Impact Inc. or its licensors.)

Background: The cognitive theory of panic disorder proposes that individuals with panic disorder have a relatively enduring tendency to catastrophically misinterpret bodily sensations resulting in panic attacks., Aims: We investigated whether the evidence is consistent with the theory and its predictions, if updates are required and sought to identify future research considerations., Methods: We searched Scopus, Web of Science, PsycInfo, EMBASE, MEDLINE and CINAHL (1986 to July 2024). Inclusion criteria were studies collecting quantitative data derived from panic disorder patients, testing one of the predictions and using appropriate outcome measures. Exclusion criteria were non-English language publications, all participants under the age of 18 and studies that were not published in a peer-reviewed journal. Quality was assessed using 'QualSyst' and synthesis was based on each prediction tested. PROPSERO registration #CRD42022332211., Results: 53 studies were identified amongst 49 publications. There was substantial evidence for all predictions. Three studies did not support the prediction tested and none were inconsistent., Limitations: Most studies were 'medium' in quality and were predominately from female samples., Conclusions: Findings are consistent with the theory and its predictions. Higher quality research is needed and implications for future research are discussed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Paul Salkovskis conducts training from time to time on the treatment of panic disorder, for which he receives honoraria. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The network theory of psychopathology posits that mental disorders are systems of mutually reinforcing symptoms. This framework has proven highly generative but does not specify precisely how any specific mental disorder operates as such a system. Cognitive behavioral theories of mental disorders provide considerable insight into how these systems may operate. However, the development of cognitive behavioral theories has itself been stagnant in recent years. In this article, we advance both theoretical frameworks by developing a network theory of panic disorder rooted in cognitive behavioral theory and formalized as a computational model. We use this computational model to evaluate the theory's ability to explain five fundamental panic disorder-related phenomena. Our results demonstrate that the network theory of panic disorder can explain core panic disorder phenomena. In addition, by formalizing this theory as a computational model and using the model to evaluate the theory's implications, we reveal gaps in the empirical literature and shortcomings in theories of panic disorder. We use these limitations to develop a novel, theory-driven agenda for panic disorder research. This agenda departs from current research practices and places its focus on (a) addressing areas in need of more rigorous descriptive research, (b) investigating novel phenomena predicted by the computational model, and (c) ongoing collaborative development of formal theories of panic disorder, with explanation as a central criterion for theory evaluation. We conclude with a discussion of the implications of this work for research investigating mental disorders as complex systems. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Aim: The aim of the present study was to identify clinical and socio-demographic factors associated with duration of untreated illness (DUI) in patients affected by panic disorder (PD)., Methods: Data were collected from patients' medical records (N = 157) of two mental health services respectively located in Milan and in Monza (Italy). Correlation analyses and analysis of variance (ANOVAs) were run to analyse the relation between DUI and quantitative/qualitative variables respectively. Statistically significant variables in uni- variate analyses were then inserted in a linear multivariable regression model (backward procedure)., Results: Mean DUI was 27.33 (±50.56) months. Patients with an earlier age at onset (r = -0.270; p < .01), a longer duration of illness (r = 0.483; p < .01) and who received a lifetime psychotherapy (F = 6.86; p = .01) had a longer DUI. The final global model showed that a longer DUI was associated with pre-onset poly-substance misuse (p = .05) and a longer duration of illness (p < .01)., Conclusion: The results of our study showed that a longer DUI was predicted by clinical factors such as the presence of a pre-onset poly-substance use disorder and that delayed proper treatment can lead to a chronicization of PD, as indicated by a longer duration of illness. Further studies are needed to in-depth investigate the role of DUI in influencing the course and outcome of anxiety disorders, including PD., (© 2024 John Wiley & Sons Australia, Ltd.)

Importance: This report details a case of effectively managing severe panic attacks in a panic disorder (PD) patient with agoraphobia by acupuncture treatment., Case Presentation: A 38-year-old Japanese woman suffering from PD with agoraphobia presented at our acupuncture clinic with complaints of repeated panic attacks and anxiety. Initially starting to experience symptoms in her late teens, she avoided psychiatric consultation due to reluctance toward psychotropic medications. An unbiased psychiatrist used the Panic Disorder Severity Scale (PDSS) to assess her PD severity. The PDSS score decreased from 21 on the first to 12 points on the sixth visit. The patient experienced reduced frequency and severity of panic attacks, with restored confidence to go into public despite agoraphobia., Conclusions and Relevance: This is the first report to demonstrate the effectiveness of acupuncture on PD with agoraphobia using PDSS, suggesting its potential as a nonpharmacological treatment for patients with PD and agoraphobia.

