Prediction of declarative memory profile in panic disorder patients: a machine learning-based approach

Objective: To develop a classification framework based on random forest (RF) modeling to outline the declarative memory profile of patients with panic disorder (PD) compared to a healthy control sample. Methods: We developed RF models to classify the declarative memory profile of PD patients in comparison to a healthy control sample using the Rey Auditory Verbal Learning Test (RAVLT). For this study, a total of 299 patients with PD living in the city of Rio de Janeiro (70.9% females, age 39.9 ± 7.3 years old) were recruited through clinician referrals or self/family referrals. Results: Our RF models successfully predicted declarative memory profiles in patients with PD based on RAVLT scores (lowest area under the curve [AUC] of 0.979, for classification; highest root mean squared percentage [RMSPE] of 17.2%, for regression) using relatively bias-free clinical data, such as sex, age, and body mass index (BMI). Conclusions: Our findings also suggested that BMI, used as a proxy for diet and exercises habits, plays an important role in declarative memory. Our framework can be extended and used as a prospective tool to classify and examine associations between clinical features and declarative memory in PD patients.

Avoidant restrictive eating disorder and panic attacks in an adult man: A case report / Trastorno evitativo restrictivo de la ingesta alimentaria y ataques de pánico en un hombre adulto: Reporte de caso

Abstract Avoidant or Restrictive Food Intake Disorder (ARFID) is an eating disorder (ED) not common in adults. In this article we present a clinical case of ARFID in a 37-year-old male patient treated in an ED center in Medellin, Colombia; displaying anxious symptoms that began a year earlier and concomitant weight loss, following a traumatic event causing an overall impairment with that patient. Several medical evaluations/examinations looking for organic causes, were excluded. Interventions were implemented by a psychiatry, a psychotherapist using cognitive-behavior therapy (CBT), and a nutritionist, all in face-to-face modality, which were carried out weekly for the first three months, then biweekly and subsequently quarterly. each lasting approximately 40-60 minutes. After the set of pharmacological interventions and psychotherapy, a great improvement in the functionality of the patient was observed. Improvement was found with respect to eating in public, food variation and panic attacks. In the absence of guidelines, it is important to use standardized and replicable treatments in this population.

Resumen El trastorno evitativo restrictivo de la ingesta (TERIA) es un trastorno alimentario (TCA) raro en adultos. Se presenta el caso de un hombre de 37 años con TERIA y trastorno de pánico atendido en un centro para TCA en Medellín, Colombia, quien presentó un año de síntomas ansiosos y pérdida de peso después de evento traumático, generando disfuncionalidad. Fue evaluada y excluida organicidad. Se realizaron intervenciones por parte de psiquiatría, psicoterapia con enfoque cognitivo conductual y nutrición, todas en modalidad presencial, las cuales se realizaron semanalmente los primeros tres meses, luego quincenalmente y posteriormente trimestralmente. Cada una con una duración de 40-60 minutos aproximadamente por sesión. Posterior al conjunto de intervenciones farmacológicas y psicoterapia, se observó una gran mejoría la funcionalidad del paciente, se encontró mejoría con respecto a comer en público, variación en los alimentos y ataques de panico. Ante la ausencia de guías de manejo de TERIA en adultos es relevante realizar tratamientos estandarizados que puedan ser replicados.

Evidence from Cochrane systematic reviews on pharmacological treatment compared to placebo for panic disorder / Evidências das revisões sistemáticas cochrane sobre o tratamento farmacológico comparado ao placebo para transtorno de pânico

ABSTRACT. Panic disorder is an anxiety condition characterized by recurrent and unexpected panic attacks. The comparison between active treatment and placebo is essential to analyze an intervention's efficacy and safety. It is important to identify and summarize the studies with higher evidence to assist health professionals and public policy managers in clinical decision-making. Objective: The aim of this study was to identify and summarize all Cochrane systematic reviews (SRs) that compared the efficacy and safety of any drug treatment compared to placebo for panic disorder patients. Methods: SRs published in the Cochrane Library were included without date restriction. All outcomes presented were analyzed. The methodological quality of the SRs was evaluated using the AMSTAR-2 tool. Results: We included three Cochrane SRs of high methodological quality on the effects of antidepressants, benzodiazepines, and azapirones for panic disorder. All medications showed benefits in response to treatment, symptom improvement, and reduced panic attacks. Dropouts were lower with tricyclic antidepressants and benzodiazepines and higher with azapirones. The occurrence of adverse events was higher for drug groups. Conclusions: Very low to moderate certainty evidence (GRADE) showed that antidepressants and benzodiazepines seem to improve clinical symptoms in individuals with short-term panic disorder compared to placebo. In addition, the use of azapirones seems to have greater adherence by patients than placebo. However, there is insufficient evidence to support its clinical efficacy.

