Risk Factor For Panic Disorder Research Articles

Investigating the Relationship between Smoking and Panic Disorder: A Cross-Sectional Study among US Adults

Background. Previous research on panic risk factors within the US population has been limited. This cross-sectional study is aimed at exploring the association between smoking and panic among adults in the United States. Methods. We conducted an analysis of data from the National Health and Nutrition Examination Survey. Results. The study included 2,222 participants. Those diagnosed with panic disorder were more likely to be female, unmarried, have lower income, engage in higher rates of smoking, and exhibit greater alcohol consumption. Participants who smoke cigarettes occasionally indicated a significant increase in panic disorder (unadjusted OR 95% CI: 4.396 [2.032-9.513]; P<0.001). The significance of our results remained even after performing the multivariate analysis (full-adjusted OR 95% CI: 2.89 [1.30-6.42]). Furthermore, participants who never smoked cigarettes demonstrated strong and significantly low odds for panic disorder, regardless of adjustment (unadjusted OR 95% CI: 0.180 [0.055-0.591]). There was no association between pipe and cigar smoking and panic disorder in both unadjusted and full-adjusted models. Conclusion. This study highlights that smoking remains a significant risk factor for panic disorder, even after accounting for potential confounding variables. Further prospective longitudinal research should be done to investigate the causality between smoking and panic disorder.

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.

Cytokine profile in drug-na\xefve panic disorder patients

Although accumulating evidence suggests that inflammatory processes play a role in the pathophysiology of mental disorders, few studies have investigated this matter in panic disorder (PD). Furthermore, no studies to date have evaluated cytokine levels in drug-naïve patients with PD. Therefore, little is known about the presence of inflammation at the onset of this disorder. The aim of the present study was to determine the levels of the proinflammatory interleukins IL-1B and IL-2R and the anti-inflammatory cytokine IL-10 in drug-naïve PD patients. Analysis of serum chemokine levels revealed increased proinflammatory activity in the early phase of PD through increased IL-2R and IL-1B levels and a decrease in IL-10 levels in drug-naïve PD patients compared to matched healthy controls. Neurotransmitters and neurocircuits that are targets of inflammatory responses are discussed, followed by an examination of brain–immune interactions as risk factors for PD. This study is the first to identify a proinflammatory cytokine response in drug-naïve PD subjects. These findings indicate that treatments targeting proinflammatory markers may ameliorate anxiety symptoms in PD patients.

Disruption of estrogen regulation of orexin neurons: a novel mechanism in the pathophysiology of respiratory manifestations of panic disorder in females

Panic disorder (PD) is an anxiety disorder that affects ~5% of the population. A significant group of PD patients are characterised by excessive behavioral and physiological responses to CO2 inhalation. The prevalence of PD is 2 to 3 times more frequent in women yet, the origins of this sexual dimorphism are unknown; the fact that excessive responsiveness to CO2 inhalation peaks during the pre‐menstrual phase suggest a role of ovarian hormones. Early life stress is a significant risk factor for PD and there is growing evidence indicating that stress‐related increase in the function of orexin‐producing neurons (ORX) is key to PD. Based on data suggesting that 17b‐estradiol (E2) inhibits ORX, we tested the hypothesis that insufficient E2‐regulation of ORX neurons contributes to stress‐related respiratory manifestations of PD in females. Experiments were performed on adult female rats previously subjected to neonatal maternal separation (NMS; 3h/day postnatal days 3 to 12) or raised under standard conditions. In this model, NMS females show an excessive hyperventilatory response to CO2 by comparison with controls; this effect is greatest during the proestrus phase. Inactivation of ORX1 receptors by SB 33486 (15 mg/kg; ip) prevents this effect. Whole cell recordings (voltage clamp) were performed on GFP‐labeled ORX neurons by AAV microinjection. Excitatory post‐synaptic currents (EPSCs) converging onto ORX neurons were recorded under basal conditions and following E2 bath application (100nM; 10 min). Monitoring of the estrus cycle showed that in control females, EPSC frequency was inversely proportional to circulating E2 levels associated with each phase. This relationship was not observed in NMS females; EPSC frequency of NMS females was greater than controls during the proestrus phase. E2 application reduced EPSC frequency (but not amplitude); however, this effect was not affected by stress or the estrus cycle phase. We conclude that NMS disrupts E2‐mediated inhibition of ORX neurons. This is a novel mechanism in the pathophysiology of PD.Support or Funding InformationSupported by an operating grant from the Canadian Institutes of Health Research