Abnormal functional connectivity (FC) within the fear network model (FNM) has been identified in panic disorder (PD) patients, but the specific local structural and functional properties, as well as effective connectivity (EC), remain poorly understood in PD. The purpose of this study was to investigate the structural and functional patterns of the FNM in PD. Magnetic resonance imaging data were collected from 33 PD patients and 35 healthy controls (HCs). Gray matter volume (GMV), degree centrality (DC), regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) were used to identify the structural and functional characteristics of brain regions within the FNM in PD. Subsequently, FC and EC of abnormal regions, based on local structural and functional features, and their correlation with clinical features were further examined. PD patients exhibited preserved GMV, ReHo, and ALFF in the brain regions of the FNM compared with HCs. However, increased DC in the bilateral amygdala was observed in PD patients. The amygdala and its subnuclei exhibited altered EC with rolandic operculum, insula, medial superior frontal gyrus, supramarginal gyrus, opercular part of inferior frontal gyrus, and superior temporal gyrus. Additionally, Hamilton Anxiety Scale score was positively correlated with EC from left lateral nuclei (dorsal portion) of amygdala to right rolandic operculum and left superior temporal gyrus. Our findings revealed a reorganized functional network in PD involving brain regions regulating exteroceptive-interoceptive signals, mood, and somatic symptoms. These results enhance our understanding of the neurobiological underpinnings of PD, suggesting potential biomarkers for diagnosis and targets for therapeutic intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Patients who have experienced child abuse often have complex clinical presentations; whether a history of child abuse (HCA) affects psychotherapy outcomes is unclear. The authors examined relationships between HCA, clinical baseline variables, and change in these variables after three different psychotherapies for panic disorder (PD)., Methods: Two hundred adults with PD (with or without agoraphobia) were randomly assigned to one of three treatments across two sites: panic-focused psychodynamic psychotherapy (PFPP), cognitive-behavioral therapy (CBT), or applied relaxation training (ART). Differences in demographic and clinical variables between those with and without HCA were compared. The primary analysis addressed odds of meeting clinical response criteria on the Panic Disorder Severity Scale (PDSS) between treatments, as moderated by HCA. This effect was examined via continuous outcomes on the PDSS and psychosocial functioning (Sheehan Disability Scale)., Results: Compared with patients without HCA (N=154), patients with HCA (N=46) experienced significantly more severe symptoms of PD (d=0.60), agoraphobia (d=0.47), and comorbid depression (d=0.46); significantly worse psychosocial impairment (d=0.63) and anxiety sensitivity (d=0.75); greater personality disorder burden (d=0.45)-particularly with cluster C disorders (d=0.47)-and more severe interpersonal problems (d=0.54). HCA significantly moderated the likelihood of clinical response, predicting nonresponse to ART (B=-2.05, 95% CI=-4.17 to -0.30, OR=0.13, z=-2.14, p=0.032) but not CBT or PFPP. HCA did not interact with treatment condition to predict slopes of PDSS change., Conclusions: The results of this study highlight the importance of HCA in formulating treatment recommendations. Increased awareness of HCA's effects on severity of PD and treatment responsiveness among patients with PD may improve outcomes., Competing Interests: Dr. Milrod reports receiving book royalties from the Taylor & Francis Group. Dr. Barber reports receiving book royalties from Guilford Press and Cambridge University Press. The other authors report no financial relationships with commercial interests. Holly A. Swartz, M.D., Editor of the journal, was the decision editor during peer review.

