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Atrial fibrillation is a significant cardiovascular disease, and the increased risk of its occurrence may be influenced by mental disorders. Currently, the causal relationship between them remains controversial. Our aim is to ascertain the relationship between atrial fibrillation and mental disorders including depression, anxiety, and panic, as well as the risk factors mediating this relationship, through the judgment of genetic susceptibility. We utilized the summarized statistics from nine large-scale genome-wide association studies (in European populations), including depression (PGC, N = 807,553), anxiety (FinnGen, N = 429,209), panic (PGC, N = 230,878), diabetes (UK Biobank, N = 655,666), smoking (IEU, 607,291), hypertension (UK biobank, N = 463,010), obstructive sleep apnea (IEU, N = 476,853), obesity (UK biobank, N = 463,010), and AF (IEU, N = 1,030,836). By applying bidirectional two-sample Mendelian randomization and multivariable Mendelian randomization to depression, anxiety, panic, and AF, we analyzed their causal relationships and the independent influence of specific risk factors. Furthermore, a two-step MR approach was used to assess the mediating effects of diabetes, smoking, hypertension, obstructive sleep apnea, and obesity. Results from the Two-Sample Mendelian Randomization Inverse Variance Weighted Random Effects Model show: the occurrence of genetically predicted depression is related to an increased risk of atrial fibrillation (AF) (OR: 1.073; [95 % CI: 1.005–1.146] P < 0.05), and panic is more significantly associated than depression (OR: 1.017; [95 % CI: 1.008–1.027] P < 0.001), while anxiety has no causal relationship with the occurrence of AF (OR: 1.023; [95 % CI: 0.960–1.092], P > 0.05), and AF is not significantly related to the occurrence of depression, anxiety, or panic (P > 0.05). After correcting for the other two risk factors using multivariable Mendelian randomization, depression remains significantly related to the occurrence of AF (β: 0.075; 95 % CI: [0.006, 0.144], P < 0.05), while panic and anxiety are not related to the occurrence of AF. Among them, the risk factors for AF occurrence, hypertension and obesity, are mediators between depression and AF, with mediation proportions of 74.9 % and 14.3 %, respectively. The mediating effects of diabetes, smoking, and obstructive sleep apnea were found to be not statistically significant. The above results are robust after sensitivity analysis. Our results identified that the genetic susceptibility to depression is an independent risk factor for the occurrence of AF, and that hypertension and obesity can mediate this process. Panic also poses some risk to the onset of AF. This demonstrates that controlling hypertension and obesity for emotional management is of great importance in preventing the occurrence of AF. • Provided evidence for the potential link between depression and atrial fibrillation. • Proved the existence of a correlation between depression and atrial fibrillation independent of panic and anxiety. • Hypertension and obesity are mediators between depression and AF. • Conducted research utilizing multiple large-scale GWAS databases. [ABSTRACT FROM AUTHOR]

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. We investigated whether the evidence is consistent with the theory and its predictions, if updates are required and sought to identify future research considerations. 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. 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. Most studies were 'medium' in quality and were predominately from female samples. Findings are consistent with the theory and its predictions. Higher quality research is needed and implications for future research are discussed. • Predictions for the cognitive theory of panic disorder were systematically evaluated. • Fifty-three studies testing four predictions of the theory were identified. • Findings were consistent with the predictions with three studies not consistent. • Most studies were rated 'medium' in quality. • Findings support the use of the theory in understanding and treating panic disorder. [ABSTRACT FROM AUTHOR]

Background: Anxiety might be a potentially modifiable risk factor of cardiovascular diseases (CVDs). Evidence relating anxiety symptoms and generalized anxiety disorder (GAD) to CVDs from prospective cohort study was still lacking in China.Methods: Participants aged 30 to 79 years old from 10 areas across China were recruited during 2004-2008 and were followed up until 2017. 487,209 participants without CVDs at baseline remained for analyses. Anxiety symptoms (panic attacks and continuous anxiety) during the past 12 months were identified in a face-to-face interview. Participants with continuous anxiety were further assessed for GAD using Composite International Diagnostic Interview-Short Form. The primary outcomes were incident CVD, ischaemic heart disease (IHD), haemorrhagic stroke (HS), and ischaemic stroke (IS).Results: During 4.7 million person-years of follow-up, we documented 140,365 incident cases of CVD. For panic attacks, the multivariable-adjusted HRs (95 % CI) were 1.08 (1.04-1.13), 1.10 (1.02-1.19), 1.20 (1.05-1.38) and 1.20 (1.11-1.30) for CVD, IHD, HS and IS, respectively. Continuous anxiety was positively associated with incident CVD and IHD, and the corresponding HRs were 1.12 (1.04-1.20) and 1.21 (1.07-1.37).Limitations: Anxiety symptoms were examined according to self-reported questionnaires, which could constitute key study limitations.Conclusions: Among the Chinese adults, those with anxiety symptoms or GAD might be important at-risk population of CVD. [ABSTRACT FROM AUTHOR]

The study's significance lies in the multitude of challenges facing individuals today, such as the COVID-19 pandemic, military conflicts like the war in Ukraine, and the escalating rates of cancer morbidity and mortality. These factors contribute to the onset of anxiety and depressive disorders, disrupting various aspects of individuals' mental functioning and social interactions. Addressing these disorders effectively necessitates a comprehensive approach, combining pharmacological interventions with psychotherapeutic strategies under the guidance of specialized professionals. In this regard, the study is aimed at identifying aspects and features of the development of psychological problems and personality disorders in the modern world filled with various stressors. The leading methods of studying this problem are analysis, synthesis, induction, deduction, comparison, experiment and systematisation of approaches that will help determine a wide range of mental disorders. Theoretical methods were used to analyze the literature and summarize theoretical material on anxiety and depressive disorders. Diagnostic methods were used to assess the psychological state of the study population. The study examines significant clinical syndromes and vegetative disorders that disrupt normal lifestyle, hinder daily activities, and impede professional growth. It evaluates the roles of psychologists, psychiatrists, and social workers in assisting individuals with anxiety disorders. It outlines preventive measures for anxiety and depression, while also delving into various types of anxiety disorders. The research proposes diverse methods to prevent emotional anxiety and instability. It underscores the importance of devising novel strategies for diagnosis and therapy, emphasizing a comprehensive approach involving psychotherapeutic support, medical intervention, and adaptive behavioral techniques. The findings of the study hold both practical and theoretical significance for professionals in psychology, psychiatry, psychoanalysis, and sociology who provide support for individuals with anxiety and depressive disorders. Furthermore, the insights provided may be pertinent to researchers and scholars investigating the psychological well-being of contemporary society amidst adverse external circumstances. [ABSTRACT FROM AUTHOR]

Given the high prevalence and considerable clinical and societal burden of anxiety disorders, preventive measures are urgently warranted to reduce their incidence and overall healthcare impact. Anxiety sensitivity (AS) – a key element in learning theories of anxiety disorders in the context of interoceptive conditioning – constitutes a malleable risk factor of particularly panic disorder and separation anxiety, which share developmental, nosological, epidemiological and pathomechanistic characteristics. The computer-assisted 'Cognitive Anxiety Sensitivity Treatment' (CAST) targeting interoceptive anxiety symptoms (cf. Schmidt et al., 2014) was translated, intensified and culturally adapted to German and evaluated in a sample of 105 healthy adult volunteers with elevated AS (mean ASI-3: 29.5) applying a randomized design. Success of the intervention was measured as a function of AS and separation anxiety (ASA-27) ∼6 weeks (T1) and ∼6 months (T2) after the intervention. As compared to waitlist, CAST resulted in a significant reduction of AS at both T1 and T2. Separation anxiety was not directly reduced by the intervention, but decreased mediated by a decline in AS. A composite interoceptive score capturing changes in sensitivity to respiratory symptoms during the baseline therapist-accompanied CAST session was shown to be predictive of overall response at T1. In sum, CAST-German Version was successfully established as an effective intervention reducing AS, while at the same time indirectly decreasing separation anxiety. A composite interoceptive score predicting treatment response might aid in further delineating risk markers informing targeted preventive interventions for anxiety disorders. [ABSTRACT FROM AUTHOR]

