Subtype Of Panic Disorder Research Articles

Emotional processing in panic disorder and its subtypes: An fMRI study using emotional faces

Inconsistent findings regarding the pathophysiology of panic disorder (PD) could result from clinical heterogeneity. Identifying subtypes could enhance insights into the neurobiological substrates of PD. An emotional faces fMRI paradigm was used in a group of PD patients (n=73) and healthy controls (n=58). The overall PD group was further divided into three previously identified subtypes: a cognitive-autonomic (n=22), an autonomic (n=16) and an aspecific (n=35) subtype. Differences in brain activity levels in response to emotional facial expressions between groups were examined for six regions of interests, namely the amygdala, ventromedial prefrontal cortex, anterior cingulate, fusiform gyrus, lingual gyrus and insula. PD patients showed lower activity in the rostral anterior cingulate in response to angry faces than healthy controls, which was mainly driven by the autonomic subtype. No significant differences were found in other brain regions when comparing PD patients with controls or when comparing across PD subtypes. Sample sizes in subgroups were relatively small CONCLUSIONS: The role of the rostral anterior cingulate cortex for emotional processes critical in panic disorder is highlighted by this study and provides, albeit preliminary, evidence for the use of a subtype approach to advance our neurobiological insights in PD considering its involvement in the appraisal of autonomic viscero-sensory symptoms.

Pituitary-adrenal axis hormones in early-onset versus late-onset panic disorder

Objective It has been hypothesised that early-onset panic disorder (PD) may constitute a biologically distinct subtype of PD, but the few relevant data are inconclusive. We systematically explored for potential psychopathological and hormonal differences between early-onset (age at onset ≤ 27 years) versus late-onset PD, in consecutively-referred, medication-free, acutely-ill PD outpatients, moreover without comorbid mental disorders except agoraphobia (N = 54; age = 32.3 ± 7.5 years; early-onset = 27; females = 38). Methods Hormones assessed (plasma levels) included adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS). Psychopathological measures included panic attacks’ number during last three weeks, the Agoraphobic Cognitions and the Body Sensations Questionnaires and the Hamilton Anxiety Rating Scale. Results Early-onset PD patients – compared to their late-onset counterparts – had longer duration of the disease. The two onset-groups demonstrated similar panic and anxiety symptoms and similar ratios of smokers/never-smokers. However, early-onset patients demonstrated significantly greater ACTH and DHEAS levels and higher (marginally significant) cortisol levels than the late-onset patients. Moreover, in the early-onset patients only, significant positive correlations emerged between ACTH levels and the severity of both panic and anxiety symptomatology. Conclusions These findings suggest that the two onset-groups demonstrate significant differences in the hypothalamic-pituitary-adrenal axis functioning, at least when acutely-ill. Key points Early-onset panic disorder (EOPD) may differ biologically from late-onset PD (LOPD). EOPD was correlated with greater adrenocorticotropic hormone (ACTH) plasma levels. EOPD was correlated with greater dehydroepiandrosterone sulphate plasma levels. In EOPD only, ACTH levels were positively correlated with panic and anxiety symptoms.

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

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

Prospective associations between sleep problems and subtypes of anxiety symptoms among disaster-exposed adolescents

This study aimed to investigate longitudinal relationships between sleep problems and subtypes of anxiety symptoms among adolescent earthquake survivors. Participants were 1573 adolescents (male, 45.8%; mean age at baseline 15.01 years, standard deviation (SD)=1.26) in the Wenchuan Earthquake Adolescent Health Cohort. The Pittsburgh Sleep Quality Index and the Screen for Child Anxiety Related Emotional Disorders were used to assess participants' sleep problems and anxiety symptoms four times during 2.5 years after the earthquake. Anxiety symptoms included subtypes of panic disorder (PD), generalized anxiety disorder (GAD), separation anxiety disorder (SeAD), social phobia (SP), school phobia (ScP). Longitudinal lagged generalized estimating equations (GEE) models were used to determine the prospective associations. Overall, there was a bidirectional relationship between sleep problems and anxiety symptoms. For the specific sleep problems and anxiety subtypes, short sleep duration predicted symptoms of PD, GAD, and ScP, and was predicted by GAD; difficulty falling asleep predicted GAD symptoms, whereas PD symptoms increased difficulty falling asleep; poor sleep quality predicted ScP symptoms and was predicted by symptoms of GAD and ScP; difficulty maintaining sleep was not associated with any subtype of anxiety symptoms in any direction; SeAD and SP were not associated with any specific sleep problems in any direction. While sleep problems and anxiety symptoms are bidirectional, the associations vary by subtypes of sleep problems and anxiety symptoms. The potential biological mechanisms for the specific associations between dimensional sleep and anxiety symptoms and their clinical implications should be further investigated.

