Search

Individual responses to behavioral treatment of anxiety disorders vary considerably, which requires a better understanding of underlying processes. In this study, we examined the violation and change of threat beliefs during exposure. From 8,484 standardized exposure records of 605 patients with different anxiety disorders, learning indicators were derived: expectancy violation as mismatch between threat expectancy before exposure and threat occurrence, expectancy change as difference between original and adjusted expectancy after exposure, and prediction-error learning rate as extent to which expectancy violation transferred into change. Throughout sessions, high threat expectancy but low occurrence and adjusted expectancy indicated successful violation and change of threat beliefs by exposure. Expectancy violation, change, and learning rate substantially varied between patients. Not expectancy violation itself, but higher learning rate and expectancy change predicted better treatment outcome. Successful exposure thus requires expectancy violation to induce actual expectancy change, supporting learning from prediction error as transdiagnostic mechanism underlying successful exposure therapy.

Objective: The cognitive and motivational impairments observed in psychotic disorders may reflect early developmental alterations that, when combined with later environmental exposures, may drive the onset of positive psychotic symptoms. The epidemiological predictions of this model were tested. Method: A longitudinal prospective cohort study (the Early Developmental Stages of Psychopathology Study) was conducted with a representative general population sample of adolescents and young adults from Munich (N=3,021), who were 14-24 years of age at baseline. Sociodemographic factors, environmental exposures, and measures of psychopathology and associated clinical relevance were assessed across three waves, covering a period of up to 10 years, by clinical psychologists using the Composite International Diagnostic Interview. Results: Both negative/disorganized and positive psychotic symptoms were frequent (5-year cumulative prevalence rates of around 12%) and occurred in combination more often than predicted by chance. Negative/disorganized symptoms revealed a pattern of sociodemographic associations indicative of developmental impairment, whereas the positive symptoms were associated with environmental exposures such as trauma, cannabis use, and urbanicity. Negative/disorganized symptoms predicted positive symptoms over time, and co-occurrence of positive and negative/disorganized symptoms was predictive of clinical relevance in terms of secondary functional impairment and help-seeking behavior. Conclusions: The results suggest that the negative/disorganized features associated with psychotic disorder are distributed at the population level and drive the ontogenesis of positive psychotic experiences after exposure to environmental risks, increasing the likelihood of impairment and need for care.

Objective: This study evaluated the associations between suicidal ideation and suicide attempts in mothers and various aspects of suicidality in their offspring in a representative community sample. Method: Baseline and 4-year follow-up data were used from the Early Developmental Stages of Psychopathology study, a prospective, longitudinal community study of adolescents and young adults. Results are based on 933 adolescents who completed follow-up and for whom direct diagnostic information for the biological mother was available. Suicidal ideation and suicide attempts were assessed in adolescents and mothers with the Munich-Composite International Diagnostic Interview. Results: Compared to offspring of mothers without suicidality, offspring of mothers reporting suicide attempts showed a remarkably higher risk for suicidal thoughts and suicide attempts and a tendency toward suicide attempts at an earlier age. Associations were comparable for male and female offspring. Transmission of maternal suicidality was roughly stable with control for maternal comorbid psychopathology. Conclusions: The offspring of mothers with suicide attempts are at a markedly increased risk for suicidality themselves and tend to manifest suicide attempts earlier than offspring of mothers without suicidality. Suicidality seems to run in families, independent of depression and other psychopathology.

Objective: Few studies have focused on the natural course of posttraumatic stress disorder (PTSD) and its determinants in samples of the general population. The authors examined determinants of remission and chronicity of PTSD and associations with other disorders in a prospective community sample. Method: The data were drawn from a prospective, longitudinal epidemiological study of adolescents and young adults (age 14-24 years) in Munich, Germany (N=2,548). The course of PTSD from baseline to follow-up 34-50 months later was studied in 125 respondents with DSM-IV PTSD or subthreshold PTSD at baseline. Results: Although 52% of the PTSD cases remitted during the follow-up period, 48% showed no significant remission of PTSD symptoms. Respondents with a chronic course were more likely to experience new traumatic event(s) during follow-up (odds ratio-5.21, 95% confidence interval [CI]=1.95-13.92), to have higher rates of avoidant symptoms at baseline (odds ratio=10.16, 95% CI=1.73-59.51), and to report more help seeking (odds ratio=5.50, 95% CI=1.04-29.05), compared to respondents with remission. Rates of incident somatoform disorder (odds ratio=4.24, 95% CI=1.60-11.19) and other anxiety disorders (odds ratio=4.07, 95% CI=1.15-14.37) were also significantly associated with a chronic course. Conclusions: PTSD is often a persistent and chronic disorder. Specific symptom clusters--especially avoidant symptoms--might be associated with the course of PTSD. In addition, the occurrence of new traumatic events differentiates PTSD cases with a chronic course from those with remission.

Objective: The purpose of the study was to examine the relationship between panic attack and the onset of specific mental disorders and severe psychopathology across the diagnostic spectrum among adolescents and young adults. Method: Data were drawn from the Early Developmental Stages of Psychopathology Study (N = 3,021), a 5-year prospective longitudinal study of psychopathology among youths ages 14-24 years at baseline in the community. Multiple logistic regression analyses were used to examine the associations between panic attacks at baseline, comorbid mental disorders in adolescence, and the risk of mental disorders across the diagnostic spectrum at follow-up. Results: The large majority of subjects with panic attacks at baseline developed at least one DSM-IV mental disorder at baseline (89.4% versus 52.8% of subjects without panic attacks). Subjects with panic attacks at baseline had significantly higher baseline levels of any anxiety disorder (54.6% versus 25.0%), any mood disorder (42.7% versus 15.5%), and any substance use disorder (60.4% versus 27.5%), compared to subjects without panic at tacks at baseline. Preexisting panic attacks significantly increased the risk of onset of any anxiety disorder, social phobia, specific phobia, generalized anxiety disorder, any substance use disorder, and any alcohol use disorder at follow-up in young adulthood, and these associations persisted after adjustment for all comorbid mental disorders assessed at baseline. More than one-third (37.6% versus 9.8%) of the subjects with panic attack at baseline met the criteria for at least three mental disorders at follow-up during young adulthood. Conclusions: Panic attacks are associated with significantly increased odds of mental disorders across the diagnostic spectrum among young persons and appear to be a risk factor for the onset of specific anxiety and substance use disorders. Investigation of key family, environmental, and individual factors associated with the onset of panic attacks, especially in youth, may be an important direction for future research.

