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.

Terapia Cognitivo Conductual presencial y remota para adultos con pánico en Servicios de Emergencias: tres estudios de caso / Face-to-face and remote Cognitive Behavioral Therapy for adults with panic in Emergency Services: study of three cases

Most patients with panic attacks or panic disorder who seek emergency department care go unnoticed and do not receive appropriate treatment. Although first-line psychological treatments exist for these patients, they may be insensitive and inaccessible to their characteristics. The aim of this study was to describe three different brief protocols based on Cognitive Behavioral Therapy that were adapted for face-to-face or videoconferencing application for patients with panic attacks or panic disorder seeking care in emergency department. Three cases of adult patients, two diagnosed with panic disorder and one with panic attacks, are presented to show the implementation and outcomes of the protocols on diagnostic severity, anxiety sensitivity, quality of life, health services utilization, and patient satisfaction with the protocols. As well as the use of a panic screening diagram designed for the initial evaluation of these patients. After one to seven sessions, a decrease in panic disorder severity or frequency of panic attacks, and anxiety sensitivity was observed. Quality of life improved, patients stopped using emergency department and showed satisfaction with the intervention they received. Brief interventions based on Cognitive Behavioral Therapy, both face-to-face and remote, can be implemented in emergency department to overcome some barriers to mental health access and fit the diverse care possibilities of panic patients. (AU)

A causal relationship between panic disorder and risk of alzheimer disease: a two-sample mendelian randomization analysis.

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

Evaluation of effect of brief-intensive cognitive behavior therapy on symptoms severity in relation with catastrophic cognition in patients with panic disorder: a randomized controlled trial.

INTRODUCTION: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Brain-derived neurotrophic factor (BDNF) levels in panic disorder: A systematic review and meta-analysis.

BACKGROUND: The existing literature on the association between brain-derived neurotrophic factor (BDNF) protein levels and panic disorder presents inconsistent findings. This systematic review and meta-analysis aim to synthesize the available evidence and determine the overall effect of BDNF protein levels in individuals diagnosed with panic disorder. METHODS: A comprehensive literature search was conducted using electronic databases (PubMed, Embase, Scopus, PsycINFO, and Web of Science) from inception to April 21, 2023. The search strategy included relevant keywords and medical subject headings terms related to BDNF, panic disorder, and protein levels. A random-effects model was used for the meta-analysis, and subgroup analyses were performed to explore heterogeneity. Publication bias was assessed using funnel plots and statistical tests. RESULTS: A total of 12 studies met the inclusion criteria. The meta-analysis demonstrated a significant decrease in BDNF protein levels in individuals with panic disorder (SMD = -.53, 95% CI: -1.02 to -.04, p < .001; I2 : 92%). The results of subgroup and meta-regression analyses were not statistically significant. No significant publication bias was observed based on the results of Egger's regression test (p-value = .3550). CONCLUSION: This systematic review and meta-analysis provide evidence of lower BDNF protein levels in individuals diagnosed with panic disorder compared to healthy controls. The findings suggest a potential role for BDNF dysregulation in the pathophysiology of panic disorder. Further research is warranted to elucidate the underlying mechanisms and potential therapeutic implications.

Panicolytic-like effects of environment enrichment on male mice threatened by Bothrops jararaca lancehead pit vipers.

Environment enrichment (EE) is a well-known eustress model showing beneficial effects in different psychiatric diseases, but its positive properties in panic disorders are not yet established. The confrontation between prey and predator in complex arenas has been validated as a putative panic attack model. The principal aim of this work was to investigate the role of the EE on panic-like defensive responses elicited by mice threatened by venomous snakes. After 6 weeks of exposure either to an enriched or standard environments, 36 male mice were habituated in a complex polygonal arena for snakes containing an artificial burrow and elevated platforms for escape. The animals were confronted by Bothrops jararaca for 5 min, and the following antipredatory responses were recorded: defensive attention, stretched attend posture, flat back approach, prey versus predator interaction, oriented escape behavior, time spent in a safe place, and number of crossings. Mice threatened by snakes displayed several antipredatory reactions as compared to the exploratory behavior of those animals submitted to a nonthreatening situation (toy snake) in the same environment. Notably, EE causes anxiolytic- and panicolytic-like effects significantly decreasing the defensive attention and time spent in safe places and significantly increasing both prey versus predator interaction and exploratory behavior. In conclusion, our data demonstrate that EE can alter the processing of fear modulation regarding both anxiety- and panic-like responses in a dangerous condition, significantly modifying the decision-making defensive strategy.