Respiratory subtype of panic disorder: Can serum phosphate levels be a possible outcome to group cognitive-behavior therapy?

Panic disorder (PD) respiratory subtype (RS) was described in order to cluster patients according to their symptoms. These patients are characterized by experiencing a relatively high number of noticeable respiratory symptoms during a panic attack (PA) and a higher reactivity to CO2. In this study, we aimed to evaluate the clinical relevance of this diagnostic category, evaluating if there are different responses to cognitive-behavioral therapy in patients with panic disorder RS as compared to those with the non-respiratory subtype (NRS), using serum phosphate as a biological marker. Patients were assessed by a clinical interview followed by a structured diagnostic interview (M.I.N.I) and classified as RS or NRS based on symptoms. The severity of PD was evaluated throughout the PDSS, CGI, HAM-A, STAI and the BDI rating scales. All patients underwent 12 structured sessions of group-CBT for PD and had their blood collected at baseline and after treatment to assess phosphate levels. One hundred and thirty-eight patients have been assessed, and 102 were included in this trial. Sixty-nine patients completed the treatment protocol, 42 were classified as RS and 27 as NRS. Both RS and NRS patients improved in all clinical scales (p < 0.001). The mean phosphate levels increased from 2.44 mg/dl ± 0.49 at baseline to 3.38 mg/dl ± 0.52 (p < 0.01) in the RS group as well as from 2.46 mg/dl ± 0.64 at baseline to 3.46 mg/dl ± 0.61 (p < 0.01) in the NSR group. Small sample size and the lack of assessment of other clinical and physiological parameters, such as respiratory variables. Our findings suggest that both RS and NRS benefit from group CBT and that there was a change in phosphate levels after effective treatment in both groups. Our data support the idea that there is a reversal of the conditions that promote hypophosphatemia as chronic hyperventilation after CBT treatment, whereas it is in disagreement to the presence of two different PD subtypes based on phosphate levels once their rates did not differ at baseline and had a similar increase after effective treatment.

Structural and functional correlates of anxious responses to hypercapnia: Cortico-limbic evidence for a respiratory subtype of panic disorder

Structural and functional correlates of anxious responses to hypercapnia: Cortico-limbic evidence for a respiratory subtype of panic disorder

Does Personality Matter? Temperament and Character Dimensions in Panic Subtypes.

Symptomatic heterogeneity in the clinical presentation of Panic Disorder (PD) has lead to several attempts to identify PD subtypes; however, no studies investigated the association between temperament and character dimensions and PD subtypes. The study was aimed to verify whether personality traits were differentially related to distinct symptom dimensions. Seventy-four patients with PD were assessed by the Mini-International Neuropsychiatric Interview (M.I.N.I.), and the Temperament and Character Inventory (T.C.I.). Thirteen panic symptoms from the M.I.N.I. were included in a factor analysis with varimax rotation. A correlation analysis (Pearson's correlation), a linear regression analysis, and a forward stepwise regression analysis between the identified factors and T.C.I. variables were performed for evaluating the association between panic subtypes and personality features. Three factors were obtained: "Somato-dissociative", "Respiratory", and "Cardiologic" explaining respectively 18.31%, 13.71%, and 12.78% of the total variance. Correlations analyses showed that only "Somato-dissociative" factor was significantly correlated with T.C.I. "Self-directedness" (p<0.0001) and "Cooperativeness" (p=0.009) variables. Results from the regression analysis indicate that the predictor models account for 33.3% and 24.7% of the total variance respectively in "Somatic-dissociative" (p<0.0001) and "Cardiologic" (p=0.007) factors, while they do not show statistically significant effects on "Respiratory" factor (p=0.222). After performing stepwise regression analysis, "Self-directedness" resulted the unique predictor of "Somato-dissociative" factor (R²=0.186; β=-0.432; t=-4.061; p<0.0001). Current results, although preliminary, suggest the importance of assessing personality and temperament features that may be potentially related to poor treatment response for a better understanding and characterization of PD subtypes.

