Panic attacks as a risk for later psychopathology: results from a nationally representative survey

Background: There is a growing body of literature suggesting that panic attacks without panic disorder are associated with increases in a wide range of psychopathology and impairment. However, the majority of the literature to date has been cross‐sectional. Some longitudinal research supports the view that panic attacks are a nonspecific risk factor for future psychopathology. Using a large nationally representative longitudinal survey of adults, we sought to determine whether panic attacks predict new onset Axis I disorders. Methods: The Alcohol Use Disorder and Associated Disabilities Interview Schedule—DSM‐IV Version was used to make diagnoses of psychiatric disorders in the National Epidemiologic Survey on Alcohol and Related Conditions Waves 1 and 2 (n = 34,653, aged 18 and older, response rate = 70.2%). Incident psychiatric disorders at Wave 2 were compared between people with and without panic attacks at Wave 1. Results: Panic attacks at Wave 1 were significantly associated with increased incidents of generalized anxiety disorder, panic disorder, social phobia, major depression, dysthymia, mania and hypomania, any anxiety disorder, and any mood disorder even after adjusting for sociodemographic variables, Wave 1 Axis I disorders, and Axis II disorders (OR's ranging from 1.62 to 2.77). Conclusions: The presence of panic attacks may be an important indicator of overall psychological distress and the risk of more severe psychopathology in the future. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Tryptophan hydroxylase and serotonin transporter gene polymorphism does not affect the diagnosis, clinical features and treatment outcome of panic disorder in the Korean population

Panic disorder may be associated with defective serotonin (5-HT) neurotransmission. This study was to investigate the association between the tryptophan hydroxylase (TPH) gene and a serotonin transporter gene promoter polymorphism (5-HTTLPR), with panic disorder in a Korean population.

244 Korean patients with panic disorder and the 227 controls were genotyped by a polymerase chain reaction-based method. The severity of panic disorders was assessed by number of panic attacks during the previous 1 month, as well as scores for anticipatory anxiety, panic distress, and agoraphobic distress, as determined by a visual analogue scale (VAS). All the subjects completed the assessment measures including Spielberger State-Trait Anxiety Inventory-State (STAI-S), Spielberger State-Trait Anxiety Inventory-Trait (STAI-T), Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R), Revised Anxiety Sensitivity Index (ASI-R), Clinical Global Impression Scale – Severity of Illness (CGI-S), Panic Disorder Severity Scale (PDSS), and the Hamilton Depression Rating Scale (HAMD). Responder analyses were conducted based on changes in CGI-I scores after 10 weeks of treatment.

We found no significant differences in the genotype and allele frequencies in TPH A218C and 5-HTTLPR polymorphisms between the panic patients and the control group. Subgroup analyses in terms of comorbidities, response, and other primary clinical variables, indicated no differences in these polymorphisms. Our findings suggest that the TPH A218C polymorphism and 5-HTTLPR play no significant roles in the pathogenesis and clinical symptomatologies, at least in a Korean population.     

Derealization and panic attacks: a clinical evaluation on 150 patients with panic disorder/agoraphobia

One hundred fifty patients with Panic Disorder (PD) with or without Phobic Avoidance were subdivided into two groups on the basis of presence/absence of derealization and/or depersonalization (D-D) during panic attacks. D-D was found in 34.7% of the sample. By comparing the two groups, the patients with D-D were found to be younger and had an earlier onset of the disorder; they had a higher prevalence of avoidance behavior and a higher severity of the agoraphobic spectrum phobias. They were also more frequently subject to concomitant disorders such as Generalized Anxiety, Obsessive-Compulsive, and depressive symptomatology. The authors have hypothesized a correlation between the presence of D-D during panic attacks and a more frequent clinical evolution toward agoraphobia. This view is supported by finding that D-D in panic attacks corresponds to severer forms of PD, both in terms of the earlier onset of PD, and because PD shows higher levels of anxiety, depression, and disability.     

Clinical Characteristics of the Respiratory Subtype in Panic Disorder Patients

Objective

Panic 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.

Methods

Among 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).

Results

The 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.

Conclusion

Panic 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.     

