Originalbeiträge (Originals). High Young schema levels predict manualized confrontation therapy outcome in patients with panic disorder / Der Einfluss von Schemata nach Young auf das Therapieergebnis von Patienten mit Panikstörung.

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.

Childhood Separation Anxiety Disorder and Panic Disorder: Differences Between Respiratory and Nonrespiratory Subtypes.

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 (CO2). Patients with the respiratory subtype (RS) of PD are known to be more sensitive to CO2 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.

Predicting treatment outcomes in patients with panic disorder: Cross-sectional and two-year longitudinal structural connectome analysis using machine learning methods.

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.

The cognitive theory of panic disorder: A systematic narrative review.

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.

Self-esteem mediates child abuse predicting adulthood anxiety, depression, and substance use symptoms 18 years later.

According to biopsychosocial models, experiencing parental child abuse increases susceptibility to adulthood psychopathology. However, there is a paucity of studies examining potential mechanisms of the parental child abuse and adulthood psychopathology relationship. The purpose of the current study was to determine if Time 2 (T2) trait self-esteem mediated levels of Time 1 (T1) retrospectively recalled parental child abuse predicting (T3) past-year major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder (PD), alcohol use disorder (AUD), and substance use disorder (SUD) symptoms. The 18-year Midlife Development in the United States (MIDUS) study included participants (N = 3294; T1 average age of 45.62 years) assessed at three different time points, each spaced about nine years apart. We performed structural equation mediation modeling analyses to determine how maternal and paternal child abuse at T1 would independently predict T3 MDD, GAD, PD, AUD, and SUD symptoms. We also examined whether T2 self-esteem mediated these relations while controlling for adulthood T1 psychopathology symptoms, demographics, socioeconomic status, somatic symptoms, and parental psychopathology. Consistent with our hypotheses, higher T1 maternal and paternal abuse predicted increased T3 GAD, PD, AUD, and SUD symptoms via diminished T2 self-esteem as the mediator (% proportion mediated = 33.0-100). However, childhood paternal, but not maternal, abuse predicted adulthood MDD symptoms via reduced self-esteem. Findings remained after adjusting for covariates. Our research highlights the importance of understanding retrospectively recalled parental child abuse-adulthood psychopathology relations, their potential mechanisms, and self-esteem as a malleable treatment target for adults with heightened child abuse.

Childhood Trauma and Panic Disorder: The Impact of History of Child Abuse on Illness Severity and Treatment Response.

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.

Association between 5-HT1A receptor C-1019G, 5-HTTLPR polymorphisms and panic disorder: a meta-analysis.

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.

Correlates of treatment-seeking in DSM-5 generalized anxiety disorder: Findings from the National Epidemiologic Survey on Alcohol and Related Conditions-III.

Generalized Anxiety Disorder (GAD) presents a significant personal and societal burden and is associated with chronic medical comorbidities and markedly lower quality of life. Effective treatments exist, less than half of individuals with lifetime GAD will ever seek psychotherapeutic or pharmacological treatment. A thorough understanding of the factors that influence treatment seeking for GAD is warranted. The present study investigates the correlates of GAD treatment seeking, using data from the National Epidemiological Survey on Alcohol and Related Disorders-III (NESARC-III), which assessed for psychiatric disorders using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-5 Version (AUDADIS-5). A series of logistic regressions were run to identify demographic, diagnostic, and symptom-level correlates of treatment seeking in those meeting DSM-5 diagnostic criteria for GAD. Comorbid depression, panic disorder, and PTSD were all uniquely associated with higher rates of GAD-related treatment seeking. Additionally, several accompanying anxiety symptoms were also uniquely predicted treatment seeking, including fatigue, panic attacks, reassurance-seeking, and interpersonal avoidance. Findings underscore the multi-factorial nature of treatment seeking behavior in GAD and highlight the need for further research to fully understand these relationships and devise effective strategies to improve treatment seeking in this population.

The functional and structural alterations in brain regions related to the fear network model in panic disorder: A resting-state fMRI and T1-weighted imaging study.

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.

Neurochemical and genetic factors in panic disorder: a systematic review.

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.

Biochemical challenges for testing novel anti-panic drugs in humans.