RESUMO. O transtorno de pânico é uma condição de ansiedade caracterizada por ataques de pânico recorrentes e inesperados. A comparação entre tratamento ativo e placebo é essencial para analisar a eficácia e a segurança de uma intervenção. É importante identificar os estudos com maiores evidências para auxiliar os profissionais de saúde e gestores de políticas públicas nas decisões clínicas. Objetivo: Identificar e sumarizar todas as revisões sistemáticas (RS) publicadas na Cochrane que relatam a eficácia e a segurança de qualquer tratamento medicamentoso comparado ao placebo para pacientes com transtorno de pânico. Métodos: Foram selecionadas e analisadas todas as RS publicadas na base de dados Cochrane, sem restrição de data. A qualidade metodológica das RS foi avaliada utilizando a ferramenta AMSTAR-2. Resultados: Foram incluídas três RS Cochrane com alta qualidade metodológica que avaliaram os efeitos de antidepressivos, benzodiazepínicos e azapironas para transtorno de pânico. Todos os medicamentos mostraram benefícios na resposta ao tratamento, melhora dos sintomas e redução das crises de pânico. O número de desistências do tratamento foi baixo com antidepressivos tricíclicos e benzodiazepínicos e alto com azapironas. A ocorrência de eventos adversos foi elevada para os grupos das medicações analisadas Conclusões: Evidências de certeza muito baixa a moderada (pela Classificação de Recomendações, Avaliação, Desenvolvimento e Análises - GRADE) mostraram que antidepressivos e benzodiazepínicos parecem melhorar os sintomas clínicos em indivíduos com transtorno de pânico em menor prazo, em comparação ao placebo. Além disso, o uso de azapironas parece ter maior adesão por parte dos pacientes do que o placebo. No entanto, não há evidências suficientes para comprovar sua eficácia clínica.

A Case Report of Painful Legs and Moving Toes Syndrome and Painful Arms and Moving Fingers Syndrome with Severe Blood Stasis and Panic Disorder Successfully Treated with Tokakujokito-Based Kampo Prescriptions / 日本東洋医学雑誌

The patient was a 47-year-old woman. Four years previously, she began to suffer from left lower leg pain and numbness, and involuntary movements. She received further examination in the department of neurology at other hospitals, but had an uncertain etiology and was provisionally diagnosed with restless legs syndrome. She was treated with Western medicine such as gabapentin and gabapentin enacarbil, but they were ineffective. She subsequently visited our hospital and was hospitalized. She was diagnosed with painful legs and moving toes syndrome, and painful arms and moving fingers syndrome after further examination. We prescribed tokakujokito because she had severe blood stasis and panic disorder on Kamp medical findings. As a result, her left lower leg numbness disappeared and pain was reduced. We report a case of a patient who could not be effectively treated using Western medicine and was successfully treated with tokakujokito-based Kampo prescriptions.

The course and clinical correlates of panic disorder during the postpartum period: a naturalistic observational study

Objective: To investigate the course of panic disorder and its demographic and clinical correlates during the postpartum period. Methods: Data were collected from 38 consecutive postpartum women diagnosed with panic disorder. Psychiatric assessments were carried out on the first day after delivery and at 6-8 weeks postpartum. During the first assessment, the Panic and Agoraphobia Scale (PAS), Hospital Anxiety and Depression Scale (HADS), Coping Orientation to Problems Experienced (COPE), Multidimensional Scale of Perceived Social Support (MSPSS), and Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) were administered to the participants. PAS was also administered at the second assessment. Results: The mean PAS score reduced significantly from baseline to the second assessment. Logistic regression analysis indicated that a shorter duration of panic disorder independently predicted a ≥ 50-point decrease in the severity of panic symptoms during the postpartum period. Conclusion: These findings suggest that patients with a short duration of illness may experience significant alleviation in the severity of panic symptoms during the postpartum period.

