Agoraphobia Research Articles

Neural Abnormalities in Panic Disorder and Agoraphobia: A Meta-Analysis of Functional Activation Studies

IntroductionPanic disorder (PD) and agoraphobia (AG) are highly comorbid anxiety disorders with an increasing prevalence that have a significant clinical and public health impact but are not adequately recognized and treated. Although the current functional neuroimaging literature has documented a range of neural abnormalities in these disorders, primary studies are often not sufficiently powered and their findings have been inconsistent.ObjectivesThis meta-analysis aims to advance our understanding of the neural underpinnings of PD and AG by identifying the most robust patterns of differential neural activation that differentiate individuals diagnosed with one of or both these disorders from age-matched healthy controls.MethodsWe conducted a comprehensive literature search in the PubMed database for all peer-reviewed, whole-brain, task-based functional magnetic resonance imaging (fMRI) activation studies that compared adults diagnosed with PD and/or AG with age-matched healthy controls. Each of these articles was screened by two independent coding teams using formal inclusion criteria and according to current PRISMA guidelines. We then performed a voxelwise, whole-brain, meta-analytic comparison of PD/AG participants with age-matched healthy controls using multilevel kernel density analysis (MKDA) with ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias and 10,000 Monte Carlo simulations to correct for multiple comparisons.ResultsWith data from 34 primary studies and a substantial sample size (N=2138), PD/AG participants, relative to age-matched healthy controls, exhibited a reliable pattern of statistically significant, (p<.05-0.0001; FWE-corrected) abnormal neural activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.ConclusionsIn this meta-analysis we found robust patterns of differential neural activation in participants diagnosed with PD/AG relative to age-matched healthy controls. These findings advance our understanding of the neural underpinnings of PD and AG and inform the development of brain-based clinical interventions such as non-invasive brain stimulation (NIBS) and treatment prediction and matching algorithms. Future studies should also investigate the neural similarities and differences between PD and AG to increase our understanding of possible differences in their etiology, diagnosis, and treatment.Disclosure of InterestNone Declared

The role of subjective, interpersonal, and structural social isolation in 12-month and lifetime anxiety disorders

BackgroundAnxiety disorders are among the most prevalent psychiatric conditions worldwide, and the incidence of anxiety disorders among adults in the U.S. have increased over the last decade. Anxiety disorders can have debilitating effects on multiple areas of functioning and quality of life. Recently, social isolation has emerged as an important public health problem associated with worse health and well-being outcomes. Research on the connection between social isolation and mental health has found that multiple dimensions of social isolation may negatively impact mental health, but few inquiries have focused on the association between social isolation and anxiety. This study examined the relationships between multiple dimensions of social isolation and anxiety disorders in a nationally representative sample of adults aged 18 and older.MethodsThe sample includes 6082 individuals from the National Survey of American Life. This study examined whether three different dimensions of social isolation—subjective, interpersonal, and structural—were associated with 12-month and lifetime anxiety disorders (any anxiety disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD), and agoraphobia (AG). Logistic regressions were used to test the associations between the three social isolation variables and the anxiety outcomes.ResultsThis study found that of the three dimensions of social isolation, subjective isolation was most consistently related to both lifetime and 12-month anxiety disorders. Those who were subjectively isolated had increased odds of meeting criteria for any anxiety disorder, PTSD, GAD, PD, and AG over the past 12 months and throughout their lifetimes. Structural isolation was negatively associated with lifetime and 12-month AG.ConclusionsPublic health approaches should include mental health and primary care providers and need to target social isolation, especially subjective isolation, which may be key in preventing anxiety disorders and the worsening of anxiety disorders. Future public health research is needed on how and in what ways the differing dimensions of social isolation impact mental health.