Background: Heightened public anxiety was observed at the early stage of the COVID-19 pandemic. Our study enriches scholarly understanding of this mass response by investigating both generic and pandemic-specific anxiety that explain preventive health behavior.Methods: In our two-phase, mixed-methods study, pandemic-specific anxiety items elicited during the qualitative phase from March 2-8, 2020 were then tested in the quantitative phase from March 16-22, 2020. Eligible participants were U.S. or U.K. residents aged 18-65.Results: Of the 1,400 participants, 52% met the criteria for moderate to severe anxiety. In addition to anxiety over possible personal COVID-19 infection, participants were also anxious about others' health, others' reactions (e.g., panic-buying, discrimination), societal problems (e.g., economic slowdown, healthcare system breakdown), and personal finances. The positive association between generic anxiety and hygiene practice frequency was explained by two interpersonal-oriented forms of pandemic-specific anxiety: anxiety over others' health (b = 0•0040, 95% CI: 0•0031-0•0050) and others' reactions (0•0031, 0•0021-0•0042).Limitations: The study was conducted with participants from developed countries at an early stage of the pandemic, and the results were not necessarily generalizable to developing countries or other stages of the pandemic. Also, hygiene practices was the sole behavior of interest, and the findings may differ for other behaviors.Conclusions: The new findings indicate the importance of adopting a nuanced approach that unveils the multifaceted nature of anxiety using a mixed-methods design. Individuals from COVID-19-affected regions experience pandemic-specific anxiety due to concerns related to not only personal but also interpersonal-oriented issues. [ABSTRACT FROM AUTHOR]

The portrayal of crowd accidents by the media can influence public understanding and emotional response, shaping societal perceptions and potentially impacting safety measures and preparedness strategies. This paper critically examines the portrayal of crowd accidents in news coverage by analyzing the texts of 372 media reports of crowd accidents spanning 26 diverse news sources from 1900 to 2019. We investigate how media representations of crowd accidents vary across time and geographical origins. Our methodology combines lexical analysis to unveil prevailing terminologies and sentiment analysis to discern the emotional tenor of the reports. The findings reveal the prevalence of the term "stampede" over "panic" in media descriptions of crowd accidents. Notably, divergent patterns are observable when comparing Western versus South Asian media (notably India and Pakistan), unveiling a cross-cultural dimension. Moreover, the analysis detects a gradual transition from "crowd stampede" to "crowd crush" in media and Wikipedia narratives in very recent years, suggesting evolving lexical sensitivities. Sentiment analysis uncovers a consistent association with fear-related language, indicative of media's propensity toward sensationalism. This fear-infused narrative has intensified over time. The study underscores the potential impact of language and sentiment in shaping public perspectives on crowd accidents, revealing a pressing need for responsible and balanced reporting that moves beyond sensationalism and promotes a nuanced understanding. This will be crucial for increasing public awareness and preparedness against such accidents. • A dataset containing 372 news media reports on crowd accidents is created. • Media reports are analyzed to identify trends in the portrayal of crowd accidents. • Lexical and sentiment analysis are used in combination to analyze the texts. • Stampede and panic emerge as controversial and problematic words. • A trend toward the dramatization in the reporting of crowd accidents is observed. [ABSTRACT FROM AUTHOR]

Background: Precisely how the COVID-19 pandemic has impacted mental health worldwide is currently poorly understood. The study aimed to assess panic and anxiety among individuals in the general Bangladesh population early in the COVID-19 outbreak.Methodology: A cross-sectional online survey was conducted from March 29 to April 06, 2020, involving 1311 community-dwelling individuals aged between 13 and 63 years and residing in Bangladesh. After providing informed consent, participants completed an online survey assessing socio-demographic variables and using the Panic Disorder Severity Scale and Generalized Anxiety Disorder (GAD-7) to assess panic and anxiety symptomatology, respectively. Binary logistic regression analyses were conducted.Results: Estimates of panic and generalized anxiety were 79.6%, and 37.3%, respectively. Factors statistically predicting panic were being older (more than 30 years), having higher education (above bachelor), being married, and living with a joint family. Factors statistically predicting generalized anxiety were being female, being older (more than 30 years), having higher education (above bachelor), being married, being a non-governmental employee.Limitations: As this study employs the cross-sectional and self-reported measures, causal inferences cannot be indicated. Sampling biases may have influenced estimates of panic and generalized anxiety.Conclusion: Sizable proportions of respondents reported panic and generalized anxiety in the setting of COVID-19. The findings suggest the need for additional surveillance of panic and generalized anxiety through longitudinal assessments. Evidence-based intervention programs and supportive services to address panic and generalized anxiety appear important for Bangladeshi individuals during this stage (and likely later stages) of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

With the rapid spread of global pandemic coronavirus disease 2019 (COVID-19), people around the world express panic in various behaviors. This affects the economy of the county, social values, and psychological stress of the people involved regardless of the directness of contact with the infected. This study aims to analyze the panic responses of the people as well as the perception on the global issue through an online survey. The researchers used Health Anxiety Inventory and open ended questions regarding the feelings, thoughts and actions of people during the enhanced community quarantine. Quantitative and qualitative data were both analyzed and interpreted interactively. Results also show that there is a significant difference (p = 0.028) in the Avoidance behavior between locations. Furthermore, a significant difference (p = 0.000) also shows on the Symptoms of Hypochondriasis between exposure to COVID-19. COVID-19 Panic Framework were also conceptualized with the following themes arranged from negative to positive behaviors: Indifference, Annihilation, Nihilism, Paranoia, Sadness, Fear, Transmission of Virus, Shock, Government Blaming, Anxiety, Relating to Past Pandemics, Worry on Self/Family/Others, Information Dissemination, Composure, Compliance, Protection, Cautiousness, Optimism, and Health Consciousness. In conclusion, levels of health anxiety were consistent regardless of location and exposure to COVID-19 patients. Lastly, spectrum of panic consequences due to COVID-19 pandemic were constructed. [ABSTRACT FROM AUTHOR]

Anxiety disorders and symptoms disproportionately impact women relative to men, but it is unclear what mechanism(s) contribute to this phenomenon. The present study examined sensitivity to unpredictable threat as a potential mechanism of gender differences in panic symptoms. The sample included 67 participants (35 women) who completed the no, predictable, and unpredictable threat (NPU-threat) startle paradigm with electric shocks as the aversive stimulus. Participants also completed the self-report Inventory of Depression and Anxiety Symptoms to assess current panic and depression symptoms. Results indicated that women, relative to men, reported greater panic symptoms and demonstrated increased startle potentiation in anticipation of predictable and unpredictable threat. Furthermore, across all participants increased startle potentiation in anticipation of unpredictable (but not predictable) threat was associated with greater panic symptoms, but there was no relationship with depression symptoms. Finally, the gender difference in panic symptoms was mediated by startle potentiation in anticipation of unpredictable (but not predictable) threat. The present study suggests that a heightened sensitivity to unpredictable threat might be a mechanism that contributes to increased anxiety in women. • Examined gender differences in startle reflex to predictable and unpredictable threat • Women demonstrated greater startle to unpredictable threat compared to men. • Women reported greater panic symptoms compared to men. • Panic symptoms were associated with greater startle to unpredictable threat. • Startle to unpredictable threat mediated gender difference in panic symptoms. [ABSTRACT FROM AUTHOR]

Anxiety and panic symptoms are widespread in the general population. The physical manifestations of anxiety and panic commonly account for people presenting to Emergency Departments (EDs). It is therefore important for ED clinicians to be informed of the numerous causes of anxiety and panic and equipped to respond effectively. This paper describes the underlying pathophysiology of the physical symptoms of anxiety and panic and differential diagnoses to consider. Organic conditions that are associated with symptoms of anxiety and panic are highlighted. Brief interventions are tabled for ED clinicians to use when explaining symptoms, and to promote individual self-management. [ABSTRACT FROM AUTHOR]

Background: This study employed a structural equation model to examine the relationships between poor physical health, suicide, depression, psychosocial stress, interpersonal conflict, and panic.Methods: The sample consisted of a large, archived set of mental health treatment-seeking adults who completed a behavioral outcome questionnaire prior to beginning treatment.Results: Results supported the extant literature indicating that poor physical health, depression, psychosocial stress, interpersonal conflict, and panic impose increased risk for suicidal ideation, with depression demonstrating the highest risk for increased suicidal ideation. The results also supported the hypotheses that depression, psychosocial stress, interpersonal conflict, and panic would mediate the association between poor physical health and suicidal ideation. Although no a priori hypotheses were made regarding relationships among the 15 physical illnesses examined, results indicated that HIV/AIDS had the strongest correlation with depression and the weakest correlation with interpersonal conflict.Limitations: Firstly, the study sample was primarily Caucasian, limiting its generalizability. Secondly, causal inferences should be interpreted with caution, due to the quasi-experimental design. Thirdly, these data were self-reported, which create response biases since suicidal ideation is stigmatized.Conclusions: These findings highlight the importance of considering interpersonal factors as potential mediators in the relationship between poor physical health, mental illness, and suicide. Clinically, the impact of an active major depressive episode on an individual who is struggling with a serious physical illness may be strongly predictive of suicidal ideation. [ABSTRACT FROM AUTHOR]

