Unexpected Panic Attacks Research Articles

Catching your breath: unraveling the intricate connection between panic disorder and asthma

Respiratory changes are often associated with anxiety disorders, particularly panic disorder (PD). Individuals experiencing PD are subjected to unexpected panic attacks, marked by overwhelming anxiety and fear, leading to a variety of autonomic and respiratory symptoms. PD patients have increased sensitivity to carbon dioxide (CO2). In response to respiratory stimulants like CO2, patients with PD tend to hyperventilate and panic, triggering the activation of an excessively reactive fear network. While their respiratory physiology may appear normal, the presence of subtle breathing abnormalities and other functions related to bodily homeostasis. This fear network, comprising the hippocampus, medial prefrontal cortex, amygdala, and its connections to the brainstem, seems to be hypersensitive in PD’s patients. This review aims to present a comprehensive overview of the current landscape on the link between PD and respiratory disorders. In July 2023 a literature search was undertaken for articles examining the relationship between PD, respiratory disorders, and psychological implications. Multiple databases were searched: PubMed, PubMed Central, PsycINFO, Web of Science, Elsevier Journal, Health & Medical Collection, and Springer. The analysis of six studies focused on the correlation between PD and asthma revealed important links between these two disorders. Anxiety and panic can have significant impacts on the manifestation and aggravation of asthma. Furthermore, the review indicates that psychological therapeutic approaches, in particular cognitive-behavioral therapy, may represent a valid intervention to improve clinical outcomes in patients suffering from both disorders. Future investigations in this field may help highlight new intervention strategies in the psychological area to help individuals with PD decrease concomitant asthma, significantly improving their quality of life.

Prevalence and Predictive Factors of Panic Disorder among Adults in Saudi Arabia: A Cross-Sectional Study.

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

Antidepressant-induced mania in panic disorder: a single-case study of clinical and functional connectivity characteristics.

Mental health issues, including panic disorder (PD), are prevalent and often co-occur with anxiety and bipolar disorders. While panic disorder is characterized by unexpected panic attacks, and its treatment often involves antidepressants, there is a 20-40% risk of inducing mania (antidepressant-induced mania) during treatment, making it crucial to understand mania risk factors. However, research on clinical and neurological characteristics of patients with anxiety disorders who develop mania is limited. In this single case study, we conducted a larger prospective study on panic disorder, comparing baseline data between one patient who developed mania (PD-manic) and others who did not (PD-NM group). We enrolled 27 patients with panic disorder and 30 healthy controls (HCs) and examined alterations in amygdala-based brain connectivity using a seed-based whole-brain approach. We also performed exploratory comparisons with healthy controls using ROI-to-ROI analyses and conducted statistical inferences at a threshold of cluster-level family-wise error-corrected p < 0.05, with the cluster-forming threshold at the voxel level of uncorrected p < 0.001. The patient with PD-mania showed lower connectivity in brain regions related to the default mode network (left precuneous cortex, maximum z-value within the cluster = -6.99) and frontoparietal network (right middle frontal gyrus, maximum z-value within the cluster = -7.38; two regions in left supramarginal gyrus, maximum z-value within the cluster = -5.02 and -5.86), and higher in brain regions associated with visual processing network (right lingual gyrus, maximum z-value within the cluster = 7.86; right lateral occipital cortex, maximum z-value within the cluster = 8.09; right medial temporal gyrus, maximum z-value within the cluster = 8.16) in the patient with PD-mania compared to the PD-NM group. One significantly identified cluster, the left medial temporal gyrus (maximum z-value within the cluster = 5.82), presented higher resting-state functional connectivity with the right amygdala. Additionally, ROI-to-ROI analysis revealed that significant clusters between PD-manic and PD-NM groups differed from HCs in the PD-manic group but not in the PD-NM group. Here, we demonstrate altered amygdala-DMN and amygdala-FPN connectivity in the PD-manic patient, as reported in bipolar disorder (hypo) manic episodes. Our study suggests that amygdala-based resting-state functional connectivity could serve as a potential biomarker for antidepressant-induced mania in panic disorder patients. Our findings provide an advance in understanding the neurological basis of antidepressant-induced mania, but further research with larger cohorts and more cases is necessary for a broader perspective on this issue.

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

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. 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. 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). 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.

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.