Racial discrimination and 12-month and lifetime anxiety disorders among African American men and women: Findings from the National Survey of American Life

BackgroundThe purpose of this study was to assess the associations between racial discrimination and 12-month and lifetime DSM-IV anxiety disorders among African American men and women. MethodsData was drawn from the African American sample of the National Survey of American Life (N = 3570). Racial discrimination was assessed with the Everyday Discrimination Scale. 12-month and lifetime DSM-IV outcomes were any anxiety disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD), and agoraphobia (AG). Logistic regressions were utilized to assess the relationships between discrimination and anxiety disorders. ResultsThe data indicated that racial discrimination was associated with increased odds for 12-month and lifetime anxiety disorders, AG, and PD and lifetime SAD among men. Regarding 12-month disorders among women, racial discrimination was associated with increased odds for any anxiety disorder, PTSD, SAD, and PD. With respect to lifetime disorders among women, racial discrimination was associated with increased odds for any anxiety disorder, PTSD, GAD, SAD, and PD. LimitationsThe limitations of this study include the utilization of cross-sectional data, self-reported measures, and the exclusion of non-community dwelling individuals. ConclusionsThe current investigation showed that African American men and women are not impacted by racial discrimination in the same ways. These findings suggest that the mechanisms through which discrimination operates among men and women to influence anxiety disorders is potentially a relevant target for interventions to address gender disparities in anxiety disorders.

Incidences of anxiety disorders among active duty service members between 1999 and 2018

PurposeAnxiety disorders can impact the health, performance, and retention of military service members. To inform prevention initiatives and long-term treatment planning, incidence rates across anxiety disorders were evaluated among U.S. active-duty service members over a 20-year period. MethodData were extracted from the Defense Medical Epidemiological Database to examine incidence rates of generalized anxiety disorder (GAD), panic disorder (PD), agoraphobia (AG), social anxiety disorder (SAD), obsessive compulsive disorder (OCD), agoraphobia with panic disorder (AWPD), agoraphobia without history of panic disorder (AWOPD), and unspecified anxiety disorder (UAD) among 151,844 service members between 1999 and 2018 in relation to sex, age, race, marital status, military pay grade, service branch. ResultsIncidence rates of anxiety disorders increased significantly over the 20-year period. Anxiety disorder incidence rates ranged widely from 0.01 to 23.70 (per 1000 service members). There were significant differences in observed versus expected diagnostic rates across all demographic variables examined (p < 0.001). ConclusionIncidence rates varied considerably across the anxiety disorders, with UAD being the highest. These data highlight the importance of health care professionals attending to anxiety disorders, in order to plan for service member needs, develop preventative interventions, address early detection, and deliver treatments to improve combat readiness.

Self-guided digital treatment with virtual reality for panic disorder and agoraphobia: a study protocol for a randomized controlled trial

BackgroundCognitive behavioral therapy is the first-line treatment for patients with panic disorder (PD) and agoraphobia (AG). Yet, many patients remain untreated due to limited treatment resources. Digital self-guided short-term treatment applications may help to overcome this issue. While some therapeutic applications are already supported by health insurance companies, data on their efficacy is limited. The current study investigates the effect of self-guided digital treatment comprising psychoeducation and virtual reality exposure therapy (VRET).MethodsThirty patients diagnosed with PD, AG, or panic disorder with agoraphobia (PDA) will be randomly assigned to either the experimental group (EG) or the control group (CG). Participants of both groups will undergo baseline diagnostics in the first two sessions. The subsequent treatment for the EG consists of a self-guided 6-week phase of application-based psychoeducation, one therapy session preparing for the VRET, and 4 weeks of application-based self-guided VRET. To control for the potential effects of the therapy session with the therapist, the CG will receive relaxation and stress-reduction training instead. All patients will then undergo a closing session which terminates with the post-assessment (~ 10 weeks after baseline assessment) and a follow-up assessment 6 weeks following the closing session. Symptom severity (primary outcome) will be assessed at baseline, interim, post-treatment, and follow-up. Additionally, remission status (secondary outcome) will be obtained at follow-up. Both measures will be compared between the groups.DiscussionThe current study aims at providing insights into the efficacy of short-term treatment applications including psychoeducation and self-guided VRET. If successful, this approach might be a feasible and promising way to ease the burden of PD, AG, and PDA on the public health system and contribute to a faster access to treatment.Trial registrationISRCTN ISRCTN10661970. Prospectively registered on 17 January 2022.