Clinical and cognitive insight in panic disorder: phenomenology and treatment effects in internet cognitive behavior therapy.

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.

Alpha1- and Beta-norepinephrinergic receptors of dorsomedial and ventromedial hypothalamic nuclei modulate panic attack-like defensive behaviour elicited by diencephalic GABAergic neurotransmission disinhibition.

Gamma-aminobutyric acid (GABA) disinhibition in medial hypothalamus (MH) nuclei of rats elicits some defensive reactions that are considered panic attack-like behaviours. Recent evidence showed that the norepinephrine-mediated system modulates fear-related defensive behaviours organised by MH neurons at least in part via noradrenergic receptors recruitment on midbrain tegmentum. However, it is unknown whether noradrenergic receptors of the MH also modulate the panic attack-like reactions. The aim of this work was to investigate the distribution of noradrenergic receptors in MH, and the effects of either α1-, α2- or ß-noradrenergic receptors blockade in the MH on defensive behaviours elaborated by hypothalamic nuclei. Defensive behaviours were evaluated after the microinjection of the selective GABAA receptor antagonist bicuculline into the MH that was preceded by microinjection of either WB4101, RX821002, propranolol (α1-, α2- and ß-noradrenergic receptor selective antagonists, respectively), or physiological saline into the MH of male Wistar rats. The α1-, α2- and ß-noradrenergic receptors were found in neuronal perikarya of all MH nuclei, and the α2-noradrenergic receptor were also found on glial cells mainly situated in the ventrolateral division of the ventromedial hypothalamic nucleus. The α1- and ß-noradrenergic receptors blockade in the MH decreased defensive attention and escape reactions elicited by the intra-MH microinjections of bicuculline. These findings suggest that, despite the profuse distributions of α1-, α2- and ß-noradrenergic receptors in the MH, both α1- and ß-noradrenergic receptor- rather than α2-noradrenergic receptor-signalling in MH are critical for the neuromodulation of panic-like behaviour.

Effects of panic-specific cognitive behavioural and psychodynamic psychotherapies on work ability in a doubly randomised clinical trial.

Objective: The effects of panic-specific psychotherapy on occupational functioning remain under-researched. This study tests whether two brief psychotherapies for Panic Disorder with or without Agoraphobia (PD/A) may generate improvement in work ability. Methods: Adults (N = 221) with a primary diagnosis of PD/A were randomised to wait-list, panic-focused psychodynamic psychotherapy (PFPP), panic control treatment (PCT), or to the choice between the two treatments. Participants completed the Work Ability Inventory (WAI) at baseline, post-treatment, and during 24-month follow-ups. Change in WAI scores were assessed using segmented multilevel linear growth models, and mediation was explored through path analysis. Results: WAI scores changed from the moderate to good range between baseline and post-treatment (SMD = 0.45; 95% CI [0.33, 0.57]) and continued to increase throughout the follow-up (SMD = 0.16; 95% CI [0.03, 0.28]) with no differences between treatments or allocation forms. In PFPP (but not in PCT) pre- to post-treatment change in WAI was mediated by reduction in panic symptoms and WAI predicted employment status and absences. Conclusions: Two brief panic specific psychotherapies, one cognitive behavioural and one psychodynamic, produced short and long-term increases in work ability.

Impact of preterm birth on the onset of panic disorder in later life - Results from the Gutenberg Prematurity Study (GPS).