Les modèles théoriques actuels du trouble panique : examen conceptuel et implications cliniques

ObjectivesPanic disorder (PD) is defined by recurring and unexpected panic attacks accompanied by anticipatory anxiety about future attacks and their consequences. This generally involves avoiding situations and behaviors that can produce panic attacks (American Psychiatric Association [APA], 2013). Among anxiety disorders, PD is associated with some of the greatest burdens in terms of personal suffering, occupational disability, and societal cost. Since the introduction of PD in the DSM-III (1980) and the distinction of PD from generalized anxiety disorder following the work of Klein (1964), several biological and psychological theories of PD have been developed. These theories have highlighted several risk factors (for the onset, maintenance and relapse associated with the disorder) that have strongly influenced research on PD and have guided its treatment. However, a comprehensive and universally accepted theoretical framework of PD to guide its treatment is lacking. This article reviews the previously described theoretical frameworks of PD and related treatments while examining the strength of the scientific evidence supporting their validity as well as their limitations. MethodologyA review of the literature was undertaken by searching PsycINFO database to list all the articles published between January 2000 and November 2020 and referring to a theoretical model or a conceptual framework of PD. The conceptual frameworks identified were reviewed based on the recent scientific researches to determine the strength of the evidence supporting their validity. ResultsOf the 928 articles initially identified, 54 referred to fourteen different conceptual frameworks relating to PD. Two models are exclusively biological: the false suffocation alarm and the neuroanatomical hypothesis of PD. Six models are psychological, one of which is psychodynamic and five are derived from the cognitive-behavioral paradigm. Finally, six models are integrative: triple vulnerability of Barlow, integrated cognitive vulnerability of Schmidt & Woolaway-Bickel, unified model of vulnerability of McGinn, causal model of Fava & Morton, causal model based on the evidence by Pilecki and integrated model of Busch. These models highlight biological, environmental, developmental and psychological vulnerability factors. ConclusionThe analysis of these different models shows that few conceptual frameworks have been used consistently to guide the treatment of PD, and that not all frameworks are empirically well supported. The theoretical approaches that have strongly influenced the treatment of PD are the cognitive model of Clark, the expectation model of Reiss as well as the triple vulnerability model of Barlow. Although treatments based on these models benefit a large percentage of patients, at least 25% of patients are classified as resistant to these treatments. In addition, relapses and persistence of symptoms remain common results of these treatments. This suggests that other vulnerability factors such as emotional regulation skills should be taken into consideration and integrated into these models especially as several studies have suggested that research focused on emotion regulation may improve our understanding of panic.

Panic disorders as somatic and neurotic states of personality: conditioning, behavioural learning

Panic disorder is examined in the article as a clinical syndrome which sets a context to study relevance of basic principles of conditioning and learning to the questions of origin and development of psychopathologies. It is proven that panic attack is sudden experiencing of strong fear or discomfort accompanied by various somatic and psychical symptoms, for example, heart palpitation, stethalgia, feeling of breath shortage, dizziness, ideas about madness, loss of self-control or death. It is mentioned that experiencing of unexpected panic attacks however is not a sufficient criterion for establishment of panic disorder. Except listed above, an individual must feel substantial anxiety or deep concern about possibility of next attack and/or its consequences, for example, cardiac attack, madness or loss of (sels)control. Nowadays there are at least three main psychological theories related to the origin of panic disorder as a mental disorder. Two of them, cognitive theory and theory of anxiety sensitivity, mark cognitive aspects of the disorder, and historically earlier conditioning theory was yielded to various criticism. Taking into account earlier perspectives of panic disorder, our understanding of this phenomenon underlines the key role of early conditioning episodes in etiology of the disorder. Such perspective can be considered as a strength of learning theories, since it includes empirically verifiable explanation of etiology of panic disorder. Anxiety and panic are examined as separate states within panic disorder; anxiety is not simply weaker version of panic, and panic accordingly isn’t just stronger or more expressed version of anxiety. Anxiety prepares psyche of an individual to future trauma, while panic works (as a mean of mental defense) with a trauma that is being experienced here and now. Conditioned anxiety, caused by interoceptive and exteroceptive signals, serves for augmentation of future panic reactions. Thus anxiety becomes precursor of panic. It is summarized that therapeutic approaches that include extinction or counterconditioning of conditional stimuli which influence the disorder, will be the most successful.