Purpose: This study examined the relationship between structural brain networks and long-term treatment outcomes in patients with panic disorder (PD) using machine learning methods., Method: The study involved 80 participants (53 PD patients and 27 healthy controls) and included clinical assessments and MRI scans at baseline and after two years (160 MRIs). Patients were categorized based on their response to two-year pharmacotherapy. Brain networks were analyzed using white matter tractography and network-based statistics., Results: Results showed structural network changes in PD patients, particularly in the extended fear network, including frontal regions, thalamus, and cingulate gyrus. Longitudinal analysis revealed that increased connections to the amygdala, hippocampus, and insula were associated with better treatment response. Conversely, overconnectivity in the amygdala and insula at baseline was associated with poor response, and similar patterns were found in the insula and parieto-occipital cortex related to non-remission. This study found that SVM and CPM could effectively predict treatment outcomes based on network pattern changes in PD., Conclusions: These findings suggest that monitoring structural connectome changes in limbic and paralimbic regions is critical for understanding PD and tailoring treatment. The study highlights the potential of using personalized biomarkers to develop individualized treatment strategies for PD., Competing Interests: Declaration of Competing Interest All authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The association between childhood separation anxiety disorder (CSAD) and panic disorder (PD) has been demonstrated, although some findings are contradictory. The separation anxiety hypothesis postulates that both CSAD and PD encompass a heightened sensitivity to carbon dioxide (CO 2 ). Patients with the respiratory subtype (RS) of PD are known to be more sensitive to CO 2 than those from the nonrespiratory subtype (NRS). Therefore, the primary objective centered on the comparative analysis of CSAD prevalence between RS and NRS groups, with secondary objectives focusing on the comparative assessment of RS and NRS groups and the control group., Methods: Sixty RS-PD patients, 60 NRS-PD patients, and 60 controls were assessed for retrospective diagnosis of CSAD between March 2020 and August 2023 using a diagnostic categorical instrument, DSM-5 criteria, and a dimensional one, the Separation Anxiety Symptom Inventory., Results: RS patients had a significantly greater history of CSAD (55%) compared to the NRS (23%) and control (17%) groups ( P < .001), which shows stronger association with the RS group. As seen in logistic regression, RS patients had 3.02 more chances of having CSAD when compared the NRS group and 5.11 when compared to the control group, which shows stronger association with the RS group., Conclusion: This study supports the hypothesis that RS-PD is associated with CSAD, while there is a weak association between NRS-PD and CSAD. It is advisable for clinicians to screen individuals with RS-PD for symptoms of separation anxiety, as these symptoms may have a negative impact on the prognosis of PD., Prim Care Companion CNS Disord 2024;26(5):24m03709 ., Author affiliations are listed at the end of this article., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

HTR1A C-1019G polymorphism (rs6295) and serotonin transporter promoter polymorphism (5-HTTLPR) have been linked with panic disorder (PD) in different ethnic backgrounds. Both these polymorphisms are in the promoter regions. However, results are inconsistent and contrasting evidence makes reliable conclusions even more challenging. A meta-analysis was conducted to test whether C-1019G polymorphism and 5-HTTLPR were involved in the etiology of PD. Articles researching the link between C-1019G, 5-HTTLPR polymorphisms, and PD were retrieved by database searching and systematically selected on the basis of selected inclusion parameters. 21 studies were included that examined the relationship of rs6295,5-HTTLPR polymorphisms with PD risk susceptibility (rs62957 polymorphism - 7 articles, and 5-HTTLPR polymorphism - 14 articles). A significant association was seen between the rs6295 polymorphism and PD pathogenesis, especially in Caucasian PD patients. No significant genetic linkage was found between the 5-HTTLPR polymorphism and PD. C-1019G polymorphism was involved in the etiology of PD in Caucasian patients. The 5-HTTLPR polymorphism was not a susceptibility factor of PD.

Abstract 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).

Abstract 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.

