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Background: The outcome expectations of patients have long been considered a common factor in psychotherapy. Objective: The present study examines whether the outcome expectations of patients are significant predictors of treatment success above and beyond established predictors. It considers both positive and negative expectations (hope of improvement / fear of change). Methods: We assessed both positive and negative outcome expectations in 453 completers of outpatient cognitive-behavioral therapy at baseline via a questionnaire. We performed hierarchical logistic regression to test whether and how outcome expectations influence treatment success, defining the latter in terms of a clinically significant change at the individual case level. Results: Beyond the influence known from already proven predictors, positive and, to a lesser degree, negative outcome expectations showed a significant influence on treatment success. Conclusions: Routine assessment of outcome expectations at baseline seems helpful in identifying factors that might impede a good treatment outcome. Hintergrund: Erwartungen von Patient_innen hinsichtlich des Erfolgs ihrer Therapie gelten schon lange als allgemeine Wirkfaktoren in der Psychotherapie. Fragestellung: Die vorliegende Studie untersucht, ob Therapieerwartungen als Prädiktoren für den Behandlungserfolg über etablierte Prädiktoren hinaus bedeutsam sind und betrachtet hierbei sowohl positive als auch negative Erwartungen (Hoffnung auf Besserung bzw. Furcht vor Veränderung). Methoden: Bei 453 Completern einer ambulanten kognitiv-verhaltenstherapeutischen Behandlung wurden mittels eines Fragebogens zu Therapiebeginn positive und negative Therapieerwartungen erfasst. Mit einer hierarchischen logistischen Regression wurde geprüft, ob und wie Therapieerwartungen einen Einfluss auf den Therapieerfolg der Patient_innen haben. Therapieerfolg wurde dabei im Sinne einer klinisch bedeutsamen Veränderung im Einzelfall definiert. Ergebnisse: Über den Einfluss bereits belegter Prädiktoren hinaus, zeigten vor allem positive, für die Remission auch negative Therapieerwartungen einen signifikanten Einfluss auf den Therapieerfolg. Schlussfolgerungen: Die routinemäßige Erfassung von Therapieerwartungen zu Beginn der Therapie scheint sinnvoll, um Hindernisse für ein möglichst gutes Therapieergebnis früh genug zu identifizieren.

Many patients with major depressive disorder (MDD) remain untreated or do not respond to cognitive behavioral therapy (CBT). Physical exercise shows antidepressive effects and may serve as an effective augmentation treatment. However, research on combining exercise with CBT is sparse in MDD and underlying mechanisms of exercise are not well understood to date.120 outpatients with MDD were randomized to either a high intensity exercise group (HEX), a low intensity exercise group (LEX), or a waiting list control group (WL). After 12 weeks of exercise training or waiting period, all patients received a manualized CBT.Seventy-five patients with MDD completed both the exercise program/ waiting period and the CBT. While physical fitness improved in HEX after the exercise program, it did not change in LEX and WL. Depressive symptoms improved in all three groups from baseline to post-CBT and the group by time interaction was not significant. Regression analyses revealed that the amount of fitness improvement during exercise predicted the subsequent CBT response.The dropout rate was relatively high, preparatory CBT sessions during exercise / waiting period may have influenced depressive symptoms, and no patients with severe MDD were included.High intense physical exercise did not lead to a general enhancement of CBT outcome, but higher increases in physical fitness seem to improve symptom change during CBT. Our results suggest that the implementation of more individually tailored exercise programs could be a promising approach for future research and clinical practice.

Selbstwertprobleme können Einfluss auf die Entstehung und Aufrechterhaltung einer psychischen Störung nehmen, aber auch eine Folge der Störung sein. Interventionen, die auf den Selbstwert bezogen sind, spielen bei der Behandlung zahlreicher psychischer Störungen eine zentrale Rolle, insbesondere bei Depressionen, Essstörungen und Persönlichkeitsstörungen. Der Band fasst Wissenswertes zu Selbstwert und dessen Zusammenhang mit unterschiedlichen psychischen Störungen zusammen und grenzt den Begriff gegenüber anderen psychotherapeutisch relevanten Konstrukten, etwa soziale Kompetenz oder Selbstmitgefühl, ab. Es folgen Überlegungen zur Indikation selbstwertbezogener Interventionen und den diagnostischen Möglichkeiten von Selbstwert. Praxisorientiert wird veranschaulicht, wie selbstwertbezogene Interventionen in der Behandlung umgesetzt werden können. Zunächst werden Hinweise zur Psychoedukation und zum Einbezug von Selbstwert in die Fallkonzeptualisierung gegeben. Anschließend wird gezeigt, wie klassisch-verhaltenstherapeutische sowie achtsamkeitsbasierte Interventionen transdiagnostisch zur Bearbeitung von Selbstwertproblemen eingesetzt werden können. Dabei wird auf verschiedene selbstwertspezifische Interventionen eingegangen, z.B. auf die Förderung der Selbstfürsorge, die Förderung einer ausgewogenen Sichtweise auf sich selbst oder die Arbeit mit inneren selbstkritischen oder wohlwollenden Anteilen. Ausführlich vorgestellt werden zudem zwei im deutschen Sprachraum bislang weniger bekannte Ansätze, die spezifisch für die Behandlung von Selbstwertproblemen konzipiert wurden: Das kognitive Therapiekonzept für Selbstwertprobleme von Fennell sowie das Selbstwerttraining „COMET“ der niederländischen Arbeitsgruppe um Korrelboom. Hinweise zu Besonderheiten der Nutzung selbstwertbezogener Interventionen im Gruppenkontext runden den Band ab.

