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Background: Despite the well-known association between anxiety and risk-avoidant decision making, it is unclear how pathological anxiety biases risk learning. We propose a Bayesian inference model with bias parameters of prior, learning, and perception during risk learning in individuals with pathological anxiety.Methods: Patients with panic disorder (PD, n = 40) and healthy control subjects (n = 84) completed the balloon analog risk task (BART). By fitting our computational model of three bias parameters (prior belief, learning rate, and perceptual bias) to the participants' behavior, we estimated the degree of bias in risk learning and its relationship with anxiety symptoms.Results: Relative to the healthy control subjects, the pathologically anxious participants exhibited a biased underestimation of perceptual evidence rather than differences in priors and learning rates. The degree of perceptual bias was correlated with the anxiety and depression symptom severity in the patients with PD. Furthermore, our proposed model was the winning model for BART data in an external data set from different patient groups.Conclusions: Our results showed that individuals with pathological anxiety demonstrate perceptual bias in evidence accumulation, which may explain why patients with anxiety overestimate risk in their daily lives. This clarification highlights the importance of interventions focusing on perceptual bias, such as enhancing the clarity of favorable outcome probabilities. [ABSTRACT FROM AUTHOR]

Background: Approximately half of US service members are married, equating to 1.1 million military spouses, yet the prevalence of psychiatric morbidity among military spouses remains understudied. We assessed the prevalence and correlates of eight mental health conditions in spouses of service members with 2-5 years of service.Method: We employed baseline data from the Millennium Cohort Family Study, a 21-year longitudinal survey following 9,872 military-affiliated married couples representing all US service branches and active duty, Reserve, and National Guard components. Couples were surveyed between 2011 and 2013, a period of high military operational activity associated with Operation Iraqi Freedom and Operation Enduring Freedom. Primary outcomes included depression, anxiety, posttraumatic stress disorder (PTSD), panic, alcohol misuse, insomnia, somatization, and binge eating, all assessed with validated self-report questionnaires.Results: A total of 35.90% of military spouses met criteria for at least one psychiatric condition. The most commonly endorsed conditions were moderate-to-severe somatization symptoms (17.63%) and moderate-to-severe insomnia (15.65%). PTSD, anxiety, depression, panic, alcohol misuse, and binge eating were endorsed by 9.20%, 6.65%, 6.05%, 7.07%, 8.16%, and 5.23% of spouses, respectively. Having a partner who deployed with combat resulted in higher prevalence of anxiety, insomnia, and somatization. Spouses had lower prevalence of PTSD, alcohol misuse, and insomnia but higher rates of panic and binge eating than service members. Both members of a couple rarely endorsed having the same psychiatric problem.Conclusions: One third of junior military spouses screened positive for one or more psychiatric conditions, underscoring the need for high-quality prevention and treatment services. [ABSTRACT FROM AUTHOR]

Background: No studies of psychotherapies for panic disorder (PD) have examined effects on comorbid personality disorders (PersD), yet half such patients have a PersD.Methods: In a randomized trial for PD with and without agoraphobia comparing Cognitive-Behavioral Therapy (CBT) and Panic-Focused Psychodynamic Psychotherapy (PFPP), PersD was assessed pre-to-post treatment with the Structured Clinical Interview for the Diagnosis of Axis-II Disorders (SCID-II). For patients completing therapy (n = 118, 54 with PersD), covariance between panic and SCID-II criteria improvements was analyzed. SCID-II diagnostic remission and recovery were evaluated. Comparative efficacy of PFPP versus CBT for improving PersD was analyzed both for the average patient, and as a function of PersD severity.Results: 37 and 17% of PersD patients experienced diagnostic PersD remission and recovery, respectively. Larger reductions in PersD were related to more panic improvement, with a modest effect size (r = 0.28). Although there was no difference between treatments in their ability to improve PersD for the average patient (d = 0.01), patients meeting more PersD criteria did better in PFPP compared to CBT (P = .007), with PFPP being significantly superior at 11 criteria and above (d = 0.66; 3 more criteria lost).Conclusions: PersD presenting in the context of primary PD rarely resolves during psychotherapies focused on PD, and change in PersD only moderately tracks panic improvements, indicating non-overlap of the constructs. Patients receiving panic-focused psychotherapies may require additional treatment for their PersD. PFPP may be superior at improving severe PersD, but replication of this finding is required. [ABSTRACT FROM AUTHOR]