Objective: Panic disorder is a modestly heritable condition. Currently, diagnosis is based only on clinical symptoms; identifying objective biomarkers and a more reliable diagnostic procedure is desirable. We investigated whether people with panic disorder can be reliably diagnosed utilizing combinations of multiple polygenic scores for psychiatric disorders and their intermediate phenotypes, compared with single polygenic score approaches, by applying specific machine learning techniques., Methods: Polygenic scores for 48 psychiatric disorders and intermediate phenotypes based on large-scale genome-wide association studies ( n = 7556-1,131,881) were calculated for people with panic disorder ( n = 718) and healthy controls ( n = 1717). Discrimination between people with panic disorder and healthy controls was based on the 48 polygenic scores using five methods for classification: logistic regression, neural networks, quadratic discriminant analysis, random forests and a support vector machine. Differences in discrimination accuracy (area under the curve) due to an increased number of polygenic score combinations and differences in the accuracy across five classifiers were investigated., Results: All five classifiers performed relatively well for distinguishing people with panic disorder from healthy controls by increasing the number of polygenic scores. Of the 48 polygenic scores, the polygenic score for anxiety UK Biobank was the most useful for discrimination by the classifiers. In combinations of two or three polygenic scores, the polygenic score for anxiety UK Biobank was included as one of polygenic scores in all classifiers. When all 48 polygenic scores were used in combination, the greatest areas under the curve significantly differed among the five classifiers. Support vector machine and logistic regression had higher accuracy than quadratic discriminant analysis and random forests. For each classifier, the greatest area under the curve was 0.600 ± 0.030 for logistic regression (polygenic score combinations N = 14), 0.591 ± 0.039 for neural networks ( N = 9), 0.603 ± 0.033 for quadratic discriminant analysis ( N = 10), 0.572 ± 0.039 for random forests ( N = 25) and 0.617 ± 0.041 for support vector machine ( N = 11). The greatest areas under the curve at the best polygenic score combination significantly differed among the five classifiers. Random forests had the lowest accuracy among classifiers. Support vector machine had higher accuracy than neural networks., Conclusions: These findings suggest that increasing the number of polygenic score combinations up to approximately 10 effectively improved the discrimination accuracy and that support vector machine exhibited greater accuracy among classifiers. However, the discrimination accuracy for panic disorder, when based solely on polygenic score combinations, was found to be modest., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

The role of schemas is well established in personality disorders. Their influence on therapy outcome of patients with Axis I disorders remains unclear. Therefore, patients with a panic disorder (PD) with/without agoraphobia varying in their expression of early maladaptive schemas were examined regarding therapy outcomes after exposure therapy. In this study, a sample of 216 patients with panic disorder with/without agoraphobia were recruited in a day clinic. After the initial diagnosis with the Structured Clinical Interview, the patients filled out the Young Schema Questionnaire (YSQ-S2), Beck Depression Inventory and Revised Symptom Checklist. Afterwards, they participated in a five-week manualized exposure therapy by Lang et al. (2011). Subjects with high schema scores showed lower therapeutic success rates than subjects with a weaker pattern score. In addition, it was found that high schema levels, especially of schemas regarding impaired autonomy and achievement (YSQ-S2: domain 2), influenced therapy outcome by either predicting more/severe or less/milder anxiety-, phobicrelated and general symptoms after therapy. The results of this study emphasize the role of schemas not only for personality disorders but also for disorders on Axis I. For PD with/without agoraphobia, schemas regarding impaired autonomy and achievement seem to play the most important role regarding the influence on therapy outcome.

This systematic review addresses the complex nature of Panic Disorder (PD), characterized by recurrent episodes of acute fear, with a focus on updating and consolidating knowledge regarding neurochemical, genetic, and epigenetic factors associated with PD. Utilizing the PRISMA methodology, 33 original peer-reviewed studies were identified, comprising 6 studies related to human neurochemicals, 10 related to human genetic or epigenetic alterations, and 17 animal studies. The review reveals patterns of altered expression in various biological systems, including neurotransmission, the Hypothalamic-Pituitary-Adrenal (HPA) axis, neuroplasticity, and genetic and epigenetic factors leading to neuroanatomical modifications. Noteworthy findings include lower receptor binding of GABAA and serotonin neurotransmitters in the amygdala. The involvement of orexin (ORX) neurons in the dorsomedial/perifornical region in triggering panic reactions is highlighted, with systemic ORX-1 receptor antagonists blocking panic responses. Elevated Interleukin 6 and leptin levels in PD patients suggest potential connections between stress-induced inflammatory changes and PD. Brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) signaling are implicated in panic-like responses, particularly in the dorsal periaqueductal gray (dPAG), where BDNF's panicolytic-like effects operate through GABAA-dependent mechanisms. GABAergic neurons' inhibitory influence on dorsomedial and posterior hypothalamus nuclei is identified, potentially reducing the excitability of neurons involved in panic-like responses. The dorsomedial hypothalamus (DMH) is highlighted as a specific hypothalamic nucleus relevant to the genesis and maintenance of panic disorder. Altered brain lactate and glutamate concentrations, along with identified genetic polymorphisms linked to PD, further contribute to the intricate neurochemical landscape associated with the disorder. The review underscores the potential impact of neurochemical, genetic, and epigenetic factors on the development and expression of PD. The comprehensive insights provided by this systematic review contribute to advancing our understanding of the multifaceted nature of Panic Disorder and pave the way for targeted therapeutic strategies., (© 2024. The Author(s).)

