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.

BACKGROUND: Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR).
METHODS: To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran\'s Q-test and the MR Egger intercept test.
RESULTS: The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209-2.021, P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044-1.324, P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062-2.345; P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039-1.425, P = 0.015).
CONCLUSIONS: Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs.

BACKGROUND: Despite the availability of pharmacotherapy and psychotherapy for treating obsessive-compulsive disorder (OCD), alternative approaches need to be explored due to the high likelihood of treatment resistance. Neuronavigated 20 Hz theta burst stimulation (TBS-20 Hz), targeting the bilateral dorsolateral prefrontal cortex (DLPFC) augmented with the right orbitofrontal cortex (ROFC), was tested for treating OCD comorbid with depression and anxiety disorders.
METHODS: A retrospective chart review was performed on fourteen patients treated for moderate-to-severe OCD in a private outpatient clinic. Twelve patients had comorbid major depressive disorder (MDD), and thirteen patients had either generalized anxiety disorder (GAD) or panic disorder (PD). Patients completed the Y-BOCS-SR, BDI-II, and BAI rating scales weekly, which were used to measure the changes in OCD, depression, and anxiety symptoms, respectively.
RESULTS: Neuronavigated TBS-20 Hz was sequentially applied to the right DLPFC (RDLPFC), left DLPFC (LDLPFC), and ROFC. A total of 64% (9/14) of patients achieved remission from OCD (Y-BOCS-SR ≤ 14) in an average of 6.1 weeks of treatment (SD = 4.0). A total of 58% (7/12) of patients remitted from MDD (BDI < 13) in an average of 4.1 weeks (SD = 2.8), and 62% (8/13) of patients remitted from GAD/PD (BAI < 8) in an average of 4.3 weeks (SD = 2.5).
CONCLUSIONS: The neuronavigated TBS-20 Hz sequential stimulation of RDLPFC and LDLPFC, followed by ROFC, significantly reduced OCD, MDD, and GAD/PD symptoms. Randomized sham controls are warranted to validate these results.

Musculoskeletal chronic pain is a leading cause of global disability and laboral incapacity. However, there is a lack of population-based studies that investigate the relationship between chronic pain and mental disorders with a control group, particularly among low- and middle-income countries. Chronic pain is a serious public health problem in terms of human suffering, and in terms of socioeconomic implications. Frequent association with different mental disorders increases disability, decreases quality of life, and makes diagnosis and treatment challenging. The present study aimed to evaluate the presence of mental disorders in patients with chronic musculoskeletal pain and compare with a control group without pain.
We selected 100 patients in a regular follow-up at the Musculoskeletal Pain Outpatient Clinic of the University Hospital and compared them with 100 painless individuals from the control group from June 2016 to June 2018. The instruments used were the Mini International Neuropsychiatric Interview (MINI-PLUS) and a structured questionnaire to collect sociodemographic data. Statistical analysis used t-test, chi-square, Fisher\'s exact test, Mann-Whitney, Kolmogorov-Smirnov tests, and multiple logistic regression.
In the sample evaluated, the majority of patients were women (83%), of brown color (54%), with lower-level education (51%), lower salary range (73%) and high absenteeism rate at work (60,7%). Patients with chronic pain had more psychiatric disorders (88% vs. 48% in the control group; p < 0.001). The most frequent diagnoses were anxiety disorders with panic attacks (44%), generalized anxiety (36%), mixed anxiety and depression disorder (33%), social phobia (30%), agoraphobia (29%), suicide risk (28%), and major depression (27%).
Positive correlations of mental disorders and chronic musculoskeletal pain have been documented. This suggests that psychiatric components must be taken into account in the management of chronic pain syndromes. The use of Mini Plus as a diagnostic tool for psychiatric disorders can contribute to optimizing the diagnosis and treatment of patients with chronic pain and encourage the creation of policies with strategies and criteria for quick access to Multi-professional Services.