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.

Contextual Fear Conditioning and Fear Generalization in Individuals With Panic Attacks.

Context conditioning is characterized by unpredictable threat and its generalization may constitute risk factors for panic disorder (PD). Therefore, we examined differences between individuals with panic attacks (PA; N = 21) and healthy controls (HC, N = 22) in contextual learning and context generalization using a virtual reality (VR) paradigm. Successful context conditioning was indicated in both groups by higher arousal, anxiety and contingency ratings, and increased startle responses and skin conductance levels (SCLs) in an anxiety context (CTX+) where an aversive unconditioned stimulus (US) occurred unpredictably vs. a safety context (CTX−). PA compared to HC exhibited increased differential responding to CTX+ vs. CTX− and overgeneralization of contextual anxiety on an evaluative verbal level, but not on a physiological level. We conclude that increased contextual conditioning and contextual generalization may constitute risk factors for PD or agoraphobia contributing to the characteristic avoidance of anxiety contexts and withdrawal to safety contexts and that evaluative cognitive process may play a major role.

Consequences of Microglial Depletion on the Hypercapnic Ventilatory Response of Female Rats

Panic disorder (PD) is a neurological disorder associated with an abnormally high hypercapnic ventilatory response. In humans and rodents, early life stress is a significant risk factor for PD. Based on recent data indicating that CO2/H+ sensing by microglia is an important mechanism in the translation of hypercapnic stimulation into physiological responses, we tested the hypothesis that depletion of microglia by pharmacological treatment can decrease the hypercapnic ventilatory response. We also proposed that this effect is greater in stressed rats than controls. The prevalence of PD being ~2 times greater in women than men, experiments were performed on female rats. Following birth, rats were either raised under control conditions or subjected to neonatal maternal separation (NMS; 3h/day, postnatal days 3 to 12). At 8 weeks, females were fed a palatable treat containing either vehicle (DMSO) or PLX3397 (40mg/kg). Treatment was performed daily for 10 consecutive days. 1 day after completion of the treatment, rats were placed in a plethysmography chamber to measure ventilatory activity at rest (room air) followed by hypercapnic exposure (FiCO2 = 0.05; 10 min). Iba‐1 immunohistochemistry was used to quantify microglial density; measurements performed in hypothalamic structures containing orexin neurons showed that PLX3397 treatment educed microglial density by 31%; this effect did not differ between the structures quantified. Furthermore, our preliminary results suggest that oestrus cycle influences the impact of microglial depletion on the CO2 response. During the estrus phase, PLX3397 attenuated the hypercapnic ventilatory response of controls but augmented the response of NMS females. These data suggest that microglia contribute to the abnormal effects that ovarian hormones exert on the neural networks regulating CO2/H+ chemoreflex respiratory regulation in NMS rats. These data provide the basis for the exploration of new treatment for respiratory manifestations of PD.Support or Funding InformationSupported by the Canadian Institutes of Health Research (RK &amp; FB).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Prevalence of patients with panic attacks (PAs) and panic disorder (PD) visiting Emergency Departments of the Verona Hospital.