BACKGROUND: The present study aimed to investigate whether prematurity and perinatal stress exert long-term effects on the onset of panic disorder in later life. METHODS: From 40,189 adults born in Germany between 1969 and 2002, a study cohort (n = 427) stratified by gestational age (GA) (extremely preterm: GA < 29 weeks; very preterm: GA 29-32 weeks; moderately preterm: GA 33-36 weeks; and full-term GA ≥ 37 weeks) was selected (age 28.5 ± 8.7 years). Multivariable logistic regression analyses were conducted to investigate associations between gestational age at birth and panic disorder adjusting for age, gender, socioeconomic status, and perinatal factors. RESULTS: The prevalence of panic disorder was roughly equal in moderate to very preterm and full-term birth groups at 1.9%-3.8%. However, this rate significantly increased to 14.3% in the extreme preterm category (GA <2 9: 14.3 %, p = 0.002). In multivariable analyses, female gender and GA were independently associated with panic disorder. Adjusting for age, gender and socioeconomic status, panic disorder was associated with lower GA at birth (OR = 1.12 per week (CI95%: 1.01-1.26, p = 0.037). Whereas adjustment for nutrition status or indicators of perinatal stress had no effect, correction for the length of postnatal ICU-stay eliminated the association between preterm birth and later panic disorder. LIMITATIONS: Limitations include the small number of cases and the reliance on questionnaires to assess mental status. CONCLUSIONS: Prematurity likely increases the risk of panic disorder later in life, and the subsequent postnatal ICU-stay appears to be of critical importance. However, due to strong collinearity and other associated factors with preterm births, it remains unclear which is the primary determinant.

Exposure traced in daily life: improvements in ecologically assessed social and physical activity following exposure-based psychotherapy for anxiety disorders.

BACKGROUND: Although exposure-based cognitive-behavioral therapy for anxiety disorders has frequently been proven effective, only few studies examined whether it improves everyday behavioral outcomes such as social and physical activity. METHODS: 126 participants (85 patients with panic disorder, agoraphobia, social anxiety disorder, or specific phobias, and 41 controls without mental disorders) completed smartphone-based ambulatory ratings (activities, social interactions, mood, physical symptoms) and motion sensor-based indices of physical activity (steps, time spent moving, metabolic activity) at baseline, during, and after exposure-based treatment. RESULTS: Prior to treatment, patients showed reduced mood and physical activity relative to healthy controls. Over the course of therapy, mood ratings, interactions with strangers and indices of physical activity improved, while reported physical symptoms decreased. Overall results did not differ between patients with primary panic disorder/agoraphobia and social anxiety disorder. Higher depression scores at baseline were associated with larger changes in reported symptoms and mood ratings, but smaller changes in physical activity CONCLUSIONS: Exposure-based treatment initiates increased physical activity, more frequent interaction with strangers, and improvements in everyday mood. The current approach provides objective and fine-graded process and outcome measures that may help to further improve treatments and possibly reduce relapse.

Resting-state cortico-limbic functional connectivity pattern in panic disorder: Relationships with emotion regulation strategy use and symptom severity.

Cognitive reappraisal is an effective emotion regulation strategy involving prefrontal cortex (PFC) control of the amygdala. Its aberrant functioning is closely associated with panic disorder (PD). However, the resting-state functional connectivity (rsFC) between the PFC, implicated in cognitive reappraisal, and the amygdala in PD has not been studied. Thus, this study aims to investigate the rsFC patterns and their association with cognitive reappraisal and PD. This study involved 51 participants, including 26 untreated patients with PD and 25 healthy controls (HC). We evaluated the habit of cognitive reappraisal assessment and the severity of PD using neuropsychological and clinical measures. Resting-state fMRI was utilized to evaluate the rsFC pattern between the PFC, engaged in cognitive reappraisal, and the amygdala. Mediation analysis was performed to explore the role of this rsFC in the relationship between cognitive reappraisal and PD severity. PD patients showed reduced rsFC between the PFC and the amygdala compared to HC. This weakened rsFC was associated with the severity of PD symptoms. Moreover, cognitive reappraisal was negatively correlated with PD severity, and mediation analysis indicated that the rsFC of the PFC-amygdala played a mediating role in this association. Abnormal PFC-amygdala rsFC may play a pivotal role in PD development and/or manifestation and mediate the association between cognitive reappraisal and PD severity, potentially serving as a clinical indicator for monitoring and intervention.

Electrocardiographic frontal QRS-T angle is independently associated with panic disorder.

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.

Cognitive change before sudden gains in cognitive behavioural therapy for panic disorder.

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.

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

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

Sleep, physical activity and panic attacks: A two-year prospective cohort study using smartwatches, deep learning and an explainable artificial intelligence model.