Audiovestibular functioning in patients with panic disorder

OBJECTIVE: The objective of this study was to investigate audiovestibular function in patients with panic disorder and healthy subjects by using vestibular and audiologic tests. METHODS: Thirty-four panic disorder patients and 20 healthy control subjects were assessed by using clinical otoneurological examination, pure tone audiometry, tympanometry, and electronystagmography (ENG). All patients were evaluated with the Panic and Agoraphobia Scale (PAS), the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the State-Trait Anxiety Inventory (STAI). RESULTS: On vestibular testing, abnormal responses were more prevalent in panic disorder patients compared to healthy controls. The presence of agoraphobia in panic disorder patients did not make a significant difference on vestibular test results. The only variable that may be a predictor of vestibular abnormalities in panic disorder patients was found to be dizziness between attacks. CONCLUSION: The results show that dizziness between panic attacks may warrant audiovestibular testing among other medical investigations.     

Psychological characteristics of early remitters in patients with panic disorder

We aimed to examine whether anxiety sensitivity and agoraphobic fear could affect the time taken to remission after 24 weeks of open-label escitalopram treatment of patients with panic disorder (PD). We recruited 158 patients, and 101 patients completed the study. Clinical severity and psychological characteristics were assessed at baseline and 4, 12, and 24 weeks after the treatment, using the Clinical Global Impression-Severity (CGI-S), the Hamilton Rating Scales for Anxiety and Depression, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany Panic and Phobia Questionnaire (APPQ), and the Panic Disorder Severity Scale (PDSS). Remission was defined as the absence of full panic attacks and PDSS scores of 7 or less. Completing patients were stratified according to the time taken to remit: early (n=20) and late (n=58) remission and non-remission groups (n=23). There were no significant differences among the three groups at baseline on the CGI-S and the PDSS mean scores. However, early remitters had significantly lower scores than late remitters and non-remitters on the ASI-R and APPQ. In conclusion, anxiety sensitivity and agoraphobic fear can affect the time to remission after pharmacotherapy, and clinicians should consider the psychological characteristics of PD patients in order to achieve an optimal response to pharmacotherapy.     

Panic disorders and agoraphobia: Freudian concepts and DSM IV

This paper refers to the relationship between panic and agoraphobia, regarding Panic Disorder and Agoraphobia (DSM IV), from two different points of view coming from Psychoanalysis and Psychiatry. Psychoanalysis (S. Freud) considers agoraphobia as a defensive organization to avoid anxiety, not bound to the original conflict, but to substitutive formation. The exposure to space (its unconscious significance) provokes panic attack. The psychiatric approach considers agoraphobia, meaningless by its own, as a consequence of spontaneous panic attacks. The etiology is referred to neurophysiological mechanisms. The authors reviewd D Klein's hypothesis about panic and Freud's theories on anxiety, partiularly Anxiety Neurosis.     

Panic attacks as risk markers for mental disorders*

Abstract Objective This paper extends previous epidemiological findings linking panic attacks with future episodes of depression and examines whether this relationship is independent of the effects of gender and neuroticism. Methods Composite International Diagnostic Interview (CIDI) DSM-IV diagnoses from a stratified multi-stage population survey of 10,641 Australian adults were analysed using logistic regression to examine the relationship between lifetime panic attacks, gender, neuroticism and mental disorders. Results People who experienced full CIDI DSM-IV panic attacks more than 12 months ago were 4 times more likely to meet criteria for current Depressive Disorder than those who reported no attacks. Those with panic attacks in the past 12 months were 13.3 times more likely to report current Depressive Disorders. A similar pattern was also present for non-panic Anxiety Disorders (odds ratio=7.5 for lifetime, but not 12-month panic attacks, and 21.46 for 12-month panic attacks) and for Substance Use Disorders (2.1 and 4.6, respectively) suggesting a broader relationship with psychopathology than previously reported. For each of these groupings of mental disorders, panic attacks accounted for significant variability over and above the effects of gender, neuroticism, and comorbid Anxiety Disorders. Conclusions Panic attacks are associated with current and future Anxiety, Depressive, and Substance Use Disorders, and this relationship is not solely accounted for by differences in gender and neuroticism.* Previous Presentation: An earlier version of this paper was included in an unpublished PhD thesis by Andrew Baillie under the supervision of Prof Ron Rapee.     