Multimodal MRI of fear network in panic disorder / 中华行为医学与脑科学杂志

The etiology and pathological mechanism of panic disorder (PD) are still unclear, which hinders the development of clinical diagnosis and treatment. In order to clarify the pathogenesis, biological diagnostic markers, curative effect prediction of PD, and ultimately provide a basis for individualized treatment, this article reviews the magnetic resonance imaging (MRI) research on PD in the past 5 years in conjunction with the hypothesis of the " fear network model" . It is found that the brain function and structural abnormalities of PD patients are not limited to the classic " fear network model" , but also a wider range of brain areas such as the cingulate gyrus, fronto-temporal cortex, insula, striatum, thalamus, sensorimotor related brain regions and cerebellum, together with classic brain regions such as the amygdala, form an expanded fear network. Among them, the amygdala, insula, medial prefrontal lobe, somato-motor network (SMN) and cerebellum are specific brain areas that differentiate PD from other anxiety disorders. The changes in the activity of the frontal lobe-limbic loop included in the fear network model can predict the treatment outcome of different methods for PD. This article improved the fear network hypothesis of PD, and more accurately identifies the biological indicators that can be used for accurate diagnosis and efficacy prediction of PD, which lays the foundation for the ultimate realization of personalized diagnosis and treatment of PD.

Presença de sintomas de fobia social, transtorno do pânico e ansiedade de separação em estudantes de 11 a 17 anos, em uma escola da rede pública de ensino de Salvador / Presence of symptoms of social phobia, panic and separation anxiety in students aged 11 to 17 years from a school of th public system of Salvador

Introdução: crianças e adolescentes, não raro, apresentam sintomas de fobia social, transtorno do pânico e ansiedade de separação, que podem causar comprometimento nas habilidades sociais e dificultar as relações de forma incapacitante. Objetivo: Este estudo tem como objetivo verificar a presença de sintomas fóbicos sociais, transtorno de pânico e ansiedade de separação em adolescentes, com idade entre 11 e 17 anos, de uma escola pública da cidade de Salvador. Metodologia: este é um estudo observacional, transversal, que integra outro mais amplo, realizado em escola pública de Salvador, entre março e dezembro de 2015. A escala Revised Children's Anxiety and Depression foi aplicada em uma amostra de 674 alunos. Resultados: os alunos apresentaram sintomas de fobia social, transtorno do pânico e ansiedade de separação, em escala crescente, de acordo com a idade.

Introduction:children and adolescents often present symptoms of social phobia, panic disorder and separation anxiety disorder, which can cause social impairments and hinder relationships in a disabling way. Objective: this study aims to investigate the presence of social phobia, panic disorder and separation anxiety symptoms in adolescents aged between 11 and 17 years from a public school in the city of Salvador. Methodology: the present study is an observational cross-sectional research, which is part of a broader study conducted in a public school in Salvador, between March and December 2015. The Revised Children's Anxiety and Depression Scale (RCADS) was used in a sample of 674 students. Results: the students presented symptoms of social phobia, panic disorder and separation anxiety on an increasing scale proportional to age.

Panic disorder respiratory subtype: psychopathology and challenge tests - an update

Panic disorder (PD) pathophysiology is very heterogeneous, and the discrimination of distinct subtypes could be very useful. A subtype based on respiratory symptoms is known to constitute a specific subgroup. However, evidence to support the respiratory subtype (RS) as a distinct subgroup of PD with a well-defined phenotype remains controversial. Studies have focused on characterization of the RS based on symptoms and response to CO2. In this line, we described clinical and biological aspects focused on symptomatology and CO2 challenge tests in PD RS. The main symptoms that characterize RS are dyspnea (shortness of breath) and a choking sensation. Moreover, patients with the RS tended to be more responsive to CO2 challenge tests, which triggered more panic attacks in this subgroup. Future studies should focus on discriminating respiratory-related clusters and exploring psychophysiological and neuroimaging outcomes in order to provide robust evidence to confirm RS as a distinct subtype of PD.

