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Psoriasis is a chronic skin disease associated with lower quality of life and higher risk of anxiety and depression in adults. We investigate whether adolescents with psoriasis also experience poorer mental health than their peers. In this cross-sectional study, we included questionnaire data on psoriasis and mental health from the 18-year follow-up of the Danish National Birth Cohort. We estimated odds ratios (OR) and 95 % confidence intervals (CI) using a logistic regression with inverse probability weighting to account for potential selection bias, adjusted for potential confounders identified a priori. We estimated associations between self-reported psoriasis and multiple aspects of mental health (self-rated health, life satisfaction, mental well-being, loneliness, overall and internalizing behavioral difficulties, depressive symptoms, and anxiety symptoms). In sensitivity analyses, we examined doctor-diagnosed psoriasis and psoriasis with and without joint pain. Of the 44,838 included in this study, 1147 (2.6 %) reported psoriasis. Adolescents with psoriasis had a higher risk of nearly all outcomes, including depressive symptoms (OR 1.38; 1.19–1.58) and panic/agoraphobia among both males (OR 1.72; 1.33–2.19) and females (OR 1.60; 1.33–1.92). Associations attenuated when restricted to doctor-diagnosed psoriasis. Associations with poor mental health were mainly observed for adolescents with psoriasis also reporting joint pain. We could not establish temporality and lacked data on joint pain in referents. Psoriasis is associated with poor mental health in adolescents. This appears to be driven by adolescents with psoriasis also reporting joint pain and is less evident in those with a doctor-confirmed diagnosis. • Psoriasis is associated with poor mental health in adolescents. • Even milder forms of psoriasis can impact young people's mental health. • Joint pain has a negative impact on the mental health of adolescents with psoriasis. [ABSTRACT FROM AUTHOR]

Anxiety-related disorders feature elevated negative affect (NA), and in some cases, diminished positive affect (PA). It remains unclear how well extant psychotherapies for anxiety-related disorders improve PA versus NA. We systematically searched the Cochrane Central Register of Controlled Trials, PubMed, PsychInfo, and Web of Science databases. Records included studies involving (1) patients with a principal or co-principal diagnosis of at least one anxiety-related disorder (i.e., generalized anxiety, social anxiety, panic, agoraphobia, health anxiety, specific phobia, obsessive-compulsive disorder, or posttraumatic stress disorder), and (2) pre- and post-treatment PA and NA scores or a change index between pre- and post-treatment PA and NA scores. Effect sizes were calculated for meta-analyses. Fourteen studies with 1001 adults with an anxiety-related disorder were included. Psychotherapeutic interventions included cognitive behavioral, present-centered, and imagery-based approaches. Treatments reduced NA (g = −0.90; 95%CI [−1.19, −0.61]) to a greater extent than they improved PA (g = 0.27; 95%CI [0.05, 0.59]), Z = −5.26, p <.001. The limited number of studies available precluded analyses of the relationship between changes in affect and symptoms. Results should be considered with caution given the small number and heterogeneity of included studies. Current psychotherapeutic interventions for anxiety-related disorders may not improve PA and NA to comparable levels. • Systematic review and meta-analysis of the effect of psychotherapies on affective change for anxiety-related disorders. • There is a large effect of improvement in negative affect (g = −0.90). • There is a small effect of improvement in positive affect (g = 0.27). • Extant psychotherapies for anxiety-related disorders repair negative affect to a greater extent than positive affect. [ABSTRACT FROM AUTHOR]

It has been suggested that gender differences in anxiety and depressive symptoms characterize panic disorder (PD) in terms of vulnerability to stressful life events, anxiety, depressive symptom patterns, and brain structure. However, few studies have investigated the gender differences in PD using a network approach. This study included 619 participants with PD (313 men). The Panic Disorder Severity Scale, Albany Panic and Phobia Questionnaire, and Beck Depression Inventory-II were used to evaluate symptomatology. To investigate the PD-related white matter (WM) neural correlates, tract-based spatial statistics were used. The PD-related clinical scales and WM neural correlates were included in the network analysis to identify associations between variables. To evaluate network differences between genders, network comparison tests were conducted. Our findings revealed that agoraphobia in men was the strongest central symptom. In addition, loss of pleasure, and not anxiety or panic symptoms, was the strongest central symptom in women with PD. The network comparison test revealed that the bridge strength score was higher in agoraphobia and tiredness in men and in self-criticalness in women. Furthermore, in the network that includes neural correlates of WM, the bridge strength score was higher in the cingulate gyrus WM in men and the cingulum hippocampus in women. Since this is a cross-sectional network study of PD patients, the causal relationship between interactions in this network analysis for both genders may not be accurately determined. Network structures of anxiety and depressive symptomatology and related WM neural correlates can differ according to gender in PD patients. • Agoraphobia in male panic disorder (PD) and loss of pleasure in female PD are central symptoms. • The bridge strength was higher in the agoraphobia and tiredness in male, and higher in the self-criticalness in female. • Cingulate gyrus white matter in male PD showed higher bridge centrality with psychopathology than in female PD. • Cingulum hippocampus in female PD showed higher bridge centrality with psychopathology than in male PD. [ABSTRACT FROM AUTHOR]

Objective: Prior studies support that younger age of onset would be associated with poorer psychiatric and mental health outcomes for many psychiatric disorders. However, such relationship has never been examined for social anxiety disorder (SAD) in a nationally representative sample.Methods: Using data from the second Wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we have identified four groups of participants with a lifetime DSM-IV diagnosis of SAD based on the self-reported age of onset (childhood onset (<12 years, N = 658), adolescence onset (12-17 years, N = 663), early-adulthood onset (18-39 years, N = 663), and late-adulthood onset (>39 years, N = 415)), and a control group without a lifetime history of SAD (N = 32,205). We performed multinomial logistic regression models to compare lifetime DSM-IV psychiatric disorders and current mental health-related quality of life (assessed with the mental component summary score (MSC) of the SF-12) across these groups.Results: The lifetime prevalence rates of panic disorder, agoraphobia and post-traumatic stress disorder were significantly higher in the adulthood onset groups than in groups with an onset during childhood or adolescence (p < 0.01 for most models). MCS score was significantly higher in the childhood (46.0 (SE = 0.5)) or adolescence (46.5 (SE = 0.5)) onset groups than in the groups with an onset during adulthood (early-adulthood onset: 43.5 (SE = 0.6), and late-adulthood onset: 43.0 (SE = 0.8)).Limitations: Our results relied on retrospective self-reported data.Conclusion: Among individuals with SAD, a later age of onset was significantly associated with greater lifetime rates of psychiatric disorders and diminished quality of life. [ABSTRACT FROM AUTHOR]

Background: Panic disorder is an anxiety disorder presenting panic attacks as a defining feature, with cognitive and behavioral symptoms that are associated with the panic attacks. Recently, the use of network analysis is increasing to determine the symptoms and mutual reinforcing patterns that conceptualize a mental disorder. This study aimed to improve our understanding of panic disorder by estimating a network structure of its symptoms.Method: Data from 257 patients diagnosed with panic disorder who visited the outpatient psychiatric clinic from 2018 to 2020 were collected. Panic attacks, cognitive and behavioral symptoms concerning the panic attacks, depression, and anxiety sensitivity dimensions such as fear of cardiovascular symptom, fear of publicly observable anxiety reaction, fear of respiratory symptom, and fear of cognitive dyscontrol were computed. Bootstrapping was applied to estimate the 95% confidence intervals for each edges.Results: The resulting network indicated fear of cognitive dyscontrol, impairment in social functioning, phobic avoidance of situations, and panic-focused anticipatory anxiety to be central symptoms in panic disorder. Interestingly, panic attacks and distress during panic did not emerge as central. Depression was strongly linked to fear of cognitive dyscontrol.Limitations: The sample size limits network comparison tests between those with comorbid depression or agoraphobia. In addition, the cross-sectional design limits the opportunity to draw causal conclusions regarding the symptoms.Conclusions: These results have implications in etiology of panic disorder and support the efficaciousness of Cognitive Behavioral Therapy. Future network analyses may employ longitudinal designs to investigate causal relationships between the symptoms. [ABSTRACT FROM AUTHOR]