Panic-agoraphobic spectrum: reliability and validity of assessment instruments

DSM IV is a simple, reliable diagnostic system with many advantages. However, DSM diagnostic criteria may not provide sufficient characterization of clinically significant symptoms. We have undertaken a project to assess an array (spectrum) of clinical features associated with different DSM Disorders. The purpose of this paper is to report on reliability of assessment instruments for Panic-Agoraphobic Spectrum (PAS), to document convergent validity of PAS symptom groupings, and to confirm the relationship between PAS and DSM IV Panic Disorder (PD). We studied 22 normal controls and 95 outpatients who met criteria for Panic Disorder with and without lifetime Major Depression, and Major Depression or Obsessive Compulsive Disorder without lifetime Panic Disorder. Assessment instruments had excellent reliability and there was good concordance between interview and self-report formats. PAS scores were highest in subjects with PD, followed by outpatients without PD, and were lowest in normal controls. PAS scores varied among PD patients, and a subgroup of patients without PD scored high on PAS. We conclude that PAS can be reliably assessed, and that it describes a valid, coherent constellation of features associated with DSM IV Panic Disorder, but providing additional important clinical information.     

Relations between anxiety sensitivity and panic symptoms in nonreferred children and adolescents

Anxiety sensitivity (AS), the fear of anxiety-related sensations, has been posited to be a cognitive risk factor for the development of anxiety disorders but has been understudied in youth. The purpose of the present investigations was to evaluate relations between AS and panic symptoms in nonreferred children and adolescents. In Study 1, (N = 113, mean age, 13.98). scores on the Childhood Anxiety Sensitivity Index (CASI) predicted the experience of uncued panic attacks after controlling for general anxiety and depression, although the total variance accounted for was small. In Study 2 (N = 52; mean age, 9.48), the Panic/ Agoraphobia subscale of the Spence Children's Anxiety Scale was used as the criterion variable. CASI score again predicted panic symptoms after controlling for trait anxiety and depression. Identification of a risk factor for panic attacks and panic disorder in youth will have important implications for etiologic theory, intervention, and prevention.     

Can panic be induced in deep sleep? Examining the necessity of cognitive processing for panic

This study examines the relative contribution of biological and psychological processes to the induction of panic attacks by a biochemical challenge agent. Panicogenic doses of caffeine were administered to 8 panic disorder (PD) patients and 11 healthy volunteers during stage 3–4 sleep, when cognitive processing is minimal and the threshold to external stimuli is high. Panic attacks were induced directly from sleep in 3 subjects and subclinical panics in an additional 3. Subjects who experienced full panic attacks spent periods of time ranging from 4 to 52 minutes in stage 2 sleep before awakening in a panic, while those who awakened in subclinical panic awakened almost directly from stage 4 sleep. PD patients experienced significantly more panic symptoms than healthy volunteers. Although limited by a small sample size, this study suggests a combined biological-psychological model of panic induction in which panic disorder patients are more biologically predisposed than healthy controls to panic symptoms but may require cognitive processing for the elaboration of a full panic attack. Depression and Anxiety 8:126–130, 1998. © 1998 Wiley-Liss, Inc.     

Comorbid bipolar disorder and panic disorder in families with a high prevalence of bipolar disorder.

OBJECTIVE: Panic attacks are a common complication of affective disorder, although the etiologic relationship of panic and affective symptoms has not been determined. Evidence from a family study suggests that panic attacks and panic disorder may be related genetically to bipolar disorder. This study used diagnostic data from the NIMH Bipolar Disorder Genetics Initiative to assess in a separate, larger family set the familiality of panic combined with bipolar disorder. METHOD: First-degree relatives (N=966) of probands with bipolar I disorder (N=192) and schizoaffective disorder, bipolar type, (N=11) were included in the study. All subjects were interviewed directly and were assigned best-estimate diagnoses for major affective and other psychiatric disorders. The risk of a family member being diagnosed with panic disorder if the proband with bipolar disorder had panic attacks or panic disorder was calculated with logistic regression analysis with generalized estimating equations that controlled for sex and affective disorder subdiagnosis. RESULTS: More than 90% of the probands and first-degree relatives with panic disorder also had an affective disorder diagnosis. Panic disorder was present in 17% of the relatives with recurrent major affective disorder and in 3% of the relatives without recurrent major affective disorder. Risk of panic disorder in relatives with bipolar disorder was increased significantly if the proband had panic attacks or panic disorder. CONCLUSIONS: Risk for panic disorder with familial bipolar disorder appears to be inherited. Inherited risk for panic disorder with bipolar disorder may indicate a shared genetic etiology for both disorders in some families. The patterns of bipolar disorder and panic disorder comorbidity observed in families imply a complex genetic etiology, which may be elucidated by using endophenotypes.     