Background: Prospective studies consistently find that smoking is a risk factor for the development of panic disorder (PD). A possible explanation is that nicotine deprivation promotes heightened sensitivity to bodily sensations and/or arterial carbon dioxide (CO2 ). Abrams et al. (2011) previously found that, in response to a CO2 rebreathing challenge, smokers experiencing more (vs. less) intense nicotine withdrawal had more severe panic symptoms and a stronger urge to escape. However, participants were aware of the last time they smoked, leaving unclear the extent to which fear reactivity was influenced by the pharmacologic effects of nicotine deprivation versus beliefs regarding when nicotine was most recently used. The present study aimed to ascertain whether nicotine deprivation, independent of beliefs regarding recent nicotine use, promotes fear reactivity among smokers.Methods: Moderate to heavy smokers without PD (N = 25) participated in a placebo-controlled, double-blind study consisting of two sessions spaced 1 week apart. Participants abstained from nicotine for 2 hr prior to sessions. During one session participants were given a 21 mg nicotine replacement patch and, during the other, a placebo patch, with the order counterbalanced. For both sessions, after a 3-hr absorption period, participants underwent a 10-min CO2 rebreathing challenge.Results: Wearing a nicotine (vs. placebo) patch increased self-reported panic reactivity among participants, but did not significantly affect physiological and behavioral measures of reactivity.Conclusions: In smokers without a history of PD, nicotine deprivation attenuates subjective panic reactivity. Possible explanations for the contrast between theory and laboratory findings as well as clinical implications are discussed. [ABSTRACT FROM AUTHOR]

Context: The scarcity of cross-national reports and the changes in Diagnostic and Statistical Manual version 5 (DSM-5) regarding panic disorder (PD) and panic attacks (PAs) call for new epidemiological data on PD and PAs and its subtypes in the general population.Objective: To present representative data about the cross-national epidemiology of PD and PAs in accordance with DSM-5 definitions.Design and Setting: Nationally representative cross-sectional surveys using the World Health Organization Composite International Diagnostic Interview version 3.0.Participants: Respondents (n = 142,949) from 25 high, middle, and lower-middle income countries across the world aged 18 years or older.Main Outcome Measures: PD and presence of single and recurrent PAs.Results: Lifetime prevalence of PAs was 13.2% (SE 0.1%). Among persons that ever had a PA, the majority had recurrent PAs (66.5%; SE 0.5%), while only 12.8% fulfilled DSM-5 criteria for PD. Recurrent PAs were associated with a subsequent onset of a variety of mental disorders (OR 2.0; 95% CI 1.8-2.2) and their course (OR 1.3; 95% CI 1.2-2.4) whereas single PAs were not (OR 1.1; 95% CI 0.9-1.3 and OR 0.7; 95% CI 0.6-0.8). Cross-national lifetime prevalence estimates were 1.7% (SE 0.0%) for PD with a median age of onset of 32 (IQR 20-47). Some 80.4% of persons with lifetime PD had a lifetime comorbid mental disorder.Conclusions: We extended previous epidemiological data to a cross-national context. The presence of recurrent PAs in particular is associated with subsequent onset and course of mental disorders beyond agoraphobia and PD, and might serve as a generic risk marker for psychopathology. [ABSTRACT FROM AUTHOR]