Panic Attacks (PAs) and Panic Disorder (PD) represent a heavy burden not only because of the difficulty in distinguishing them from other pathologies and in treating them appropriately but also because of their impact on public health worldwide. In Europe, PD constitutes one of the five most common mental disorders adversely affecting quality of life. The aim of this study is to evaluate the period prevalence of visits to the Emergency Departments of the University Hospital of Verona (North East of Italy) over the period between 2012-2016 because of symptoms of PAs or PD in order to quantify the burden of the disorder. This study was carried out by retrospectively collecting data from the medical records of all the patients assessed at the Emergency Departments (EDs) of the Verona Hospital because of symptoms of PAs or PD over a 5-year period (1 January 2012 - 31 December 2016). The search words used in reviewing the medical records registered in the hospital discharge reports from the Gynecological, Pediatric and General Medicine Emergency Departments were: "Anxiety" and/or "Panic". A multiple logistic regression model was also created to evaluate the predictors of ED visits for PAs or PD over the period that was investigated. The study identified 3,771 cases of PAs or PD; 62.3% were females and 37.7% were males. The female-to-male ratio was 1.7:1. The mean age was 44 years (46 for the females and 41 for the males). The majority of the patients fell into two age categories: 30 to 39 (20.6%) and 40 to 49 (23.8%). The proportion of visits to the EDs for PAs or PD was approximately 20% per year, with an average of approximately 754 patients visiting the EDs every year. The period prevalence of accesses for PAs or PD over the five year period studied in the mean resident population (1.4%) and the mean visits to the EDs (2.5%) were calculated. Study results showed that the majority of the patients (80.9%) were referred to their general practitioner (GP) at the end of the assessment protocol at the EDs. According to the regression logistic model, the following variables were significant (p<0.05) risk factors for PAs or PD: being female vs. male (OR 1.899; 95% CI 1.785-2.020), being Italian vs. Foreigner (OR 1.292; 95% CI 1.174-1.421), having a white or green priority code at arrival (low urgency) vs. the other ones (OR 1.195; 95% CI 1.100-1.297), and being aged ≤42 years old (OR 1.091; 95% CI 1.024-1.161). The role of the GP is crucial in the management of PD and PAs. Given the difficulty of implementing primary and secondary prevention programs for these conditions, public health officials should make every effort to promote tertiary prevention in order to reduce the burden of the ailment and societal cost.

Modeling the development of panic disorder with interoceptive conditioning

Panic disorder is characterized by the paroxysmal occurrence and fear of bodily symptoms. In recent years it has been proposed that patients “learn” to fear cardiorespiratory sensations through interoceptive conditioning. This study sought to model the initial stage of this process in healthy volunteers (N=44) using mild cardiac sensations. An additional aim was to explore whether anxiety sensitivity – a known risk factor for panic disorder – modulates such interoceptive learning. Infusions of pentagastrin and saline were used to manipulate the presence versus absence of cardiac sensations, respectively, and served as conditioned stimuli in a differential interoceptive conditioning paradigm. Inhalation of 35% CO2-enriched air served as the panicogenic, unconditioned stimulus (UCS). In half of the participants (“prepared” condition), cardiac sensations caused by pentagastrin were followed by inhalation of CO2-enriched air (penta CS+), whereas the absence of such sensations (saline) was followed by room air (saline CS−). The reversed combination (“unprepared” condition) was used in the other half of the participants. Conditioning effects showed up for self-reported UCS-expectancy, but not for skin conductance and anxiety ratings. Only participants from the prepared group learned to expect the UCS, and differential learning was impaired with higher scores on anxiety sensitivity. Expectancy learning was more easily established towards the presence compared to the absence of cardiac sensations, whereas the reverse effect was observed for safety learning. Modeling impaired discriminatory learning and the moderating effect of anxiety sensitivity provides new insight in the development of panic disorder.

Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing.

Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1 as a risk factor for panic disorder (PD). Allelic variation of CRHR1 was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1 mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1 risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder.