Panic disorder and hyperventilation

Respiratory abnormalities are associated with anxiety, particularly with panic attacks. Symptoms such as shortness of breath, "empty-head" feeling, dizziness, paresthesias and tachypnea have been described in the psychiatric and respiratory physiology related to panic disorder. Panic disorder patients exhibit both behaviorally and physiologically abnormal responses to respiratory challenges tests. OBJECTIVE: We aim to observe the induction of panic attacks by hyperventilation in a group of panic disorder patients (DSM-IV). METHOD: 13 panic disorder patients and 11 normal volunteers were randomly selected. They were drug free for a week. They were induced to hyperventilate (30 breaths/min) for 3 minutes. Anxiety scales were taken before and after the test. RESULTS: 9 (69.2%) panic disorder patients and one (9.1%) of control subjects had a panic attack after hyperventilating (p < 0.05). CONCLUSION: The panic disorder group was more sensitive to hyperventilation than normal volunteers. The induction of panic attacks by voluntary hyperventilation may be a useful and simple test for validating the diagnosis in some specific panic disorder patients.     

Sex differences in panic disorder with agoraphobia

Two hundred seventy-two patients (68 males and 204 females) with DSM-III diagnosis of Agoraphobia with Panic Attacks (300.21) were used in the present study to investigate sex differences in these patients. Discriminant analysis showed that female agoraphobics can be significantly differentiated from male agoraphobics on their responses to the Fear Survey Schedule (FSS), the clinicians ratings on the Hamilton Anxiety Scale (HAM-H), and Hamilton Depression Scale (HAM-D), indicating the expression of more severe symptomatology amongst the female agoraphobics. Female and male agoraphobics could not, however, be differentiated using the Fear Questionnaire (FQ), Hostility and Direction of Hostility Questionnaire (HDHQ), Maudsley Personality Inventory (MPI), and the State-Trait Anxiety Inventory (STAI), panic symptoms, and cognitions associated with panic attacks. The paper concluded that there were no real differences between the male and female agoraphobics with panic attacks.     

Psychoeducation in panic disorder patients: effect of a self-information booklet in a randomized,masked-rater study

The aim of our study was to evaluate the effectiveness of a self-information booklet (SIB) in decreasing anxiety and panic attacks in Panic Disorder (PD) patients. Eighty-four patients attending an outpatient clinic due to panic disorder were randomly chosen to receive paroxetine with/without a friendly-designed brochure. Follow-up was done by a masked rater after 1, 3,and 12 weeks in order to evaluate whether the co-administration of paroxetine and the brochure (Group A) had a beneficial effect over the administration of paroxetine alone (Group B). After 3 weeks of therapy, Group A patients had significantly greater improvement and lower scores on the Hamilton Anxiety Scale, the Panic Self Questionnaire, and the Visual Analog Scale. After 12 weeks, the differential improvement was not statistically significant and both groups had improved as compared to baseline. The administration of a psychoeducational brochure (SIB) to PD patients at the initiation of therapy had beneficial effects during the first weeks of treatment. Although this effect fades away, the role of the SIB is overstressed in its ability to increase well being and compliance, and reduce anxiety and panic attacks.     

Acid–base dysregulation and chemosensory mechanisms in panic disorder: a translational update

Panic disorder (PD), a complex anxiety disorder characterized by recurrent panic attacks, represents a poorly understood psychiatric condition which is associated with significant morbidity and an increased risk of suicide attempts and completed suicide. Recently however, neuroimaging and panic provocation challenge studies have provided insights into the pathoetiology of panic phenomena and have begun to elucidate potential neural mechanisms that may underlie panic attacks. In this regard, accumulating evidence suggests that acidosis may be a contributing factor in induction of panic. Challenge studies in patients with PD reveal that panic attacks may be reliably provoked by agents that lead to acid–base dysbalance such as CO₂ inhalation and sodium lactate infusion. Chemosensory mechanisms that translate pH into panic-relevant fear, autonomic, and respiratory responses are therefore of high relevance to the understanding of panic pathophysiology. Herein, we provide a current update on clinical and preclinical studies supporting how acid–base imbalance and diverse chemosensory mechanisms may be associated with PD and discuss future implications of these findings.     