Understanding importance of clinical biomarkers for diagnosis of anxiety disorders using machine learning models.

Anxiety disorders are a group of mental illnesses that cause constant and overwhelming feelings of anxiety and fear. Excessive anxiety can make an individual avoid work, school, family get-togethers, and other social situations that in turn might amplify these symptoms. According to the World Health Organization (WHO), one in thirteen persons globally suffers from anxiety. It is high time to understand the roles of various clinical biomarker measures that can diagnose the types of anxiety disorders. In this study, we apply machine learning (ML) techniques to understand the importance of a set of biomarkers with four types of anxiety disorders—Generalized Anxiety Disorder (GAD), Agoraphobia (AP), Social Anxiety Disorder (SAD) and Panic Disorder (PD). We used several machine learning models and extracted the variable importance contributing to a type of anxiety disorder. The study uses a sample of 11,081 Dutch citizens’ data collected by the Lifelines, Netherlands. The results show that there are significant and low correlations among GAD, AP, PD and SAD and we extracted the variable importance hierarchy of biomarkers with respect to each type of anxiety disorder which will be helpful in designing the experimental setup for clinical trials related to influence of biomarkers on type of anxiety disorder.

Expert opinion in panic disorder: The impact of COVID-19-related fears, protective devices, and lockdown on panic and agoraphobia

During the COVID-19 pandemic a perceived decline of mental well-being was reported both in people with preexisting psychiatric disorders and in people without. However, individuals with different psychiatric vulnerabilities may differ in their responses to COVID-19-related stressors. In this commentary we proposed a few considerations on possible peculiar patterns of pandemic-related behaviors or complaints in patients suffering from panic disorder (PD) with or without agoraphobia (AG). Individuals with PD may be particularly sensitive to multiple pandemic-related aspects involving respiration (e.g., wearing facial masks or COVID-19-related respiratory symptoms) that may worsen or trigger panic symptoms. In case of comorbid AG, an initial improvement of panic–phobic symptoms during the lockdown may have occurred, followed by a subsequent symptom exacerbation when the containment measures became less rigorous, possibly related to lockdown-associated negative reinforcement and impairment in consolidation of fear extinction. Personalized interventions should be offered to the patients to minimize the risk of worsening or relapse.

Association between Uncinate Fasciculus Integrity and Agoraphobia Symptoms in Female Patients with Panic Disorder.

ObjectiveAlthough neural correlates of sub-clinical agoraphobia (AG) symptoms have been previously suggested, only a few studies evaluating structural changes of the brain have been conducted in agoraphobic patients with panic disorder (PD). We investigated and compared white matter (WM) micro-structural alterations between PD patients with AG (PD ＋ AG) and those without AG (PD − AG).MethodsOur study included 56 female PD patients, of which 25 were diagnosed with AG and 31 were diagnosed without AG. Diffusion tensor imaging was performed to investigate micro-structural changes in the WM tracts related to fronto-temporo-occipital areas (uncinate fasciculus, cingulum bundle, inferior longitudinal/fronto-occipital fasciculus, fornix column and body, and fornix/stria terminalis). All participants were subjected to the Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Depression Inventory-II (BDI-II), and Albany Panic and Phobia questionnaires.ResultsThe fractional anisotropy values of the right uncinate fasciculus in PD ＋ AG were significantly lower than that of PD − AG and showed significant correlations with BDI-II and ASI-R total scores. Mean diffusivity and radial diffusivity values of the right uncinate fasciculus were significantly higher in PD ＋ AG as compared to PD − AG.ConclusionOur findings suggest that the uncinate fasciculus may be associated with AG symptoms in PD, possibly through demyelination. Our findings may contribute to the neurobiological evidence regarding the association between AG and WM structural changes in PD.

How does music performance anxiety relate to other anxiety disorders?