Current medications for panic disorder each carry significant limitations that indicate the need for novel anxiolytics. The high costs and low success rates of drug development demand that testing trials be efficient. Lab panicogenic challenges in humans allow for the rapid biochemical induction of panic symptoms and hence an efficient means of testing potential anti-panic drugs. This paper describes ideal characteristics of lab panicogens, reviews the validity and utility of various biochemical panicogenic agents, identifies key outcome measures for studies of novel anti-panic drugs, and makes broad recommendations for labs wishing to perform such studies. We conclude by presenting a four-tiered hierarchy of panicogens that matches each against ideal characteristics and reflects our recommendations for their laboratory use.

Incidence of Panic Disorder Diagnoses After Celebrity Disclosures of Panic Disorder in South Korea.

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.

Locus coeruleus noradrenaline depletion and its differential impact on CO2-induced panic and hyperventilation in male and female mice.

CO2 exposure has been used to investigate the panicogenic response in patients with panic disorder. These patients are more sensitive to CO2, and more likely to experience the "false suffocation alarm" which triggers panic attacks. Imbalances in locus coeruleus noradrenergic (LC-NA) neurotransmission are responsible for psychiatric disorders, including panic disorder. These neurons are sensitive to changes in CO2/pH. Therefore, we investigated if LC-NA neurons are differentially activated after severe hypercapnia in mice. Further, we evaluated the participation of LC-NA neurons in ventilatory and panic-like escape responses induced by 20% CO2 in male and female wild type mice and two mouse models of altered LC-NA synthesis. Hypercapnia activates the LC-NA neurons, with males presenting a heightened level of activation. Mutant males lacking or with reduced LC-NA synthesis showed hypoventilation, while animals lacking LC noradrenaline present an increased metabolic rate compared to wild type in normocapnia. When exposed to CO2, males lacking LC noradrenaline showed a lower respiratory frequency compared to control animals. On the other hand, females lacking LC noradrenaline presented a higher tidal volume. Nevertheless, no change in ventilation was observed in either sex. CO2 evoked an active escape response. Mice lacking LC noradrenaline had a blunted jumping response and an increased freezing duration compared to the other groups. They also presented fewer racing episodes compared to wild type animals, but not different from mice with reduced LC noradrenaline. These findings suggest that LC-NA has an important role in ventilatory and panic-like escape responses elicited by CO2 exposure in mice.

Psychological distress and uterine fibroids: a bidirectional two-sample mendelian randomization study.

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.

Epigenetic signatures of social anxiety, panic disorders and stress experiences: Insights from genome-wide DNA methylation risk scores.

Social anxiety disorder (SAD) and panic disorder (PD) are prevalent anxiety disorders characterized by a complex interplay of genetic and environmental factors. Both disorders share overlapping features and often coexist, despite displaying distinct characteristics. Childhood life adversity, overall stressful life events, and genetic factors contribute to the development of these disorders. DNA methylation, an epigenetic modification, has been implicated in the pathogenesis of these diseases. In this study, we investigated whether whole-genome DNA methylation risk scores (MRSs) for SAD risk, severity of social anxiety, childhood life adversity, PD risk, and overall stressful life events were associated with SAD or PD case‒control status. Preliminary epigenome-wide association studies (EWASs) for SAD risk, severity of social anxiety, and childhood life adversity were conducted in 66 SAD individuals and 77 healthy controls (HCs). Similarly, EWASs for PD risk and overall stressful life events were performed in 182 PD individuals and 81 HCs. MRSs were calculated from these EWASs. MRSs derived from the EWASs of SAD risk and severity of social anxiety were greater in PD patients than in HCs. Additionally, MRSs derived from the EWASs of overall stressful life events, particularly in PD individuals, were lower in SAD individuals than in HCs. In contrast, MRSs for childhood life adversity or PD risk were not significantly associated with PD or SAD case‒control status. These findings highlight the epigenetic features shared in both disorders and the distinctive epigenetic features related to social avoidance in SAD patients, helping to elucidate the epigenetic basis of these disorders.

Cross-sectional study of psychiatric disorders in patients with chronic musculoskeletal pain and individuals without pain.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

The Effectiveness of a Digital App for Reduction of Clinical Symptoms in Individuals With Panic Disorder: Randomized Controlled Trial.

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. TRIAL REGISTRATION: Clinical Research Information Service KCT0007280; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=21448.

Effects of antidepressant on FKBP51 mRNA expression and neuroendocrine hormones in patients with panic disorder.

OBJECTIVE: The purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD). METHODS: Seventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment. RESULTS: At baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01). CONCLUSIONS: The results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.