Psychoticism in patients with panic disorder with or without comorbid agoraphobia

Objective: A few case-reports have previously described transient psychotic-like symptoms in non-psychotic patients with panic disorder (PD). We aimed to systematically explore whether PD patients without any current or past psychosis can be differentiated according to the severity of ‘psychoticism’ as a dimension, comprising clinical features such as psychotic-like experiences, increased social alienation, hostility and suspiciousness.Methods: Sample included 35 (female = 26) medication-free, non-psychotic patients consecutively referred from our Department’s Outpatient Clinic for acute symptoms of DSM-5 PD with (PDA; N = 29) or without concurrent agoraphobia. Psychometric measures included the Symptom Checklist–90–Revised (SCL-90-R), Agoraphobic Cognitions Questionnaire (ACQ), Body Sensations Questionnaire (BSQ), and panic attacks during last 21 days PA-21d.Results: Multiple regression analysis (forward stepwise) revealed that, among all SCL-90-R subscales, the psychoticism-subscale was most significantly associated with panic-related beliefs included in the ACQ, while significant associations emerged between the paranoid ideation-subscale and the ACQ and BSQ measures. Moreover, significant correlations emerged between the SCL-90-R psychoticism-subscale and all three measures of PD symptoms (ACQ, BSQ, PA-21d) and between the SCL-90-R paranoid ideation-subscale and both the ACQ and BSQ.Conclusions: This significant association between levels of psychoticism and severity of panic symptoms may reflect a more severe subtype of PD.

Respiratory panic disorder in acute clonazepam treatment and long-term follow-up

Objectiveto describe with prospective methodology the therapeutic response to clonazepam in the respiratory panic disorder (PD) subtype versus the non-respiratory subtype in a long-term follow-up.MethodsA total of 67 PD outpatients (DSM-IV) were previously divided into respiratory (n = 35) and non-respiratory (n = 32) subtypes and then openly treated with clonazepam for 8 weeks. Those who responded were then treated for 3 years. Demographic and clinical features were compared in the two groups. The instruments used to evaluate response were the Clinical Global Impression, the Sheehan Panic and Anticipatory Anxiety Scale, and the Panic Disorder Severity Scale.ResultsIn the first 8 weeks of treatment (acute phase), the respiratory subtype had a significantly faster response on all the major scales. During the follow-up and at the end of the study (week 156), there was no difference in the scale scores, and the reduction in panic attacks from baseline to end-point did not differ significantly between the two groups. After the acute phase treatment, the patients could undergo psychotherapy. In the respiratory subtype, the disorder had a later onset, was associated with a high familial history of anxiety disorder. The non-respiratory subtype had significantly more previous depressive episodes. Clonazepam had a safe adverse event profile during both phases of treatment.ConclusionThe respiratory PD subtype had a faster response to treatment with clonazepam at 8 weeks than did the non-respiratory subtype and an equivalent response after 6 months of treatment. The response of clonazepam is clearly maintained during the long-term follow-up.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IDENTIFYING PANIC DISORDER SUBTYPES USING FACTOR MIXTURE MODELING.