Level of intolerance of uncertainty and related factors in patients with anxiety disorders / 上海交通大学学报（医学版）

Objective: To investigate the level of intolerance of uncertainty (IU) and possible related factors in the patients with anxiety disorders. Methods: The patients' diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM- ). Thirty-five cases of generalized anxiety disorder (GAD), 15 cases of panic disorder (PD) and 31 healthy controls (HC group) were recruited at the same time. IU level was assessed by using the Chinese version of Intolerance of Uncertainty Scale (IUS). The characteristics of anxiety symptoms, depressive symptoms and body perception were assessed by Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and Body Perception Questionaire (BPQ), respectively. Results: The IU levels of both GAD group and PD group were significantly higher than those of HC group (P=0.000). There was no significant difference in IU levels between GAD group and PD group (P=0.491). The IU levels of GAD patients were positively correlated with HAMA-somatic anxiety (r=0.377, P=0.025) and BPQ-awareness (r=0.342, P=0.044). Conclusion: The patients with anxiety disorders have elevated IU levels, compared with healthy people. Possibly, somatic anxiety and body perception-awareness are related factors to IU in GAD patients.

A Case of Panic Disorder Successfully Treated with Keishikyokeikabukuryobyakujutsuto / 日本東洋医学雑誌

We report a case of panic disorder treated with keishikyokeikabukuryobyakujutsuto. The patient was a 42-year-old woman who had one or two episodes of panic attacks every month for 1 year accompanied by dyspnea, fear, rigidity of hands, etc. The episodes were more frequent with physical exertion and menstruation and did not improve with kamishoyosan or kanbakutaisoto. Then, after a car accident, she had a panic attack with a stronger intensity. Blood and imaging examinations revealed no special findings, and we diagnosed her with panic disorder. We considered her complaint as Honton disease and administered ryokeikansoto. After 2 weeks, her mental condition improved, and dyspnea and fear of attacks relieved. After 2 months, office work became more strenuous, and attacks recurred once or twice a week. An abnormal sensation of the posterior cervix occurred as a prodrome of an attack, and simultaneously, she noticed neck stiffness. After switching to keishikyokeikabukuryobyakujutsuto, the cervical sensation disappeared, neck pain and neck stiffness were relieved, and the attacks did not reappear. This case suggested that keishikyokeikabukuryobyakujutsuto was useful for the prevention of panic attacks associated with neck stiffness.

Quality of life in panic disorder: the influence of clinical features and personality traits / Qualidade de vida no transtorno de pânico: a influência de características clínicas e traços de personalidade

Abstract Objective To identify which clinical features and personality traits are associated with quality of life (QoL) in panic disorder (PD) patients. Methods This was a cross-sectional study with PD patients. The brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) and the Big Five Inventory (BFI) were used to assess QoL and personality traits respectively. The strength of correlations was measured with Pearson's, Spearman's, and point-biserial correlation coefficients. We also performed multiple linear regressions, considering sociodemographic data and scores from clinical scales as independent variables and QoL scores as dependent variables. Results A total of 98 patients were evaluated. Depressive symptoms had a strong negative correlation with QoL and, to a lesser extent, panic and anxiety symptoms were also negatively correlated with QoL. While consciousness, extraversion, and agreeableness had mild positive correlations with QoL, neuroticism had a strong negative correlation. Conclusion Symptoms of depression, anxiety, and panic seem to have a negative impact on the QoL of PD patients. Personality traits, especially neuroticism, may also influence QoL in these patients.