• Two week environmental enrichment impairs avoidance responses. • Two week environmental enrichment impairs escape reactions. • Two week environmental enrichment does not alter serum corticosterone. • Environmental enrichment decreases delta FosB/serotonin immunoreactivity. In a previous study, we showed that exposure of rats to a one-week environmental enrichment (EE) protocol decreases elevated T-maze (ETM) avoidance responses, an anxiolytic-like effect, without altering escape reactions, in clinical terms related to panic disorder. These anxiolytic-like effects were followed by decreased delta FosB-immunoreactivity (delta FosB-ir) in the cingulate cortex, dorsolateral and intermediate lateral septum, hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and basolateral amygdala and ventral region of the dorsal raphe nucleus. The purpose of the present study was to further investigate behavioral and neurophysiological alterations induced by EE exposure. For that, in a first experiment we verified if increasing the time of exposure to the same EE protocol used in our previous study (from one to two weeks) altered male Wistar rats' ETM escape responses. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Since anxiety and panic-related reactions have been associated to the functioning of specific subnuclei of the dorsal raphe nucleus (DR), we also evaluated delta FosB-ir in serotonergic cells of DR regions. At last, we analyzed plasma corticosterone levels in animals submitted to EE and to standard housing. Results showed that a two-week exposure to EE decreases both ETM avoidance and escape reactions, inducing anxiolytic and panicolytic-like effects, respectively. There was also a significant decrease in the number of double staining neurons in the midrostral region of the dorsal subnucleus of the dorsal raphe. No changes in corticosterone levels, however, were observed. These results contribute to a better understanding of the effects of EE on anxiety and panic-related responses. [ABSTRACT FROM AUTHOR]

Microinjections of N-methyl- d -aspartic acid (NMDA) in the midbrain tectum structures produce panic attack-like defensive behaviours, followed by an antinociceptive response. It has been suggested that fear-related defensive responses organised by brainstem neurons can be modulated by 5-hydroxytryptamine (5-HT). However, there is a shortage of studies showing the role of dorsal raphe nucleus (DRN) 5-HT 2A receptors in the modulation of panic-like behaviour and fear-induced antinociception organised by the superior colliculus (SC). The purpose of this study was to investigate the participation of DRN 5-HT 2A receptors in the modulation of panic attack-like behaviour and antinociception evoked by intra-SC injections of NMDA. In experiment I, the animals received microinjections of physiological saline or NMDA (6, 9 and 12 nmol) in the deep layers of the SC (dlSC). In experiment II, the most effective dose of NMDA (12 nmol) or vehicle was preceded by microinjections of vehicle or the 5-HT 2A receptor selective antagonist R-96544 at different concentrations (0.5, 5 and 10 nM) in the DRN. Both proaversive and antinociceptive effects elicited by intra-dlSC injections of NMDA were attenuated by DRN pretreatment with R-96544. In addition, a morphological analysis showed that 5-HT 2A receptors are present in GABAergic interneurons in the DRN. Taken together, these findings suggest that DRN 5-HT 2A receptors are critical for the modulation of both panic attack-like defensive behaviour organised by SC neurons and unconditioned fear-induced antinociception. A possible interaction between serotonergic inputs, GABAergic interneurons and serotonergic outputs from the DRN was also considered. [ABSTRACT FROM AUTHOR]

• CB1 receptor mediates anti-aversive effects of systemic alprazolam injection. • This receptor also mediates the anxiolytic effect of intra-PAG 8-OH-DPAT injection. • CB1 receptor does not mediate the panicolytic effect of intra-PAG 8-OH-DPAT injection. • The effect of anxiolytic drugs may converge to CB1 receptor signaling facilitation. The endocannabinoid system has been implicated in the modulation of behaviors related to anxiety and panic disorders. Accordingly, facilitation of CB 1 receptor signaling reduces the consequences of aversive stimuli in animal models. However, the role of the CB 1 receptor in the effects of anxiolytic drugs has remained unclear. Here, we tested the hypothesis that the anxiolytic and panicolytic responses to systemic alprazolam injection and local 5-HT 1A receptor activation in the dorsolateral periaqueductal gray (dlPAG) depend on CB 1 receptor activation. Systemic injection of alprazolam (4 mg/kg) induced an anxiolytic-like effect in the elevated T maze (ETM) model of panic and anxiety, which was prevented by the CB 1 antagonist AM251 (0.3 mg/kg). Likewise, intra-dlPAG injection of the 5–HT 1A receptor agonist 8-OH-DPAT (3.2 nmol/0.2 u L) also reduced anxiety-like behavior, a response prevented by intra-dlPAG injection of AM251 (100 pmol/0.2 µL). 8-OH-DPAT (8 nmol/0.2 µL) also presented a panicolytic-like activity in the escape reaction induced by chemical stimulation of the dlPAG, which was not prevented by AM251 (100 pmol/0.2 µL). These results suggest that CB 1 receptor signaling is involved in the effects of anxiolytic drugs, with potential implications for developing new treatments for anxiety disorders. [ABSTRACT FROM AUTHOR]

Exposure of rats to an environment with low O 2 levels evokes a panic-like escape behavior and recruits the dorsal periaqueductal gray (dPAG), which is considered to be a key region in the pathophysiology of panic disorder. The neurochemical basis of this response is, however, currently unknown. We here investigated the role played by nitric oxide (NO) within the dPAG in mediation of the escape reaction induced by hypoxia exposure. The results showed that exposure of male Wistar rats to 7% O 2 increased nitrite levels, a NO metabolite, in the dPAG but not in the amygdala or hypothalamus. Nitrite levels in the dPAG were correlated with the number of escape attempts during the hypoxia challenge. Injections of the NO synthesis inhibitor NPA, the NO-scavenger c- PTIO, or the NMDA receptor antagonist AP-7 into the dorsolateral column of the periaqueductal gray (dlPAG) inhibited escape expression during hypoxia, without affecting the rats' locomotion. Intra-dlPAG administration of c-PTIO had no effect on the escape response evoked by the elevated-T maze, a defensive behavior that has also been associated with panic attacks. Altogether, our results suggest that NO plays a critical role in mediation of the panic-like defensive response evoked by exposure to low O 2 concentrations. • Exposure to hypoxia increases NO levels in the dorsal periaqueductal gray. • Inhibition of NO synthesis or disponibility reduces hypoxia-induced escape behavior. • Glutamate is implicated in NO' actions in the dorsal periaqueductal gray. [ABSTRACT FROM AUTHOR]

Highlights • Intra-DRN infusions of ghrelin impaired inhibitory avoidance and facilitated escape. • Pre-administration of PF-04628935 into the DRN blocked the effects induced by ghrelin. • DRN GHS-R1a receptors are involved in the control of anxiety and panic-related defensive tasks. Abstract Ghrelin is a recently discovered peptide, mainly produced in the stomach and involved in body's energy-maintenance processes. Ghrelin exerts its actions by activating the growth hormone secretagogue receptor (GHS-R). Recent analyses indicate that ghrelin targets the brain to regulate a wealth of functions, including behavioral responses that have been associated with stress and anxiety mechanisms. In this context, evidence shows the presence of GHS-R receptors in the dorsal raphe nucleus (DRN), the main source of serotonergic neurons that innervate encephalic structures involved in emotional control. Our study aims to evaluate the effects of the pharmacological manipulation of ghrelin receptors located in the DRN on the expression of the behavioral responses of Wistar rats. Such responses were assessed in the elevated T maze (ETM), an experimental model that allows the measurement, in the same animal, of two defensive tasks, inhibitory avoidance and escape. Our results showed that the intra-DRN infusion of ghrelin impaired the acquisition of inhibitory avoidance, an anxiolytic-like effect, and facilitated the expression of escape response in the ETM, indicating a panicogenic-like effect. The intra-DRN administration of the ghrelin receptor (GHS-R1a) antagonist PF-04628935 did not alter the behavioral tasks assessed in the ETM. Finally, our results revealed that intra-DRN infusions of PF-04628935 prior to the administration of ghrelin into this area neutralized the behavioral effects obtained in the ETM. Taken together, our data reveal the involvement of DRN GHS-R1a receptors in the regulation of defensive tasks that have been associated with generalized anxiety and panic disorders. [ABSTRACT FROM AUTHOR]