Background: A systematic review and meta-analysis was conducted to explore the efficacy of medication augmentation strategies compared to control treatments in patients who have had a partial or no response to initial treatment for generalized anxiety disorder, social anxiety disorder, and panic disorder.Methods: Double-blind controlled trials of medication augmentation in adult treatment-resistant anxiety disorders conducted between January 1990 and January 2015 were systematically reviewed and evaluated by two independent raters. The search identified 625 articles; 610 were excluded following abstract review and 15 had full-text screening. Studies had to include a definition of treatment resistance, exclude concomitant medications, and have a parallel or crossover design. Data extraction forms were completed in duplicate.Results: Six studies were included in the meta-analysis. Effect estimates were calculated using random effects modeling; heterogeneity was assessed and subgroup and sensitivity analyses were completed. Primary outcome was response, defined by Clinical Global Impression-Improvement score of ≤2. Augmentation was not associated with an increased risk of response, as compared with placebo (RR = 1.08, 95% CI = 0.94-1.24). A small significant effect was found in reduction in symptom severity: standard mean difference = -0.32, 95% CI = -0.56 to -0.08. No significant differences between augmentation with medication versus placebo were found in ratings of functional impairment and dropouts due to adverse events.Conclusions: Augmentation does not appear to be beneficial in treatment-resistant anxiety disorders. These results may be limited by small study samples, and a small number of overall studies in the analysis. [ABSTRACT FROM AUTHOR]

Background: Initial studies have provided a mixed perspective of the efficacy of d-cycloserine (DCS) for augmenting the efficacy of exposure-based cognitive behavioral therapy (CBT) for panic disorder. In this multicenter trial, we examine the magnitude of DCS augmentation effects for an ultra-brief program of CBT.Methods: We conducted a double-blind, controlled trial at three treatment sites, randomizing 180 adults with a primary diagnosis of panic disorder to five sessions of treatment, with study pill (50 mg DCS or matching placebo) administered 1 hr prior to the final three sessions. Two booster sessions were subsequently provided, and outcome was assessed at posttreatment and 1-month, 2-month, and 6-month follow-up assessments. The primary outcome was the degree of reduction in the Panic Disorder Severity Scale. Additional analyses examined the role of severity and current antidepressant or benzodiazepine use as moderators of DCS augmentation effects.Results: DCS augmentation resulted in significant benefit only early in the trial, with no beneficial effects of DCS augmentation evident at follow-up evaluations. We did not find that baseline severity or antidepressant or benzodiazepine use moderated DCS efficacy, but benzodiazepine use was associated with lower efficacy of CBT regardless of augmentation condition.Conclusions: Consistent with other recent multicenter trials, the benefit of DCS was less than indicated by pilot study and reflected an acceleration of treatment response evident at treatment endpoint, but no advantage in response over follow-up evaluation. Our results did not support severity or concomitant medication moderators observed in previous trials of DCS augmentation. [ABSTRACT FROM AUTHOR]

Background: Anxiety and depression display frequent comorbidity. Individuals with comorbid disorders also often have more extreme symptomatology than those with single disorders. This correlation between comorbidity and severity poses an interesting question: Are comorbid forms of anxiety and depression essentially just more severe versions of the pure disorders?Methods: In a large major depression (MD) case-control sample of individuals from the China, Oxford and VCU Experimental Research on Genetic Epidemiology project, we examined the patterns of lifetime anxiety comorbidity (including generalized anxiety disorder--GAD, panic disorder, and five phobia subtypes) among MD cases (N = 5,864) in this population. Binary and multinomial logistic regression was used to estimate associations between risk factors and outcomes including MD as well as latent class membership, which were compared using continuation ratios.Results: We found a five-class solution to fit best, and each resulting class had a distinct pattern of association with the tested risk factors. The use of continuation ratios suggests that a class characterized by high endorsement of GAD is comparable to a more severely affected "pure MD" group. The other three classes (characterized by agoraphobia, various specific phobias, and by high endorsement of all comorbid anxiety disorders, respectively) appear to differ meaningfully from MD alone.Conclusions: Risk for MD resulting from environmental and psychosocial factors may also predispose individuals to GAD, and less consistently, other anxiety disorders. Presentations of MD with certain phobias display distinguishably different patterns of risk, however, and are therefore likely qualitatively distinct. [ABSTRACT FROM AUTHOR]