Objective: Generalized anxiety disorder might be better conceptualized as a prodrome, residual, or severity marker of major depression or other comorbid disorders than as an independent diagnosis. The authors questioned whether generalized anxiety disorder itself is associated with role impairment or whether the impairment of patients with generalized anxiety disorder is due to depression or other comorbid disorders. Method: The authors assessed data from the National Comorbidity Survey and the Midlife Development in the United States Survey for generalized anxiety disorder and major depression at 12 months by using the DSM-III-R criteria with modified versions of the Composite International Diagnostic Interview. Results: The prevalences of generalized anxiety disorder at 12 months were 3.1% and 3.3%, respectively, in the National Comorbidity Survey and the Midlife Development in the United States Survey; the prevalences of major depression at 12 months were 10.3% and 14.1%. The majority of respondents with generalized anxiety disorder at 12 months in the National Comorbidity Survey (58.1%) and the Midlife Development in the United States Survey (69.7%) also met the criteria for major depression at 12 months. Comparisons of respondents with one versus neither disorder showed that both disorders had statistically significant independent associations with impairment that were roughly equal in magnitude. These associations could not be explained by the other comorbid DSM-III-R disorders or by sociodemographic variables. Conclusions: These results show that a substantial amount of generalized anxiety disorder occurs independently of major depression and that the role impairment of generalized anxiety disorder is comparable to that of major depression.

Late-life depression has multiple, heterogeneous clinical presentations. The aim of the study was to identify higher-order homogeneous clinical features (symptom complexes), while accounting for their potential causal interactions within the network approach to psychopathology. We analyzed cross-sectional data from community-dwelling adults aged 65–85 years recruited by the European MentDis_ICF65+ study (n= 2623, mean age 74, 49% females). The severity of 33 depressive symptoms was derived from the age-adapted Composite International Diagnostic Interview. Symptom complexes were identified using multiple detection algorithms for symptom networks, and their fit to data was assessed with latent network models (LNMs) in exploratory and confirmatory analyses. Sensitivity analyses included the Partial Correlation Likelihood Test (PCLT) to investigate the data-generating structure. Depressive symptoms were organized by the Walktrap algorithm into eight symptom complexes, namely sadness/hopelessness, anhedonia/lack of energy, anxiety/irritability, self-reproach, disturbed sleep, agitation/increased appetite, concentration/decision making, and thoughts of death. An LNM adequately fit the distribution of individual symptoms’ data in the population. The model suggested the presence of reciprocal interactions between the symptom complexes of sadness and anxiety, concentration and self-reproach and between self-reproach and thoughts of death. Results of the PCLT confirmed that symptom complex data were more likely generated by a network, rather than a latent-variable structure. In conclusion, late-life depressive symptoms are organized into eight interacting symptom complexes. Identification of the symptom complexes of late-life depression may streamline clinical assessment, provide targets for personalization of treatment, and aid the search for biomarkers and for predictors of outcomes of late-life depression.

Parkinson’s disease (PD) is associated with various non-motor symptoms, including cognitive deterioration. Here, we used data from the DEMPARK/LANDSCAPE cohort to describe the association between progression of cognitive profiles and the PD motor phenotypes: postural instability and gait disorder (PIGD), tremor-dominant (TR-D), and not-determined (ND). Demographic, clinical, and neuropsychological six-year longitudinal data of 711 PD-patients were included (age: M = 67.57; 67.4% males). We computed z-transformed composite scores for a prioridefined cognitive domains. Analyses were controlled for age, gender, education, and disease duration. To minimize missing data and drop-outs, three-year follow-up data of 442 PD-patients was assessed with regard to the specific role of motor phenotype on cognitive decline using linear mixed modelling (age: M = 66.10; 68.6% males). Our study showed that in the course of the disease motor symptoms increased while MMSE and PANDA remained stable in all subgroups. After three-year follow-up, significant decline of overall cognitive performance for PIGD-patients were present and we found differences for motor phenotypes in attention (β= –0.08, SE = 0.003, p <  0.006) and memory functions showing that PIGD-patients deteriorate per months by –0.006 compared to the ND-group (SE = 0.003, p = 0.046). Furthermore, PIGD-patients experienced more often difficulties in daily living. Over a period of three years, we identified distinct neuropsychological progression patterns with respect to different PD motor phenotypes, with early executive deficits yielding to a more amnestic profile in the later course. Here, in particular PIGD-patients worsened over time compared to TR-D and ND-patients, highlighting the greater risk of dementia for this motor phenotype.

Objective: The goal of this study was to determine the prevalence of DSM-III-R panic disorder and to describe its correlates. Method: The study was part of the National Comorbidity Survey, the first psychiatric epidemiologic survey of the entire U.S. population and the first to use DSM-III-R criteria for diagnosis. The 8,098 survey respondents, aged 15-54 years, were given the Composite International Diagnostic Interview. For this report, the data on panic were analyzed, and from them the prevalence of panic disorder and related experiences in the U.S. population was estimated. Results: About 15% of the survey respondents reported the occurrence of a panic attack over their lifetimes, and 3% reported a panic attack in the preceding month. About 1% met the DSM-III-R criteria for panic disorder in the month preceding the interview. Panic attacks and panic disorder had a bimodal age distribution and were associated with female sex and lower educational achievement. Fifty percent of the survey respondents with panic disorder reported no symptoms of agoraphobia. The pattern of prevalence of correlated sociodemographic factors was similar for persons with panic attacks, panic disorder, and panic disorder with agoraphobia. Conclusions: There appears to be no obvious threshold for the diagnosis of panic disorder. Panic disorder and agoraphobia, although highly comorbid, also occur separately.

Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p< 1 × 10−4were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10  × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p= 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

The residential building stock holds a large energy efficiency improvement potential related to energy upgrading of the building envelope. Details about the heterogeneity of the building stock are paramount to perform a proper assessment of attractive energy efficiency improvements for end-users. Based on a sample of buildings, the study develops methods to identify potentials for heterogeneous building-tailored energy efficiency improvements, to reduce heat consumption, and evaluates their cost-effectiveness in the framework of a district heating area in Denmark. The study accounts for rebound effects and develops both technical (gross) and more realistic (net) potentials, allowing a more accurate analysis of attractive energy efficiency improvements. The analysis is novel as the underlying model relies on building characteristics rather than synthetic archetypes, which can lead to loss of diversity (e.g. in variation of costs and potentials) and thereby discarding cost-effective potentials. The analysis also investigates the sensitivity of the results to assumptions about the discount rate and focuses on the effect of exposing the end-user to different district heating tariffs and the consequent total cost-effective investments. The outcomes show that cost-effective energy efficiency improvements vary considerably, in size and type, among the heterogeneous building stock considered. In regard to district heating tariffs, when all the cost components are variable, the total cost-effective potential increases considerably, with specific energy efficiency improvements distributed differently among building categories, and with the cost components providing different incentives to invest. Heterogeneity, and different tariff policies, thus does matter, when evaluating economically attractive investments in energy efficiency improvements for buildings.

Depression is widely acknowledged to be a heterogeneous entity, and the need to further characterize the individual patient who has received this diagnosis in order to personalize the management plan has been repeatedly emphasized. However, the research evidence that should guide this personalization is at present fragmentary, and the selection of treatment is usually based on the clinician's and/or the patient's preference and on safety issues, in a trial‐and‐error fashion, paying little attention to the particular features of the specific case. This may be one of the reasons why the majority of patients with a diagnosis of depression do not achieve remission with the first treatment they receive. The predominant pessimism about the actual feasibility of the personalization of treatment of depression in routine clinical practice has recently been tempered by some secondary analyses of databases from clinical trials, using approaches such as individual patient data meta‐analysis and machine learning, which indicate that some variables may indeed contribute to the identification of patients who are likely to respond differently to various antidepressant drugs or to antidepressant medication vs. specific psychotherapies. The need to develop decision support tools guiding the personalization of treatment of depression has been recently reaffirmed, and the point made that these tools should be developed through large observational studies using a comprehensive battery of self‐report and clinical measures. The present paper aims to describe systematically the salient domains that should be considered in this effort to personalize depression treatment. For each domain, the available research evidence is summarized, and the relevant assessment instruments are reviewed, with special attention to their suitability for use in routine clinical practice, also in view of their possible inclusion in the above‐mentioned comprehensive battery of measures. The main unmet needs that research should address in this area are emphasized. Where the available evidence allows providing the clinician with specific advice that can already be used today to make the management of depression more personalized, this advice is highlighted. Indeed, some sections of the paper, such as those on neurocognition and on physical comorbidities, indicate that the modern management of depression is becoming increasingly complex, with several components other than simply the choice of an antidepressant and/or a psychotherapy, some of which can already be reliably personalized.

d-cycloserine (DCS), a partial NMDA-receptor agonist, seems to be a promising enhancer for exposure therapy in anxiety disorders. It has been tested successfully in animal models of fear extinction, where DCS enhanced extinction learning. Applied in clinical studies, results of DCS-augmented exposure therapy remain ambiguous, calling for a deeper understanding of the underlying mechanisms of DCS and its exact effect on extinction learning and return of fear (ROF) in humans. In the present study, we investigated the effect of DCS-augmented extinction learning on behavioral, psychophysiological, and neural indices of ROF during a 24-h delayed recall test. Thirty-seven participants entered a randomized, placebo-controlled, double-blind, 3-day fear conditioning and delayed extinction fMRI design. One hour before extinction training, participants received an oral dose of 50 mg of DCS or a placebo. Behavioral arousal ratings revealed a generalized ROF during extinction recall in the placebo but not DCS group. Furthermore, participants receiving DCS compared to placebo showed attenuated differential BOLD responses in left posterior hippocampus and amygdala from extinction learning to extinction recall, due to increased hippocampal recruitment in placebo and trendwise decreased amygdala responding in DCS subjects. Our finding that DCS reduces ROF in arousal ratings and neural structures subserving defensive reactions support a role for NMDA receptors in extinction memory consolidation and encourage further translational research.