Highlights • GABA A receptor blockade in the dPAG cancels the anti-panic effect of alprazolam. • This effect is also observed after the blockade of dPAG benzodiazepine receptors. • Antagonism of these receptors does not affect the anxiolytic effect of alprazolam. Abstract Although the etiology of panic disorder (PD) remains elusive, accumulating evidence suggests a key role for the dorsal periaqueductal gray matter (dPAG). There is also evidence that this midbrain area is critically involved in mediation of the panicolytic effect of antidepressants, which with high potency benzodiazepines (e.g. alprazolam and clonazepam) are first line treatment for PD. Whether the dPAG is also implicated in the antipanic effect of the latter drugs is, however, still unknown. We here investigated the consequences of blocking GABA A or benzodiazepine receptors within the dPAG, with bicuculline (5 pmol) and flumazenil (80 nmol), respectively, on the panicolytic and anxiolytic effects of alprazolam (4 mg/kg). Microinjection of these antagonists fully blocked the anti-escape effect, considered as a panicolytic-like action, caused by a single systemic injection of alprazolam in male Wistar rats submitted to the elevated T-maze. These antagonists, however, did not affect the anxiolytic effect of the benzodiazepine on inhibitory avoidance acquisition and punished responding, measured in the elevated T-maze and Vogel conflict tests, respectively. Altogether, our findings show the involvement of GABA A /benzodiazepine receptors of the dPAG in the panicolytic, but not the anxiolytic effect caused by alprazolam. They also implicate the dPAG as the fulcrum of the effects of different classes of clinically effective antipanic drugs. [ABSTRACT FROM AUTHOR]

Background: Symptoms of depressed mood and anxiety have been associated with immune dysregulation and atopic disorders, however it is unclear whether this relationship spans other forms of psychopathology. The objective of this study was to use a large, population-based sample to examine the association between several common psychiatric conditions and two atopic disorders: seasonal allergies and asthma. This study also examined whether comorbidity between psychiatric disorders confounded the relationship between atopy and each psychiatric disorder.Methods: Data come from the Comprehensive Psychiatric Epidemiology Surveys, a nationally-representative sample of US adults (N = 10,309). Lifetime history of major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder (PD), and post-traumatic stress disorder (PTSD) was assessed using the Composite International Diagnostic Inventory. History of seasonal allergies and asthma were assessed by self-report. Weighted logistic regression was used to evaluate the association between allergies and asthma and psychopathology. Psychiatric comorbidities were also examined as potential confounders.Results: Approximately 36.6% had a history of allergies and 11.5% a history of asthma. Seasonal allergies were positively associated with odds of MDD (Odds ratio (OR): 1.24, 95% Confidence Interval (CI): 1.06-1.46), GAD (OR: 1.54 (1.28-1.84)), PD (OR: 1.54 (1.24-1.91)), and PTSD (OR: 1.32 (1.09-1.59)). Asthma was not significantly associated with any psychiatric disorder. All significant associations persisted after adjustment for psychiatric comorbidities.Limitations: Limitations include self-reporting of atopic disorder status and of all disorder ages of onset.Conclusions: This study confirms the association between MDD and PD and seasonal allergies, and extends this relationship to GAD and PTSD. [ABSTRACT FROM AUTHOR]

Abstract The simulation of pedestrian evacuation in emergency is of great significance to the public facilities design and emergency plan implementation. For study pedestrian behaviors under emergency, this paper first analyzes emergency and pedestrian characteristics. In order to describe the spread effect of emergency on pedestrian evacuation process, the concept of emergency diffusion field is put forward. In addition, the concept of panic coefficient is put forward in order to depict the effect of pedestrian panic psychology on the evacuation process. Then, the floor field model consisted of static floor field, dynamic floor field and emergency diffusion field is established, the corresponding updating rules are defined. Finally, the experiments results reproduce the pedestrian evacuation process under different conditions, and the influence factors in the process of pedestrian evacuation are analyzed, verify the validity of the model Highlights • The concept of emergency diffusion field and panic coefficient are put forward. • The floor field model consisted of static floor field, dynamic floor field and emergency diffusion field is established. • The experimental results verify the validity of the model. [ABSTRACT FROM AUTHOR]

Purpose: This study tested whether the severity of somatization, panic, generalized anxiety, and depression symptoms mediated relationships between physical activity and pain using structural equation modeling.Methods: College women (n = 1036; mean = SD age of 19.7 ± 3.0 years) reported past week physical activity and the presence of persistent pain (≥1 month). The Psychiatric Diagnostic Screening Questionnaire assessed hypothesized mediators of physical activity effects on pain via symptoms of generalized anxiety, panic, major depressive disorder, and somatization disorder.Results: The percentage of the sample screening positive was 15.7% for generalized anxiety, 5.8% for panic, 11.0% for major depressive, and 16.0% for somatization. The hypothesized model had good fit and accounted for a significant amount of variance in pain (9.1%). Direct paths from physical activity to somatization, generalized anxiety, major depressive disorder, and panic disorder were significant. Paths to pain were significant from somatization and panic disorder. The path from physical activity to pain was not direct but indirect and through significant paths to pain from somatization and panic disorder. Each standard deviation increase in physical activity decreased the probability of pain by 11.0% through panic disorder and 10.7% through somatization disorder.Conclusions: Physical activity is associated with pain indirectly through associations with panic disorder and somatization disorder symptoms in college women. [ABSTRACT FROM AUTHOR]

Background: Hypervigilance to panic-related stimuli is believed to play a critical role in the pathogenesis of panic disorder. The current event-related potential study explored whether this hyperresponsivity occurred in the absence of focused attention.Methods: Mismatch negativity (MMN) responses to panic-related vs. neutral deviants were assessed in 15 medication-free panic patients without agoraphobia and 16 healthy controls using a reverse-standard-deviant paradigm.Results: Panic patients relative to healthy controls exhibited an enhanced MMN in response to panic-related sounds but a reduced MMN in response to neutral sounds. Furthermore, MMN responses were delayed in panic patients compared to healthy controls, irrespective of stimulus type.Limitation: The sample size is relatively small.Conclusions: Our data provide evidence that panic disorder was associated with an increased sensitivity to panic-related changes, accompanied by a reduced sensitivity to other acoustic changes as well as a general slow-down of cognitive processing during the preattentive processing stage. [ABSTRACT FROM AUTHOR]

Background: Little is known specifically about the association between generalized anxiety symptoms or panic and health care costs in older age. The aim of this study was to examine the association between generalized anxiety symptoms, panic and health care costs in people aged 65 and over.Methods: Cross-sectional data from the 8-year follow-up of a large, prospective cohort study, the ESTHER study, was used. Individuals aged 65 and over, who participated in the study's home assessment, were included in this analysis (n = 2348). Total and sectoral costs were analyzed as a function of either anxiety symptoms, probable panic disorder, or a panic attack, while controlling for selected covariates, using Two Part and Generalized Linear Models. Covariates were chosen based on Andersen's Behavioral Model of Health Care Use.Results: There was no significant association between either of the anxiety or panic measures and total health care costs. Stratified by health care sectors, only the occurrence of a panic attack was significantly associated with incurring costs for outpatient non-physician services (OR: 1.99; 95% CI: 1.15-3.45) and inpatient services (OR: 2.14; 95% CI: 1.07-4.28). Other illness-related factors, such as comorbidities and depressive symptoms, were associated with health care costs in several models.Limitations: This was a cross-sectional study relying on self-reported data.Conclusion: This study points to an association between a panic attack and sector-specific health care costs in people aged 65 and over. Further research, especially using longitudinal data, is needed. [ABSTRACT FROM AUTHOR]

Highlights • We propose to combine PANIC procedure and sparse principal component analysis to estimate EER. • We apply the proposed methodology to BRICS' exchange rates. • Our results show that the procedure provides good approximations Abstract This paper deals with the difficulty to calculate the nominal effective exchange rate (EER) when international trade data are not (immediately) available, does not exist for a given period, is incomplete or not reliable which can be the case for some emerging countries. We propose to extract an EER proxy using a factor model and apply a PANIC (Panel Analysis of Non-stationarity in Idiosyncratic and Common components) methodology. In addition we propose to use sparse principal component analysis to select the bilateral exchange rates for the EER estimate. We apply the proposed methodology to approximate EER of the BRICS economies and we show that the approximation is fairly good. Finally we propose an EER estimate for the Egyptian Pound which is not provided by traditional data sources. [ABSTRACT FROM AUTHOR]