The clinical presentation of panic disorder (PD) is known to be highly heterogeneous, complicating research on its etiology, neurobiological pathways, and treatment. None of the attempts to identify PD subtypes have been independently reproduced, rendering the current literature inconclusive. Using a data-driven, case-centered approach (factor mixture modeling) on a broad range of anxiety symptoms assessed with the Beck anxiety inventory, the present study identifies PD disorder subtypes in a large (n = 658), well-documented mixed-population sample from the Netherlands Study of Depression and Anxiety (NESDA), with subtypes being validated and detailed using a variety of clinical characteristics. A three-class, one-factor model proved superior to all other possible models (Bayesian information criterion = 13,200; Lo-Mendel-Rubin = 0.0295; bootstrapped likelihood ratio test ≤ 0.0001), with the first class, a cognitive-autonomic subtype, accounting for 29.8%, the second class, the autonomic subtype, for 29.9%, and a third class, the aspecific subtype, for 40.3% of the population. The cognitive-autonomic and autonomic subtypes showed significant differences compared to the aspecific subtype (e.g., comorbidity and suicide attempts) but on severity differed between themselves only. Three qualitatively different PD subtypes were identified: a severe cognitive-autonomic subtype, a moderate autonomic subtype, and a mild aspecific subtype. Qualitative and quantitative differences were related to severity and clinical properties such as comorbidity, suicide attempts, sleep, and sense of mastery.

Laboratory, clinical and therapeutic features of respiratory panic disorder subtype.

It is our aim to elaborate on the new developments in regard to the respiratory subtype (RS) of panic disorder (PD) since it was first described. We will present psychopathological features, diagnostic criteria, genetic and physiopathological hypotheses, as well as therapeutic and prognostic characteristics. Two searches were performed in the Thomson Reuters Web of Knowledge (http://wokinfo.com/): 1 - search terms: "panic disorder" AND ("respiratory symptom" OR "respiratory symptoms" OR "respiratory subtype" OR "respiratory panic" OR "cardiorespiratory"); 2 - all articles citing Briggs and colleagues' 1993 article "Subtyping of Panic Disorder by Symptom Profile" (Br J Psychiatry 1993;163: 201-9). Only those articles involving human subjects and written English were included. In comparison with patients of the non-respiratory subtype (NRS), RS patients showed greater familial history of PD, and higher comorbidity rates for anxiety disorders and depressive disorders. These patients were also more sensitive to CO2, hyperventilation and caffeine. Certain characteristics, such as heightened sensitivity to CO2 and the higher incidence of a family history of PD, clearly distinguished the Respiratory Subtype patients from the Non-Respiratory. Nonetheless, some studies failed to demonstrate differential responses to pharmacological treatment and CBT across the subtypes. RS patients seem to respond faster than NRS to pharmacological treatment with antidepressants and benzodiazepines, but more studies are needed to confirm this finding.

Are there subtypes of panic disorder? An interpersonal perspective.

Panic disorder (PD) is associated with significant personal, social, and economic costs. However, little is known about specific interpersonal dysfunctions that characterize the PD population. The current study systematically examined these interpersonal dysfunctions. The present analyses included 194 patients with PD out of a sample of 201 who were randomized to cognitive-behavioral therapy, panic-focused psychodynamic psychotherapy, or applied relaxation training. Interpersonal dysfunction was measured with the Inventory of Interpersonal Problems-Circumplex (Horowitz, Alden, Wiggins, & Pincus, 2000). Individuals with PD reported greater levels of interpersonal distress than that of a normative cohort (especially when PD was accompanied by agoraphobia), but lower than that of a cohort of patients with major depression. There was no single interpersonal profile that characterized PD patients. Symptom-based clusters (with vs. without agoraphobia) could not be discriminated on core or central interpersonal problems. Rather, as revealed by cluster analysis based on the pathoplasticity framework, there were 2 empirically derived interpersonal clusters among PD patients that were not accounted for by symptom severity and were opposite in nature: domineering-intrusive and nonassertive. The empirically derived interpersonal clusters appear to be of clinical utility in predicting alliance development throughout treatment: Although the domineering-intrusive cluster did not show any changes in the alliance throughout treatment, the nonassertive cluster showed a process of significant strengthening of the alliance. Empirically derived interpersonal clusters in PD provide clinically useful and nonredundant information about individuals with PD.