Music performance anxiety (MPA) is considered a social anxiety disorder (SAD). Recent conceptualizations, however, challenge existing MPA definitions, distinguishing MPA from SAD. In this study, we aim to provide a systematic analysis of MPA interdependencies to other anxiety disorders through graphical modeling and cluster analysis. Participants were 82 music students ( Mage = 23.5 years, SD = 3.4 years; 69.5% women) with the majority being vocal (30.5%), string (24.4%), or piano (19.5%) students. MPA was measured using the German version of the Kenny Music Performance Anxiety Inventory (K-MPAI). All participants were tested for anxiety-related symptoms using the disorder-specific anxiety measures of the Diagnostic and Statistical Manual of Mental Disorders (5th ed., DSM-5), including agoraphobia (AG), generalized anxiety disorder (GAD), panic disorder (PD), separation anxiety disorder (SEP), specific phobia (SP), SAD, and illness anxiety disorder (ILL). We found no evidence of MPA being primarily connected to SAD, finding GAD acted as a full mediator between MPA and any other anxiety type. Our graphical model remained unchanged considering severe cases of MPA only (K-MPAI ⩾ 105). By means of cluster analysis, we identified two participant sub-groups of differing anxiety profiles. Participants with pathological anxiety consistently showed more severe MPA. Our findings suggest that GAD is the strongest predictor for MPA among all major DSM-5 anxiety types.

Arctic Phobias, Social Fears of Russians, Russophobia

The purpose of this paper is to study the concepts and content of phobias in societies, to understand the differences between them, and to classify people’s fears. In their study, the authors use methods of the Humanities: philosophy, conflictology, historicism; data from sociological surveys of the population. The formation of fears in the life of any society occurs both under the influence of traditional views of people inherent in antiquity, and under the influence of the societal pattern as a whole — culture, civilization, as well as modern transformations related to ecology, climate, development of natural resources, security, Russophobia, fears of coronavirus, racism. The paper considers historical phobias in the Arctic as well. The problems of social phobias in the scientific literature have not yet received such a wide and deep study as in social phobia, Agora phobia, and specific phobias.

Association of Serotonin Transporter Gene (5-HTTLPR/rs25531) Polymorphism with Comorbidities of Panic Disorder

Introduction: Panic disorder (PD) has many comorbidities such as depression, bipolar disorder (BPD), and agoraphobia (AG). PD is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Recently, a tri-allelic serotonin transporter (5-HTTLPR/rs25531) polymorphism was reported to be more sensitive to personality traits compared to the bi-allelic 5-HTTLPR polymorphism. We hypothesized that the 5-HTTLPR/rs25531 polymorphism may lead to a pathological anxious state depending on the presence or absence of a comorbidity in PD. Methods: In this study, we investigated the relationship between comorbidities in PD and tri-allelic 5-HTTLPR polymorphisms. A total of 515 patients with PD (148 males, 367 females) were genotyped, and the Revised NEO Personality Inventory as well as anxiety-related psychological tests were administered. Depression, BPD, and AG were diagnosed as comorbidities. Results: For the tri-allele 5-HTTLPR genotype, a significant interaction effect was found between openness to experience and comorbid depression. Examination of the interaction between AG and the tri-allelic 5-HTTLPR genotype revealed that L’ allele carriers are associated with higher trait anxiety than the S’S’ genotype group in PD without AG. Conclusion: Some anxiety and personality traits can be characterized by the tri-allelic gene effect of 5-HTTLPR. These results suggest that tri-allelic 5-HTTLPR genotypes have genetic effects on the presence of comorbidities of PD.