Background Physical activity has been discussed as a therapeutic alternative or add-on for the treatment of anxiety disorders. We studied whether aerobic exercise compared to physical activity with low impact can improve the effect of cognitive behavioral therapy (CBT) in patients with panic disorder (PD) with/without agoraphobia. Methods Forty-seven patients received group CBT treatment over 1 month, which was augmented with an 8-week protocol of either aerobic exercise (three times/week, 30 min, 70% VO2max; n = 24) or a training program including exercises with very low intensity ( n = 23) in a randomized controlled double-blind design. The primary outcome measure was the total score on the Hamilton Anxiety Scale (Ham-A). A 2 × 3 analysis of covariance (ANCOVA) with baseline value as a covariate was conducted for data analysis. Results Time × group interaction for the Ham-A revealed a significant effect ( P = .047, η2 p = .072), which represented the significant group difference at a 7-month follow-up. For the other clinical outcome measures no statistical significance emerged, although improvement was more sustained in the exercise group. Conclusions For patients with PD, regular aerobic exercise adds an additional benefit to CBT. This supports previous results and provides evidence about the intensity of exercise that needs to be performed. [ABSTRACT FROM AUTHOR]

Background Panic disorder (PD) is highly comorbid with major depressive disorder (MDD) with potential impact on patient-reported outcomes of quality of life (QOL), functioning, and depressive symptom severity. Methods Using data from the sequenced treatment alternatives to relieve depression (STAR*D) trial, we compared entry and post-SSRI-treatment QOL, functioning, and depressive symptom severity scores in MDD patients with comorbid PD (MDD+PD) to MDD patients without PD (MDDnoPD). We also compared pre- and posttreatment proportions of patients with severe impairments in quality of life and functioning. Results MDD+PD patients experienced significantly lower QOL and functioning and more severe depressive symptoms than MDDnoPD patients at entry. Following treatment with citalopram, both groups showed significant improvements, however, nearly 30-60% of patients still suffered from severe quality of life and functioning impairments. MDD+PD patients exited with lower QOL and functioning than MDDnoPD patients, a difference that became statistically insignificant after adjusting for baseline measures of depressive symptom severity, functioning, and QOL, comorbid anxiety disorders (PTSD, GAD, social, and specific phobias), age, and college education. Conclusions Functional outcomes using QOL and functioning measures should be utilized in treating and researching MDD so that shortfalls in traditional treatment can be identified and additional interventions can be designed to address severe baseline QOL and functioning deficits in MDD comorbid with PD. [ABSTRACT FROM AUTHOR]

Background Identification of youth at risk for anxiety and unipolar mood disorders (UMDs) can improve public health by targeting those who may warrant early or preventive intervention. This study examined whether endorsing core features of anxiety and UMDs predicted onset of later anxiety and UMDs across the next 7-9 years, and whether having subthreshold or subclinical manifestations of these disorders similarly predicted onset. Methods Data from this study come from the Youth Emotion Project (YEP), a two-site investigation of common and specific risk factors for emotional disorders. Endorsement of core features of a disorder and subclinical or subthreshold anxiety and UMD diagnoses were determined using data from the Structured Clinical Interview for DSM-IV (SCID) at the baseline assessment. Participants completed annual SCIDs over the course of the next 7-9 years (depending on cohort). Results Endorsement of panic attacks, obsessions and/or compulsions, and depression and/or anhedonia predicted onset of panic disorder, obsessive compulsive disorder, and major depressive disorder, respectively. When including all anxiety disorders in a model, only the presence of panic attacks uniquely predicted anxiety disorder onset. The presence of subclinical or subthreshold panic disorder, obsessive compulsive disorder, and social phobia at baseline predicted the full onset of these disorders over the follow-up period. Conclusions Experiencing some symptoms of anxiety and UMDs in the absence of meeting diagnostic criteria is indicative of risk for later onsets of clinically significant DSM manifestations of these disorders. These individuals should be identified and targeted for prevention programs. [ABSTRACT FROM AUTHOR]