Aims.Although associations between various somatic diseases and depression are well established, findings concerning the role of gender and anxiety disorders for these associations remain fragmented and partly inconsistent. Combining data from three large-scaled epidemiological studies in primary care, we aim to investigate interactions of somatic diseases with gender and anxiety disorders in the association with depression.Methods.Self-reported depression according to the International Classification of Diseases, Tenth Edition (ICD-10) was assessed in n= 83 737 patients from three independent studies [DETECT (Diabetes Cardiovascular Risk Evaluation: Targets and Essential Data for Commitment of Treatment), Depression-2000 and Generalized Anxiety and Depression in Primary Care (GAD-P)] using the Depression Screening Questionnaire (DSQ). Diagnoses of depression, anxiety disorders and somatic diseases were obtained from treating physicians via standardised clinical appraisal forms.Results.In logistic regressions, adjusted for gender, age group and study, each somatic disease except for arterial hypertension and endocrine diseases was associated with self-reported depression (odds ratio, OR 1.3–2.6) and each somatic disease was associated with physician-diagnosed depression (OR 1.1–2.4). Most of these associations remained significant after additional adjustment for anxiety disorders and other somatic diseases. The associations with depression increased with a higher number of somatic diseases. Cardiovascular diseases (OR 0.8), diabetes mellitus (OR 0.8) and neurological diseases (OR 0.8) interacted with gender in the association with self-reported depression, while endocrine diseases (OR 0.8) interacted with gender in the association with physician-diagnosed depression. That is, the associations between respective somatic diseases and depression were less pronounced in females v.males. Moreover, cardiovascular diseases (OR 0.7), arterial hypertension (OR 0.8), gastrointestinal diseases (OR 0.7) and neurological diseases (OR 0.6) interacted with anxiety disorders in the association with self-reported depression, and each somatic disease interacted with anxiety disorders in the association with physician-diagnosed depression (OR 0.6–0.8). That is, the associations between respective somatic diseases and depression were less pronounced in patients with v.without anxiety disorders; arterial hypertension was negatively associated with self-reported depression only in patients with anxiety disorders, but not in patients without anxiety disorders.Conclusions.A range of somatic diseases as well as anxiety disorders are linked to depression – and especially patients with co-/multi-morbidity are affected. However, interactions with gender and anxiety disorders are noteworthy and of relevance to potentially improve recognition and treatment of depression by physicians. Somatic diseases are associated more strongly with depression in males v.females as well as in patients without v.with anxiety disorders, primarily because women and patients with anxiety disorders per se are characterised by considerably increased depression prevalence that only marginally changes in the presence of somatic comorbidity.

ObjectivesParkinson’s disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function.MethodsDemographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration.ResultsCompared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungspru¨fungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314).ConclusionThe three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.

The role of behavioral inhibition (BI), parental rearing, and adverse life events in the development of obsessive–compulsive disorder (OCD) is unresolved. We prospectively examined whether BI and perceived parental rearing predicted the subsequent first onset of OCD and whether BI moderated the association between perceived parental rearing/adverse life events and the first onset of OCD. Data come from a prospective-longitudinal study among community adolescents and young adults (aged 14–24) who were followed up over 10 years (N = 2210). OCD and adverse life events were assessed with the DSM-IV/M-CIDI. BI and parental rearing were assessed by self-report. In adjusted logistic regressions, BI (risk ratio, RR = 8.8,95% confidence interval, CI,[3.3,23.2]), both the social (RR = 2.6,95%CI[1.04,6.3]) and nonsocial fear (RR = 4.5,95%CI[2.3,8.6]) components, and paternal rejection (RR = 3.9,95%CI[1.6,9.7]) predicted OCD. Social BI moderated the association of adverse life event (RR = 11.98,95%CI[1.8,82.1]) and paternal overprotection (RR = 5.5,95%CI[2.1,14.8]) with OCD. Nonsocial fear BI moderated the association between paternal emotional warmth (RR = 0.37,95%CI[0.1,0.99]) and OCD. BI and paternal rejection were associated with an increased risk of first onset of OCD. Individuals with high social BI who experienced paternal overprotection or any adverse life events may profit from early targeted prevention. Emotional warmth may buffer the association between nonsocial fear BI and OCD.

Supplemental Digital Content is available in the text.

Rnd3 and p190RhoGAP regulate RhoA activity downstream of TGF-b and matrix rigidity in idiopathic pulmonary fibrosis fibroblasts. Profibrotic agents TGF-b and matrix rigidity enhance RhoA activity through suppression of Rnd3 and a decrease in p190 activity. Antifibrotic drugs nintedanib and pirfenidone both enhance Rnd3 levels, thereby increasing p190 activity and decreasing RhoA activity.

•The prevalence rate of anxiety disorders is higher in elderly, when assessed with a specific age-associated interview, in contrast to previously used adult age interviews.•The chance to have an anxiety disorder drops by 40% after the age of 75 years, and by 47% after the age of 80 years.•Women show at least twice as my anxiety disorders than men, independently of their age.•The anxiety-depression association is limited to panic disorder and specific phobia in old age, contrary to other anxiety disorders.•We found no evidence of an association between anxiety disorder and alcohol abuse/dependency in old age.

AbstractThe aim of this paper is to demonstrate the application of a reflective diffraction grating and a MWIR thermographic camera for gas identification and its concentration estimation. For this purpose a special setup was built using an infrared camera, a diffraction grating, a black body as infrared source and an air-tight tube that was filled with different mixtures of carbon monoxide, carbon dioxide and nitrogen. Both ends of the tube were closed using infrared transmission windows, allowing the radiation from the blackbody to pass through the tube and be measured with the camera. After spectral calibration of the setup, it was used for the detection, identification and concentration measurements of different gas mixtures.

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRBgene (rs78726293, P=3.3 × 10−8; rs191260602, P=3.9 × 10−8). We followed up on this finding in a larger dimensional ACQ sample (N=2547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3845) and a case–control sample with the categorical phenotype PD/AG (Ncombined=1012) obtaining highly significant P-values also for GLRBsingle-nucleotide variants rs17035816 (P=3.8 × 10−4) and rs7688285 (P=7.6 × 10−5). GLRBgene expression was found to be modulated by rs7688285 in brain tissue, as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network, as well as general sensory activation by GLRBrisk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrbknockout mice demonstrated an agoraphobic phenotype. In conjunction with the clinical observation that rare coding GLRBgene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, although functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.