Risk factors for Panic Disorder in pregnancy: A cohort study

BackgroundThe study investigates the prevalence of Panic Disorder (PD) with or without comorbid Major (MD) or Minor Depressive (md) disorder during pregnancy and focuses its attention on the different pattern of risk factors in these two subgroups in a sample of women attending two Centres for Prenatal Care of the Public Health Service. MethodsTwo-hundred and seventy-seven pregnant women were assessed monthly throughout the whole pregnancy period using the Primary Care Evaluation of Mental Disorders (PRIME-MD) for the screening of PD and the Hospital Anxiety and Depression Scale (HADS) for the evaluation of severity of anxious and depressive symptoms. ResultsTwenty-one women (7.5%) were diagnosed as affected by PD, of whom 12 (57.1%) showed MD or md comorbidity. The development of PD without depressive comorbidity is predicted by a history of previous episodes of Anxiety Disorders while the development of PD plus depressive comorbidity is predicted by a history of previous depressive episodes and by the lack of familiar support. LimitationsGiven the small sample size of our anxious and depressed women, the present data need to be verified by using larger samples. ConclusionsThe frequent association between PD and MD or md, the analysis of risk factors and of temporal relationship strongly suggests that the panic-depressive comorbidity might represent in fact depressive disorders with intense anxiety symptoms. These findings raise the question if the PD-depressive association is a true comorbidity or reveals the anxious symptomatology of a depressive disorder (MD or md).

Parental Bonds in Children at High and Low Familial Risk for Panic Disorder

A rejecting and overprotective parenting style is considered to be an important risk factor for the development of anxiety disorders. This study examined the role of perceived parental bonding as a potential environmental risk factor for panic disorder (PD) in unaffected offspring with parental PD. Children with a biological parent with PD (n = 71) and children of parents with no psychiatric history (n = 80) participated in the study. Results indicate that high risk children do not perceive their parents as being more protective and less caring than low risk controls. The optimal bonding type (high care, low protection) was the most frequently reported parenting style across groups. The constraining type of maternal bonding (high care, high protection) was less frequently reported by high risk children (p < 0.05). Overall, these data suggest that parental PD does not compromise the parent-child bonds in never-ill offspring.

Temperament, Character and Anxiety Sensitivity in Panic Disorder: A High-Risk Study

Background: Adult patients with panic disorder (PD) show high levels of harm avoidance and anxiety sensitivity. Peculiar temperament profiles and high anxiety sensitivity have been proposed as developmental risk factors for PD in adult age. Since familial-genetic influences play a role both in PD and in anxiety sensitivity and temperament profiles, this study aims to investigate the possible association between family history of PD and peculiar temperament-character profiles or high anxiety sensitivity in offspring of patients with PD. Sampling and Methods: Thirty-four children of patients with PD with/without agoraphobia and 30 children of healthy subjects were compared. Temperament and character dimensions and anxiety sensitivity levels of children were obtained by the Junior Temperament and Character Inventory and the Childhood Anxiety Sensitivity Index. Results: Children of patients with PD and children of healthy subjects differed neither in temperament and character dimensions nor in anxiety sensitivity levels. Conclusions: Our results show that family history of PD is not associated with peculiar temperament and character profiles or high anxiety sensitivity in children, suggesting that these factors may not be early expressions of familial vulnerability to PD. Since the sample is small and the study has a cross-sectional design, longitudinal studies in larger samples are warranted to confirm these findings and to clarify the role of anxiety sensitivity and temperament-character dimensions in the development of PD.

Monoamine oxidase A gene DNA hypomethylation – a risk factor for panic disorder?