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

The aim of this study is to investigate the effectiveness of Eye Movement Desensitization and Reprocessing (EMDR) treatment in adolescents with panic disorder (PD). This follow-up study consists of 30 adolescents with PD without agoraphobia, aged 14-17 (15.53 ± .97). They were evaluated with Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Present, also the Panic and Agoraphobia Scale (PAS) and Beck Anxiety Inventory (BAI) were administered at baseline, at the end of the 4th and 12th weeks of treatment. EMDR therapy which is an eight-phase treatment approach composed of standardized protocols and procedures was applied for 12 weeks, one session per week. The baseline mean of the total PAS score decreased from 40.06 to 13.13 at fourth week and 1.2 at the end of 12th week of treatment. In addition, BAI score decreased significantly from 33.67 to 13.83 at 4 weeks and 5.31 at the end of 12 th week of treatment. Overall, our results underscore the effectiveness of EMDR in adolescents with PD. Moreover, the current study suggests that EMDR may represent an effective intervention technique for PD in adolescents to protect against relapses and to overcome a fear of future attacks., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: The persistent stigma associated with mental health conditions is a major challenge worldwide. Celebrities may improve this by openly discussing their own mental health issues, potentially influencing public attitudes and encouraging individuals to seek treatment for these conditions., Objective: To evaluate the impact of celebrity mental health disclosures on the incidence and prevalence of panic disorder diagnosis in South Korea., Design, Setting, and Participants: This cohort study included the entire South Korean population from January 2004 to December 2021, as reflected in the National Health Insurance Service data. Analysis was conducted from May 2022 through January 2024., Exposure: Time periods analyzed included the timeframe before (from January 2004 to December 2010) and after the public disclosures of panic disorder by 3 high-profile Korean celebrities between December 2010 and January 2012 (from January 2011 to December 2021)., Main Outcomes and Measures: Monthly incidence and prevalence of panic disorder, defined by the presence of a clinical diagnosis of the condition. Trends were assessed using interrupted time series analysis with autoregressive integrated moving average models. To assess public interest in panic disorder, trends in search data were analyzed, examining the association between the timing of increased searches and changes in the incidence and prevalence of panic disorder. Data on obsessive-compulsive disorder (OCD) were included as a control., Results: The study covered the entire population of South Korea, including 48 559 946 individuals in January 2004 and 52 593 886 individuals in December 2021. Before 2011, the mean (SD) annual prevalence of panic disorder was stable at 560 (140) persons per 100 000 persons per year. The celebrity disclosure in December 2010 was associated with higher monthly incidence rates of panic disorder, as measured by insurance claims data, changes that were observed in both the level (5.8 persons; 95% CI, 2.2-9.5 persons) and slope (0.78 persons per month; 95% CI, 0.19-1.40 persons per month) per 100 000 persons. By 2021, the observed annual prevalence per 100 000 persons reached 7530 persons, an increase of 775.6% compared with the 860 persons (95% CI, 330-1400 persons) estimated if the disclosures had not occurred. Internet searches anticipated changes in monthly prevalence with a lag of 2 or 3 months (F = 4.26, P = .02 and F = 3.11, P = .03, respectively). The celebrity disclosures had no significant association with the incidence or prevalence of OCD., Conclusions and Relevance: In this observational cohort study, celebrity disclosure of mental health conditions was associated with a sustained reduction in stigma, as reflected in increased help-seeking behavior for the condition over more than a decade. This underscores the influential role celebrities can play in shaping public health perceptions and behaviors, offering valuable insights for the development of future mental health policies and public awareness campaigns.

Importance: This report details a case of effectively managing severe panic attacks in a panic disorder (PD) patient with agoraphobia by acupuncture treatment. Case presentation: A 38-year-old Japanese woman suffering from PD with agoraphobia presented at our acupuncture clinic with complaints of repeated panic attacks and anxiety. Initially starting to experience symptoms in her late teens, she avoided psychiatric consultation due to reluctance toward psychotropic medications. An unbiased psychiatrist used the Panic Disorder Severity Scale (PDSS) to assess her PD severity. The PDSS score decreased from 21 on the first to 12 points on the sixth visit. The patient experienced reduced frequency and severity of panic attacks, with restored confidence to go into public despite agoraphobia. Conclusions and Relevance: This is the first report to demonstrate the effectiveness of acupuncture on PD with agoraphobia using PDSS, suggesting its potential as a nonpharmacological treatment for patients with PD and agoraphobia.