Rapid onset: A valid panic disorder criterion?

This study examined the value of the DSM-IV time criterion for panic disorder (PD) requiring an abrupt onset to panic attacks (Pas) with a time to peak intensity (TTPI) of less than 10 min, and evaluated features distinguishing rapid onset (TTPI < 10) from prolonged onset (TTPI > 10) panickers. Eight hundred and sixty-four respondents to the National Institute of Mental Health Panic Disorder Questionnaire (NIMH PQ) who met the first three PD criteria were compared based on the time criterion. The prolonged onset panickers (18.2%) did not differ significantly from rapid onset panickers (81.8%) on any of 100 items assessing clinical symptoms, course of illness, and comorbidity of PD. These results suggest that many patients with otherwise classic features of PD have a prolonged TTPI of Pas, and that patients with prolonged-onset PAs are similar to patients with rapid-onset PAs on most measures. The reliability, validity, and clinical relevance of the current DSM-IV TTPI criterion should be evaluated in future studies. Depression and Anxiety 5:121–126, 1997. © 1997 Wiley-Liss, Inc. This article was prepared by a group consisting of both United States government employees and non-United States government employees, and as such is subject to 17 U.S.C. Sec. 105.     

Panic Disorder Severity Scale: reliability and validity of the Turkish version

We assessed the reliability and validity of the Turkish version of the seven-item Panic Disorder Severity Scale (PDSS). We recruited 174 subjects, including 104 with current DSM-IV panic disorder with (n=76) or without(n=28)agoraphobia, 14 with a major depressive episode, 24 with a non-panic anxiety disorder, and 32 healthy controls. Assessment instruments were Panic Disorder Severity Scale, Panic and Agoraphobia Scale, both the observer-rated (P&Ao) and self-rating (P& Asr); Clinical Global Impression Scale (CGI); Hamilton Anxiety Scale, and Beck Depression Inventory. We repeated the measures for a group of panic disorder patients (n = 51) after 4 weeks to assess test-retest reliability. The internal consistency (Cronbach's alpha) of the PDSS was .92-94. The inter-rater correlation coefficient was .79. The test-retest correlation coefficient after 4 weeks was .63. In discriminant validity analyses, the highest correlation for PDSS was with P&Ao, P&Asr (r=.87 and.87, respectively) and CGI (r=.76) and the lowest with Beck Depression Inventory (r=.29). The cut-off point was six/seven, associated with high sensitivity (99%) and specificity (98%). This study confirmed the objectivity, reliability and validity of the Turkish version of the PDSS.     

The association between serotonin-related gene polymorphisms and panic disorder

Dysfunction of the serotonergic system has been hypothesized to play an important role in panic disorder. We investigated the 5-HT2A receptor (5HTR2A) and tryptophan hydroxylase (TPH) genes for an association with panic disorder (PD). Patients with PD (n=107) and control subjects (n=161) were genotyped for 5HTR2A 1438A/G, 5HTR2A 102T/C, and TPH218 A/C. The severity of their symptoms was measured using the Spielberger State-Trait Anxiety Inventory (STAI), Panic Disorder Severity Scale (PDSS), Anxiety Sensitivity Index (ASI), Acute Panic Inventory (API), and Hamilton's Rating Scale for Depression (HAMD). There were no significant differences in the genotype distributions or allelic frequencies in the three serotonergic polymorphisms between PD patients and normal controls. However, we found a significant difference in symptom severity among the genotypes of both the 5HTR2A 1438A/G and 102T/C polymorphisms. Although there were no significant differences in the genotype and allele distributions, we found a significant association between panic symptom severity and the serotonin 2A receptor gene. This result suggests that 5HTR2A 1438A/G and 102T/C polymorphic regions can be associated with the phenotype or the pathogenesis of panic disorder.