The monoamine oxidase A (MAOA) gene has been suggested as a prime candidate in the pathogenesis of panic disorder. In the present study, DNA methylation patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for association with panic disorder with particular attention to possible effects of gender and environmental factors. Sixty-five patients with panic disorder (44 females, 21 males) and 65 healthy controls were analysed for DNA methylation status at 42 MAOA CpG sites via direct sequencing of sodium bisulfate treated DNA extracted from blood cells. The occurrence of recent positive and negative life events was ascertained. Male subjects showed no or only very minor methylation with some evidence for relative hypomethylation at one CpG site in intron 1 in patients compared to controls. Female patients exhibited significantly lower methylation than healthy controls at 10 MAOA CpG sites in the promoter as well as in exon/intron 1, with significance surviving correction for multiple testing at four CpG sites (p≤0.001). Furthermore, in female subjects the occurrence of negative life events was associated with relatively decreased methylation, while positive life events were associated with increased methylation. The present pilot data suggest a potential role of MAOA gene hypomethylation in the pathogenesis of panic disorder particularly in female patients, possibly mediating a detrimental influence of negative life events. Future studies are warranted to replicate the present finding in independent samples, preferably in a longitudinal design.

Adenosine A 2A receptor gene: Evidence for association of risk variants with panic disorder and anxious personality

Adenosine A 2A receptors are suggested to play an important role in different brain circuits and pathways involved in anxiety reactions. A variant within the corresponding ADORA2A gene (rs5751876) increased the risk for panic disorder (PD), for elevated anxiety during challenge tests in healthy probands and for anxiety-related arousal in blood-injury phobia. These multiple effects may mirror a more general effect of the SNP on basic personality traits. In the present study we therefore aimed to replicate the original finding in a large PD sample and extend it by investigating an additional proband sample characterized for different anxiety-related personality scores. In addition, as rs5751876 is assumed not to be the disease variant itself but to be in linkage disequilibrium (LD) with the true functional polymorphism other SNPs of potentially functional relevance were identified by re-sequencing the whole gene including several newly identified regions of putative regulatory potential and analysed for their impact on PD and anxious personality. We were indeed able to replicate rs5751876 as risk factor for PD, particularly PD with agoraphobia. Rs5751876 and several other variants in high LD (rs5751862, rs2298383 and rs3761422) as well as the corresponding haplotypes were also associated with different anxiety-related personality scores (Bonferroni corrected P all < 0.05). Of these variants, rs2298383 shows functional potential based on in silico analyses and might therefore represent the true underlying causal variant. Our data provide further support for an important role of ADORA2A variants in the pathogenesis of anxiety disorders and anxious personality reflecting their potential as basic susceptibility factors.

Flight behaviour in humans is intensified by a candidate genetic risk factor for panic disorder: evidence from a translational model of fear and anxiety

Flight behaviour in humans is intensified by a candidate genetic risk factor for panic disorder: evidence from a translational model of fear and anxiety

Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder

Genetic markers in the serotonin transporter are associated with panic disorder (PD). The associated polymorphisms do not include the serotonin transporter-linked polymorphic region and display no obvious functional attributes. A common polymorphism (rs3813034) occurs in one of the two reported polyadenylation signals for the serotonin transporter and is in linkage disequilibrium with the PD-associated markers. If functional, rs3813034 might be the risk factor that explains the association of the serotonin transporter and PD. Quantitative polymerase chain reaction on human brain samples (n = 65) and lymphoblast cultures (n = 71) was used to test rs3813034 for effects on expression of the polyadenylation forms of the serotonin transporter. rs3813034 was also tested for association in a sample of PD cases (n = 307) and a control sample (n = 542) that has similar population structure. The balance of the two polyadenylation forms of the serotonin transporter is associated with rs3813034 in brain (p < .001) and lymphoblasts (p < .001). The balance of the polyadenylation forms is also associated with gender in brain only (p < .05). Association testing of rs3813034 in PD identified a significant association (p = .0068) with a relative risk of 1.56 and 1.81 for the heterozygous and homozygous variant genotypes, respectively. rs3813034 is a functional polymorphism in the serotonin transporter that alters the balance of the two polyadenylation forms of the serotonin transporter. rs3813034 is a putative risk factor for PD and other behavioral disorders that involve dysregulation of serotonergic neurotransmission.