This study aimed to detect alterations in interhemispheric interactions in patients with panic disorder (PD), determine whether such alterations could serve as biomarkers for the diagnosis and prediction of therapeutic outcomes, and map dynamic changes in interhemispheric interactions in patients with PD after treatment. Fifty-four patients with PD and 54 healthy controls (HCs) were enrolled in this study. All participants underwent clinical assessment and a resting-state functional magnetic resonance imaging scan at (i) baseline and (ii) after paroxetine treatment for 4 weeks. A voxel-mirrored homotopic connectivity (VMHC) indicator, support vector machine (SVM), and support vector regression (SVR) were used in this study. Patients with PD showed reduced VMHC in the fusiform, middle temporal/occipital, and postcentral/precentral gyri, relative to those of HCs. After treatment, the patients exhibited enhanced VMHC in the lingual gyrus, relative to the baseline data. The VMHC of the fusiform and postcentral/precentral gyri contributed most to the classification (accuracy = 87.04%). The predicted changes were accessed from the SVR using the aberrant VMHC as features. Positive correlations (p < 0.001) were indicated between the actual and predicted changes in the severity of anxiety. These findings suggest that impaired interhemispheric coordination in the cognitive-sensory network characterized PD and that VMHC can serve as biomarkers and predictors of the efficiency of PD treatment. Enhanced VMHC in the lingual gyrus of patients with PD after treatment implied that pharmacotherapy recruited the visual network in the early stages., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Panic disorder is a serious anxiety disorder that can significantly impact an individual's mental health. If left undetected, this disorder can disrupt daily life, social relationships, and overall quality of life. Early detection and intervention are crucial for managing panic disorder and improving the well-being of those affected. Technology plays a pivotal role in facilitating early detection through data-driven approaches that employ algorithms to identify patterns of behavior or symptoms associated with panic disorder. Accurate classification of panic disorder is crucial for effective diagnosis and treatment. However, machine learning models trained on imbalanced datasets, such as those containing panic disorder patients, are prone to overfitting, leading to poor generalization performance. This study investigates the effectiveness of the Synthetic Minority Oversampling Technique (SMOTE) in addressing overfitting in panic disorder dataset classification using the Random Forest algorithm. The results demonstrate that SMOTE significantly improves the classification performance of Random Forest. By mitigating overfitting and improving generalization to unseen data, SMOTE increases accuracy by 15 percentage points. Before using SMOTE, the accuracy was 82%, and after using SMOTE it is 97%. The findings underscore the promise of SMOTE as a tool for boosting the performance of machine learning algorithms in classifying panic disorder from imbalanced data.

Background: Non-cardiac chest pain, a term that serves as a broad canvas, has a multitude of potential causes in which panic disorder emerges as a prevailing cause. The recognition and accurate diagnosis of panic disorder among patients with non-cardiac chest pain is important. Hence a study was conducted to understand the prevalence of panic disorder among patients with non-cardiac chest pain in a tertiary care center in Kerala. Methods: A hospital-based, cross-sectional study was done among 118 patients who were diagnosed with non-cardiac chest pain by a cardiologist. The study was conducted in the cardiology OPD in a tertiary care center in Kerala. Mini-International Neuropsychiatric Interview Panic disorder – Version 6.0.0 (M.I.N.I.) was used to diagnose panic disorder among these patients. Results: It was found that panic disorder was present in 39.8% (95% Confidence Interval - 30.9-49.3%). Conclusion: The prevalence of panic disorder in patients diagnosed with non-cardiac chest pain was 39.8%. Consultation liaison treatment using pharmacotherapy and/or psychotherapy with the help of a psychiatrist may benefit such patients.