Resumo Objetivo Identificar quais características clínicas e traços de personalidade são mais associados à qualidade de vida (QdV) em pacientes com transtorno de pânico (TP). Métodos Este foi um estudo transversal, realizado em pacientes com TP. A versão breve do Questionário de Qualidade de Vida da Associação Mundial de Saúde (World Health Organization Quality of Life Questionnaire - WHOQOL-BREF) e o Inventário dos Cinco Grande Fatores (Big Five Inventory - BFI) foram utilizados para avaliar QdV e traços de personalidade, respectivamente. A força de associação foi medida através da correlação de Pearson, de Spearman ou ponto bisserial. Foram também realizadas regressões lineares múltiplas, considerando os dados sociodemográficos e escores obtidos nas escalas clínicas como variáveis independentes, e os escores de QdV como variáveis dependentes. Resultados Um total de 98 pacientes foram avaliados. Sintomas depressivos apresentaram uma forte relação negativa com QdV; em menor intensidade, sintomas de TP e ansiosos também se correlacionaram com QdV. Nos domínios de personalidade, enquanto conscienciosidade, extroversão e amabilidade apresentaram uma leve correlação positiva com QdV, neuroticismo apresentou forte correlação negativa. Conclusão Sintomas depressivos, ansiosos e de TP parecem ter forte impacto negativo na QdV dos pacientes com TP. Traços de personalidade, principalmente neuroticismo, podem influenciar QdV nesses pacientes.

The relationship of peripheral blood single uncoding RNA-25-3p expression level and the sertraline efficacy in patients with panic disorder / 中华行为医学与脑科学杂志

Objective@#To identify potential relationship between single uncoding RNA-25-3p (miR-25-3p) expression level and the sertraline efficacy in patients with panic disorder.@*Methods@#Sixty cases of patients with panic disorder(case group) and sixty healthy-controls(control group) were collected with demographic data and peripheral venous blood before and after treatment.All the patients were evaluated using the 14-item Hamilton Anxiety Rating Scale (HAMA) and Panic Disorder Severity Scale (PDSS) at baseline, and then received sertraline treatment for 6 weeks.After six-week treatment, each patient was evaluated again with HAMA and PDSS.RT-PCR was used to detect the level of miR-25-3p expression.@*Results@#There was no significant difference in the miR-25-3p levels between control group (1.27±0.32) and case group (1.73±1.09) before treatment(t=1.53, P=0.14), but the levels in case group were much higher than that in control group after the treatment (5.72±4.13 vs 1.73±1.09, t=-2.15, P=0.04). Besides, the changes of the miR-25-3p levels were positively related with both the changes of PDSS3 and PDSS7 items before and after the treatment (r=0.60, P=0.02 for PDSS3 and r=0.61, P=0.02 for PDSS7).@*Conclusions@#miR-25-3p is associated with the drug efficacy and the outcome of some clinical symptoms of panic disorder.These findings might provide some evidence for the individualized treatment of patients with panic disorder according to regulation of gene expression in the future.

The relationship of peripheral blood single uncoding RNA-25-3p expression level and the sertraline efficacy in patients with panic disorder / 中华行为医学与脑科学杂志

Objective To identify potential relationship between single uncoding RNA-25-3p (miR-25-3p) expression level and the sertraline efficacy in patients with panic disorder.Methods Sixty cases of patients with panic disorder(case group) and sixty healthy-controls(control group) were collected with demographic data and peripheral venous blood before and after treatment.All the patients were evaluated using the 14-item Hamilton Anxiety Rating Scale (HAMA) and Panic Disorder Severity Scale (PDSS) at baseline,and then received sertraline treatment for 6 weeks.After six-week treatment,each patient was evaluated again with HAMA and PDSS.RT-PCR was used to detect the level of miR-25-3p expression.Results There was no significant difference in the miR-25-3p levels between control group (1.27±0.32) and case group (1.73±1.09) before treatment(t=1.53,P=0.14),but the levels in case group were much higher than that in control group after the treatment (5.72±4.13 vs 1.73±1.09,t=-2.15,P=0.04).Besides,the changes of the miR-25-3p levels were positively related with both the changes of PDSS3 and PDSS7 items before and after the treatment (r=0.60,P=0.02 for PDSS3 and r=0.61,P=0.02 for PDSS7).Conclusions miR-25-3p is associated with the drug efficacy and the outcome of some clinical symptoms of panic disorder.These findings might provide some evidence for the individualized treatment of patients with panic disorder according to regulation of gene expression in the future.