The continuing growth of the population with end-stage renal disease (ESRD) in the past two decades has been recognized as a global health burden. In 2002, a definition of chronic kidney disease (CKD) was introduced and different categories of CKD have been reported in the general population. In this study, we examined the prevalence of CKD in primary health care in Germany. From 2004 to 2007 the prevalence of CKD was estimated in the Diabetes Cardiovascular Risk-Evaluation Targets and Essential Data for Commitment of Treatment (DETECT) study using the Simplified Modification of Diet in Renal Disease (MDRD) and the CKD Epidemiology Collaboration (CKD-EPI) equations. A sample of 4,080 subjects were analysed with detailed laboratory and comorbidity assessment from 851 primary care centres across Germany. The prevalence of CKD (≤60 ml/min/1.73 m2) was 27.9 % estimated by CKD-EPI equation (MDRD eGFR 36.1 %) and the prevalence of CKD increased with age and during follow-up. The overall decline in eGFR per year was −1.83 ml/min/year (CKD-EPI). Women have shown a higher decline in eGFR than men. The prevalence of CKD was highest in coronary artery disease patients, followed by diabetes mellitus and arterial hypertension. Individuals with diabetes mellitus have shown the highest progress developing CKD. In this representative sample of patients seeking medical advice in primary care, the prevalence of impaired kidney function was almost one third. Given the therapeutic implications, our results call for focused measures to increase the awareness of CKD in primary care.

Aims.Provision and need for mental health services among military personnel are a major concern across nations. Two recent comparisons suggest higher rates of mental disorders in US and UK military personnel compared with civilians. However, these findings may not apply to other nations. Previous studies have focused on the overall effects of military service rather than the separate effects of military service and deployment. This study compared German military personnel with and without a history of deployment to sociodemographically matched civilians regarding prevalence and severity of 12-month DSM-IV mental disorders.Method.1439 deployed soldiers (DS), 779 never deployed soldiers (NS) and 1023 civilians were assessed with an adapted version of the Munich Composite International Diagnostic interview across the same timeframe. Data were weighted using propensity score methodology to assure comparability of the three samples.Results.Compared with adjusted civilians, the prevalence of any 12-month disorder was lower in NS (OR: 0.7, 95% CI: 0.5–0.99) and did not differ in DS. Significant differences between military personnel and civilians regarding prevalence and severity of individual diagnoses were only apparent for alcohol (DS: OR: 0.3, 95% CI: 0.1–0.6; NS: OR: 0.2, 95% CI: 0.1–0.6) and nicotine dependence (DS: OR: 0.5, 95% CI: 0.3–0.6; NS: OR: 0.5, 95% CI: 0.3–0.7) with lower values in both military samples. Elevated rates of panic/agoraphobia (OR: 2.7, 95% CI: 1.4–5.3) and posttraumatic stress disorder (OR: 3.2, 95% CI: 1.3–8.0) were observed in DS with high combat exposure compared with civilians.Conclusions.Rates and severity of mental disorders in the German military are comparable with civilians for internalising and lower for substance use disorders. A higher risk of some disorders is reduced to DS with high combat exposure. This finding has implications for mental health service provision and the need for targeted interventions. Differences to previous US and UK studies that suggest an overall higher prevalence in military personnel might result from divergent study methods, deployment characteristics, military structures and occupational factors. Some of these factors might yield valuable targets to improve military mental health.

Abstract.Aim:To examine in subjects aged > = 55 years the association between preceding mental disorders (MD), gender, and partnership and past 12-month problematic alcohol use (PAU; daily drinking, binge drinking, drinking in excess of health guidelines). Methods:Based on a subsample aged > = 55 years of the nationally representative DEGS1-MH study (n = 2045/4483), we examined the association of single retrospectively assessed MD, gender, partnership, and latent risk profiles with subsequent 12-month PAU-outcomes using logistic regression and latent class analysis (LCA) with auxiliary variables. Results:Younger and male subjects, subjects with one vs. no MD, and those living with a partner had a higher PAU risk. In a four-class LCA-solution, two normative classes (45.5 %, 44.9 %) with low MD and high male respectively female gender probabilities, a “male-substance use disorder-depression”- (4.0 %) and a “female-internalizing”-class (5.5 %) were found. The male-normative and the “male-substance use disorder”-class were associated with a higher PAU risk, including drinking in excess of different health guidelines (p < 0.05). Conclusions:The large group of male individuals with low MD probabilities may be relevant for predicting critical alcohol use behaviors in middle and older adulthood and may profit from low-threshold general preventive measures, while the smaller male group with elevated lifetime substance use disorder and depression risk may profit from targeted clinical interventions.

Living in line with one's values is believed to be beneficial for a person's well-being. Working with values in the therapeutic context often reveals that individuals do no live congruent with their chosen values. This study aimed to investigate how patients’ valued behaviors change during an Acceptance and Commitment Therapy (ACT) and how these changes are associated with functioning. Further, this study aimed to examine whether valued behaviors changed depending on pre-treatment levels of symptomatology.

Patients with Alzheimer's disease (AD) need early caregiver support. Caregivers often have poor health, but usually do not have time to seek medical advice for their own conditions. Patients' physicians, who are frequently the sole medical practitioner caregivers contact regularly, have an important function in recognizing family caregivers' burdens. The current study investigated to what extent medical practitioners recognized family caregivers' problems. In a two-staged survey in neurology outpatient care, caregivers of patients with mild or moderate AD were enrolled and assessed by physicians regarding their physical and mental burden, as well as need for help and advice about AD. Subsequently, caregivers' mental health was evaluated in a comprehensive diagnostic interview by blinded psychologists. Overall, 73.7% of caregivers had at least one somatic condition and 43.7% had clinically relevant depressive symptoms (of these, 37.5% met criteria for major depression). The findings suggest that the burden of a substantial proportion of affected family caregivers is overlooked.[Res Gerontol Nurs. 2016; 9(4):167–174.]

Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic–pituitary–adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1as a risk factor for panic disorder (PD). Allelic variation of CRHR1was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1in PD and clarify the mechanisms by which genetic variation in CRHR1is linked to this disorder.