Clinical observations suggest that individuals with panic disorder (PD) vary in their beliefs about the causes of their panic attacks. Some attribute these attacks to psychological factors, while others to physiological or medical factors. These beliefs also extend to whether individuals perceive panic attacks as dangerous. In other areas of psychiatric nosology, these phenomena are commonly called clinical insight (recognition of disorder and the need for treatment) and cognitive insight (the ability to reflect on one's beliefs). Despite its importance, limited research exists on insight in PD and its relation to symptoms and treatment outcomes. This study examines clinical and cognitive insight in 83 patients with PD who received internet-based cognitive behavioral therapy, investigating their relationship with symptoms, treatment outcomes, and changes in insight. We assessed patients using interview and self-report measures of insight and symptoms. Clinical and cognitive insight were correlated and both constructs improved significantly during treatment. Good clinical insight pretreatment was positively correlated with more severe pretreatment symptoms. Pretreatment clinical and cognitive insight were not correlated with symptom change or attrition. Greater change in clinical and cognitive insight was related to greater change in symptoms. The findings highlight the significance of clinical and cognitive insight in PD, and the importance of distinguishing between them. This suggests the need to develop interventions according to patients' level of insight, particularly focusing on those lacking insight. Further research is essential to advance our understanding of the relationship between insight and the phenomenology and treatment of PD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Panic disorder (PD) may cause serious cardiac arrhythmias by causing electrical abnormalities. Abnormal P-wave axis (aPwa), presence of fragmented QRS (fQRS), wide frontal QRS-T angle (fQRSTa), QRS duration corrected (QRSdc) and log/ logQRS duration/RR interval (log/logQRS/RR) have been correlated with increased risk of serious supraventricular and ventricular cardiac arrhythmias in a general population. The purpose of this study was to compare these newly explored atrial and ventricular arrhythmia indicators in patients with PD and in healthy subjects., Method: A total of 169 newly diagnosed PD patients and 128 healthy subjects were included in the study. The Panic and Agoraphobia Scale (PAS) was administered, and 12-lead electrocardiography (ECG) measurements were obtained. Electrocardiographic parameters including aPwa, fQRSTa, presence of fQRS, QRS duration corrected (QRSdc), and log/logQRS duration/RR distance (log/logQRS/RR) were compared between the two groups., Results: aPwa and fQRS, in addition to fQRSTa, QRSdc, and log/ logQRS/RR ratio values, were significantly increased in the PD group compared to healthy controls. Correlation analyses revealed that wider fQRSTa, number of fQRS derivation, number of total fQRS, wider QRSdc, and log/logQRS/RR ratio significantly correlated with PAS score. Logistic regression analysis demonstrated that fQRSTa and the number of total fQRS were independently associated with PD., Conclusion: PD is associated with wider fQRSTa, QRSdc, and log/logQRS/RR in addition to the increased abnormal aPwa and presence of fQRS. These findings suggest that untreated PD patients may be susceptible to supraventricular and ventricular arrhythmia, indicating that ECG should be routinely obtained in the management of PD patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Sudden gains occur in a range of disorders and treatments and are of clinical and theoretical significance if they can shed light on therapeutic change processes. This study investigated the relationship between sudden gains in panic symptoms and preceding cognitive change during cognitive behavioural therapy (CBT) for panic disorder., Method: Participants with panic disorder completed in session measures of panic symptoms and catastrophic cognitions. Independent samples t -tests were used to compare the post-treatment score of those who met criteria for one or more sudden gain during treatment with those who did not, and to compare within-session cognitive change between pre-sudden gain sessions and the previous (control) session., Results: Twenty-two (42%) of 53 participants experienced a sudden gain during treatment. Participants demonstrating a sudden gain showed more improvement in panic symptoms from pre- to post-treatment than those without a sudden gain. The within-session cognitive change score in the pre-gain session was significantly greater than in the control session., Conclusions: Sudden gains occurred in individual CBT for panic disorder and within-session cognitive change was associated with sudden gains. This is consistent with the cognitive model of panic disorder and highlights how sudden gains can help to identify key change processes.

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., Competing Interests: Declaration of Competing Interest This study was conducted on the basis of a proof-of-concept (POC) version of a virtual-reality-based treatment program for panic disorder and agoraphobia. This version was commissioned by Hallym University and developed by Orcasoft (Chuncheon, Gangwon, Republic of Korea). The technical advice and support for this study were provided by nGarden (Daegu, Republic of Korea). Currently, Hallym University College of Medicine has no direct affiliation with Orcasoft and nGarden, but the treatment principles or concepts established in this study may influence future digital therapeutics for panic disorder and agoraphobia that are being developed at Hallym University., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)