BACKGROUND: Sleep and physical activity suggestions for panic disorder (PD) are critical but less surveyed. This two-year prospective cohort study aims to predict panic attacks (PA), state anxiety (SA), trait anxiety (TA) and panic disorder severity (PDS) in the upcoming week. METHODS: We enrolled 114 PD patients from one general hospital. Data were collected using the DSM-5, the MINI, clinical app questionnaires (BDI, BAI, PDSS-SR, STAI) and wearable devices recording daily sleep, physical activity and heart rate from 16 June 2020 to 10 June 2022. Our teams applied RNN, LSTM, GRU deep learning and SHAP explainable methods to analyse the data. RESULTS: The 7-day prediction accuracies for PA, SA, TA, and PDS were 92.8 %, 83.6 %, 87.2 %, and 75.6 % from the LSTM model. Using the SHAP explainable model, higher initial BDI or BAI score and comorbidities with depressive disorder, generalized anxiety disorder or agoraphobia predict a higher chance of PA. However, PA decreased under the following conditions: daily average heart rate, 72-87 bpm; maximum heart rate, 100-145 bpm; resting heart rate, 55-60 bpm; daily climbing of more than nine floors; total sleep duration between 6 h 23 min and 10 h 50 min; deep sleep, >50 min; and awake duration, <53 min. LIMITATIONS: Moderate sample size and self-report questionnaires were the limitations. CONCLUSIONS: Deep learning predicts recurrent PA and various anxiety domains with 75.6-92.8 % accuracy. Recurrent PA decreases under adequate daily sleep and physical activity.

Spatiotemporal expression patterns of anxiety disorder-associated genes.

Anxiety disorders (ADs) are the most common form of mental disorder that affects millions of individuals worldwide. Although physiological studies have revealed the neural circuits related to AD symptoms, how AD-associated genes are spatiotemporally expressed in the human brain still remains unclear. In this study, we integrated genome-wide association studies of four human AD subtypes-generalized anxiety disorder, social anxiety disorder, panic disorder, and obsessive-compulsive disorder-with spatial gene expression patterns. Our investigation uncovered a novel division among AD-associated genes, marked by significant and distinct expression enrichments in the cerebral nuclei, limbic, and midbrain regions. Each gene cluster was associated with specific anxiety-related behaviors, signaling pathways, region-specific gene networks, and cell types. Notably, we observed a significant negative correlation in the temporal expression patterns of these gene clusters during various developmental stages. Moreover, the specific brain regions enriched in each gene group aligned with neural circuits previously associated with negative decision-making and anxious temperament. These results suggest that the two distinct gene clusters may underlie separate neural systems involved in anxiety. As a result, our findings bridge the gap between genes and neural circuitry, shedding light on the mechanisms underlying AD-associated behaviors.

Discovering Digital Biomarkers of Panic Attack Risk in Consumer Wearables Data.

Panic attacks are an impairing mental health problem that impacts more than one out of every 10 adults in the United States (US). Clinical guidelines suggest panic attacks occur without warning and their unexpected nature worsens their impact on quality of life. Individuals who experience panic attacks would benefit from advance warning of when an attack is likely to occur so that appropriate steps could be taken to manage or prevent it. Our recent work suggests that an individual's likelihood of experiencing a panic attack can be predicted by self-reported mood and community-level Twitter-derived mood the previous day. Prior work also suggests that physiological markers may indicate a pending panic attack. However, the ability of objective physiological, behavioral, and environmental measures collected via consumer wearable sensors (referred to as digital biomarkers) to predict next-day panic attacks has not yet been explored. To address this question, we consider data from 38 individuals who regularly experienced panic attacks recruited from across the US. Participants responded to daily questions about their panic attacks for 28 days and provided access to data from their Apple Watches. Mixed Regressions, with an autoregressive covariance structure were used to estimate the prevalence of a next-day panic attack Results indicate that digital biomarkers of ambient noise (louder) and resting heart rate (higher) are indicative of experiencing a panic attack the next day. These preliminary results suggest, for the first time, that panic attacks may be predictable from digital biomarkers, opening the door to improvements in how panic attacks are managed and to the development of new preventative interventions.Clinical Relevance- Objective data from consumer wearables may predict when an individual is at high risk for experiencing a next-day panic attack. This information could guide treatment decisions, help individuals manage their panic, and inform the development of new preventative interventions.