Aims.To prospectively examine whether negative life events (NLE) and low perceived coping efficacy (CE) increase the risk for the onset of various forms of psychopathology and low CE mediates the associations between NLE and incident mental disorders.Methods.A representative community sample of adolescents and young adults (N =3017, aged 14–24 at baseline) was prospectively followed up in up to three assessment waves over 10 years. Anxiety, depressive and substance use disorders were assessed at each wave using the DSM-IV/M-CIDI. NLE and CE were assessed at baseline with the Munich Event List and the Scale for Self-Control and Coping Skills. Associations (odds ratios, OR) of NLE and CE at baseline with incident mental disorders at follow-up were estimated using logistic regressions adjusted for sex and age.Results.NLE at baseline predicted the onset of any disorder, any anxiety disorder, panic disorder, agoraphobia, generalised anxiety disorder, any depression, major depressive episodes, dysthymia, any substance use disorder, nicotine dependence and abuse/dependence of illicit drugs at follow-up (OR 1.02–1.09 per one NLE more). When adjusting for any other lifetime disorder prior to baseline, merely the associations of NLE with any anxiety disorder, any depression, major depressive episodes, dysthymia and any substance use disorder remained significant (OR 1.02–1.07). Low CE at baseline predicted the onset of any disorder, any anxiety disorder, agoraphobia, generalised anxiety disorder, any depression, major depressive episodes, dysthymia, any substance use disorder, alcohol abuse/dependence, nicotine dependence and abuse/dependence of illicit drugs at follow-up (OR 1.16–1.72 per standard deviation). When adjusting for any other lifetime disorder prior to baseline, only the associations of low CE with any depression, major depressive episodes, dysthymia, any substance use disorder, alcohol abuse/dependence, nicotine dependence and abuse/dependence of illicit drugs remained significant (OR 1.15–1.64). Low CE explained 9.46, 13.39, 12.65 and 17.31% of the associations between NLE and any disorder, any depression, major depressive episodes and dysthymia, respectively. When adjusting for any other lifetime disorder prior to baseline, the reductions in associations for any depression (9.77%) and major depressive episodes (9.40%) remained significant, while the reduction in association for dysthymia was attenuated to non-significance (p-value > 0.05).Conclusions.Our findings suggest that NLE and low perceived CE elevate the risk for various incident mental disorders and that low CE partially mediates the association between NLE and incident depression. Subjects with NLE might thus profit from targeted early interventions strengthening CE to prevent the onset of depression.

Zusammenfassung.Zielsetzung:Erfassung der Prävalenz und Behandlungsraten von Störungen durch Alkoholkonsum (SdA) in der primärärztlichen Versorgung in Deutschland. Methodik:Die Stichprobe umfasst 1356 von 2304 diagnostizierten Patienten mit SdA aus 76 von 207 zufällig gezogenen Hausarztpraxen in Berlin, Brandenburg und Sachsen. Daten zu Diagnosen, störungsbezogener Behandlung und Behandlungskorrelaten wurden 2013/2014 durch Dokumentation der Ärzte sowie durch persönliche/telefonische Patientenbefragung erfasst (Stichtagserhebung). Ergebnisse:In der primärärztlichen Versorgung lag die 12-Monatsprävalenz der Alkoholabhängigkeit bei 17.0 % für Männer und 6.4 % für Frauen, die Behandlungsrate betrug für Männer 22.3 % und für Frauen 6.7 %. Die Prävalenz von Alkoholmissbrauch (nur Patientenbefragung) lag bei 3.6 %, hier befand sich keiner der Fälle aktuell in einer störungsbezogenen Behandlung. Konsummenge und -muster (Hochkonsum, Rauschtrinken) sowie somatische (Lebererkrankung) und psychische (schwere psychische Belastung) Komorbidität waren positiv mit dem Behandlungsstatus assoziiert. Schlussfolgerungen:Trotz hoher Prävalenz ist die Behandlungsrate von SdA in der primärärztlichen Versorgung gering, wobei v. a. Patienten mit einer schweren SdA sowie somatischen und psychischen Folgeerscheinungen behandelt werden. Durch frühzeitiges Erkennen von SdA und eine frühere Initiierung einer Behandlung könnten niedergelasssene Ärzte zur Vermeidung einer Chronifizierung mit entsprechenden Folgeschäden beitragen.

Macrophage-derived tumor necrosis factor (TNF)-α has been found in choroidal neovascularization (CNV) surgically removed from patients with age-related macular degeneration. However, the role of TNF-α in CNV development remains unclear. In a murine laser-induced CNV model, compared with un-lasered controls, TNF-α mRNA was increased in retinal pigment epithelial and choroidal tissue, and TNF-α colocalized with lectin-stained migrating choroidal endothelial cells (CECs). Inhibition of TNF-α with a neutralizing antibody reduced CNV volume and reactive oxygen species (ROS) level around CNV. In CECs, pretreatment with the antioxidant apocynin or knockdown of p22phox, a subunit of NADPH oxidase, inhibited TNF-α–induced ROS generation. Apocynin reduced TNF-α–induced NF-κB and Rac1 activation, and inhibited TNF-α–induced CEC migration. TNF-α–induced Rac1 activation and CEC migration were inhibited by NF-κB inhibitor Bay11-7082. Overexpression of Rap1a prevented TNF-α–induced ROS generation and reduced NF-κB and Rac1 activation. Activation of Rap1 by 8-(4-chlorophenylthio)adenosine-2′-O-Me-cAMP prevented TNF-α–induced CEC migration and reduced laser-induced CNV volume, ROS generation, and activation of NF-κB and Rac1. These findings provide evidence that active Rap1a inhibits TNF-α–induced CEC migration by inhibiting NADPH oxidase-dependent NF-κB and Rac1 activation and suggests that Rap1a de-escalates CNV development by interfering with ROS-dependent signaling in several steps of the pathogenic process.

Mental and brain disorders represent the greatest health burden to Europe—not only for directly affected individuals, but also for their caregivers and the wider society. They incur substantial economic costs through direct (and indirect) health-care and welfare spending, and via productivity losses, all of which substantially affect European development. Funding for research to mitigate these effects lags far behind the cost of mental and brain disorders to society. Here, we describe a comprehensive, coordinated mental health research agenda for Europe and worldwide. This agenda was based on systematic reviews of published work and consensus decision making by multidisciplinary scientific experts and affected stakeholders (more than 1000 in total): individuals with mental health problems and their families, health-care workers, policy makers, and funders. We generated six priorities that will, over the next 5–10 years, help to close the biggest gaps in mental health research in Europe, and in turn overcome the substantial challenges caused by mental disorders.