Cognitive Behavioral Therapy Implementations and Techniques in Panic Disorder: A Review

In this review, Cognitive Behavioral Techniques (CBT) that are applied for people with panic disorder are examined. Panic Disorder (PD), in the category of anxiety disorders, is identified as extreme fear and uneasiness, repeated and unexpected panic attacks. When coexisting with agoraphobia associated with poor quality of life, it becomes a chronic feature, which can disable the person functionally. The study shows that childhood traumas, domestic violence, smoking, alcohol abuse, marriage problems, specific tragic events, tend to be anxious, and such like situations increase the risk of suffering from panic disorder. Applications of CBT-based technique specific to panic disorder aim to break the vicious cycle and restructure the patients' thoughts. The purpose of the review is to explain different concepts such as bibliotherapy, cognitive restructuring, Socratic questioning, relaxation techniques, systematic desensitization, exposure, psycho-education, coping strategies, homework and mindfulness techniques. The review also aims to evaluate the effectiveness of these concepts. Generally, CBT techniques can help patients regulate cognition by handling their emotions and behavior caused by thoughts. Thus, the study also examines internet-based CBT, family, and group therapy works used in the panic disorder CBT model. The literature shows that CBT is an effective therapy technique for panic disorder.

Complementary Therapy of Pranic Healing in Managing Moderate Panic Disorder with Mild Agoraphobia during COVID-19 Pandemic: A Case Report

Panic disorder refers to recurrent unexpected panic attacks, including symptoms such as dizziness, chest pain or discomfort, a feeling of unreality, fear of losing control, and fear of dying which could last for few minutes. Here, authors presents a case of 71-year-old male during Coronavirus Disease-2019 (COVID-19) lockdown experienced moderately distressing panic attack symptoms and feared going out by himself, due to the worry of future attacks. These symptoms made significant interference with social activities. The subject was under homeopathic medication and later referred to take Pranic Healing as an add-on therapy. Panic disorder severity (panic disorder severity scale-self report) and severity of agoraphobia (severity measure for agoraphobia-adult) were measured at day 0, day 60 and day 240. Moderate panic disorder (raw score was 12) with mild agoraphobia (raw score was 10) was reduced after 14 pranic healing sessions given in two months duration. No symptoms of agoraphobia or panic disorder were found after six months follow-up. Pranic healing along with homeopathic treatment were found effective in reducing moderate panic disorder with mild agoraphobia. Psychological therapies, combined with medication can be used as gold standards in treating panic disorder.

Association of cannabinoid receptor genes (CNR1 and CNR2) polymorphisms and panic disorder

ABSTRACTBackground and objectives: Panic disorder (PD) is an anxiety disorder characterized by recurrent and unexpected panic attacks along with sudden onset of apprehension, fear or terror. The endocannabinoid system (ECS) has a role in stress recovery, regulating anxiety. The aim of this study was to analyze potential genetic alterations in key ECS targets in patients suffering from panic disorders.Design and methods: We analyzed single nucleotide polymorphisms (SNPs) of the cannabinoid receptors (CNR1; CNR2) and the endocannabinoid hydrolytic enzyme fatty acid amide hydrolase (FAAH) genes in 164 Spanish PD patients and 320 matched controls.Results: No significant differences were observed in the SNPs of the CNR2 and FAAH genes tested. However, when analyzing genotype-by-sex interaction at A592G (rs2501431) and C315T (rs2501432) in the CNR2 gene, the presence of the G-allele in males was associated with a protective haplotype. Genotyping analysis revealed that variants in CNR1 confer vulnerability to PD, with a significantly increased risk associated with the G-allele (rs12720071) and C-allele (rs806368). This finding was consistent when analyzing genotype-by-sex interaction, where females presented a greater PD risk.Conclusions: Polymorphisms at the CNR1 gene may be a risk factor for PD contributing to sex-specific dysfunction in females.

Benzodiazepines versus placebo for panic disorder in adults.