Clinical and preclinical studies point towards anxiolytic actions of cannabidiol (CBD), but its effect in panic disorder has been less explored and few studies consider effects in females. We here compared the effect of CBD on the response of male and female rats and mice to a panicogenic challenge; exposure to low O 2 (rats) or high CO 2 (mice) paying attention in females to possible effects of estrous cycle phase. Male and female Sprague-Dawley rats and C57BL/6 J mice were exposed to 7% O 2 for 5 min (rats) or 20% CO 2 (mice) and escape behaviour, which has been associated with panic attacks, was quantified as undirected jumps towards the gas chamber's ceiling. The effect of pretreatment with CBD (1–10 mg kg−1 i.p. in rats or 10–60 mg kg−1 i.p. in mice) was tested. The results showed that low O 2 (rats) or high CO 2 (mice) evoked escape in both sexes. In female rats the response was estrous cycle-sensitive: females in late diestrus made significantly more jumps than females in proestrus. In female mice escape was not influenced by estrous cycle phase and CBD was panicolytic. In female rats CBD attenuated escape behaviour in late diestrus phase but not in proestrus. In male rats and mice CBD had no effect on escape behaviour. Therefore, CBD is panicolytic in female rats and mice but not in males. In rats the effect is estrous cycle-sensitive: rats were most responsive to CBD in late diestrus. In mice higher doses were required to elicit effects and estrous cycle had no effect. • Acute exposure to low O 2 and high CO2 evoked panic-like escape behavior. • CBD was panicolytic in female rats and mice but not in males of both species • In female rats CBD was panicolytic in late diestrus phase but not in proestrus [ABSTRACT FROM AUTHOR]

How do people behave when disasters strike? Popular media accounts depict panic and cruelty, but in fact individuals often cooperate with and care for one another during crises. I summarize evidence for such 'catastrophe compassion', discuss its roots, and consider how it might be cultivated in more mundane times. [ABSTRACT FROM AUTHOR]

Abstract A large body of work links parental sick role reinforcement behavior to adolescent panic vulnerability. To date, however, little work has examined the role of the adolescent in this process. The current study addressed this gap in the literature, using a novel method to experimentally test the impact of adolescent anxiety during a straw-breathing task on parental propensity to engage in sick role reinforcement behavior. An unselected sample of 51 early adolescents (26 female, 10–14 years) and their parents participated in the study. Adolescents were trained to mimic a straw-breathing task, and adolescent reactions to the task were scripted. Parents were randomly assigned to watch their adolescent react either a) anxiously or b) non-anxiously to the straw-breathing task. Parents who viewed their adolescent react anxiously ended the task earlier, reported that they would reinforce more sick role behavior, and reported more negatively valenced reactions during the task than parents who viewed their adolescent react non-anxiously to the task. No group differences emerged in terms of parental self-reported or physiological arousal during the task. Results suggest that adolescent anxiety increases parental sick role reinforcement behavior. Findings are discussed in terms of future directions for reducing parenting behaviors thought to increase vulnerability for panic among adolescents. Highlights • Adolescent anxiety during a straw breathing task is related to parental self reported and behavioral sick role reinforcement. • Parents valence became more negative in response to adolescent anxious reactions to a straw breathing task. • Parents did not evidence more self reported or physiological arousal in the presence of adolescent anxiety. [ABSTRACT FROM AUTHOR]

Despite the consistent clinically-significant relation between smoking and anxiety and its disorders, there is limited understanding of how specific fears relate to smoking processes. To isolate therapeutic targets for smoking-anxiety treatment development, there is a need to identify the underlying situational fears most related to smoking processes. Thus, the present study examined the association between interoceptive, agoraphobic, and social fears in terms of clinically significant negative affect-related smoking cognitions including negative affect reduction expectancies, coping motives, and perceived internal barriers to cessation. Participants were 469 treatment seeking smokers (48.2% female, Mage = 36.59, SD = 13.58) enrolled in a smoking cessation trial and completed baseline measures of smoking cognitions and situational fears. Results indicated that the there was a significant effect for social fears, relative to interoceptive and agoraphobic fears, for each of the studied clinically relevant smoking variables. Overall, this study offers initial empirical evidence that social fears are significantly and consistently related to several clinically-significant types of smoking cognition. [ABSTRACT FROM AUTHOR]

Introduction: Psychogenic Non-Epileptic Seizures (PNES) are events that appear epileptic but are instead thought to have a psychological origin. Increased rates of several psychiatric disorders have been reported in PNES, including anxiety and panic disorders. Some theories suggest panic and/or hyperventilation have aetiological roles in PNES, though these remain unproven.Methods: We conducted a systematic review of associations of panic and hyperventilation with PNES using Ovid Medline and PubMed, and a meta-analysis where appropriate.Results: We found eighteen studies reporting rates of panic in PNES and eight studies reporting hyperventilation. The reported rate of panic attacks in PNES ranged from 17% to 83%, with physical symptoms more commonly reported, and affective symptoms less so. 'Dizziness or light-headedness' was found to be more prevalent than 'fear of dying' by random-effects meta-analysis (68% vs. 23%). A proportion meta-analysis found a weighted occurrence of 20% of panic disorder in PNES. A pooled meta-analytic rate of PNES events following voluntary hyperventilation induction was 30%, while the clinically observed rates of peri-ictal hyperventilation in PNES without induction varied from 15 to 46%.Conclusions: Previous studies have reported moderate rates of association of panic in PNES, though the proportions varied considerably across the literature, with physical symptoms more commonly reported than affective. Hyperventilation is an effective inducer of PNES events in a minority, and can be observed occurring in a minority of patients without induction. These results support an important, albeit not essential, role for panic and hyperventilation in the pathogenesis of PNES events. [ABSTRACT FROM AUTHOR]

Exposure-based Cognitive Behavioral Therapy (eb-CBT) represents the most evidence-based psychotherapeutic approach in anxiety disorders. However, its efficacy may be limited by a delay in onset of action and a substantial number of patients does not respond sufficiently to treatment. In this context, aerobic exercise was found to be effective in reducing clinical anxiety as well as to improve (elements of) disorder-specific CBT in some mental disorders. We therefore investigated the effect of aerobic exercise supplementary to an eb-CBT in panic disorder and agoraphobia (PD/AG). 77 patients with PD/AG performed a 30 min treadmill task with moderate or low intensity (70% or 30% of the maximal oxygen uptake [VO 2max ]) prior to five exposure sessions within a standardized seven-week CBT. At baseline, after completing the treatment period (post) and six month after post (follow-up), several measures of (un)specific psychopathology (Hamilton Anxiety Rating Scale [Ham-A], Mobility Inventory [MI], Panic and Agoraphobia Scale [PAS], Agoraphobic Cognitions Questionnaire [ACQ], Body Sensations Questionnaire [BSQ]) were established to assess for clinical changes. All patients experienced a significant improvement of symptoms from baseline to post (for all measures p < .001) but repeated-measures analyses of variance found a trend towards a significant time × group interaction in the Ham-A in favor for the moderate intense exercise group ( f [1, 74] = 4.15, p  = .045, α = .025 ). This trend, however, disappeared at follow-up since the low-intense exercise group further improved significantly in Ham-A after post. Our findings therefore might point to an accelerating effect of moderate-intense exercise within an exposure-based CBT for AG/PD. [ABSTRACT FROM AUTHOR]

The present study examined whether early life maternal separation (MS), a model of childhood separation anxiety, predisposes to panic at adulthood. For this purpose, male pups were submitted to 3-h daily maternal separations along postnatal (PN) days of either the ‘stress hyporesponsive period’ (SHRP) from PN4 to PN14 (MS11) or throughout lactation from PN2 to PN21 (MS20). Pups were further reunited to conscious (CM) or anesthetized (AM) mothers to assess the effect of mother-pup interaction upon reunion. Controls were subjected to brief handling (15 s) once a day throughout lactation (BH20). As adults (PN60), rats were tested for the thresholds to evoke panic-like behaviors upon electrical stimulation of dorsal periaqueductal gray matter and exposed to an elevated plus-maze, an open-field, a forced swim and a sucrose preference test. A factor analysis was also performed to gain insight into the meaning of behavioral tests. MS11-CM rather than MS20-CM rats showed enhanced panic responses and reductions in both swimming and sucrose preference. Panic facilitations were less intense in mother-neglected rats. Although MS did not affect anxiety, MS11-AM showed robust reductions of defecation in an open-field. Factor analysis singled out anxiety, hedonia, exploration, coping and gut activity. Although sucrose preference and coping loaded on separate factors, appetite (adult weight) correlated with active coping in both forced swim and open-field (central area exploration). Concluding, whereas 3h-daily maternal separations during SHRP increased rat’s susceptibility to experimental panic attacks, separations throughout lactation had no effects on panic and enhanced active coping. [ABSTRACT FROM AUTHOR]