Meta‐analysis of COMT val158met in panic disorder: Ethnic heterogeneity and gender specificity

There is strong evidence for a genetic contribution to the pathogenesis of panic disorder, with the functional catechol-O-methyltransferase (COMT) val158met polymorphism having been suggested as a potential susceptibility factor. In the present study, a meta-analysis of six available case-control studies (557 patients with panic disorder and 763 healthy controls in total) on the role of the COMT val158met polymorphism in panic disorder was conducted in an attempt to reconcile previous conflicting results and to facilitate evaluation of the role of COMT gene variation in panic disorder. Overall, no significant association, but strong between-study heterogeneity, was discerned. Analysis of studies pooled by ancestry yielded a significant association of the COMT 158val allele with panic disorder in Caucasian samples and, conversely, a trend towards association of the COMT 158met allele with the disorder in Asian samples. Interestingly, stratification for gender as well as ethnicity revealed that association of the 158val allele in Caucasians and, reciprocally, the 158met allele in Asian samples was restricted to females. The present meta-analysis provides tentative support for the COMT val158met polymorphism as a possible risk factor for panic disorder, with differential effects in Caucasian and Asian populations, and suggests a female-specific effect. However, given the relatively small number of case-control studies presently available, several more association studies, preferably including a larger number of family-based studies, are warranted for conclusive evaluation of the COMT val158met polymorphism as a vulnerability factor in panic disorder.

Childhood Antecedents to Panic Disorder in Referred and Nonreferred Adults

We used a recursive partitioning method to examine antecedent childhood anxiety disorders in large samples of referred and nonreferred subjects with and without panic disorder. Referred subjects included adults treated for panic disorder (n = 131) and comparison adults with neither major anxiety nor mood disorders (n = 61). The nonreferred adult group derived from an opportunistic sample originally ascertained through family studies of probands with and without attention-deficit/hyperactivity disorder (ADHD), yielding 58 adults with panic disorder and 587 who were free of major anxiety and mood disorders. The majority of referred (65%) and nonreferred (52%) adults with panic disorder had antecedent childhood anxiety or disruptive behavior disorders. Classification and Regression Trees (CART) analysis showed that both separation anxiety disorder and overanxious disorder were independent predictors of subsequent panic disorder in both referred and nonreferred samples. These results confirm and extend previously reported findings by documenting that childhood anxiety disorders are important antecedent risk factors for panic disorder, independently of referral bias.

Panic disorder and bipolar disorder: Anxiety sensitivity as a potential mediator of panic during manic states

Background Panic disorder (PD) occurs at high rates in bipolar disorder and more commonly than in unipolar depression. Reports of PD onset during hypomania and depressive mania (i.e., mixed states) raise questions about whether the affective disturbances of bipolar disorder play a specific role in the exacerbation or onset of PD. Anxiety sensitivity (AS), a risk factor for PD appears greater in bipolar disorder compared to unipolar depression, although the association of specific mood states with AS remains unknown. Methods We examined the association of current mood state (i.e., mixed state, mania or hypomania, bipolar depression, unipolar depression, and euthymia) with Anxiety Sensitivity Index (ASI) scores in 202 individuals with bipolar disorder ( n = 110) or major depressive disorder ( n = 92). Results Current mood state was significantly associated with ASI score (Chi-square = 21.2, df = 4, p = 0.0003). In multiple regression analyses, including covariates for comorbid anxiety disorders, current mania or hypomania was a significant predictor of ASI scores ( p < 0.04). Current mixed state tended toward a similar association ( p < 0.10). Limitations Conclusions are limited by the study's cross-sectional nature and relatively small sample size. Conclusions These findings of elevated AS during manic states, independent of comorbid anxiety disorders, provide preliminary support for the hypothesis that manic states contribute to risk for the development or exacerbation of PD, and that AS may contribute to the high prevalence and severity of PD comorbid with bipolar disorder.