Clinical Characteristics of Female Panic Disorder Patients with Abortion History

OBJECTIVES: The objective of this study is to investigate differences in clinical characteristics between female panic disorder (PD) patients with abortion history (PD+A) and without abortion history (PD−A).METHODS: We examined data from 341 female patients diagnosed with PD. We divided the patients with PD into PD+A (82 patients) and PD−A (259 patients) to compare demographic and clinical characteristics. The following instruments were applied : stress coping strategies, NEO-neuroticism, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Depression Inventory, the Beck Anxiety Inventory (BAI) and the Sheehan Disability Scale.RESULTS: Compared to the PD−A, the PD+A group showed no significant difference in coping strategies. However, significantly higher scores in neuroticism, the ASI-R, the APPQ and the BAI were observed. In terms of health-related disability, the PD+A group did not show significant difference.CONCLUSIONS: Our results suggest that the PD+A group may differ from the PD−A group in trait markers such as neuroticism and anxiety sensitivity, and abortion history may be associated with panic-related symptom severity. Our study suggests that further consideration is needed on such clinical characteristics in PD patients with abortion history.

PET imaging on neurofunctional changes after optogenetic stimulation in a rat model of panic disorder / 医学前沿

Panic disorder (PD) is an acute paroxysmal anxiety disorder with poorly understood pathophysiology. The dorsal periaqueductal gray (dPAG) is involved in the genesis of PD. However, the downstream neurofunctional changes of the dPAG during panic attacks have yet to be evaluated in vivo. In this study, optogenetic stimulation to the dPAG was performed to induce panic-like behaviors, and in vivo positron emission tomography (PET) imaging with F-flurodeoxyglucose (F-FDG) was conducted to evaluate neurofunctional changes before and after the optogenetic stimulation. Compared with the baseline, post-optogenetic stimulation PET imaging demonstrated that the glucose metabolism significantly increased (P < 0.001) in dPAG, the cuneiform nucleus, the cerebellar lobule, the cingulate cortex, the alveus of the hippocampus, the primary visual cortex, the septohypothalamic nucleus, and the retrosplenial granular cortex but significantly decreased (P < 0.001) in the basal ganglia, the frontal cortex, the forceps minor corpus callosum, the primary somatosensory cortex, the primary motor cortex, the secondary visual cortex, and the dorsal lateral geniculate nucleus. Taken together, these data indicated that in vivo PET imaging can successfully detect downstream neurofunctional changes involved in the panic attacks after optogenetic stimulation to the dPAG.

The relationship study on alexithymia and interoception in patents with panic disorder / 中华行为医学与脑科学杂志

Objective To explore the characteristics of alexithymia and interoception in patients with panic disorder(PD) and its relationship. Methods Thirty-seven patients with PD and 45 healthy con-trols who met the diagnostic criteria of DSM-Ⅳ were selected. Toronto Alexithymia Scale ( TAS) and state-trait anxiety inventory ( STAI) were used to assess the characteristics of alexithymia and anxiety symptoms respectively. The heartbeat perception levels were tested by the Mental Tracking Paradigm. Results The de-tection rate of alexithymia in patients with panic disorder was 37. 83% (14/37),but the rate in the normal control group was only 4. 44%(2/45),and the difference was statistically significant (χ2=14. 42,P<0. 05). The total score of TAS (55. 11±10. 99),factor Ⅰ (20. 62±6. 78) and factor Ⅱ (14. 68±3. 70) in the PD group were higher than those in the control group (42. 93± 9. 25,12. 82± 4. 99,11. 42±3. 04; F=20. 72, 31. 08,15. 31,P<0. 01). The levels of the heartbeat perception were higher in the PD group than that in the control group (0. 75±0. 15,0. 58±0. 19;t=4. 13,P<0. 05). In PD group,the score of STAI were positively correlated with TAS total score and factor Ⅰ and Ⅱ scores( r=0. 57,0. 61,0. 47;r=0. 54,0. 62,0. 39,P<0. 05). There was no significant correlation between the scores of STAI and the level of interoception. The mediating effect of interoception level on alexithymia and state anxiety was not significant while the mediating effect on alexithymia and trait anxiety was also not significant. Conclusions The alexithymia detection rate and interoception sensitivity in patients with panic disorder were higher than those of healthy people. There may be interaction between alexithymia and anxiety symptoms. Interoception may be a clinical feature of panic disorder.