BACKGROUND: Panic disorder is a common and important disease in clinical practice that decreases individual productivity and increases health care use. Treatments comprise medication and cognitive behavioral therapy. However, adverse medication effects and poor treatment compliance mean new therapeutic models are needed.
OBJECTIVE: We hypothesized that digital therapy for panic disorder may improve panic disorder symptoms and that treatment response would be associated with brain activity changes assessed with functional near-infrared spectroscopy (fNIRS).
METHODS: Individuals (n=50) with a history of panic attacks were recruited. Symptoms were assessed before and after the use of an app for panic disorder, which in this study was a smartphone-based app for treating the clinical symptoms of panic disorder, panic symptoms, depressive symptoms, and anxiety. The hemodynamics in the frontal cortex during the resting state were measured via fNIRS. The app had 4 parts: diary, education, quest, and serious games. The study trial was approved by the institutional review board of Chung-Ang University Hospital (1041078-202112-HR-349-01) and written informed consent was obtained from all participants.
RESULTS: The number of participants with improved panic symptoms in the app use group (20/25, 80%) was greater than that in the control group (6/21, 29%; χ21=12.3; P=.005). During treatment, the improvement in the Panic Disorder Severity Scale (PDSS) score in the app use group was greater than that in the control group (F1,44=7.03; P=.01). In the app use group, the total PDSS score declined by 42.5% (mean score 14.3, SD 6.5 at baseline and mean score 7.2, SD 3.6 after the intervention), whereas the PDSS score declined by 14.6% in the control group (mean score 12.4, SD 5.2 at baseline and mean score 9.8, SD 7.9 after the intervention). There were no significant differences in accumulated oxygenated hemoglobin (accHbO2) at baseline between the app use and control groups. During treatment, the reduction in accHbO2 in the right ventrolateral prefrontal cortex (VLPFC; F1,44=8.22; P=.006) and the right orbitofrontal cortex (OFC; F1,44=8.88; P=.005) was greater in the app use than the control group.
CONCLUSIONS: Apps for panic disorder should effectively reduce symptoms and VLPFC and OFC brain activity in patients with panic disorder. The improvement of panic disorder symptoms was positively correlated with decreased VLPFC and OFC brain activity in the resting state.
BACKGROUND: Clinical Research Information Service KCT0007280; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=21448.

Due to a dearth of evidence, we examined the effectiveness of brief-intensive CBT on symptom severity and catastrophic cognition in patients with panic disorder (PD).
In this randomized controlled trial, 155 patients were assigned to either the experimental group (2 successive days of brief-intensive CBT-3 h per day) or the control group (regular pharmacotherapy only). After excluding ineligible participants, 20 patients in the brief intensive CBT group and 18 patients in the control group completed the study and were included in the final analysis. The primary outcome was symptom severity, and the secondary outcome was catastrophic cognition, assessed by the Panic Disorder Severity Scale (PDSS) for symptoms severity and the Agoraphobic Cognition Scale (ACS) for cognitive assessment, respectively.
The study showed that after one month of treatment, the PDSS (1.70 vs. 4.78; p = 0.0172) in the brief-intensive CBT group was significantly lower compared to the control group in contrast with the ACS (5.10 vs. 5.44; p = 0.8533). The mean score of PDSS and ACS significantly decreased from 21.60 to 1.7 (p < 0.0001) and from 22.55 to 5.10 (p < 0.0001) in the brief CBT group and from 19.44 to 4.78 (p < 0.0001) and 20.00 to 5.44 (p < 0.0001) in the control group, respectively. After treatment, the mean scores of PDSS and ACS significantly decreased in the brief intensive CBT and control groups. Both higher ACS and lower education levels contributed to higher PDSS in the brief intensive CBT group. However, only the PDSS correlated to the ACS in the control group.
The study showed that brief-intensive CBT is an effective technique for reducing the severity of symptoms among PD patients. But, it was not effective to improve the cognitive level in PD patients at one month.

BACKGROUND: Panic disorder (PD) involves emotion dysregulation, but its underlying mechanisms remain poorly understood. Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance. However, there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.
OBJECTIVE: To study the neural mechanisms of implicit emotion regulation in PD with event-related potentials (ERP).
METHODS: A total of 25 PD patients and 20 healthy controls (HC) underwent clinical eva-luations. The study utilized a case-control design with random sampling, selecting participants for the case group from March to December 2018. Participants performed an affect labeling task, using affect labeling as the experimental condition and gender labeling as the control condition. ERP and behavioral data were recorded to compare the late positive potential (LPP) within and between the groups.
RESULTS: Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling. In the HC group, late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease. Importantly, a significant group × condition interaction effect was observed. Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group. Furthermore, among PD patients under the affect labeling, the late LPP was negatively correlated with disease severity, symptom frequency, and intensity.
CONCLUSIONS: PD patients demonstrate abnormalities in implicit emotion regulation, hampering their ability to mobilize cognitive resources for downregulating negative emotions. The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.

BACKGROUND: Individuals wrestling with panic disorder (PD) know all too well its debilitating impact. Sudden, intense fear episodes disrupt lives and erode well-being. Fortunately, integrating complementary therapies like yoga with standard treatment offers a glimmer of hope for improved outcomes. Yoga\'s unique blend of physical postures (asanas), breathing exercises (pranayama), and meditative practices holds promise for mitigating anxiety and fostering a sense of inner peace, potentially making it a valuable tool in the fight against panic disorder.
METHODS: This study investigated the effect of yoga as an adjuvant to standard care for panic disorder. Sixty-four panic disorder patients of both genders previously diagnosed with panic disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria were randomly assigned to the yoga group (n = 32) and the control group. The yoga group participated in integrated yoga sessions lasting 60 minutes, five days a week, for 12 weeks. Both groups received standard care. Pre- and post-intervention data were collected for HAM-A and WHOQOL-BREF.
RESULTS: The yoga group exhibited a significant reduction in HAM-A scores (Pre: 49.13 ± 4.55, Post: 13.53 ± 5.54, p < 0.001) with a substantial effect size of 7.02. Quality of life significantly improved across all domains (physical, psychological, social, and environmental) in the yoga group (p < 0.001), demonstrating effect sizes ranging from 4.11 to 4.57. Control group participants also experienced improvements, though less pronounced. Between-group comparisons revealed significant differences in anxiety reduction (p = 0.042) and quality of life enhancement (p < 0.001), favouring the yoga group.
CONCLUSIONS: The results suggest that yoga can be a valuable complementary or alternative approach to traditional treatments for anxiety disorders.