Panic disorder is characterised by recurrent unexpected panic attacks consisting of a wave of intense fear that reaches a peak within a few minutes. Panic disorder is a common disorder, with an estimated lifetime prevalence of 1% to 5% in the general population and a 7% to 10% prevalence in primary care settings. Its aetiology is not fully understood and is probably heterogeneous.Panic disorder is treated with psychological and pharmacological interventions, often used in combination. Although benzodiazepines are frequently used in the treatment of panic disorder, guidelines recommend antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as first-line treatment for panic disorder, particularly due to their lower incidence of dependence and withdrawal reaction when compared to benzodiazepines. Despite these recommendations, benzodiazepines are widely used in the treatment of panic disorder, probably because of their rapid onset of action. To assess the efficacy and acceptability of benzodiazepines versus placebo in the treatment of panic disorder with or without agoraphobia in adults. We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR Studies and References), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-), and PsycINFO (1967-) up to 29 May 2018. We handsearched reference lists of relevant papers and previous systematic reviews. We contacted experts in the field for supplemental data. All double-blind (blinding of patients and personnel) controlled trials randomising adults with panic disorder with or without agoraphobia to benzodiazepine or placebo. Two review authors independently checked the eligibility of studies and extracted data using a standardised form. Data were then entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in terms of efficacy, acceptability, and tolerability. We included 24 studies in the review with a total of 4233 participants, of which 2124 were randomised to benzodiazepines and 1475 to placebo. The remaining 634 participants were randomised to other active treatments in three-arm trials. We assessed the overall methodological quality of the included studies as poor. We rated all studies as at unclear risk of bias in at least three domains. In addition, we judged 20 of the 24 included studies as having a high risk of bias in at least one domain.Two primary outcomes of efficacy and acceptability showed a possible advantage of benzodiazepines over placebo. The estimated risk ratio (RR) for a response to treatment was 1.65 (95% confidence interval (CI) 1.39 to 1.96) in favour of benzodiazepines, which corresponds to an estimated number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 7). The dropout rate was lower among participants treated with benzodiazepines (RR 0.50, 95% CI 0.39 to 0.64); the estimated NNTB was 6 (95% CI 5 to 9). We rated the quality of the evidence as low for both primary outcomes. The possible advantage of benzodiazepine was also seen for remission (RR 1.61, 95% CI 1.38 to 1.88) and the endpoint data for social functioning (standardised mean difference (SMD) -0.53, 95% CI -0.65 to -0.42), both with low-quality evidence. We assessed the evidence for the other secondary outcomes as of very low quality. With the exception of the analyses of the change score data for depression (SMD -0.22, 95% CI -0.48 to 0.04) and social functioning (SMD -0.32, 95% CI -0.88 to 0.24), all secondary outcome analyses showed an effect in favour of benzodiazepines compared to placebo. However, the number of dropouts due to adverse effects was higher with benzodiazepines than with placebo (RR 1.58, 95% CI 1.16 to 2.15; low-quality evidence). Furthermore, our analyses of adverse events showed that a higher proportion of participants experienced at least one adverse effect when treated with benzodiazepines (RR 1.18, 95% CI 1.02 to 1.37; low-quality evidence). Low-quality evidence shows a possible superiority of benzodiazepine over placebo in the short-term treatment of panic disorders. The validity of the included studies is questionable due to possible unmasking of allocated treatments, high dropout rates, and probable publication bias. Moreover, the included studies were only short-term studies and did not examine the long-term efficacy nor the risks of dependency and withdrawal symptoms. Due to these limitations, our results regarding the efficacy of benzodiazepines versus placebo provide only limited guidance for clinical practice. Furthermore, the clinician's choice is not between benzodiazepines and placebo, but between benzodiazepines and other agents, notably SSRIs, both in terms of efficacy and adverse effects. The choice of treatment should therefore be guided by the patient's preference and should balance benefits and harms from treatment in a long-term perspective.

Fluoxetine Modulates Spontaneous and Conditioned Behaviors to Carbon Dioxide (CO2) Inhalation and Alters Forebrain–Midbrain Neuronal Activation