Bidirectional Association between First-Episode Panic Disorder and Major Depressive Disorder in a Nationwide General Population Survey in Korea

BACKGROUND: Panic disorder (PD) and major depressive disorder (MDD) can occur concurrently, despite different clinical manifestations. Because MDD and PD patients tend to have more complicated conditions, understanding the co-occurrence and pattern of these conditions is important. Here, we investigated the influence of PD and MDD on each other, with respect to time interval. METHODS: Data from three national representative surveys were pooled (total 18,807 respondents), and the age of onset (AOO) of PD and MDD was analyzed. We performed Kaplan-Meier analysis to estimate separate survival functions, using the AOO of MDD and PD as the outcome. To understand the temporal effect of other disorders, we used a Cox proportional hazard model to estimate the hazard ratios for the onset of MDD/PD with other comorbidities as time-dependent covariates. RESULTS: PD elevated the risk of subsequent MDD by 1.5-fold, whereas MDD elevated the risk of subsequent PD by 3.8-fold. The effect of such an elevation risk was significant for up to 2 years. CONCLUSION: The results revealed a bidirectional relationship between MDD and PD. Each disease represents a risk of a subsequent occurrence of the other, which lasts for a considerable duration.

A Novel Bio-Psychosocial-Behavioral Treatment Model of Panic Disorder

To conceptualize a novel bio-psychosocial-behavioral treatment model of panic disorder (PD), it is necessary to completely integrate behavioral, psychophysiological, neurobiological, and genetic data. Molecular genetic research on PD is specifically focused on neurotransmitters, including serotonin, neuropeptides, glucocorticoids, and neurotrophins. Although pharmacological interventions for PD are currently available, the need for more effective, faster-acting, and more tolerable pharmacological interventions is unmet. Thus, glutamatergic receptor modulators, orexin receptor antagonists, corticotrophin-releasing factor 1 receptor antagonists, and other novel mechanism-based anti-panic therapeutics have been proposed. Research on the neural correlates of PD is focused on the dysfunctional “cross-talk” between emotional drive (limbic structure) and cognitive inhibition (prefrontal cortex) and the fear circuit, which includes the amygdala-hippocampus-prefrontal axis. The neural perspective regarding PD supports the idea that cognitive-behavioral therapy normalizes alterations in top-down cognitive processing, including increased threat expectancy and attention to threat. Consistent with the concept of “personalized medicine,” it is speculated that Research Domain Criteria can enlighten further treatments targeting dysfunctions underlying PD more precisely and provide us with better definitions of moderators used to identify subgroups according to different responses to treatment. Structuring of the “negative valence systems” domain, which includes fear/anxiety, is required to define PD. Therefore, targeting glutamate- and orexin-related molecular mechanisms associated with the fear circuit, which includes the amygdala-hippocampus-prefrontal cortex axis, is required to define a novel bio-psychosocial-behavioral treatment model of PD.

Fear Network Model in Panic Disorder: The Past and the Future

The core concept for pathophysiology in panic disorder (PD) is the fear network model (FNM). The alterations in FNM might be linked with disturbances in the autonomic nervous system (ANS), which is a common phenomenon in PD. The traditional FNM included the frontal and limbic regions, which were dysregulated in the feedback mechanism for cognitive control of frontal lobe over the primitive response of limbic system. The exaggerated responses of limbic system are also associated with dysregulation in the neurotransmitter system. The neuroimaging studies also corresponded to FNM concept. However, more extended areas of FNM have been discovered in recent imaging studies, such as sensory regions of occipital, parietal cortex and temporal cortex and insula. The insula might integrate the filtered sensory information via thalamus from the visuospatial and other sensory modalities related to occipital, parietal and temporal lobes. In this review article, the traditional and advanced FNM would be discussed. I would also focus on the current evidences of insula, temporal, parietal and occipital lobes in the pathophysiology. In addition, the white matter and functional connectome studies would be reviewed to support the concept of advanced FNM. An emerging dysregulation model of fronto-limbic-insula and temporooccipito-parietal areas might be revealed according to the combined results of recent neuroimaging studies. The future delineation of advanced FNM model can be beneficial from more extensive and advanced studies focusing on the additional sensory regions of occipital, parietal and temporal cortex to confirm the role of advanced FNM in the pathophysiology of PD.