Background: Social support has been found to be a key correlate of many psychiatric disorders including several mood and anxiety disorders. However, research on social support is largely investigated in individual disorders, despite the high co-occurrence of these diagnoses, and has typically relied on pre-DSM-5 diagnostic criteria. Additionally, differences in structural and functional social support are rarely explored. Thus, the present study investigated the unique association between these two aspects of social support and past-year DSM-5 mood and anxiety disorders while adjusting for comorbidity and socio-demographic variables.Methods: Multivariate regression and relative weights analyses were conducted to determine the association of functional and structural social support with these disorders in the National Epidemiologic Survey on Alcohol and Related Conditions consisting of 36,309 participants.Results: Results indicated depression, bipolar I, social anxiety, generalized anxiety, and posttraumatic stress disorder were significantly associated with functional support, while depression and agoraphobia were uniquely associated with structural support. Major depression and persistent depression were the two most important predictors of functional social support.Limitations: The current study utilized cross-sectional data and does not allow for causal or directional conclusions. Further, additional studies with diverse samples are needed to determine the generalizability of the current results.Conclusions: This study highlights differences in functional and structural social support in various disorders and explores how this varies when accounting for comorbidity. A deeper understanding of how specific aspects of social support relate to individual psychiatric disorders could inform future prevention and treatment efforts. [ABSTRACT FROM AUTHOR]

Background: A routinely collected dataset was analyzed (1) to determine the naturalistic effectiveness of inpatient psychotherapy for depression in routine psychotherapeutic care, and (2) to identify potential predictors of change.Methods: In a sample of 22,681 inpatients with depression, pre-post and pre-follow-up effect sizes were computed for various outcome variables. To build a probabilistic model of predictors of change, an independent component analysis generated components from demographic and clinical data, and Bayesian EFA extracted factors from the available pre-test, post-test and follow-up questionnaires in a subsample (N = 6377). To select the best-fitted model, the BIC of different path models were compared. A Bayesian path analysis was performed to identify the most important factors to predict changes.Results: Effect sizes were large for the primary outcome and moderate for various secondary outcomes. Almost all pretreatment factors exerted significant influences on different baseline factors. Several factors were found to be resistant to change during treatment: suicidality, agoraphobia, life dissatisfaction, physical disability and pain. The strongest cross-loadings were observed from suicidality on negative cognitions, from agoraphobia on anxiety, and from physical disability on perceived disability.Limitations: No causal conclusions can be drawn directly from our results as we only used cross-lagged panel data without control group.Conclusions: The results indicate large effects of inpatient psychotherapy for depression in routine clinical care. The direct influence of pretreatment factors decreased over the course of treatment. However, some factors appeared stable and difficult to treat, which might hinder treatment outcome. Findings of different predictors of change are discussed. [ABSTRACT FROM AUTHOR]

Background: Early and accurate diagnosis of panic disorder with or without agoraphobia (PDA) is crucial to reducing disease burden and individual suffering. However, its diagnosis is challenging for lack of validated biomarkers. This study aimed to investigate whether radiomic features extracted from T1-weighted images (T1) of major fear-circuit structures (amygdala, insula, and anterior cingulate cortex [ACC]) could differentiate patients with PDA from healthy controls (HCs).Methods: The 213 participants (93 PDA, 120 HCs) were allocated to training (n = 149) and test (n = 64) sets after undergoing magnetic resonance imaging. Radiomic features (n = 1498) were extracted from T1 of the studied structures. Machine learning models were trained after feature selection and then validated in the test set. SHapley Additive exPlanations (SHAP) explored the model interpretability.Results: We identified 29 radiomic features to differentiate participants with PDA from HCs. The area under the curve, accuracy, sensitivity, and specificity of the best performing radiomics model in the test set were 0.84 (95% confidence interval: 0.74-0.95), 81.3%, 75.0%, and 86.1%, respectively. The SHAP model explanation suggested that the energy features extracted from the bilateral long insula gyrus and central sulcus of the insula and right ACC were highly associated with the risk of PDA.Limitations: This was a cross-sectional study with a relatively small sample size, and the causality of changes in radiomic features and their biological and clinical meanings remained to be elucidated.Conclusions: Our findings suggest that radiomic features from the fear-circuit structures could unveil hidden microstructural aberrations underlying the pathogenesis of PDA that could help identify PDA. [ABSTRACT FROM AUTHOR]

Aim: Anxiety disorders are amongst the most commonly diagnosed mental illnesses amongst men; however male-specific anxiety research is lacking. This review explores men's anxiety symptoms and disorders including help-seeking, coping and the role of masculinity.Method: Four electronic database searches identified 8,333 citations, with 25 studies meeting inclusion criteria. Nineteen studies employed quantitative methods, five studies reported qualitative research, and one utilised mixed methods.Results: Unique profiles of anxiety, including psychosomatic symptoms, were identified and persisted over extended periods of time. Men commonly reported self-reliance over formal help-seeking, and typically managed anxiety symptoms through problem-based coping. Masculinity was related to anxiety in complex ways; adherence to norms of toughness could be protective against anxiety onset, while adherence to emotional restrictiveness and heterosexual presentation norms were positively associated with anxiety. The experience of, and help-seeking for anxiety transgressed many men's adherence to masculinity norms resulting in significant social and self-stigmas.Limitations: The anxiety measurement scales utilised were inconsistent across included studies and there was limited scope of research into panic disorders, phobias and agoraphobia.Conclusion: Findings demonstrate the enduring nature of anxiety for men and a potential under-reporting of symptoms, especially amongst younger men. To better tailor clinical care and public health resources to the needs of men with anxiety disorders, targeted research examining men's lived experiences of (and coping strategies for) anxiety is essential. [ABSTRACT FROM AUTHOR]

Background Infertility is associated with increased anxiety, depressive symptoms and mood disorders. Unfortunately, mental health is not often addressed in infertility treatment and infertile patients could be at higher risk of self-administration of not prescribed drugs or/and be exposed to alternative emotional treatments. Therefore, the aim of the present study is to investigate the use of psychotropic medication and to evaluate the frequency of psychiatric diagnosis among infertile women seeking assisted reproductive technology (ART) therapy. Methods All infertile women starting treatment at an ART clinic who agreed to participate in the study were included. Patients were submitted to a structured psychiatric interview, the Mini International Neuropsychiatric Interview (M.I.N.I.). Current and lifetime use of psychotropic medication were assessed. Results Ninety patients who agreed to participate completed the research protocol.  A total of 12/90  were on current use of psychotropic medication.Thirty-six out of ninety patients  had at least one psychiatric disorder. Mood disorders were detected in 19 of the 90. Anxiety disorders were highly frequent, reaching 27/90 of the patients, as agoraphobia the most common diagnosis (12/90). Limitations The study has several limitations, such as the absence of a control group of fertile patients and strict inclusion criteria, in which only subjects that spontaneously agreed to participate were enrolled. Conclusion Women suffering from infertility seeking ART treatment are at high risk for depression and anxiety disorders and a considerable number of them are in use of medication. Its implications on infertility treatments and offspring are uncertain. [ABSTRACT FROM AUTHOR]