Collective movement of animal in emergency condition has attracted growing attentions among researchers. However, many rules still need to be confirmed with adequate explanation. Study of collective behavior of mice can improve our understanding about the dynamics of pedestrian movement. However, its rules still need to be confirmed with adequate explanation. In this paper, collective behavior of mice passing through an exit under panic was investigated. The results showed that the total evacuation time decreased with exit width increasing in a certain range. Based on the different tendency of the curve in temporal evolution, the process of mice flow was divided into three stages. The density of mice near the exit peaks at a certain horizontal offset and starts to decrease over time. With the increase of the exit width, the duration of the higher density state decreased. We found that the frequency of time intervals obeyed a lognormal distribution or an exponential decay for different exit widths. In addition, the relationship between the group size and the group flow rate in different scenarios was analyzed. The phenomena found in our experiments show the collective behavioral characteristic of mice under panic. Our analysis in this paper will deepen our understanding of crowd dynamics in emergency condition. [ABSTRACT FROM AUTHOR]

Exposure to elevated concentrations of CO 2 or hypoxia has been widely used in psychiatric research as a panic provoking stimulus. However, the use of these respiratory challenges to model panic-like responses in experimental animals has been less straightforward. Little data is available, from behavioral and endocrine perspectives, to support the conclusion that a marked aversive situation, such as that experienced during panic attacks, was evoked in these animals. We here compared the behavioral responses of male CB57BL/6 mice during exposure to 20% CO 2 or 7% O 2 and its consequence on plasma levels of corticosterone. We also evaluated whether clinically-effective panicolytic drugs affect the behavioral responses expressed during CO 2 exposure. The results showed that whereas hypoxia caused a marked reduction in locomotion, inhalation of CO 2 -enriched air evoked an active escape response, characterized by bouts of upward leaps directed to the border of the experimental cage, interpreted as escape attempts. Corticosterone levels were increased 30 min after either of the respiratory challenges used, but it was higher in the hypoxia group. Chronic (21 days), but not acute, treatment with fluoxetine or imipramine (5, 10 or 15 mg/kg) or a single injection of alprazolam (0.025, 0.05 or 0.1 mg/kg), but not of the anxiolytic diazepam (0.025, 0.05 or 0.1 and 1 mg/kg) reduced the number of escape attempts, indicating a panicolytic-like effect. Altogether, the results suggest that whereas hypoxia increased anxiety, exposure to 20% CO 2 evoked a panic-like state. The latter condition/test protocol seems to be a simple and validated model for studying in mice pathophysiological mechanisms and the screening of novel drugs for panic disorder. [ABSTRACT FROM AUTHOR]

Background In patients with post-traumatic stress disorder (PTSD) two open pilot studies about the effects of 35% carbon dioxide (CO 2 ) exist. One shows an augmented panicogenic and anxiogenic response (Muhtz et al., 2011), the other does not (Talesnik et al. 2007). We further characterized the CO 2 reactivity in PTSD using for the first time placebo-controlled and double-blind conditions. Methods In 20 patients with PTSD we assessed panic, anxiety, dissociative and PTSD symptoms after a single vital capacity inhalation of 35% CO 2 compared to a placebo gas condition in a within-participant cross-over, placebo-controlled, double-blind and randomized design. Results Inhalation of 35% CO 2 versus placebo provoked significantly increased panic, anxiety, dissociative and PTSD symptoms. The reaction to placebo gas was minimal. Order of inhalation, patients' sex or age did not influence the results. The panic and anxiety response under CO 2 was considerably higher in the PTSD patients than in healthy controls from our previous open study. Conclusions The results corroborate that our preceding findings of an increased CO 2 reactivity in patients with PTSD are not false positive due to the open design or the lack of placebo control. Replication in a larger number of PTSD patients and matched control subjects is needed. The potential role of childhood traumatisation, psychiatric comorbidity, psychotropic medication and trait dissociation in prior contradictory reports should be clarified. [ABSTRACT FROM AUTHOR]

Background: Although research suggests that (a) childhood adversities and more recent stressful life events/conditions are risk factors for panic pathology and that (b) early life stress increases vulnerability to later psychopathology, it remains unclear whether childhood adversities amplify the association between more recent stressful life events/conditions and panic pathology.Methods: Data were derived from a general population sample (Study of Health in Pomerania, SHIP). Lifetime panic pathology was assessed with the Munich Composite International Diagnostic Interview (M-CIDI). Childhood adversities (emotional, physical and sexual abuse; emotional and physical neglect) were assessed with the Childhood Trauma Questionnaire (CTQ). More recent separation/loss events and long-lasting stressful conditions were assessed with the Stralsund Life Event List (SEL). Individuals with lifetime panic pathology (fearful spell, panic attack or panic disorder, N = 286) were compared to controls without any psychopathology (N = 286, matched for sex and age).Results: Conditional logistic regressions revealed that childhood adversities as well as more recent separation/loss events and long-lasting stressful conditions were associated with panic pathology (OR 1.1-2.5). Moreover, more recent separation/loss events - but not long-lasting stressful conditions - interacted statistically with each of the examined childhood adversities except for sexual abuse in predicting panic pathology (OR 1.1-1.3). That is, separation/loss events were associated more strongly with panic pathology among individuals with higher childhood adversities.Limitations: Data were assessed retrospectively and might be subject to recall biases.Conclusions: Findings suggest that early childhood adversities amplify the risk of developing panic pathology after experiencing separation or loss events. [ABSTRACT FROM AUTHOR]

A series of experiments were conducted to study the effect of obstacle on the evacuation efficiency of mice under different competitive condition. Firstly, experiments were conducted under low competitive condition. The mice were drove to escape in two typical settings. Setting I is an area of 1.5m wide and 1.5m long and Setting II is a laterally constrained area. For both conditions, tests with and without the obstacle were conducted to study the impact of obstacle on the efficiency of evacuation. At setting I, the average escape time is 305s and 298s respectively for non-obstacle condition and obstacle condition. At setting II, the average escape time is 313s and 298s respectively for non-obstacle condition and obstacle condition. Under low competitive condition, the presence of obstacle has little effect on the evacuation efficiency for both settings. Secondly, experiments were conducted in the same two setting with and without the obstacle under high competitive condition. At setting I, the average escape time is 334s and 297s respectively for non-obstacle condition and obstacle condition. At setting II, the mean escape time is 297s and 328s respectively for non-obstacle condition and obstacle condition. Under high competitive condition, the presence of obstacle reduces the escape time by 11.1% at setting I, whilst it increases the escape time by 10.4% at setting II. The force of mice on the wall close to the exit is recorded to study of impact of obstacle on the pressure. [ABSTRACT FROM AUTHOR]

Previously we showed that Deep Brain Stimulation (DBS) of the dorsal region (DRD) and of the lateral wings of the dorsal raphe (lwDR) respectively decreases anxiety and panic-like responses in the elevated T-maze (ETM). This study investigates neurobiological alterations which might respond for these behavioral effects. Male Wistar rats were submitted to high-frequency stimulation (100 µA, 100 Hz) of the DRD or of the lwDR for 1 h, and subsequently tested in the avoidance or escape tasks of the ETM. Since serotonin (5-HT) reuptake inhibitors are first line pharmacological treatment for anxiety disorders, we also tested the effects of chronic fluoxetine administration (10 mg/kg, IP, 21 days) on a separate group of rats. An open field was used for locomotor activity assessment. Additionally, we evaluated c-Fos immunoreactivity (Fos-ir) in serotonergic cells of the dorsal raphe (DR). Results showed that DBS of the DRD decreases avoidance reactions, an anxiolytic-like effect, without altering escape or locomotor activity. Both fluoxetine and DBS of the lwDR decreased escape responses in the ETM, a panicolytic-like effect, without altering avoidance measurements or locomotor activity. While DBS of the DRD decreased double immunostaining in the DRD, DBS of the lwDR increased Fos-ir and double immunostaining in the DRD and lwDR. Fluoxetine also increased double immunostaining in the lwDR and in the DRV but decreased it in the DRD. These results suggest that both the anxiolytic and panicolytic-like effects of DBS and fluoxetine are related to 5-HT modulation in different subnuclei of the DR. • DBS of the DRD decreases avoidance and serotonin activation in the nucleus. • Both DBS of the lwDR and fluoxetine decrease escape and increase serotonin activation in the nucleus. • Fluoxetine also increased serotonin activation in the DRV, but decreased it in the DRD. [ABSTRACT FROM AUTHOR]