Identifying panic disorder subtypes using factor mixture modeling

Identifying panic disorder subtypes using factor mixture modeling

Panic disorder and exercise avoidance

1) To identify whether patients with panic disorder in general and those with the respiratory subtype in particular actively avoid exercise; 2) to investigate physiological differences in cardiopulmonary function parameters in patients with panic disorder in general, patients with the respiratory subtype of panic disorder, and healthy controls upon exercise challenge. Patients with panic disorder were classified as having either the respiratory or the non-respiratory subtype. Both groups were compared to controls in terms of exercise avoidance patterns and performance on cardiopulmonary exercise testing. Patients with panic disorder exhibited higher exercise avoidance scores and worse performance on cardiopulmonary exercise testing as compared with controls. No differences were found between patients with the respiratory and non-respiratory subtypes. Exercise avoidance is present in panic disorder and is associated with poorer performance on cardiopulmonary exercise testing. These findings are not limited to patients with the respiratory subtype of the disorder.

Clinical characteristics of the respiratory subtype in panic disorder patients.

ObjectivePanic disorder has been suggested to be divided into the respiratory and non-respiratory subtypes in terms of its clinical presentations. The present study aimed to investigate whether there are any differences in treatment response and clinical characteristics between the respiratory and non-respiratory subtypes of panic disorder patients.MethodsAmong the 48 patients those who completed the study, 25 panic disorder patients were classified as the respiratory subtype, whereas 23 panic disorder patients were classified as the non-respiratory subtype. All patients were treated with escitalopram or paroxetine for 12 weeks. We measured clinical and psychological characteristics before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS), Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D).ResultsThe prevalence of the agoraphobia was significantly higher in the respiratory group than the non-respiratory group although there were no differences in gender and medication between the two groups. The respiratory group showed higher scores on the fear of respiratory symptoms of the ASI-R. In addition, after pharmacotherapy, the respiratory group showed more improvement in panic symptoms than the non-respiratory group.ConclusionPanic disorder patients with the respiratory subtype showed more severe clinical presentations, but a greater treatment response to SSRIs than those with non-respiratory subtype. Thus, classification of panic disorder patients as respiratory and non-respiratory subtypes may be useful to predict clinical course and treatment response to SSRIs.

Ana bileşenler analizi ile panik bozukluğu alt tiplerinin değerlendirilmesi

Evaluating the subtypes of panic disorder by using principal component analysis Objective: Panic disorder is put forward to have a heterogeneous structure and multiple subtypes. Evaluating the different subtypes is important for diagnosis, treatment and prognosis. Studies about the quantitative psychopathology assessment are so rare. We aim to determine the subtypes with principal component analysis of panic attack symptoms. Method: 159 outpatients with panic disorder who had referred to the anxiety disorder outpatient unit in Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery were included in the study. A sociodemographic questionnaire that was prepared by the investigators, The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Panic and Agoraphobia Scale (PAS), Hamilton Depression Rating Scale (HAM-D), Beck Anxiety Inventory (BAI) were used in the study. Variables with 15 items were created adding ‘Fear of stroke’ and ‘desire to escape, restlessness’. Principal Component Analysis was applied according to the panic symptoms that the patiens declared. Results: Six loading factors were obtained explaning 56% of total variance in Principal Component Analysis. The first set was named autonomic activation, the second was vestibular symptoms, the third was cardiovascular symptoms, the fourth was pseudoneurologic symptoms, the fifth was respiratory system symptoms and the sixth was fear of death. Conclusion: Symptom profiles in our study were compatible with DSM-IV-TR diagnostic criteria. Significant panic disorder subtypes were found in principal component analysis.