N-glycosylation is identified as a novel regulator of JAM-A function. Human JAM-A carries a single N-glycan at N185, which regulates the protein’s role in barrier function, migration, and leukocyte binding.

Zusammenfassung.Fragestellung:Schlafprobleme, ihre Auswirkungen und Implikationen sind besonders im Kontext militärischer Missionen ein bedeutsames, jedoch wenig untersuchtes Thema. Methoden:Eine repräsentative Stichprobe von 1478 deutschen Bundeswehrsoldaten wurde 12 Monate nach Ende ihres Auslandseinsatzes mittels des Pittsburgh Sleep Quality Index (PSQI) sowie zu psychischen Störungen (DSM-IV-TR) und traumatischen Ereignissen persönlich untersucht und mit N =880 Soldaten ohne Auslandseinsatz verglichen. Ergebnisse:41 % der Soldaten mit und 38 % der Soldaten ohne Auslandseinsatz erfüllten die PSQI-Kriterien für Schlafprobleme. Traumatische Einsatzereignisse waren mit mehr Schlafproblemen assoziiert (β:0.7, 95 % KI: 0.4 – 1.0, p< .001). In Abhängigkeit der Anzahl traumatischer Einsatzereignisse wurde ein höherer PSQI-Gesamtwert bei inzidenten psychischen Störungen (β:1.2, 95 % KI: 0.3 – 2.1, p= .011), aber auch bei Soldaten ohne psychische Störungen (β:0.7, 95 % KI: 0.3 – 1.1, p= .001) berichtet. Schlussfolgerung:Auslandseinsätze scheinen in Abhängigkeit traumatischer Ereignisse das Ausmaß von Schlafproblemen bei Soldaten sowohl innerhalb als auch außerhalb des Kontextes psychischer Störungen zu erhöhen.

The paper deals with the application of multispectral imaging to estimate steel quality directly after it is produced in the steelworks. In particular, thermal and visual cameras are used to estimate FeO content in the slag. This is done by analysis of the steel stream images that are acquired during discharge from an oxygenic converter. The analysis involves statistical analysis for determined primary and secondary radiative parameters of steel and slag.

Background:The prognostic significance of chest pain is well established in patients with coronary artery disease, but still ill defined in primary prevention. Therefore, the aim of our analysis was to assess the prognostic value of different forms of chest pain in a large cohort of primary care subjects under the conditions of contemporary modalities of care in primary prevention, including measurement of serum levels of the biomarker NT-pro-BNP.Design:We carried out a post-hoc analysis of the prospective DETECT cohort study.Methods:In a total of 5570 unselected subjects, free of coronary artery disease, within the 55,518 participants of the cross-sectional DETECT study, we assessed chest pain history by a comprehensive questionnaire and measured serum NT-pro-BNP levels. Three types of chest pain, which were any chest pain, exertional chest pain and classical angina, were defined. Major adverse cardiovascular events (MACEs = cardiovascular death, myocardial infarction, coronary revascularization procedures) were assessed during a 5-year follow-up period.Results:During follow-up, 109 subjects experienced a MACE. All types of reported chest pain were associated with an approximately three-fold increased risk for the occurrence of incident MACEs, even after adjusting for cardiovascular risk factors. Any form of reported chest pain had a similar predictive value for MACEs as a one-time measurement of NT-pro-BNP. However, adding a single measurement of NT-pro-BNP and the information on chest pain resulted in reclassification of approximately 40% of subjects, when compared with risk prediction based on established cardiovascular risk factors.Conclusions:In primary prevention, self-reported chest pain and a single measurement of NT-pro-BNP substantially improve cardiovascular risk prediction and allow for risk reclassification of approximately 40% of the subjects compared with assessing classical cardiovascular risk factors alone.

ObjectiveThis article reports on the test–retest reliability and sensitivity to change of a set of brief dimensional self-rating questionnaires for social anxiety disorder (SAD-D), specific phobia (SP-D), agoraphobia (AG-D), panic disorder (PD-D), and generalized anxiety disorder (GAD-D), as well as a general cross-cutting anxiety scale (Cross-D), which were developed to supplement categorical diagnoses in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5).MethodsThe German versions of the dimensional anxiety scales were administered to 218 students followed up approximately 2 weeks later (Study 1) and 55 outpatients (23 with anxiety diagnoses) followed-up 1 year later (Study 2). Probable diagnostic status in students was determined by the DIA-X/M-CIDI stem screening-questionnaire (SSQ). In the clinical sample, Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses were assessed at Time 1 using the DIA-X/M-CIDI. At Time 2, the patient-version of the Clinical Global Impression—Improvement scale (CGI-I) was applied to assess change.ResultsGood psychometric properties, including high test–retest reliability, were found for the dimensional scales except for SP-D. In outpatients, improvement at Time 2 was associated with significant decrease in PD-D, GAD-D, and Cross-D scores.DiscussionMajor advantages of the scales include that they are brief, concise, and based on a consistent template to measure the cognitive, physiological, and behavioral symptoms of fear and anxiety. Further replication in larger samples is needed. Given its modest psychometric properties, SP-D needs refinement.ConclusionIncreasing evidence from diverse samples suggests clinical utility of the dimensional anxiety scales.