Agorafobinin eslik ettigi ve etmedigi panik bozukluk ile agorafobinin bilissel ozellikler acisindan karsilastirilmasi

Panic disorder (PD) and Agoraphobia (AG) exhibit both similar and distinct cognitive features. The aim of this study was to compare patients with PD, AG and panic disorder with agoraphobia (PBA) in terms of agoraphobic cognitions, body sensations, catastrophic cognitions, and meta-cognitions. 64 PDA, 52 AG, and 36 PD patients were included in the study. The Structural Clinical Interview for Axis-I (SCID-I), Agoraphobic Cognitions Questionnaire (ACQ), Body Sensations Questionnaire (BSQ), Catastrophic Cognitions Questionnaire (CCQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Meta-Cognitions Questionnaire (MCQ) were administered to the participants. Chi-square test and Kruskal Wallis analysis were used to compare sociodemographic data and scale scores between the three groups. The results showed that ACQ total scores of the PDA group were significantly higher compared to the other groups. There were no statistically significant differences between PD, AG and PDA groups in terms of BSQ, CCQ, and MCQ total scores. BDI total scores of PD group were significantly lower than AG and PDA groups. BAI total scores of PDA group were significantly higher compared to the other groups. Studies on cognitive features among patients with PD, AG or PDA will contribute to cognitive behavioral models and treatment process of these disorders.

EHealth-supported case management for patients with panic disorder or depression in primary care: Study protocol for a cRCT (PREMA)

BackgroundPanic disorder (PD), frequently occurring with agoraphobia (AG), and depression are common mental disorders in primary care and associated with considerable individual and societal costs. Early detection and effective treatment of depression and PD/AG are of major importance. Cognitive behavioural exposure exercises have been shown to be effective in reducing anxiety and depressive symptoms. Practice team-based case management can improve clinical outcomes for patients with chronic diseases in primary care. The present study aims at evaluating the effects and cost-effectiveness of a primary care team-based intervention using behavioural therapy elements and case management supported by eHealth components in patients with PD/AG or depression compared to treatment as usual.Methods/designThis is a two-arm cluster-randomized, controlled trial (cRCT). General practices represent the units of randomisation. General practitioners recruit adult patients with depression and PD ± AG according to the International Classification of Diseases, version 10 (ICD-10). In the intervention group, patients receive cognitive behaviour therapy-oriented psychoeducation and instructions to self-managed exposure exercises in four manual-based appointments with the general practitioner. A trained health care assistant from the practice team delivers case management and is continuously monitoring symptoms and treatment progress in ten protocol-based telephone contacts with patients. Practice teams and patients are supported by eHealth components. In the control group, patients receive usual care from general practitioners. Outcomes are measured at baseline (T0), at follow-up after 6 months (T1), and at follow-up after 12 months (T2). The primary outcome is the mental health status of patients as measured by the Mental Health Index (MHI-5). Effect sizes of 0.2 standard deviation (SD) are regarded as relevant. Assuming a drop-out rate of 20% of practices and patients each, we aim at recruiting 1844 patients in 148 primary care practices. This corresponds to 12.5 patients on average per primary care practice. Secondary outcomes include depression and anxiety-related clinical parameters and health-economic costs.DiscussionIf the intervention is more effective than treatment as usual, the three-component (cognitive behaviour therapy, case-management, eHealth) primary care-based intervention for patients suffering from PD/AG or depression could be a valuable low-threshold option that benefits patients and primary care practice teams.Trial registrationGerman clinical trials register, DRKS00016622. Registered on February 22nd, 2019.