Background: The paradox of similar diagnostic criteria but potentially different neuropathologies in panic disorder (PD) and social anxiety disorder (SAD) needs to be clarified.Methods: We performed a qualitative systematic review and a quantitative whole-brain voxel-based morphometry (VBM) meta-analysis with an anisotropic effect-size version of seed-based D mapping (AES-SDM) to explore whether the alterations of grey matter volume (GMV) in PD are similar to or different from those in SAD, together with potential confounding factors.Results: A total of thirty-one studies were eligible for inclusion, eighteen of which were included in the meta-analysis. Compared to the respective healthy controls (HC), qualitative and quantitative analyses revealed smaller cortical-subcortical GMVs in PD patients in brain areas including the prefrontal and temporal-parietal cortices, striatum, thalamus and brainstem, predominantly right-lateralized regions, and larger GMVs in the prefrontal and temporal-parietal-occipital cortices, and smaller striatum and thalamus in SAD patients. Quantitatively, the right inferior frontal gyrus (IFG) deficit was specifically implicated in PD patients, whereas left striatum-thalamus deficits were specific to SAD patients, without shared GMV alterations in both disorders. Sex, the severity of clinical symptoms, psychiatric comorbidity, and concomitant medication use were negatively correlated with smaller regional GMV alterations in PD patients.Conclusion: PD and SAD may represent different anxiety sub-entities at the neuroanatomical phenotypes level, with different specific neurostructural deficits in the right IFG of PD patients, and the left striatum and thalamus of SAD patients. This combination of differences and specificities can potentially be used to guide the development of diagnostic biomarkers for these disorders. [ABSTRACT FROM AUTHOR]

Background: Mismatch negativity (MMN) or its magnetic counterpart (MMNm) is a neurophysiological signal to reflect the automatic change-detection ability. However, MMN studies in patients with panic disorder (PD) showed contrasting results using electroencephalographic (EEG) recordings. The present study attempted to overcome the limitations of EEG methodology by means of a whole-head magnetoencephalography (MEG) combined with the depth-weighted minimum norm estimate method to conduct an in-depth investigation on the MMNm at the cortical level in patients with PD.Methods: We recruited 22 healthy controls (HC) and 20 patients with PD to perform auditory oddball paradigm during MEG recordings. The cortical MMNm amplitudes and latencies in the superior temporal gyrus, inferior parietal lobule, and inferior frontal gyrus (IFG) were compared between the HC and PD groups. The correlations between MMNm responses and clinical measurement were also examined.Results: Compared with the HC group, the PD group demonstrated significantly reduced MMNm amplitudes in the IFG. Furthermore, higher trait scores of the State-Trait Anxiety Inventory were associated with lower MMNm amplitudes of the right IFG among patients with PD.Limitations: Generalization of the current results to other settings or samples should be made cautiously due to the use of different medication regimens and presence of comorbidities in our patients.Conclusions: Our data suggest dysfunctional pre-attentive change-detection ability in patients with PD, particularly in the IFG. [ABSTRACT FROM AUTHOR]

Background: Obese patients seeking bariatric surgery are known to show high rates of mental disorders, mainly mood and eating disorders. The aim of the present study is to evaluate psychiatric comorbidities, affective temperamental dimensions, emotional dysregulation and impulsivity in a sample of obese bariatric patients, exploring the differences between obese patients with and without mood disorders (MD).Methods: A total of 69 obese patients were consecutively enrolled between March and November 2019 during the presurgical evaluation routinely performed before the bariatric intervention. Sociodemographic and clinical features were collected by psychiatrists during a single consultation. Affective temperaments, emotional dysregulation and impulsivity were also investigated through self-report questionnaires. Epidemiological and clinical variables were compared between patients with and without MD.Results: In our sample, almost 3 out of 4 patients presented a lifetime psychiatric disorder, mainly MD (n=33, 48%), binge eating disorder (BED) (n=34, 49%) and anxiety disorders (n=30, 43%). Compared to N-MD patients, those with MD showed higher rates of psychiatric comorbidity with BED, bulimia and panic disorder. In addition, obese patients with MD showed more frequently cyclothymic, depressive and anxious temperaments, and higher mean scores on the psychometric questionnaires assessing emotional dysregulation and impulsivity compared to obese subjects without MD.Limitations: the small sample size, the retrospectively assessment of psychiatric disorders and the self-report questionnaires.Conclusions: A subgroup of obese patients, especially among those with MD, show high emotional dysregulation, affective lability and impulsiveness that could represent suitable substrates for the development of compulsive and addictive eating habits. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD) has a major impact on public health. Reduction of depression burden in general population is of greatest importance and might be achieved by implementation of depression prevention measures into routine care. We evaluate an online prevention measure as part of a national project aiming to reduce depression in the occupational group of green professions.Methods: This two-armed pragmatic RCT (n = 360) evaluates the effectiveness of a tailored internet-based intervention (IMI) program compared to enhanced treatment as usual. The IMI program entailed access to one of six guided IMIs each focusing on different symptom areas (depressive mood with optional comorbid diabetes, perceived stress, insomnia, panic and agoraphobia and harmful alcohol consumption). Eligible were entrepreneurs, spouses, family members and pensioners in green professions with adequate insurance status and at least subthreshold depression (PHQ≥5). Primary outcome was depressive symptom severity (QIDS-SR16) at 9-weeks post-treatment (T1). Various secondary outcomes were assessed at T1.Results: A small effect of depression reduction (d=-0.28, 95%-CI: -0.50 to -0.07) was found at T1 favouring the IMI program (β=-0.22, 95%-CI: -0.41 to -0.02, p=.033). Categorical analysis indicated a reduced risk of potential MDD with NNTB=28.11. Adherence to the IMI program at T1 was exceptionally low.Limitations: Results are limited to green professions and representativeness might be restricted by self-selection of participants.Conclusion: Depression burden in green professions can be reduced by this online prevention measure. Yet, short-term effectiveness is restricted by low adherence rates.Trial Registration: German Clinical Trial Registration: DRKS00014000. Registered: 09 April 2018. [ABSTRACT FROM AUTHOR]

Background: Although recent neuroimaging studies have suggested that functional deficits in facial perception are associated with panic disorder (PD), the possibility of cortical thickness and perfusion abnormalities have not been studied in patients with PD. We aimed to investigate alterations in cortical thickness and regional cerebral blood flow (CBF) between PD patients and healthy controls (HCs) using three-dimensional (3D) T1-weighted magnetic resonance imagery (MRI) and 3D arterial spin labeling (ASL) perfusion MRI.Method: An automated surface-based method (Cat12) measured the cortical thickness of each subject. Z-score normalization for CBF maps was used to generate Z-score maps. Statistical comparisons were performed using statistical parametric mapping with two-sample t-tests.Results: Subjects with PD, unlike HCs, displayed cortical thinning in the right fusiform gyrus (FG). Post hoc analysis also revealed a decreased Z-score in the right FG. There was significant positive correlation between the Z-score and the cortical thickness of the right FG. The cortical thickness and Z-score were negatively correlated with the Panic Disorder Severity Scale and Hamilton Rating Scale for Anxiety scores.Limitations: The small sample size may have restricted the identification of additional differences. Other caveats included the use of medication by nine participants.Conclusions: These results provide further evidence of the significant role structural and functional deficits in the right FG play in patients with PD. Due to the observed regional specificity, this finding bears important clinical implications for potential treatment strategies. [ABSTRACT FROM AUTHOR]