Theoretischer Hintergrund: Noch immer ist wenig über die empirische Struktur von traumatischem Stress und die Assoziationen zwischen Stressoren und psychischen Erkrankungen bekannt, insbesondere nach militärischen Auslandseinsätzen. Methode: 1483 Bundeswehrsoldaten, die 2009/2010 in Afghanistan eingesetzt waren, wurden mittels der militärischen Version eines diagnostischen Interviews (MI-CIDI) untersucht. Zwei Klassifikationsmodelle wurden auf die Items der Liste einsatzbezogener Stressoren des US-MHAT-VI-Reports angewendet und konfirmatorische Faktorenanalysen durchgeführt. Ergebnisse: Aufgrund hoher polychorischer Korrelationen zwischen Items verschiedener Klassen und hoch negativer Korrelationen innerhalb derselben Klasse ergaben die Faktorenanalysen keine zufriedenstellende Modellpassung. Es wurden auch keine unterschiedlichen prädiktiven Wertigkeiten im Hinblick auf einsatzbedingte psychische Erkrankungen gefunden. Schlussfolgerungen: Die Ergebnisse stimmen nicht mit denen vergangener Studien überein und sprechen für den Einfluss von spezifischen Einsatzbedingungen auf die Struktur traumatischer Stressoren.

Panic disorder (PD) is a common mental disorder, ranking highest among the anxiety disorders in terms of disease burden. The pathogenesis of PD is multifactorial with significant heritability, however only a few convincing risk genes have been reported thus far. One of the most promising candidates is the gene encoding monoamine oxidase A (MAOA), due to its key role in monoaminergic neurotransmission, established validity of animal models, and the efficacy of MAO inhibitors in the treatment of PD. A promoter repeat polymorphism in MAOA(MAOA‐uVNTR) impacts on gene expression; high‐expression alleles have been reported to increase the risk for PD. To further scrutinize the role of this polymorphism, we performed a formal meta‐analysis on MAOA‐uVNTR and PD using original data from four published European (Estonian, German, Italian, and Polish) samples and genotypes from three hitherto unpublished German PD samples, resulting in the largest (n = 1,115 patients and n = 1,260 controls) genetic study on PD reported to date. In the unpublished samples, evidence for association of MAOA‐uVNTR with PD was obtained in one of the three samples. Results of the meta‐analysis revealed a significant and female‐specific association when calculating an allelic model (OR = 1.23, P= 0.006). This sex‐specific effect might be explained by a gene‐dose effect causing higher MAOAexpression in females. Taken together, our meta‐analysis therefore argues that high‐expression MAOA‐uVNTR alleles significantly increase the risk towards PD in women. However, epigenetic mechanisms might obfuscate the genetic association, calling for ascertainment in larger samples as well as assessment of the MAOApromoter methylation status therein. © 2012 Wiley Periodicals, Inc.

Background: Several selected population-based studies have emphasized the significance of resting heart rate as an independent cardiovascular risk factor. However, there are no data available for using resting heart rate as a cardiovascular risk predictor in contemporary primary care. Thus, the aim of our analysis was to examine the clinical value of the measurement of resting heart rate in a large, unselected population-based cohort of primary care subjects under the conditions of contemporary primary prevention.Design: Prospective, population-based cohort study.Methods: We examined a subgroup of 5320 unselected primary care subjects free of coronary artery disease from the nationwide, longitudinal Diabetes Cardiovascular Risk Evaluation Targets and Essential Data for Commitment of Treatment (DETECT) cohort study, which was conducted from 2003 to 2008.Results: During the follow-up time of 5 years, 258 events were reported. Elevated resting heart rate was not associated with an increased risk for cardiovascular events (HR = 0.75, p = 0.394), cardiovascular mortality (HR = 0.71, p = 0.616) or major cardiovascular events (HR = 0.77, p = 0.376). By cross-sectional analysis, elevated heart rate clustered with markers of the metabolic syndrome, like increased blood pressure (systolic: OR = 5.54, p < 0.0001; diastolic: OR = 3.82, p < 0.0001), elevated fasting plasma glucose levels (OR = 8.84, p < 0.0001), hypertriglyceridaemia (OR = 22.16, p = 0.001), and obesity (body mass index OR = 0.89, p < 0.0001). Assessment of resting heart rate in clinical practice had minimal and non-significant additional prognostic value compared to established cardiovascular risk factors as judged by C statistics (C = 0.001, p = 0.979).Conclusion: The measurement of resting heart rate in the daily routine of primary care does not provide incremental prognostic information for cardiovascular risk stratification.

Zusammenfassung.Theoretischer Hintergrund:Die Rolle der Therapeutenbegleitung während Expositionsübungen bei Panikstörung mit Agoraphobie (P/A) ist bislang ungeklärt. Eine kürzlich durchgeführte klinische Studie (MAC-Studie) lieferte Hinweise auf ein günstigeres Behandlungsergebnis bei Therapeutenbegleitung. Fragestellung:Wie lassen sich Effekte therapeutenbegleiteter Exposition (T) im Vergleich zu Exposition ohne Therapeutenbegleitung (T–) erklären? Methode:Daten von 301 Patienten, die eine expositionsbasierte KVT mit bzw. ohne Therapeutenbegleitung erhalten hatten, wurden analysiert. Untersucht wurden der Einfluss der initialen Störungsschwere, des Sicherheitsverhaltens sowie differenzielle Effekte der Bedingungen auf die Angst vor der Angst. Zusätzlich wurde überprüft, inwieweit die Übungshäufigkeit in den Behandlungsbedingungen variiert und einen Mediator des Behandlungserfolgs darstellt. Ergebnisse:Störungsschwere und Sicherheitsverhalten zeigten keine differenziellen Effekte zwischen den Bedingungen; die T Bedingung führte jedoch zu stärkeren Reduktionen der Angst vor der Angst im Angstsensitivitätsindex. Patienten der T Bedingung führten häufiger selbständig Expositionsübungen durch, während Patienten in T– im Durchschnitt länger übten. Die Übungshäufigkeit stellte dabei einen Mediator des Behandlungserfolgs dar. Schlussfolgerungen:Günstigere Effekte einer therapeutenbegleiteten Exposition gehen auf stärkere Reduktionen der Angst vor der Angst sowie auf eine höhere Übungshäufigkeit im Selbstmanagement zurück.