BACKGROUND: Cognitive behavioral therapy (CBT) is effective in treating anxiety disorders. Accessibility to CBT has been limited in Japan due to the shortage of therapists. While an open-source e-learning system can be used to create a simple internet-based cognitive behavioral therapy (ICBT) program, the safety and outpatient acceptance of this treatment approach have not been explored in Japan.
OBJECTIVE: The aim of this study was to investigate whether outpatients with anxiety disorders could accept and successfully complete the ICBT program with guidance by CBT therapists when implementing therapeutic modules and CBT tasks. Due to being in the initial phase of a novel treatment in Japan, this study was intended for verification with a small sample size.
METHODS: In total, 6 adults, including 4 male participants and 2 female participants, were enrolled in a single-arm trial. The intervention involved guided ICBT comprising 12 sessions, including CBT text, comprehension confirmation tests, and explanatory videos about cognitive behavioral models, accessible through a website. The therapist guided the participants in accessing the ICBT program and answering their questions using a chat tool. The primary outcome was anxiety severity assessed using the State-Trait Anxiety Inventory-Trait. Secondary outcomes included the Panic Disorder Severity Scale, Liebowitz Social Anxiety Scale (LSAS), Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Working Alliance Inventory-Short Form (WAI-SF). Statistical analyses were performed using paired 2-tailed t tests to assess the changes in clinical symptoms. The total WAI-SF score at the final session was used to evaluate the therapeutic alliance. For statistical analyses, mean changes for total State-Trait Anxiety Inventory-Trait, BAI, Panic Disorder Severity Scale, LSAS, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 scores were analyzed using the paired 2-tailed t test. The 2-sided significance level for hypothesis testing was set at 5%, and 2-sided 95% CIs were calculated.
RESULTS: Most participants diligently engaged with the ICBT program. No adverse events were reported. The mean total scores for the primary outcome decreased by 11.0 (SD 9.6) points (95% CI -22.2 to 0.20; Hedges g=0.95), but it was not statistically significant. The mean total scores for the secondary outcomes that assess clinical symptoms decreased, with a significant reduction observed in the BAI of 15.7 (SD 12.1) points (95% CI -28.4 to -3.0; P=.03; Hedges g=1.24). The mean total scores for PDSS and LSAS decreased significantly, by 12.0 (SD 4.24) points (95% CI -50.1 to 26.1; P=.16; Hedges g=1.79) and 32.4 (SD 11.1) points (95% CI -59.7 to -4.3; P=.04; Hedges g=1.38), respectively. Of the participants, 67% (n=4) showed treatment response, and 50% (n=3) achieved remission after the intervention. The therapeutic alliance, measured using the WAI-SF, was moderate.
CONCLUSIONS: Guided ICBT may be feasible for the treatment of outpatients with panic disorder and social anxiety disorder in Japan.
BACKGROUND: University Hospital Medical Information Network Clinical Trials Registry UMIN0000038118; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043439.

Panic disorder (PD) is a severe anxiety disorder characterized by recurrent and unexpected panic attacks that cause intense distress. Despite the high prevalence of panic disorder and its significant impact on life, limited research has been conducted on its prevalence and their associated factors in Saudi Arabia. This study seeks to contribute to the understanding of PD among adults in Saudi Arabia by examining its prevalence and associated factors, using an online survey method. A validated questionnaire-based cross-sectional study was conducted targeting 1276 Saudi adults. Data were collected electronically via Google Forms from the eligible participants. The questionnaire comprised three sections: sociodemographic information, medical history, and a validated diagnostic tool for PD. The prevalence of PD among Saudi adults was 13.1%. Most individuals with PD experienced their first panic attack before the age of 18. Only 38.3% individuals with PD sought medical attention, and approximately one-third of those who sought help did not receive a diagnosis. Multiple logistic regression analysis revealed that significant risk factors for PD included being female; having chronic health problems, a comorbid psychiatric disorder, a high body mass index; and experiencing suicidal ideation (P < 0.05). The highest risk was associated with chronic diseases (adjusted odds ratio = 3.1, 95% confidence interval: 2.1-4.6). This study demonstrates that PD is a prevalent and debilitating mental health condition among Saudi Arabian adults. Non-mental health physicians should be aware of PD, as many cases remain undiagnosed.