Panic disorder (PD), a prevalent anxiety disorder, is characterized by unexpected panic attacks, persistent anxiety and avoidance of panic contexts. Selective serotonin reuptake inhibitors (SSRIs) are effective in treating PD; however, the mechanisms underlying SSRI efficacy are poorly understood. Using CO2-inhalation, a PD-relevant translational paradigm, we examined the effect of chronic SSRI (fluoxetine) treatment on unconditioned and context-conditioned defensive behaviors, as well as respiratory responses, in mice. In addition, cFos expression was evaluated as a measure of the functional activity and interregional correlation matrices were used to explore the neurocircuitry recruited in CO2-conditioned behavior and SSRI treatment response. Chronic fluoxetine attenuated CO2-induced passive (freezing) behavior during inhalation and active (rearing) behavior on re-exposure to context, in addition to reducing CO2-evoked respiratory responses. Brain mapping in CO2-context-conditioned mice revealed altered regional neuronal activation within and correlations across midbrain regions subserving defensive behaviors (periaqueductal gray (PAG) and raphe nuclei) and forebrain emotional and contextual processing loci (medial prefrontal cortex, insular cortex and hippocampus). Importantly, fluoxetine treatment normalized these alterations. Collectively, our results provide novel information on fluoxetine modulation of panic-relevant defensive behaviors and neurocircuitry, facilitating increased understanding of panic neurobiology in the context of treatment response.

Assessing Panic: Bridging the Gap Between Fundamental Mechanisms and Daily Life Experience

Panic disorder (PD) is one of the most common psychiatric disorders. Recurrent, unexpected panic attacks (PAs) are the primary symptom and strongly impact patients’ quality of life. Clinical manifestations are very heterogeneous between patients, emphasizing the need for a dimensional classification integrating various aspects of neurobiological and psychological circuits in line with the Research Domain Criteria (RDoC) proposed by the US National Institute of Mental Health. To go beyond data that can be collected in the daily clinical situation, experimental panic provocation is widely used, which has led to important insights into involved brain regions and systems. Genetic variants can determine the sensitivity to experimental models such as carbon dioxide (CO2) exposure and can increase the risk to develop PD. Recent developments now allow to better assess the dynamic course of PAs outside the laboratory in patients’ natural environment. This can provide novel insights into the underlying mechanisms and the influence of environmental factors that can alter gene regulation by changing DNA methylation. In this mini review, we discuss assessment of PAs in the clinic, in the laboratory using CO2 exposure, genetic associations, and the benefits of real-life assessment and epigenetic research.

Antidepressants versus placebo for panic disorder in adults.

Antidepressants versus placebo for panic disorder in adults.

Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder

Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case–control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4). Statistical analyses of these three genes showed that PLA2G4E yielded the lowest p value in gene-based rare variant association tests by Efficient and Parallelizable Association Container Toolbox algorithms; however, the p value did not reach the significance threshold in the Japanese. Likewise, in a German case–control study (96 sporadic PD patients and 96 controls), PLA2G4E showed the lowest p value but again did not reach the significance threshold. In conclusion, we failed to find any significant variants or genes responsible for the development of PD. Nonetheless, our results still leave open the possibility that rare protein-altering variants in PLA2G4E contribute to the risk of PD, considering the function of this gene.

P.1.i.002 - White matter neural correlates associated with anxiety sensitivity in panic disorder

Panic Disorder (PD) is mainly characterized by recurrent unexpected panic attacks. Although the presence of emotional functioning deficits in PD is well established, their neuronal bases are still less known. Therefore, in this review, we aim to summarize the available functional Magnetic Resonance Imaging (fMRI) studies investigating the neural correlates associated with the processing of facial emotional expressions in patients with PD.A comprehensive search on PubMed was performed and 10 fMRI studies meeting our inclusion criteria were included in this review.The majority of the studies reported selective deficits in key brain regions within the prefronto-limbic network in PD patients. Specifically, a mixed picture of hyperactivation and hypoactivation patterns were observed in limbic regions, including the amygdala and the anterior cingulate cortex (ACC), as well as in areas within the prefrontal cortex (PFC), either during negative or positive valenced stimuli, as compared to healthy controls (HC) or other anxiety disorders. Limitations: The limited number of studies and the clinical and methodological heterogeneity make it difficult to draw definite conclusions on the neural mechanism of emotional processing associated with PD.Although the results of the available evidence suggest the presence of selective dysfunctions in regions within the cortico-limbic network in PD patients during processing of emotional stimuli, the direction of these abnormalities is still unclear. Therefore, future larger and more homogeneous studies are needed to elucidate the neural mechanisms underpinning the emotional processing dysfunctions often observed in PD patients.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

Interoceptive fear learning to mild breathlessness as a laboratory model for unexpected panic attacks.