Background: There is no meta-analysis that specifically evaluates the effectiveness of Internet- and mobile-based interventions (IMIs) in adults with diagnosed panic disorder and/or agoraphobia (PD/A) so far. The current meta-analysis aims to fill this gap (PROSPERO CRD 42016034016).Methods: Systematic literature searches in six databases for randomised and controlled clinical trials investigating IMIs in adults, who met diagnostic criteria for PD/A. Study selection and data extraction were conducted independently by two reviewers. Random-effects meta-analyses, pre-planned subgroup and sensitivity analyses were conducted when appropriate. Primary outcomes were PD and A symptom severity. In addition, adherence, response, remission, quality of life, anxiety and depression symptom severity were examined.Results: A total of 16 trials (1015 patients), with 21 comparisons (9 IMI vs. waitlist; 7 IMI vs. IMI; 5 IMI vs. active treatment condition), were included. IMIs revealed beneficial effects on panic (Hedges' g range -2.61 to -0.25) and agoraphobia symptom severity when compared to waitlist (pooled g = -1.15, [95%-CI = -1.56; -0.74]). Studies comparing IMIs to active controls (i.e., face-to-face CBT and applied relaxation) did not find significant differences for reductions in panic (g = -0.02, [95%-CI = -0.25; 0.21]) and agoraphobia symptom severity (g = -0.10, [95%-CI = -0.39; 0.19]). Furthermore, IMIs were superior to waitlist controls regarding anxiety and depression symptom severity and quality of life.Limitations: Tests for publication bias were not feasible due to the limited number of trials per comparison, and the risk of bias assessment indicated some methodological shortcomings.Conclusions: Findings from this meta-analytic review provide support for the effectiveness of IMIs in patients with verified PD/A. However, before IMIs can be included in treatment guidelines for PD/A, future high quality research is needed that substantiates and extends the evidence base, especially in regard to intervention safety. [ABSTRACT FROM AUTHOR]

Background: Although the pathogenesis of panic attacks has been well studied in patients with panic disorder (PD), the neurobiological basis of the long-term fear memories and avoidance behavior that are often observed in PD have not been well investigated. Recent animal studies have suggested that nucleus accumbens (NAcc) plays an important role in neurobiological basis of long-term fear memories and avoidance behavior.Methods: Thirty-eight patients with PD and 38 matched healthy control subjects (HC) participated in this study. Differences in relative volumes and shape deformations of NAcc were evaluated between groups. Correlation analyses were conducted to quantify the association between structural abnormalities in the NAcc and trait, state anxiety measured by the State-Trait Anxiety Inventory (STAI).Results: Significant volume reductions were observed in the bilateral NAcc in the patients with PD, relative to the HC. In terms of shape differences, the PD patients demonstrated significant inward deformation of the NAcc bilaterally, compared to the HC. Degree of shape deformation in the right NAcc was associated with higher scores of the STAI-Trait, and STAI-State measures in the PD patients.Limitations: All the patients received medication such as Psychotropic drug.Conclusion: Patients with PD showed reduced volumes in the NAcc, especially in lateral regions, compared with HC. Furthermore, shape deformation in the right NAcc was associated with trait anxiety and state anxiety, which has been associated with avoidance behavior. [ABSTRACT FROM AUTHOR]

Background: Anxiety disorders are debilitating conditions that can be treated with cognitive behavioral therapy (CBT). Increased understanding of the neurobiological correlates of CBT may inform treatment improvements and personalization. Prior neuroimaging studies point to treatment-related changes in anterior cingulate, insula, and other prefrontal regions during emotional processing, yet to date the impact of CBT on neural substrates of "top down" emotion regulation remains understudied. We examined the relationship between symptom changes assessed over the course of CBT treatment sessions and pre- to post-treatment neural change during an emotion regulation task.Method: In the current study, a sample of 30 participants with panic disorder or generalized anxiety disorder completed a reappraisal-based emotion regulation task while undergoing fMRI before and after completing CBT.Results: Reduced activation in the parahippocampal gyrus was observed from pre- to post-treatment during periods of reducing versus maintaining emotion. Parahippocampal activation was associated with change in symptoms over the course of treatment and post-treatment responder status. Results suggest that, from pre- to post-CBT, participants demonstrated downregulation of neural responses during effortful cognitive emotion regulation.Limitations: Effects were not observed in frontoparietal systems as would be hypothesized based on prior literature, suggesting that treatment-related change could occur outside of fronto-parietal and limbic regions that are central to most models of neural functioning in anxiety disorders.Conclusions: Continued work is needed to better understand how CBT affects cognitive control and memory processes that are hypothesized to support reappraisal as a strategy for emotion regulation. [ABSTRACT FROM AUTHOR]

Objectives: Bipolar Disorder (BD) is frequently comorbid with other psychiatric disorders. However, few studies systematically examine which disorders are more likely to occur pre- or post-BD onset. We examine the prevalence and Age At Onset (AAO) of psychiatric conditions in adults with BD.Methods: A structured clinical interview was used to assess lifetime history and AAO of alcohol and cannabis misuse, suicide attempts, anxiety and eating disorders in a French sample of euthymic patients with BD (n = 739). Regression analyses were used to test for statistically significant associations between rates and AAO of comorbidities in BD groups stratified by sex or subtype.Results: Prevalence of alcohol and cannabis misuse was associated with male sex and BD-I subtype; whilst most anxiety and eating disorders were associated with female sex. The AAO of most comorbid conditions preceded that of BD, except for panic disorder, agoraphobia and alcohol misuse. Few variations were observed in AAO of comorbidities according to groups.Limitations: All assessments were retrospective, so estimates of prevalence rates and especially exact AAO of some comorbidities are at risk of recall bias.Conclusions: Sex and BD subtype are associated with different rates of comorbid disorders. However, there were minimal between group differences in median AAO of comorbidities. By describing the chronological sequence of comorbidities in BD we were able to demonstrate that a minority of comorbidities typically occurred post-onset of BD. This is noteworthy as these disorders might be amenable to interventions aimed at early secondary prevention. [ABSTRACT FROM AUTHOR]

Background: Computer simulations (CS) and virtual reality exposure are promising techniques for research and treatment of panic disorder with agoraphobia (PDA). The objective of this study was to ascertain whether a given CS was a stimulus capable of producing panic attacks (PAs), anxiety and psychophysiological changes in patients with PDA.Methods: Thirty PDA patients and 30 healthy subjects were recruited for this study. Subjects were exposed to a 3-min CS of a situation relevant to agoraphobic patients. Anxiety, panic symptoms, PAs, heart rate, skin conductance and respiration were recorded before, during and after the CS exposure.Results: The CS effectively induced anxiety, hyperventilation and electrodermal responses in PDA patients but not in healthy subjects. Forty percent of PDA patients had a PA while none of the control subjects had a PA. A subgroup of patients who were less sensitive to the CS than the other subgroup of PDA patients and did not present full-blown PAs still had more panic symptoms, higher anxiety levels and more respiratory irregularities than the controls.Limitations: Low immersion and low sense of presence, lack of interaction with the environment.Conclusions: Exposure to the CS produced effects similar to in vivo exposure, respiratory and caffeine challenges. Subsequent studies should: make direct comparisons between CS and other challenges for PDA; investigate if CS can be a tool for predicting effects of medication; determine the potential of CS as a desensitization technique for situational PAs. [ABSTRACT FROM AUTHOR]