Background Cigarette smoking may increase the likelihood of developing panic disorder. Periods of nicotine withdrawal, in particular, may promote panic in individuals high in anxiety sensitivity. We examined the importance of nicotine withdrawal in the occurrence of smoking and panic. Methods We utilized a placebo-controlled, double-blind, randomized, crossover design. Fifty smokers underwent a breath-holding ( BH) challenge after the transdermal administration of nicotine on one test day and a placebo on another test day. Physiological and psychological variables were assessed at baseline as well as directly before and after the challenges. Results Nicotine abstinence induced a decrease in heart rate and systolic blood pressure ( BP) before the BH procedure (heart rate: 78.80 ± 11.43 under nicotine, 70.88 ± 10.83 under placebo; systolic BP: 124.90 ± 11.34 under nicotine, 121.18 ± 13.44 under placebo) and shorter BH duration relative to the nicotine patch condition. Nicotine abstinence did not, though, increase fear reactivity to the challenge. Conclusions The findings for heart rate and BP are consistent with the stimulant properties of nicotine. The reduced capacity to maintain apnea under placebo might be due to carbon dioxide ( CO2) hypersensitivity during periods of nicotine abstinence. The negative findings regarding fear reactivity might be due to BH being a relatively weak anxiogen. Future researchers are encouraged to employ CO2-inhalation procedures to study the relationship between nicotine withdrawal and panic. [ABSTRACT FROM AUTHOR]

Background Research suggests that suicidal behavior in individuals with anxiety disorders is attributable to cooccurring risk factors, such as depression. We argue that these conclusions are founded primarily in statistical adjustments that may obscure independent associations. We explored independent associations between specific anxiety disorders and suicide attempts and ideation by means of propensity score matching, a process that simulates a case-control study by creating matched groups that differ in group status (e.g., diagnosis of a specific anxiety disorder) but that are statistically equivalent on observed covariates. Methods We made use of the National Comorbidity Survey Replication (NCS-R) and the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), which include a total of 43,935 adults. Diagnoses included agoraphobia without panic disorder, generalized anxiety disorder, panic disorder with or without agoraphobia, posttraumatic stress disorder, social anxiety disorder, and specific phobia. Results Each anxiety disorder was (95% confidence intervals) associated with increased odds of lifetime suicide attempts (odds ratios 3.57-6.64 [NCS-R], 3.03-7.00 [NESARC]) and suicidal ideation (odds ratios 2.62-4.87 [NCS-R], 3.34-10.57 [NESARC]). Odds ratios for each disorder remained statistically significant after matching on diagnostic status of dysthymia, major depressive disorder, alcohol abuse/dependence, substance abuse/dependence, bipolar disorder I, bipolar disorder II, all other anxiety disorders, and on sociodemographic variables. Conclusions This is the first report to present evidence that each anxiety disorder is associated with suicide ideation and suicide attempts beyond the effects of cooccurring mental disorders. These findings warrant consideration in assessment, intervention, and related policies. [ABSTRACT FROM AUTHOR]

Background Predisaster risk factors are related to postdisaster psychopathology even at relatively low levels of disaster exposure. A history of panic attacks (PA) may convey risk for postdisaster psychopathology and has been linked to a wide range of psychiatric disorders in Western and non-Western samples. The present study examined the main and interactive effects of pretyphoon PA and level of typhoon exposure in the onset of posttyphoon posttraumatic stress disorder (PTSD), major depression (MDD), and generalized anxiety disorder (GAD) in a Vietnamese sample of typhoon survivors. Methods Typhoon Xangsane interrupted a Vietnamese epidemiological mental health needs assessment, providing a rare opportunity for preand posttyphoon assessments. Hierarchical logistic regression analyses evaluated whether the main and interactive effects of typhoon exposure severity and PA history were significantly related to posttyphoon diagnoses, above and beyond age, health status, pretyphoon psychiatric screening results, and history of potentially traumatic events. Results PA history moderated the relationship between severity of typhoon exposure and posttyphoon PTSD and MDD, but not GAD. Specifically, greater degree of exposure to the typhoon was significantly related to increased likelihood of postdisaster PTSD and MDD among individuals without a history of PA, above and beyond variance accounted for by pretyphoon psychiatric screening results. Individuals with a history of PA evidenced greater risk for postdisaster PTSD and MDD regardless of severity of typhoon exposure. Conclusions Preexisting PA may affect the nature of the relationship between disaster characteristics and prevalence of postdisaster PTSD and MDD within Vietnamese samples. [ABSTRACT FROM AUTHOR]