The carbon dioxide challenge test in panic disorder: a systematic review of preclinical and clinical research

This systematic review assesses the current state of clinical and preclinical research on panic disorder (PD) in which the carbon dioxide (CO2) challenge was used as a trigger for panic attacks (PAs). A total of 95 articles published from 1984 to 2012 were selected for inclusion. Some hypotheses for PD evolved greatly due to the reproducibility of PAs in a controlled environment using the safe and noninvasive CO2 test. The 35% CO2 protocol was the method chosen by the majority of studies. Results of the test report specific sensitivity to hypercapnia in PD patients of the respiratory PD subtype. The CO2 challenge helped assess the antipanic effects of medication and non-pharmaceutical approaches such as physical exercise and cognitive behavioral therapy. The test was also used in studies about the genetic component of PD, in which twins and relatives of PD patients were analyzed.

The Panic Disorder Respiratory Ratio: A Dimensional Approach to the Respiratory Subtype

The respiratory ratio is a dimensional construct of the respiratory subtype of panic disorder (PD). The respiratory subtype has been correlated with an increased sensitivity to CO₂ inhalation, positive family history of PD and low comorbidity with depression. The objective of our study was to determine whether the respiratory ratio is correlated with CO₂-induced panic attacks and other clinical and demographic features. We examined 91 patients with PD and submitted them to a double-breath 35% CO₂ challenge test. The respiratory ratio was calculated based on the Diagnostic Symptom Questionnaire (DSQ) scores recorded in a diary in the days preceding the CO₂ challenge. The scores of the respiratory symptoms were summed and divided by the total DSQ score. The respiratory ratio was correlated with CO₂ sensitivity, and there was a non-statistically significant trend towards a correlation with a family history of PD. The positive correlation between the respiratory ratio and the anxiety elicited by the CO₂ inhalation indicates that the intensity of respiratory symptoms may be proportional to the sensitivity to carbon dioxide.

Are patients with panic disorder respiratory subtype more vulnerable to tobacco, alcohol or illicit drug use?

BACKGROUND: Studies have documented high use of tobacco, alcohol and illicit drugs in patients with panic disorder (PD). The comorbid substance use disorders worsen the prognosis of mood and anxiety disorders. The respiratory subtype (RS) of PD seems to represent a more severe and distinct form of this disorder associated with higher familial history of PD and more comorbidity with other anxiety disorders. OBJECTIVES: Describe the patterns of tobacco, alcohol or illicit drug use in PD patients, and also to ascertain if patients with the RS use these substances more than those of the non-respiratory subtype. METHODS: This is a cross-sectional study with 71 PD patients. The Alcohol Use Disorders Identification Test and Fagerstrom Tobacco Questionnaire were used in the evaluation. Patients with four or five respiratory symptoms were classified in the RS, the remaining patients were classified as non-respiratory subtype. RESULTS: In our sample 31.0% were smokers, 11.3% were hazardous alcohol users and none of them was using illicit drugs. There were no differences between the respiratory and non-respiratory subtypes regarding the use of tobacco, alcohol, cannabis, cocaine, stimulants and hallucinogens. DISCUSSION: The RS was not correlated to the use of tobacco, alcohol and illicit drugs. Additional epidemiological and clinical studies focusing the relationship between PD and substance use are warranted.

Clonazepam for the Treatment of Panic Disorder

Clonazepam was initially licensed as an anti-epileptic agent, but its use in a wide variety of psychiatric conditions, including panic disorder (PD) has now been well established. This overview evaluates the current role of clonazepam alone or in combination with antidepressants and/or behavioral therapy in the treatment of PD. We review the data establishing the use of clonazepam in the treatment of PD as well as new information, particularly confirmation of longterm efficacy and safety. We also discuss a regimen for safely tapered withdrawal of clonazepam, the characteristics of the respiratory subtype of PD, and CO2-induced panic attacks as a diagnostic measure and predictor for therapeutic success. It has been shown that panic attacks can more readily be induced by CO2 in PD patients with the respiratory subtype than those with the non-respiratory subtype. More than 25 years after the first report of efficacy in PD in 1984, clonazepam, alone or combined with selective serotonin reuptake inhibitors (SSRIs) and/or behavioral therapy, remains an important therapeutic modality for the management of PD.