The Bovine Zero Maze: Development of a novel fear test for cattle

Fear tests for cattle are criticized as being 1) designed for animals uncomfortable in open spaces, 2) influenced by previous experience, 3) influenced by context, or 4) subjective. The Elevated Zero Maze (EZM) quantifies fear and anxiety in rodents by exploiting their fear of open spaces and propensity for dark, enclosed spaces. Inversely interpreting the EZM, the Bovine Zero Maze (BZM) was developed to quantify cattle fear and anxiety. Frequency, duration of, and latency to perform steps, escape attempts (EA), direction changes (DC), vocalizations, eliminations, entry into closed/open sections in the BZM were decoded from video recordings. Heifers (n = 14) were re-tested four weeks later. Repeatability was analyzed for both latency to perform and total number of steps, DC, EA, vocalizations, eliminations, standing bouts, and total time spent standing using Pearson correlation coefficients (PROC CORR). Test re-test reliability was evaluated using intraclass correlation coefficients (ICC). Relationships among ADG, EV, and total number and latency to perform steps, EA, DC, vocalizations, eliminations, and standing bouts were analyzed using Pearson correlation coefficients (PROC CORR). Relationships between behavior, minute, and test were analyzed using a Generalized Linear Mixed Model (PROC MIXED) and post hoc analyses were conducted with a Bonferroni adjustment. Total number of steps was the only metric that was repeatable across both tests (R2 = 0.71; P = 0.004) and had moderate reliability (ICC = 0.54). The longer heifers were in the BZM, the frequency of entries into the open and closed sections of the maze and eliminations decreased (all P < 0.01). Heifers vocalized less during the BZM re-test than during the novel BZM test (P = 0.01). Total number of steps made by heifers was impacted by minute (P = 0.006) and heifers tended to take more steps during the second minute of testing (60–120 s) than the seventh minute (P = 0.09). Test × minute affected total number of DC (P < 0.001), however no differences were detected between tests for each minute. Data from this pilot study suggest that behaviors during retesting differ from the novel test and that behaviors change as the test progresses. In addition, the lack of association between behavior in the BZM and EV indicate that the temperament traits evaluated by the BZM may not be related to productivity and may be evaluating different components of temperament than EV.

Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes

Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.

M10 - ALLELIC VARIATION IN GLRB PREDISPOSES TO AGORAPHOBIA BY INCREASING STARTLE RESPONSE AND MODULATING DEFENSIVE REACTIVITY

Background The molecular genetics of Panic Disorder (PD) with and without agoraphobia (AG) are still largely unknown and linkage, candidate gene and Genome-Wide Association Studies (GWAS) of PD/AG were mostly negative or inconsistent due to phenotypic diversity, genetic heterogeneity and underpowered sample sizes. Methods Assuming a dimension from agoraphobic cognitions to full PD/AG, we (1) conducted a GWAS on a dimensional anxiety phenotype (ACQ) in 1,370 healthy volunteers, (2) evaluated the found Glycine Receptor Beta (GLRB) locus in an extended sample of healthy 2,547 volunteers, (3) validated it in a population based sample (N=3,845) with another measure of AG symptoms [SCL-90], (4) assessed it relevance for the categorical phenotype PD/AG in 506 case-control pairs, (5) measured mRNA expression in vitro and post mortem (N=76), (6) examined the effect of GLRB risk polymorphisms on startle habituation, potentiation, and generalization (N=101 healthy volunteers), complemented by a behavior avoidance test (N=115 PD/AG patients) and fMRI analysis (N=76 healthy volunteers; N=86 patients with PD/AG) of fear network and general sensory activation and (7) performed analyses of agoraphobic behavior in partial Glrb knock-out mice. Results (1) GWAS on the ACQ phenotype resulted in two genome-wide significant (p Discussion Present results provide translational evidence that genetic variation within the GLRB gene predisposes to agoraphobia by modulation of the intermediate phenotype startle reflex. GWAS on the ACQ phenotype provided genome-wide significance for the GLRB locus, that we hence confirmed by validation in an independent cohort and by association with PD/AG. Results from behavioral studies in Glrb knockdown mice further supported that this gene is involved in agoraphobic behavior. As GLRB mutations are causal in hyperekpleksia, we probed whether the startle reflex as an intermediate phenotype is modulated by genetic variation in GLRB and demonstrated that risk alleles go along with impaired startle habituation and increased startle potentiation and generalization. Further fMRI analysis showed that GLRB risk alleles are associated with increased fear-induced activation of the fear network, but also with a general fear-independent activation of the sensory network. Our data propose how a genetic risk factor might via an intermediate neurobiological phenotype lead to development of a mental disorder, thus opening perspectives for novel therapeutic approaches.

The spouse of the phobic patient.