Background Allelic variations in TPH2, the gene encoding tryptophan hydroxylase 2, the rate-limiting enzyme for brain serotonin (5- HT) biosynthesis, may be genetic predictors of panic disorder and panic responses to panicogenic challenges in healthy volunteers. To test the hypothesis that tph2 m RNA is altered in chronic anxiety states, we measured tph2 expression in an established rat model of panic disorder. Methods We implanted 16 adult, male rats with bilateral guide cannulae and then primed them with daily injections of the corticotropin-releasing factor ( CRF) receptor agonist, urocortin 1 ( UCN1, 6 fmoles/100 nl per side, n = 8) or vehicle (n = 8) into the basolateral amygdaloid complex (BL) for 5 consecutive days. Anxiety-like behavior was assessed, 24 hr prior to and 48 hr following priming, in the social interaction ( SI) test. A third group (n = 7) served as undisturbed home cage controls. All rats were killed 3 days after the last intra-BL injection to analyze tph2 and slc6a4 (gene encoding the serotonin transporter, SERT) m RNAexpression in the dorsal raphe nucleus ( DR), the main source of serotonergic projections to anxiety-related brain regions, using in situ hybridization histochemistry. Results UCN1 priming increased anxiety-related behavior in the SI test compared to vehicle-injected controls and elevated tph2, but not slc6a4, m RNA expression in DR subregions, including the ventrolateral DR/ventrolateral periaqueductal gray ( DRVL/VLPAG), a subregion previously implicated in control of panic-related physiologic responses. Tph2 m RNA expression in the DRVL/VLPAG was correlated with increased anxiety-related behavior. Conclusion Our data support the hypothesis that chronic anxiety states are associated with dysregulated tph2 expression. [ABSTRACT FROM AUTHOR]

Context: The scarcity of cross-national reports and the changes in Diagnostic and Statistical Manual version 5 (DSM-5) regarding panic disorder (PD) and panic attacks (PAs) call for new epidemiological data on PD and PAs and its subtypes in the general population., Objective: To present representative data about the cross-national epidemiology of PD and PAs in accordance with DSM-5 definitions., Design and Setting: Nationally representative cross-sectional surveys using the World Health Organization Composite International Diagnostic Interview version 3.0., Participants: Respondents (n = 142,949) from 25 high, middle, and lower-middle income countries across the world aged 18 years or older., Main Outcome Measures: PD and presence of single and recurrent PAs., Results: Lifetime prevalence of PAs was 13.2% (SE 0.1%). Among persons that ever had a PA, the majority had recurrent PAs (66.5%; SE 0.5%), while only 12.8% fulfilled DSM-5 criteria for PD. Recurrent PAs were associated with a subsequent onset of a variety of mental disorders (OR 2.0; 95% CI 1.8-2.2) and their course (OR 1.3; 95% CI 1.2-2.4) whereas single PAs were not (OR 1.1; 95% CI 0.9-1.3 and OR 0.7; 95% CI 0.6-0.8). Cross-national lifetime prevalence estimates were 1.7% (SE 0.0%) for PD with a median age of onset of 32 (IQR 20-47). Some 80.4% of persons with lifetime PD had a lifetime comorbid mental disorder., Conclusions: We extended previous epidemiological data to a cross-national context. The presence of recurrent PAs in particular is associated with subsequent onset and course of mental disorders beyond agoraphobia and PD, and might serve as a generic risk marker for psychopathology., (© 2016 Wiley Periodicals, Inc.)