Background: A link between brain-derived neurotrophic factor (BDNF) expression and the mood regulatory effect of leptin has been suggested in the pathophysiology of major depressive disorder (MDD). We investigated treatment response and pre-treatment leptin and BDNF in patients with MDD and with panic disorder (PD).Methods: We recruited 41 patients with MDD, 52 patients with PD, and 59 matched healthy controls. All subjects completed five visits (at baseline, 2, 4, 8, and 12 weeks), and both MDD and PD patients were treated with standard pharmacotherapy for 12 weeks. Plasma BDNF (pBDNF) and blood leptin levels were obtained along with a 17-item Hamilton Depression Scale rating (HDRS-17) score at every visit.Results: The ratio of pre-treatment pBDNF to leptin was significantly lower in patients with MDD and PD compared to healthy controls (p = 0.024), but was not associated with severity of depressive or anxiety symptoms. Pre-treatment pBDNF:leptin ratio was significantly higher in treatment responders than in non-responders (p = 0.012) in MDD but not in PD. This difference was larger in MDD patients with appetite loss (p = 0.034). In multivariate analysis, pre-treatment pBDNF:leptin ratio was significantly associated with treatment responsiveness (Adjusted Odds Ration [AOR] = 2.50, 95% CI 1.02-6.14) in MDD.Limitation: small sample size; limited information on detailed pharmacological effects.Conclusions: A relatively higher ratio of pre-treatment pBDNF to leptin was associated with greater treatment response in MDD but not in PD. Further research should focus on exploration of a link between BDNF and leptin underlying neuronal plasticity in depression. [ABSTRACT FROM AUTHOR]

Objective: To minimize the burden in detecting and monitoring Panic Disorder and Agoraphobia by developing a very brief scale with selected items from the Panic Disorder Severity Scale-Self Report (PDSS-SR), and to investigate the proposed scale's psychometric properties in a comorbid sample.Methods: A sample of 5103 patients from the Internet Psychiatry Clinic in Sweden, diagnosed and treated with Internet-based cognitive behavioral therapy for panic disorder (n = 1390), social anxiety disorder (n = 1313) or depression (n = 2400), responded to the PDSS-SR. Six criteria related to factor structure, sensitivity to change and clinical representativeness were used to select items. Psychometric analyses for the selected very brief scale were performed.Results: Items 2 (distress during panic attacks) and 4 (agoraphobic avoidance), were selected to create the very brief PDSS-SR version. Correlations with the full scale were high at screening, pre and post, and for change (0.87-0.93). Categorical Omega was ⍵C = 0.74. With a cut-off of 3 points, the scale could detect panic disorder in a psychiatric sample with a sensitivity of 85% and a specificity of 66%.Limitations: Limitations include lack of healthy controls and lack of blinding on secondary outcome measures.Conclusion: The proposed 2-item PDSS-SR version is a good candidate for a very brief panic disorder questionnaire, both for detecting cases and for measuring change. This is especially useful in clinical settings when measuring more than one condition at a time. [ABSTRACT FROM AUTHOR]

Background: The presence of comorbid anxiety is generally associated with poorer treatment outcomes in people with depression. Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective for treatment resistant depression, but there has been little research examining rTMS in depressed patients with comorbid anxiety disorders. This study aimed to investigate the efficacy of rTMS in patients with treatment resistant Major Depressive Disorder (MDD) and comorbid anxiety disorders.Methods: This study included 248 patients with treatment resistant MDD who were treated with rTMS. Of these, 172 patients had one or more comorbid anxiety disorders, so their outcomes were compared with patients who did not have comorbid anxiety.Results: Patients both with and without comorbid anxiety disorders showed improvement in depression ratings after rTMS treatment, with no significant difference in remission rates between groups. In those with comorbid anxiety disorders, 23.3% met criteria for remission and 39.5% met response criteria. For each anxiety disorder diagnosis, there was a significant reduction in HAM-A, HAM-D21, MADRS and ZUNG scores (p = <0.001 for all).Limitations: This was not a sham-controlled study, so placebo response rates are not known. Patients were referred by private psychiatrists so are not representative of all patients with depression.Conclusion: Our study indicates that rTMS is an effective treatment for Major Depressive Disorder in people who have comorbid anxiety disorders. [ABSTRACT FROM AUTHOR]

Background: Studies have reported an association between allergy and panic disorder. However, few studies have explored the relationship between allergic rhinitis and panic disorder. Previous studies were limited by cross-sectional study designs, self-reported symptoms, absence of matched controls, and lack of consideration of the influence of steroid and comorbidities. This study aimed to explore the longitudinal association between allergic rhinitis and panic disorder in a large population-based cohort of young people.Methods: In this study, 79,917 new cases of allergic rhinitis between 1998 and 2012 in individuals younger than 20 years were identified from Taiwan's National Health Insurance Research Database. One control (nonallergic rhinitis) per case (allergic rhinitis) was randomly selected from the remaining sample, matching for age, sex, residence, and insurance premium. Both groups were followed until the end of 2013 for incidence of panic disorder. Cox regression analysis was performed, adjusting for sex, age, residence, insurance premium, systemic steroids, asthma, atopic dermatitis, allergic conjunctivitis, attention deficit hyperactivity disorder, depression, and Charlson index.Results: Allergic rhinitis was associated with a 2-fold increase in risk for panic disorder after adjustment for other variables. Additional independent risk factor of panic disorders were female sex, older age group, and depression.Limitations: Lifestyle, substance use, smoking by the patient or family members, and psychosocial stressors were not evaluated.Conclusions: Allergic rhinitis was associated with increased risk of panic disorder. Assessment and intervention of allergy rhinitis among young people with panic disorder are critical. [ABSTRACT FROM AUTHOR]

Background: Hypervigilance to panic-related stimuli is believed to play a critical role in the pathogenesis of panic disorder. The current event-related potential study explored whether this hyperresponsivity occurred in the absence of focused attention.Methods: Mismatch negativity (MMN) responses to panic-related vs. neutral deviants were assessed in 15 medication-free panic patients without agoraphobia and 16 healthy controls using a reverse-standard-deviant paradigm.Results: Panic patients relative to healthy controls exhibited an enhanced MMN in response to panic-related sounds but a reduced MMN in response to neutral sounds. Furthermore, MMN responses were delayed in panic patients compared to healthy controls, irrespective of stimulus type.Limitation: The sample size is relatively small.Conclusions: Our data provide evidence that panic disorder was associated with an increased sensitivity to panic-related changes, accompanied by a reduced sensitivity to other acoustic changes as well as a general slow-down of cognitive processing during the preattentive processing stage. [ABSTRACT FROM AUTHOR]

Background: Depressive disorders are a frequent comorbidity of panic disorder with agoraphobia (PD/AG). Cognitive-behavioral therapy (CBT) for PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbidities. However, as depressive comorbidities can confound fear circuitry activation (i.e. amygdalae, insulae, anterior cingulate cortex) in PD/AG, we investigated whether comorbid depressive disorders alter neural plasticity following CBT.Methods: Within a randomized, controlled clinical trial on exposure-based CBT, forty-two PD/AG patients including fifteen (35.7%) with a comorbid depressive disorder (PD/AG + DEP) participated in a longitudinal functional magnetic resonance imaging (fMRI) study. A differential fear conditioning task was used as probe of interest. A generalized psycho-physiological interaction analysis (gPPI) served to study functional connectivity patterns.Results: After CBT, only PD/AG patients without comorbid depressive disorders (PD/AG-DEP) showed reduced activation in the left inferior frontal gyrus (IFG) extending to the insula. While PD/AG-DEP patients showed enhanced functional connectivity (FC) between the left IFG and subcortical structures (anterior cingulate cortex, thalamus and midbrain), PD/AG + DEP patients exhibited increased FC between the left IFG and cortical structures (prefrontal, parietal regions). In both groups, FC decreased following CBT.Limitations: Primary depressed and medicated patients were excluded. Major depression and dysthymia were collapsed.Conclusions: Reduced activation in the left IFG, as previously shown in PD/AG, appears to be a specific substrate of CBT effects in PD/AG-DEP patients only. Differential patterns of FC pertaining to fear circuitry networks in patients without depression vs. cognitive networks in patients with comorbid depression may point towards different pathways recruited by CBT as a function of comorbidity. [ABSTRACT FROM AUTHOR]