• Research on the relationship between dissociation and anxiety in adolescents is limited. • Dissociation was significantly positively correlated with trait anxiety in adolescents. • This relationship was mediated by cognitive appraisals and perseverative thinking. • Cognitive-behavioural conceptualisations of dissociation may be valid in adolescence. Anxiety is a common problem in adolescence which is hypothesised to be associated with dissociation, a range of distressing symptoms linked to reduced psychosocial functioning. Yet, to date, research into the mechanisms of dissociation in adolescents has been limited. The present study investigated the link between trait anxiety and dissociative experiences (depersonalisation and 'felt sense of anomaly') using an online survey. Cognitive appraisals of dissociation, perseverative thinking, and body vigilance were assessed as potential mediating factors of this relationship. 1211 adolescents aged 13–18 years were recruited via social media advertisements and local schools. Linear regression showed a moderate positive relationship between trait anxiety and both dissociation constructs. Hierarchical regression indicated that cognitive appraisals of dissociation and perseverative thinking mediated the relationship between trait anxiety and both dissociation constructs, but trait anxiety was a significant predictor for felt sense of anomaly but not depersonalisation after including the mediators. The final models accounted for 58.7% of variance in depersonalisation and 68.4% of variance in felt sense of anomaly. These results support the hypothesis that dissociation is associated with anxiety in adolescence. They also demonstrate that cognitive-behavioural conceptualisations may be valid for understanding dissociation in adolescence. [ABSTRACT FROM AUTHOR]

Our current knowledge of the implications of endocannabinoids in fear and anxiety is largely based on fear conditioning paradigms and approach-avoidance conflicts. Here we establish the ethobehavioral beetle mania task (BMT), which confronts mice with an erratically moving robo-beetle. With the help of this task we demonstrate decreased tolerance yet increased avoidance responses to an approaching beetle in high-anxiety behavior (HAB) and BALBc mice compared to C57BL/6N, CD1 and normal-anxiety behavior (NAB) mice. Also DBA/2N mice showed decreased passive and increased active behavior, but followed the robo-beetle more often than HAB and BALBc mice. Treatment with diazepam (1 mg/kg) increased tolerance without affecting avoidance behavior in HAB mice. Treatment with the MAGL inhibitor JZL184 (8 mg/kg) increased flight behavior, but did not affect tolerance. The FAAH inhibitor URB597 (0.3 mg/kg), however, reduced flight behavior and enhanced tolerance to the robo-beetle. The latter effects were blocked by co-treatment with the CB1 receptor antagonist SR141716A (3 mg/kg), which failed to affect the behavior by itself. Taken together, we validate the BMT as a novel test for studying endocannabinoids beyond traditional paradigms and for assessing active fear responses in mice. Furthermore, we demonstrate panicolytic consequences of pharmacological enhancement of anandamide, but not 2-AG signaling. [ABSTRACT FROM AUTHOR]

Twenty patients with DSM5 schizophrenia were comprehensively and formally assessed by an experienced psychiatrist. All subjects were assessed for: positive and negative psychotic symptoms; social anxiety; panic anxiety; obsessive compulsive disorder, atypical depression; major depression; suicide risk; and global assessment of functioning. Different profiles of clinical presentation and symptom evolution emerged for patients with schizophrenia who had co-morbid depression (15%), OCD (15%), panic or limited symptom attacks (55%) and social anxiety (5%). At least eighty percent of the sample had one or more of these co-morbidities. Summing up, the data support our previous finding that panic is highly prevalent in Schizophrenia with Auditory Hallucinations ( > 73% here, versus 100% before), and panic was paroxysmally concurrent with voice onset. Moreover, characteristic clinical findings may help point clinicians to five specific co-morbidity psychosis subtypes. Moreover, co-morbidity dissection of psychotic diagnoses recalls and parallels the historical psychopharmacologic dissection of non-psychotic anxiety and depressive subtypes diagnoses. Larger studies should further test and explore these preliminary findings. [ABSTRACT FROM AUTHOR]

In a previous study, the administration of corticotrophin-releasing factor (CRF) into the dorsomedial hypothalamus (DMH), a region that modulates defensive reactions, was shown to facilitate elevated T-maze (ETM) avoidance responses, an anxiogenic-like effect. Intra-DMH administration of the CRF type 1 receptor (CRFR1) antagonist antalarmin induced anxiolytic-like effects and counteracted the anxiogenic effects of CRF. The present study further investigates the role played by CRF receptors of the medial hypothalamus in anxiety. For that, male wistar rats were treated with CRFR1 and CRFR2-modulating drugs in the DMH or VMH, another hypothalamic nucleus implicated with defensive and emotional behavior, and tested in the ETM for inhibitory avoidance and escape measurements. In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. The results showed that intra-VMH CRF or antalarmin did not alter ETM avoidance or escape performance. Intra-VMH injection of the CRFR2 preferential antagonist antisauvagine-30 or of the selective CRFR2 antagonist astressin 2-B inhibited escape performance, a panicolytic-like effect, without altering avoidance reactions. The CRFR2 agonist urocortin-2 intra-VMH was by itself without effect but blocked the effects of astressin 2-B. None of the drugs administered into the DMH altered ETM measurements. Additionally, none of the compounds altered locomotor activity measurements. These results suggest that VMH CRFR2 modulate a defensive response associated with panic disorder and are of relevance to the better understanding of the neural mechanisms underlying this pathological condition. [ABSTRACT FROM AUTHOR]

Although breathing CO 2 -enriched air reliably increases anxiety, there is debate concerning the nature and specificity of CO 2 hypersensitivity to panic risk and panic disorder versus anxiety disorders and related traits broadly, particularly among adolescents and emerging adults. The present study sought to clarify the association of CO 2 hypersensitivity with internalizing conditions and symptoms among adolescents and young adults. Participants (N = 628) self-reported anxiety levels every 2 min while breathing air enriched to 7.5% CO 2 for 8 min. Growth mixture models were used to examine the structure of anxiety trajectories during the task and the association of each trajectory with dimensional and diagnostic assessments of internalizing disorders. Three distinct trajectories emerged: overall low ( low ), overall high ( high ), and acutely increased anxiety ( acute ). Compared to the low class, the acute class reported elevated neuroticism, anxiety sensitivity, and stress whereas the high class reported elevated anxiety symptoms, depression symptoms, neuroticism, anxiety sensitivity, and increased likelihood of an anxiety disorder diagnosis. Moreover, the acute and high classes reported experiencing a panic-like event at a higher rate than the low class while participants in the high class terminated the task prematurely at a higher rate. The present study clarifies the nature of response to CO 2 challenge. Three distinct response profiles emerged, which clarifies the manifestation of CO 2 hypersensitivity in anxiety disorders with strong, though not unique, associations with panic-relevant traits. [ABSTRACT FROM AUTHOR]

The current experiment investigated whether overgeneralization of fear could be due to an inability to perceptually discriminate the initial fear-evoking stimulus from similar stimuli, as fear learning-induced perceptual impairments have been reported but their influence on generalization gradients remain to be elucidated. Three hundred and sixty-eight healthy volunteers participated in a differential fear conditioning paradigm with circles of different sizes as conditioned stimuli (CS), of which one was paired to an aversive IAPS picture. During generalization, each subject was presented with one of 10 different sized circles including the CSs, and were asked to categorize the stimulus as either a CS or as novel after fear responses were recorded. Linear mixed models were used to investigate differences in fear generalization gradients depending on the participant's perception of the test stimulus. We found that the incorrect perception of a novel stimulus as the initial fear-evoking stimulus strongly boosted fear responses. The current findings demonstrate that a significant number of novel stimuli used to assess generalization are incorrectly identified as the initial fear-evoking stimulus, providing a perceptual account for the observed overgeneralization in panic and anxiety disorders. Accordingly, enhancing perceptual processing may be a promising treatment for targeting excessive fear generalization. [ABSTRACT FROM AUTHOR]

The lateral wings subnucleus of the dorsal raphe nucleus (lwDR) has been implicated in the modulation of panic-like behaviors, such as escape. Infusion of non- excitotoxic doses of the excitatory amino acid kainic acid into this subnucleus promptly evokes a vigorous escape response. In addition, rats exposed to panic-inducing situations show an increase in Fos protein expression in neurons within the lwDR. In the present study, we first investigated whether key structures associated with the mediation of escape behavior are recruited after chemical stimulation of the lwDR with kainic acid. We next investigated whether the infusion of the GABA A receptor antagonist bicuculline into the lwDR also evoked escape responses measured both in a circular arena and in the rat elevated T-maze. The effects of bicuculline in the circular arena were compared to those caused by the infusion of this antagonist into the ventrolateral periaqueductal gray (vlPAG), an area in close vicinity to the lwDR. The results showed that kainic acid infusion into the lwDR increased Fos protein immunostaining in brain structures deeply involved in panic-like defensive behaviors, such as the periaqueductal gray and hypothalamus, but not the amygdala. As observed with kainic acid, bicuculline evoked a pronounced escape response in the circular arena when microinjected in the lwDR, but not in the vlPAG. The escape-promoting effect of bicuculline in the lwDR was also evidenced in the elevated T-maze. These findings strength the view that dysfunction in mechanisms controlling escape in the lwDR is critically implicated in the pathophysiology of panic disorder. [ABSTRACT FROM AUTHOR]