1. Fifty consecutive married patients with symptoms of phobic anxiety mostly agoraphobic in type and treated at the Midland Nerve Hospital were asked to complete the Cornell Medical Index and Caine9s Hysteroid-Obsessoid Questionnaire. Their spouses were asked to do likewise. There was a response rate of 96 per cent (31 women and 17 men). 2. While the patients9 mean scores were high on the C.M.I., the spouses obtained low scores, below levels previously accepted as being indicative of neurosis. 3. No evidence was found of increasing tendency towards neuroticism in the spouse with increasing length of marriage. There was, however, a significant correlation of neuroticism scores between the couples married less than ten years. 4. Neither patients nor spouses showed predominantly obsessoid characters, and by using the adaptation of the H.O.Q. they were shown to rate each other as reliably as a non-neurotic control population. 5. No correlations were found of hysteroid or obsessoid features between the spouses, neither was there any association of these features with the degree of neuroticism. 6. These findings are discussed in relation to the `assortative mating9 and `interaction9 hypotheses.

Results of systmematic desensitization with phobias re-examined.

Controlled studies of desensitization with phobic patients are re-examined. There is a consistent trend for half the subjects treated with desensitization to show marked improvement, whereas only a quarter of control subjects treated with other therapies do so. This trend could rarely result in a statistically significant difference with the number of patients used in these studies. The danger of ignoring valuable therapeutic effects because they do not reach statistical significance, or of over-interpreting findings which do, is again stressed. The evidence from these studies and from those with phobic students suggests that at follow-up patients with agoraphobia show a better response to behaviour therapy than do those with more specific phobias.

Age-related characteristics of outpatients with anxiety disorders: the Leiden routine outcome monitoring study

Objective: It has been hypothesised that clinically important age-related differences between adults with anxiety disorders exist; this study aims to elucidate these differences.Methods: We analysed data from 1950 outpatients diagnosed with DSM-IV-TR anxiety disorders treated at a Dutch hospital or affiliated mental healthcare centres. Three age-groups (young- (18–25; n = 435), mid- (26–40; n = 788) and older adult (41–65; n = 727)) were compared with regard to social demographic characteristics, diagnostic characteristics, anxiety symptom profile, general psychiatric symptom profile and generic health status, in addition, linear analyses were carried out with age as a continuous variable.Results: Average age was 36.48 years (SD 11.71), 62.8% were female. Significant associations with age emerged for gender, employment, education level, living situation, observed depression, agoraphobia (AP), social phobia, aches and pains, inner tension, sleep, interpersonal sensitivity, observed hostility, physical functioning, role limitations due to physical problems, vitality and bodily pain in categorical and continuous analyses. Self reported hostility was only significant in group-wise comparisons; role limitations due to emotional problems were only significant in linear analyses (all at p < .001).Conclusions: This study identified clinically relevant differences between younger and older adult outpatients with anxiety disorders. Clinicians should take these findings into account, as they may support treatment.

The long and complex road in the search for treatment for mental disorders: An analysis of the process in five groups of patients

Seeking treatment for mental-health problems is a complex process, with different underlying motives in each stage. However, the entire process and these motives have hardly been investigated. This study aims to analyze the different stages of the help-seeking process and their underlying motives in five groups of patients with different mental disorders.In all, 156 patients seeking treatment in outpatient mental health clinics were individually interviewed: 71 had Obsessive-Compulsive Disorder (OCD), 21 had Agoraphobia (AGO), 18 had Major Depressive Disorder (MDD), 20 had Anorexia Nervosa (AN), and 22 had Cocaine Dependence (COC). The AGO and MDD patients delayed significantly less time in recognizing their mental health symptoms. Moreover, MDD patients disclosed their symptoms and searched for professional help faster than the other groups. The most relevant variables in the recognition of disorders were the loss of control over the symptoms, the interference produced by these symptoms, and their negative impact on the person's emotional state. The most frequent barriers to seeking treatment were related to minimizing the symptoms and fear of stigma. Finally, the most important motivator for seeking treatment was the awareness that minimizing the symptoms did not help to reduce them, lessen their interference, or make them disappear.