Background: Anxiety possibly interferes with executive functioning, although most studies rely on anxiety symptoms or lack control for comorbid depression. The objective of the present study is to examine the association between executive functioning and (individual) anxiety disorders with ak,ld without controlling for depression.Method: Generalized anxiety disorder (GAD), panic disorder with and without agoraphobia, agoraphobia, social phobia, as well as depressive disorder according to DSM-IV criteria were assessed with the Mini International Neuropsychiatric Interview in 82,360 community-dwelling people participating in the Lifelines cohort. Figural fluency as a measure of executive functioning was assessed with the Ruff Figural Fluency Test (RFTT). Linear regression analyses with the RFFT score as the dependent variable and psychiatric diagnosis as independent variables (dummies) were performed, adjusted for potential confounders. Multivariate results are presented with and without adjustment for depression.Results: Presence of any anxiety disorder was associated with worse performance on the RFFT (B = - 0.78, SE = 0.32, p = .015), independent of depression. No dose-response relationship with the number of anxiety disorders was found. Only agoraphobia and generalized anxiety disorder were significantly associated with the RFFT score in the multivariate models. Agoraphobia remained significant when further adjusted for depressive disorder (B = - 1.14, SE = 0.41, p < .01), while GAD did not (B = 0.013, SE = 0.431, p = .975).Limitations: Executive function was tested by only one measure, namely figural fluency.Conclusion: Agoraphobia is associated with worse executive functioning. Treatment of agoraphobia could be influenced by the executive dysfunction which clinicians should be aware of when regular treatment fails. [ABSTRACT FROM AUTHOR]

Background: Despite increasing evidence for the diagnostic instability between and within depressive and anxiety disorders, most studies report solely on the recurrence rates of the specific index disorders. Neglecting this evidence has an inherent risk of underestimating recurrence rates of depressive and anxiety disorders. This study investigates the impact of diagnostic instability of recurrence rates in depression and anxiety.Methods: Data were derived from the Netherlands Study of Depression and Anxiety (NESDA). The sample of 656 participants had a panic disorder with or without agoraphobia, agoraphobia, social phobia, generalized anxiety disorder, major depressive disorder or dysthymia, and a subsequent remission. Recurrence rates of index disorders (diagnostically stable recurrence) and newly arisen anxiety or depressive disorders (diagnostically unstable recurrence), were calculated over a 4-year follow-up period.Results: In anxiety disorders (n=281), the recurrence rate is more than doubled, from 23.8% with a stable recurrence, to 54.8%, when diagnostically unstable recurrences are included. In depressive disorders (N=173) the recurrence rate increases from 37.6% to 49.7%, and in comorbid anxiety and depressive disorders (N=202) the diagnostically unstable recurrences increase from 54.0% to 66.3%.Limitations: Attrition during follow up may have biased the results; remission was defined as absence of symptoms for 1 month; very short-term remission and recurrence patterns were not assessed.Conclusions: Diagnostically unstable recurrences have a significant impact on recurrence rates, with the greatest instability for anxiety disorders. When only diagnostically stable recurrences are assessed, recurrence rates are highly underrated and provide biased estimates of the true course of these disorders. [ABSTRACT FROM AUTHOR]

Background: Scientific debate has long surrounded whether agoraphobia is a severe consequence of panic disorder or a frequently comorbid diagnosis. Multivariate comorbidity investigations typically treat these diagnoses as fungible in structural models, assuming both are manifestations of the fear-subfactor in the internalizing-externalizing model. No studies have directly compared these disorders' multivariate associations, which could clarify their conceptualization in classification and comorbidity research.Methods: In a nationally representative sample (N=43,093), we examined the multivariate comorbidity of panic disorder (1) without agoraphobia, (2) with agoraphobia, and (3) regardless of agoraphobia; and (4) agoraphobia without panic. We conducted exploratory and confirmatory factor analyses of these and 10 other lifetime DSM-IV diagnoses in a nationally representative sample (N=43,093).Results: Differing bivariate and multivariate relations were found. Panic disorder without agoraphobia was largely a distress disorder, related to emotional disorders. Agoraphobia without panic was largely a fear disorder, related to phobias. When considered jointly, concomitant agoraphobia and panic was a fear disorder, and when panic was assessed without regard to agoraphobia (some individuals had agoraphobia while others did not) it was a mixed distress and fear disorder.Limitations: Diagnoses were obtained from comprehensively trained lay interviewers, not clinicians and analyses used DSM-IV diagnoses (rather than DSM-5).Conclusions: These findings support the conceptualization of agoraphobia as a distinct diagnostic entity and the independent classification of both disorders in DSM-5, suggesting future multivariate comorbidity studies should not assume various panic/agoraphobia diagnoses are invariably fear disorders. [ABSTRACT FROM AUTHOR]

Background: Stability of diagnosis was listed as an important predictive validator for maintaining separate diagnostic classifications in DSM-5. The aim of this study is to examine the longitudinal stability of anxiety disorder diagnoses, and the difference in stability between subjects with a chronic versus a non-chronic course.Methods: Longitudinal data of 447 subjects with a current pure anxiety disorder diagnosis at baseline from the Netherlands Study of Depression and Anxiety were used. At baseline, 2-, 4-, and 6-year follow-up mental disorders were assessed and numbers (and percentages) of transitions from one anxiety disorder diagnosis to another were determined for each anxiety disorder diagnosis separately and for subjects with a chronic (i.e. one or more anxiety disorder at every follow-up assessment) and a non-chronic course.Results: Transition percentages were high in all anxiety disorder diagnoses, ranging from 21.1% for social anxiety disorder to 46.3% for panic disorder with agoraphobia at six years of follow-up. Transition numbers were higher in the chronic than in the non-chronic course group (p=0.01).Limitations: Due to the 2 year sample frequency, the number of subjects with a chronic course may have been overestimated as intermittent recovery periods may have been missed.Conclusions: These data indicate that anxiety disorder diagnoses are not stable over time. The validity of the different anxiety disorder categories is not supported by these longitudinal patterns, which may be interpreted as support for a more pronounced dimensional approach to the classification of anxiety disorders. [ABSTRACT FROM AUTHOR]

Background: The possible involvement of microRNAs (miRNA) in psychiatric disorders has been recently recognized. Several miRNA polymorphisms have been found to be associated with panic disorder (PD) in European populations. However, the association of miRNA polymorphisms on PD has not been reported in Asian populations. We evaluated the effect of miR-22 and miR-491 polymorphisms on susceptibility to PD in a Korean population.Methods: Genotyping for four polymorphic variants of the primary miRNA (pri-miRNA) regions of miR-22 (rs8076112 and rs6502892) and miR-491 (rs4977831 and rs2039391) was performed using blood samples of 341 Korean patients with PD and 229 healthy control subjects. To evaluate PD phenotypes, the Panic Disorder Severity Scale (PDSS) and Anxiety Sensitivity Inventory-Revised (ASI-R) were administered.Results: Three single-nucleotide polymorphisms (SNPs) were found to be associated with PD: rs8076112 miR-22 and rs4977831 and miR-491 rs2039391. The rs8076112C/rs6502892C haplotypes of miR-22 and rs4977831G/rs2039391G and rs4977831A/rs2039391A haplotypes of miR-491 were significantly overrepresented in patients with PD than in healthy control subjects. In combination analysis, miR-22 rs8076112AC/rs6502892CC and rs8076112CC/rs6502892CC and miR-491 rs4977831AG/rs2039391AA were more frequent in patients with PD. Among the phenotype assessments, ASI-R scores were significantly associated with miR-22 rs6502892 in the subgroup with the agoraphobic phenotype.Limitations: The results should be considered preliminary due to the relatively small sample size and the selection of only four SNPs.Conclusions: This is the first report to show possible associations of miR-22 and miR-491 with genetic susceptibility to PD in a Korean population. [ABSTRACT FROM AUTHOR]