Current regulations demand that at least two exits should be available for a safe evacuation during a panic situation. The second exit is expected to reduce the overall clogging, and consequently, improve the evacuation time. However, rooms having contiguous doors not always reduce the leaving time as expected. We investigated the relation between the door’s separation and the evacuation performance. We found that there exists a separation distance range that does not really improve the evacuation time, or it can even worsen the process performance. To our knowledge, no attention has been given to this issue in the literature. This work reports how the pedestrian’s dynamics differ when the separation distance between two exit doors changes and how this affects the overall performance. [ABSTRACT FROM AUTHOR]

The periaqueductal gray (PAG) has been commonly recognized as a downstream site in neural networks for the expression of a variety of behaviors and is thought to provide stereotyped responses. However, a growing body of evidence suggests that the PAG may exert more complex modulation of a number of behavioral responses and work as a unique hub supplying primal emotional tone to influence prosencephalic sites mediating complex aversive and appetitive responses. Of particular relevance, we review how the PAG is involved in influencing complex forms of defensive responses, such as circa-strike and risk assessment responses in animals. In addition, we discuss putative dorsal PAG ascending paths that are likely to convey information related to threatening events to cortico-hippocampal-amygdalar circuits involved in the processing of fear learning. Finally, we discuss the evidence supporting the role of the PAG in reward seeking and note that the lateral PAG is part of the circuitry related to goal-oriented responses mediating the motivation to hunt and perhaps drug seeking behavior. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies suggest that ictal panic symptoms are common in patients with psychogenic nonepileptic seizures (PNES). This study investigates the frequency of panic symptoms in PNES and if panic symptoms, just before or during episodes, can help distinguish PNES from the other common causes of transient loss of consciousness (TLOC), syncope and epilepsy.Methods: Patients with secure diagnoses of PNES (n=98), epilepsy (n=95) and syncope (n=100) were identified using clinical databases from three United Kingdom hospitals. Patients self-reported the frequency with which they experienced seven symptoms of panic disorder in association with their episodes. A composite panic symptom score was calculated on the basis of the frequency of symptoms.Results: 8.2% of patients with PNES reported "never" experiencing any of the seven panic symptoms in their episodes of TLOC. Patients with PNES reported more frequent panic symptoms in their attacks than those with epilepsy (p<0.001) or syncope (p<0.001), however, patients with PNES were more likely "rarely" or "never" to report five of the seven-ictal panic symptoms than "frequently" or "always" (45-69% versus 13-29%). A receiver operating characteristic analysis demonstrated that the composite panic symptom score distinguished patients with PNES from the other groups (sensitivity 71.1%, specificity 71.2%), but not epilepsy from syncope.Conclusions: Patients with PNES report TLOC associated panic symptoms more commonly than those with epilepsy or syncope. Although panic symptoms are reported infrequently by most patients with PNES, a composite symptom score may contribute to the differentiation between PNES and the other two common causes of TLOC. [ABSTRACT FROM AUTHOR]

Intravenous injections of potassium cyanide (KCN) both elicit escape by its own and facilitate escape to electrical stimulation of the periaqueductal gray matter (PAG). Moreover, whereas the KCN-evoked escape is potentiated by CO 2 , it is suppressed by both lesions of PAG and clinically effective treatments with panicolytics. These and other data suggest that the PAG harbors a hypoxia-sensitive alarm system the activation of which could both precipitate panic and render the subject hypersensitive to CO 2 . Although prior c-Fos immunohistochemistry studies reported widespread activations of PAG following KCN injections, the employment of repeated injections of high doses of KCN (>60 µg) in anesthetized rats compromised both the localization of KCN-responsive areas and their correlation with escape behavior. Accordingly, here we compared the brainstem activations of saline-injected controls (air/saline) with those produced by a single intravenous injection of 40-µg KCN (air/KCN), a 2-min exposure to 13% CO 2 (CO 2 /saline), or a combined stimulus (CO 2 /KCN). Behavioral effects of KCN microinjections into the PAG were assessed as well. Data showed that whereas the KCN microinjections were ineffective, KCN intravenous injections elicited escape in all tested rats. Moreover, whereas the CO 2 alone was ineffective, it potentiated the KCN-evoked escape. Compared to controls, the nucleus tractus solitarius was significantly activated in both CO 2 /saline and CO 2 /KCN groups. Additionally, whereas the laterodorsal tegmental nucleus was activated by all treatments, the rostrolateral and caudoventrolateral PAG were activated by air/KCN only. Data suggest that the latter structures are key components of a hypoxia-sensitive suffocation alarm which activation may trigger a panic attack. [ABSTRACT FROM AUTHOR]

Inhalation of carbon dioxide (CO 2 ) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO 2 reliably evokes panic attacks. Sensitivity to CO 2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. Preclinical models that can simulate differential responsivity to CO 2 are therefore relevant. In the current study we investigated CO 2 -evoked behavioral responses in four different rat strains: Sprague–Dawley (SD), Wistar (W), Long Evans (LE) and Wistar-Kyoto, (WK) rats. We also assessed tryptophan hydroxylase 2 (TPH-2)-positive serotonergic neurons in anxiety/panic regulatory subdivisions of the dorsal raphe nucleus (DR), as well as dopamine β hydroxylase (DβH)-positive noradrenergic neurons in the locus coeruleus, implicated in central CO 2 -chemosensitivity. Behavioral responsivity to CO 2 inhalation varied between strains. CO 2 -evoked immobility was significantly higher in LE and WK rats as compared with W and SD cohorts. Differences were also observed in CO 2 -evoked rearing and grooming behaviors. Exposure to CO 2 did not produce conditioned behavioral responses upon re-exposure to CO 2 context in any strain. Reduced TPH-2-positive cell counts were observed specifically in the panic-regulatory dorsal raphe ventrolateral (DRVL)-ventrolateral periaqueductal gray (VLPAG) subdivision in CO 2 -sensitive strains. Conversely, DβH-positive cell counts within the LC were significantly higher in CO 2 -sensitive strains. Collectively, our data provide evidence for strain dependent, differential CO 2 -sensitivity and potential differences in monoaminergic systems regulating panic and anxiety. Comparative studies between CO 2 -vulnerable and resistant strains may facilitate the mechanistic understanding of differential CO 2 -sensitivity in the development of panic and anxiety disorders. [ABSTRACT FROM AUTHOR]

Intravenous cholecystokinin-tetrapeptide (CCK-4) administration reliably and dose-dependently provokes panic anxiety in man, accompanied by adrenocorticotropic hormone (ACTH) and cortisol release. Preclinical findings suggest that behavioral and endocrine effects of CCK-4 are mediated via corticotropin-releasing hormone (CRH) release. Anxiogenic stimulation of the central CCK-receptors in man was shown to increase as well vasopressin (AVP), which acts synergistically with CRH as pituitary-adrenocortical axis stimulator during stress. Copeptin (CoP), the C-terminal part of pre-pro-AVP, is released in an equimolar ratio to AVP. It is more stable in the circulation and easier to determine than AVP and it was found to closely mirror the production of AVP. So far, CoP secretion has not been characterized during panic provocation. In 30 healthy male human subjects, we repeatedly measured CoP in plasma during a panic challenge and studied its correlation to Acute Panic Inventory (API) ratings and plasma ACTH and cortisol. CoP levels correlated positively with the increase in API ratings (r = 0.41, p = 0.03), while ACTH or cortisol did not (r = 0.08, p = 0.68 and r = 0.12, p = 0.53, respectively). CoP levels correlated also positively with ACTH (r = 0.48, p = 0.009) and cortisol (r = 0.48, p = 0.01) concentrations throughout the CCK-4 challenge. As expected, we found a positive correlation between plasma ACTH and cortisol levels (r = 0.57, p = 0.001). A vasopressinergic activation during CCK-4 induced panic was demonstrated, which was correlated positively to panic symptoms and pituitary-adrenocortical release. Our findings suggest a role of CoP as a potential surrogate marker of CCK-4 panic symptoms. Further studies are needed to replicate our results and to further clarify the role of CoP as a stress-sensitive hormone in different panic paradigms as well as in panic patients. [ABSTRACT FROM AUTHOR]