Fear learning is thought to play an important role in panic disorder. Benign interoceptive sensations can become predictors (conditioned stimuli – CSs) of massive fear when experienced in the context of an initial panic attack (unconditioned stimulus – US). The mere encounter of these CSs on a later moment can induce anxiety and fear, and precipitate a new panic attack. It has been suggested that fear learning to interoceptive cues would result in unpredictable panic. The present study aimed to investigate whether fear learning to an interoceptive CS is possible without declarative knowledge of the CS–US contingency. The CS consisted of mild breathlessness (or: dyspnea), the US was a suffocation experience. During acquisition, the experimental group received six presentations of mild breathlessness immediately followed by suffocation; for the control group both experiences were always separated by an intertrial interval. In the subsequent extinction phase, participants received six unreinforced presentations of the CS. Expectancy of the US was rated continuously and startle eyeblink electromyographic, skin conductance, and respiration were measured. Declarative knowledge of the CS–US relationship was also assessed with a post-experimental questionnaire. At the end of acquisition, both groups displayed the same levels of US expectancy and skin conductance in response to the CS, but the experimental group showed a fear potentiated startle eyeblink and a different respiratory response to the CS compared to the control group. Further analyses on a subgroup of CS–US unaware participants confirmed the presence of startle eyeblink conditioning in the experimental group but not in the control group. Our findings suggest that interoceptive fear learning is not dependent on declarative knowledge of the CS–US relationship. The present interoceptive fear conditioning paradigm may serve as an ecologically valid laboratory model for unexpected panic attacks.

Anxiety sensitivity and expectation of arousal differentially affect the respiratory response to caffeine.

This study aimed to test how expectations and anxiety sensitivity influence respiratory and autonomic responses to caffeine. The current study investigated the effects of expected vs. unexpected caffeine ingestion in a group of persons prone to the anxiety-provoking effect of caffeine (high anxiety sensitive persons, that is, persons scoring at least one SD above the mean on the Anxiety Sensitivity Index (Peterson and Reiss 1992)) as compared to low-anxious controls. Autonomic arousal (heart rate, skin conductance level), respiratory responding (expired CO2, minute ventilation), and subjective report were assessed in high and low anxiety sensitive participants immediately after beverage consumption and at absorption peak (30min post-consumption) in four separate sessions during which either coffee (expectation of caffeine) or bitter lemon soda (no expectation of caffeine) was crossed with 4mg/kg caffeine vs. no drug. High and low anxiety sensitive persons showed comparable autonomic arousal and symptom reports to caffeine which was modulated by expectation, i.e., greater for coffee. Respiratory responding (CO2 decrease, minute ventilation increase) was more accentuated when caffeine was both expected and administered in the low anxiety sensitive group but more accentuated when caffeine was unexpectedly administered in the high anxiety sensitive group. Autonomic arousal and respiratory effects were observable within a few minutes after caffeine administration and were most pronounced at maximum absorption. The results highlight the modulating role of expectancies in respiratory responding to caffeine in low vs. high anxiety sensitive persons and might have important implications for the better understanding of unexpected panic attacks.

Panic and the brainstem: clues from neuroimaging studies.

One of the most influential theories has conceived unexpected panic attack (PA) as a primal defensive reaction to threat within the internal milieu of the body. This theory is based on findings suggesting the involvement of dysfunctional respiratory regulation and/or abnormally sensitive central neural network of carbon dioxide (CO2)/hydrogen ion (H+) chemoreception in PA. Thus, unexpected PA may be related to phylogenetically older brain structures, including the brainstem areas, which process basic functions related to the organism's internal milieu. The brainstem represents a crucial area for homeostatic regulation, including chemoreception and cardio-respiratory control. In addition, the midbrain dorsal periaqueductal gray may be involved in the unconditioned defense reactions to proximal threats, including internal physical stimuli. Our aim was to specifically consider the potential involvement of the brainstem in panic disorder (PD) by a comprehensive review of the available neuroimaging studies. Available data are limited and potentially affected by several limitations. However, preliminary evidence of a role of the brainstem in PD can be found and, secondly, the brainstem serotonergic system seems to be involved in panic modulation with indications of both altered serotonergic receptors and 5-HT transporter bindings. In conclusion, our review suggests that the brainstem may be involved in psychopathology of PD and supports the relevant role of subcortical serotonergic system in panic pathogenesis.