Panic disorder patients are hypervigilant to danger cues and highly sensitive to unpredictable aversive events, what leads to anticipatory anxiety, that is one key component of the disorder maintenance. Prefrontal cortex seems to be involved in these processes and beta band activity may be related to the involvement of top-down processing, whose function is supposed to be disrupted in pathological anxiety. The objective of this study was to measure frontal absolute beta-power (ABP) with qEEG in panic disorder and agoraphobia (PDA) patients compared to healthy controls. Methods : qEEG data were acquired while participants (24 PDA patients and 21 controls) watched a computer simulation (CS), consisting of moments classified as “high anxiety” (HAM) and “low anxiety” (LAM). qEEG data were also acquired during two rest conditions, before and after the computer simulation display. The statistical analysis was performed by means of a repeated measure analysis of variance (two-way ANOVA) and ABP was the dependent variable of interest. The main hypothesis was that a higher ABP in PDA patients would be found related to controls. Moreover, in HAM the ABP would be different than in LAM. Results : the main finding was an interaction between the moment and group for the electrodes F7, F8, Fp1 and Fp2. We observed a higher ABP in PDA patients when compared to controls while watching the CS. The higher beta-power in the frontal cortex for the PDA group may reflect a state of high excitability, together with anticipatory anxiety and maintenance of hypervigilant cognitive state. Conclusions : our results suggest a possible deficiency in top-down processing reflected by a higher ABP in the PDA group while watching the CS and they highlight the recruitment of prefrontal regions during the exposure to anxiogenic stimuli. Limitations : the small sample, the wide age range of participants and the use of psychotropic medications by most of the PDA patients. [ABSTRACT FROM AUTHOR]

Background Little is currently known about predictors of follow-up outcome of psychological treatment of agoraphobia. In this study, we wished to examine predictors of short- and long-term avoidance after inpatient group interventions for agoraphobia. Methods Ninety-six (68%) of 141 agoraphobic patients (74% women) who had completed treatment in two open and one randomized controlled trial (RCT) were followed up 13 to 21 years after start of treatment. Results Major depression at pre-treatment predicted less short-term (up to one year after end of treatment) improvement in agoraphobic avoidance. Working and being married/cohabiting at pre-treatment predicted greater long-term (across one-year, two-year, and 13–21 years follow-up) improvement. In contrast, the duration of agoraphobia, amount of Axis I and II co-morbidity, being diagnosed with avoidant, dependent, and obsessive-compulsive personality disorder, and the use of antidepressants and benzodiazepines the month before intake to treatment, were unrelated to short-term as well as long-term outcome. Limitations As many as 31.9% of the included patients did not attend long-term follow-up and the power of the study was limited. The long time period between the two and 13–21 year follow-ups is a limitation, in which it is difficult to assess what actually happened. Although all the patients received some form of CBT, there was variability among the treatments. Conclusions The only short-term predictor identified represented a clinical feature, whereas the long-term predictors represented features of the patients׳ life situation. The limited power of the study precludes the inference that non-significant predictors are unrelated to follow-up outcome. [ABSTRACT FROM AUTHOR]

Background Age of onset is an important epidemiological indicator in characterizing disorders׳ subtypes according to demographic, clinical and psychosocial determinants. While investigated in various psychiatric conditions, age of onset and related characteristics in agoraphobia have yet to be examined. In light of the new diagnostic status in the DSM-5 edition of agoraphobia as independent from panic disorder, research on agoraphobia as a stand-alone disorder is needed. Methods Admixture analysis was used to determine the best-fitting model for the observed ages at onset of 507 agoraphobia patients participating in the Netherlands Study of Depression and Anxiety (age range 18–65). Associations between agoraphobia age of onset and different demographic, clinical and psychosocial determinants were examined using multivariate logistic regression analysis. Results Admixture analyses identified two distributions of age of onset, with 27 as the cutoff age (≤27; early onset, >27; late onset). Early onset agoraphobia was only independently associated with family history of anxiety disorders ( p <0.01) Limitations Age of onset was assessed retrospectively, and analyses were based on cross-sectional data. Conclusion The best distinguishing age of onset cutoff of agoraphobia was found to be 27. Early onset agoraphobia might constitute of a familial subtype. As opposed to other psychiatric disorders, early onset in agoraphobia does not indicate for increased clinical severity and/or disability. [ABSTRACT FROM AUTHOR]

Background We investigated the efficacy of an intensive 1-week behavioral therapy program focusing on agoraphobia for panic disorder patients with agoraphobia (PDA). Design and methods The study design was a case-control study. Main outcome measure was the agoraphobia score of the Fear Questionnaire (FQ-AGO). The outcomes on the FQ-AGO of a 1-week intensive therapy (96 patients) and a twice-weekly therapy (98 patients) were compared. Results Agoraphobia improved significantly in both groups, 1 week and 3 months after therapy. Effect size for changes in the 1-week intensive therapy on the FQ-AGO was 0.75. Limitations Limitations are use of antidepressants, no placebo group, and no long term follow-up. Conclusion Behavioral therapy for agoraphobia can be shortened significantly if intensified without affecting therapy outcome, thus allowing patients a more rapid return to work and resumption of daily activities. [ABSTRACT FROM AUTHOR]

Abstract: Background: Panic disorder with agoraphobia (PD-A) has been associated with abnormal neural activity for threat-related stimuli (faces, places). Recent findings suggest a disturbed neural processing of emotionally neutral stimuli at a more general level. Methods: Using functional magnetic resonance imaging (fMRI) we investigated the neural processing of emotionally neutral faces and places in PD-A. Fifteen patients with PD-A and fifteen healthy subjects participated in the study. Results: When they perceived neutral faces and places, the patients with PD-A showed significantly less brain activity in the fusiform gyrus, the inferior occipital gyrus, the calcarine gyrus, the cerebellum, and the cuneus compared with the healthy controls. However, the patients with PD-A showed significantly more brain activity in the precuneus compared with controls subjects. Limitations: It was not possible to distinguish the agoraphobia-associated effects from possible contributions due to general anxiety induced by fMRI. For future investigations, an additional clinical control group with patients suffering from panic disorder without agoraphobia would be of interest. In addition, the psychopathology concerning the agoraphobic symptoms needs to be investigated in more detail. Conclusions: The findings suggest altered neural processing of emotionally neutral faces and places in patients with PD-A. Reduced neural activity in different brain regions may indicate difficulties in recognizing the emotional content in face and place stimuli due to anxiety-related hyper-arousal. [Copyright &y& Elsevier]

Abstract: Background: This study followed on findings from a recent genome-wide association study of PTSD that implicated the retinoid-related orphan receptor alpha (RORA) gene (Logue et al., 2012) by examining its relationship to broader array of disorders. Methods: Using data from the same cohort (N=540), we analyzed patterns of association between 606 single nucleotide polymorphisms (SNPs) spanning the RORA gene and comorbidity factors termed fear, distress (i.e., internalizing factors) and externalizing. Results: Results showed that rs17303244 was associated with the fear component of internalizing (i.e., defined by symptoms of panic, agoraphobia, specific phobia, and obsessive–compulsive disorder) at a level of significance that withstood correction for gene-wide multiple testing. Limitations: The primary limitations were the modest size of the cohort and the absence of a replication sample. Conclusions: Results add to a growing literature implicating the RORA gene in a wide range of neuropsychiatric disorders and offer new insight into possible molecular mechanisms of the effects of traumatic stress on the brain and the role of genetic factors in those processes. [Copyright &y& Elsevier]

Abstract: Background: Panic attacks are thought to be a result from a dysfunctional coordination of cortical and brainstem sensory information leading to heightened amygdala activity with subsequent neuroendocrine, autonomic and behavioral activation. Prefrontal areas may be responsible for inhibitory top-down control processes and alpha synchronization seems to reflect this modulation. The objective of this study was to measure frontal absolute alpha-power with qEEG in 24 subjects with panic disorder and agoraphobia (PDA) compared to 21 healthy controls. Methods: qEEG data were acquired while participants watched a computer simulation, consisting of moments classified as “high anxiety”(HAM) and “low anxiety” (LAM). qEEG data were also acquired during two rest conditions, before and after the computer simulation display. Results: We observed a higher absolute alpha-power in controls when compared to the PDA patients while watching the computer simulation. The main finding was an interaction between the moment and group factors on frontal cortex. Our findings suggest that the decreased alpha-power in the frontal cortex for the PDA group may reflect a state of high excitability. Conclusions: Our results suggest a possible deficiency in top-down control processes of anxiety reflected by a low absolute alpha-power in the PDA group while watching the computer simulation and they highlight that prefrontal regions and frontal region nearby the temporal area are recruited during the exposure to anxiogenic stimuli. [Copyright &y& Elsevier]

Abstract: Background: Existing literature on panic disorder (PD) yields no data regarding the differential rates of improvement during Cognitive Behavioral Therapy (CBT), Selective Serotonin Reuptake Inhibitor (SSRI) or both combined (CBT+SSRI). Method: Patients were randomized to CBT, SSRI or CBT+SSRI which each lasted one year including three months of medication taper. Participating patients kept record of the frequency of panic attacks throughout the full year of treatment. Rate of improvement on panic frequency and the relationship between rate of improvement and baseline agoraphobia (AG) were examined. Results: A significant decline in frequency of panic attacks was observed for each treatment modality. SSRI and CBT+SSRI were associated with a significant faster rate of improvement as compared to CBT. Gains were maintained after tapering medication. For patients with moderate or severe AG, CBT+SSRI was associated with a more rapid improvement on panic frequency as compared to patients receiving either mono-treatment. Limitations: Frequency of panic attacks was not assessed beyond the full year of treatment. Second, only one process variable was used. Conclusions: Patients with PD respond well to each treatment as indicated by a significant decline in panic attacks. CBT is associated with a slower rate of improvement as compared to SSRI and CBT+SSRI. Discontinuation of SSRI treatment does not result in a revival of frequency of panic attacks. Our data suggest that for patients without or with only mild AG, SSRI-only will suffice. For patients with moderate or severe AG, the combined CBT+SSRI treatment is recommended. [Copyright &y& Elsevier]

Abstract: Background: Research on the generalizability of clinical trials in panic disorder is limited. The present study sought to quantify the generalizability of clinical trials'' results of individuals with DSM-IV panic disorder (PD) to a large community sample. Methods: Data were derived from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a large national representative sample of 43,093 adults of the United States population. We applied a standard set of eligibility criteria representative of PD clinical trials to all adults with past 12 months PD (n=907), and then to a subgroup of participants seeking treatment (n=105). Our aim was to determine the proportion of participants with PD who would have been excluded by typical eligibility criteria. Results: We found that more than 8 out of ten participants (80.52%; 95% CI=77.13–83.52%) with PD were excluded by at least one criterion. In the subgroup of participants who sought treatment, the exclusion rate by at least one criterion was higher (92.40%; 95% CI=84.60–96.42%). For the full sample and the treatment-seeking subsample, having currently a depression and a diagnosis of alcohol or drug abuse/dependence were the criteria excluding the highest percentage of participants. Having a lifetime history of bipolar disorder and a current significant medical condition also excluded a substantial proportion of individuals in both samples. Exclusion rates were similar when considering panic disorder with and without agoraphobia. Conclusions: Clinical trials, that exclude a majority of adults with panic disorder, should carefully consider the impact of eligibility criteria on the generalizability of their results. As required by CONSORT guidelines, reporting exclusion rate estimate and reasons of eligibility should be mandatory in both clinical trials and meta-analyses. [Copyright &y& Elsevier]

Abstract: Background: Efficacy of treatments for panic disorder is well established, but not all patients respond. Adult separation anxiety has been found to predict poorer response to CBT, but its effect on response to medication has not been previously explored. Study aim: The aim of this study is to investigate if panic–agoraphobic spectrum factors, including ‘separation anxiety’ factor predict treatment outcome in patients with panic disorder. Study sample: Participants who met criteria for PD (n=57) completed baseline assessment and 12months follow-up. Patients were administered the Panic Agoraphobic Spectrum Self-Report (PAS-SR, Lifetime and Last-Month Versions), and the Panic Disorder Severity Scale (PDSS). We examined patients who met the following criteria at baseline: 1) PDSS total score>7; 2) no current Axis I comorbidity with major depression; 3) no lifetime or current bipolar disorder. All patients were treated with evidence-based psychopharmacological treatment for panic disorder during the 12-month observation period. Results: Twenty eight patients (48.1%) achieved remission during the follow-up period. In a logistic regression model, controlling for baseline severity, gender and age, only the last-month PAS-SR ‘separation anxiety’ factor was associated with a lower likelihood of remission. Conclusions: Signs and symptoms of separation anxiety in adulthood, as assessed with the PAS-SR Last Month version, are predictors of poor treatment outcome in patients with PD. We submit that the assessment of panic–agoraphobic spectrum features, including adult separation anxiety, should become routine of clinical assessment of patients with PD. It is likely that a better psychopathological characterization of patients may inform treatment selection, and result in better treatment outcome. [Copyright &y& Elsevier]

Abstract: Objective: Bipolar-I disorder (BPI) often co-occurred with anxiety (ANX) and substance use disorders (SUD), which poses challenges in public health and clinical treatment, and adds complexity in searching for relevant etiologic factors. The present study sought to identify subgroups of BPI patients using comorbidity patterns with ANX and SUD. Methods: Clinical patients (N=306) diagnosed with BPI were recruited and interviewed using the Composite International Diagnostic Interview to collect data on demographics and clinical features, including episodic information, impairments, and lifetime diagnoses of ANX (panic, agoraphobia, generalized anxiety disorder, specific and social phobia) and SUD (nicotine dependence, alcohol use and drug use disorder). We applied latent class analysis to empirically derive classes of BPI. A number of exogenous variables were examined for each class. Results: A three-class model provides excellent discriminability for subgrouping BPI patients with different comorbidity patterns. The BPI-LOW class (83.99%) had more pure mania without most lifetime comorbidity, higher numbers of last year mania episodes, and less suicidality and impairments. The BPI-ANX class (3.60%) was female predominant, tended to comorbid with multiple anxiety disorders but no SUD, and had early onset age. The BPI-SUD class (12.42%) was male predominant, had high prevalence of lifetime SUD and frequent mood episodes in the last year. Both the BPI-ANX and BPI-SUD classes had severe functional impairments and suicidal behaviors. Limitations: Clinical information was retrospectively collected. Besides, we did not comprehensively access lifetime comorbidity for all psychiatric disorders. Conclusion: The three empirically identified subgroups of BPI patients exhibited distinguished comorbidity patterns and clinical features, including suicidal behaviors, frequent mood episodes and functional impairments. Our findings have clinical implication in intervention and treatment as well as to explore their different underlying mechanisms. [Copyright &y& Elsevier]