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. Bundesministerium für Bildung und Forschung https://doi.org/10.13039/501100002347

ZusammenfassungEinleitung Sexuelle Funktionsstörungen gelten als häufig. Gleichzeitig fehlen epidemiologische Daten zur Behandlungsprävalenz sexueller Funktionsstörungen in der ambulanten Psychotherapie. Im Rahmen eines Projekts zur Koordination der Datenerhebung an den deutschen Hochschulambulanzen für Psychotherapie wird erstmals eine Schätzung für dieses Behandlungssegment möglich.Forschungsziele Das Ziel dieser Studie ist die Darstellung der festgestellten F52-Diagnosen an deutschen Hochschulambulanzen für Psychotherapie an psychologischen Instituten.Methoden 16 Hochschulambulanzen für Erwachsene übermittelten ausgewählte Daten zur Eingangsdiagnostik ihrer Patient_innen (N = 4 504; M Alter = 37.87; SD = 13.47; Altersbereich = 15 bis 86 Jahre; 65.3 % weiblich) aus dem Jahr 2016. In der hier vorgestellten Studie wird spezifisch die Häufigkeit der Vergabe von Diagnosen aus dem ICD-Kapitel F52 analysiert.Ergebnisse Insgesamt wurde in 32 Fällen (0.7 %) die Diagnose einer sexuellen Funktionsstörung vergeben, in acht Fällen (0.2 %) als Hauptdiagnose. In 31 Fällen (96.9 %) waren auch komorbide Störungen gegeben, hauptsächlich Angststörungen (34.4 %) und affektive Störungen (53.1 %). Unter den Hauptdiagnosen war der nichtorganische Vaginismus (n = 3) der häufigste Grund, eine psychotherapeutische Hochschulambulanz eines psychologischen Instituts aufzusuchen. Die Häufigkeit von F52-Diagnosen in den 16 Ambulanzen schwankte zwischen 0 % und 1.2 %, und acht der 16 Ambulanzen vergaben überhaupt keine F52-Diagnosen.Schlussfolgerung Die Werte in der vorliegenden Behandlungsstichprobe erscheinen vor dem Hintergrund der Prävalenzdaten aus Bevölkerungsstudien als auffällig niedrig. Hierfür können neben methodischen und studienspezifischen Gründen auch Aspekte der psychotherapeutischen Versorgung sowie Beurteilungsfehler bei der Diagnosevergabe verantwortlich sein.

Prüfungsängste sind weit verbreitet und ziehen in der Mehrzahl der Fälle keine weitreichenden Beeinträchtigungen oder Belastungen nach sich. Manchmal sind Prüfungsängste jedoch so stark ausgeprägt und anhaltend vorhanden, dass sie im Rahmen einer psychotherapeutischen Behandlung thematisiert werden müssen – sei es als primäres Anliegen oder als zusätzliches Problem bei einem anderen Behandlungsanliegen. Die Neubearbeitung des Bandes stellt Informationen zur Symptomatik und Häufigkeit von Prüfungsangst bereit und berichtet den aktuellen Stand der Forschung zu Entstehungsbedingungen und Erklärungsmodellen. Weiterhin finden sich ausführliche Hinweise zur Diagnostik sowie vielfältige Anregungen zur praktischen Arbeit mit betroffenen Personen. Das therapeutische Vorgehen orientiert sich an verschiedenen möglichen Aspekten der Symptomatik und kann durch das modularisierte Vorgehen an die heterogenen Problembilder der betroffenen Personen angepasst werden. Alle Module sind der kognitiven Verhaltenstherapie zuzuordnen. Entsprechend finden sich neben verschiedenen Strategien zum Lernen, zum Zeitmanagement und zur Vorbereitung einer Prüfung auch kognitive Techniken zum Umgang mit hinderlichen Gedanken, Entspannungstechniken sowie das Verfahren der systematischen Desensibilisierung. Die Neuauflage des Bandes informiert über aktuelle Entwicklungen bei der Behandlung von Prüfungsängsten und geht hierbei auch auf neuere therapeutische Ansätze, z.B. imaginative und achtsamkeitsbasierte Interventionen, ein.

Individual responses to behavioral treatment of anxiety disorders vary considerably, calling for better understanding of underlying processes. This study examined the violation and change of threat beliefs during exposure. From 8484 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 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.

ZusammenfassungDie vorliegende Studie vergleicht in einer naturalistischen Stichprobe aus 507 ambulanten Psychotherapiepatienten ausgewählte psychometrische Eigenschaften zweier störungsübergreifender Fragebögen: des Brief Symptom Inventory 7 und des ICD-10 Symptom Rating 8. Die Reliabilität von Gesamt- und Subskalenmittelwerten wurde anhand der internen Konsistenzkoeffizienten Cronbachs α und McDonalds ω geschätzt. Messpräzision wurde mittels des Unsicherheitsbereichs operationalisiert. Zur Unterstützung der Validität der Interpretation der Gesamtmittelwerte als Maß für psychische Belastung wurden die Korrelationen mit inhaltsnahen und inhaltsfernen Maßen bestimmt. Die Validität der Skalenstruktur wurde über konfirmatorische Faktorenanalysen geprüft. Bezüglich der Reliabilitätsschätzungen weist der ISR eine zum BSI vergleichbare interne Konsistenz und Messpräzision auf. Konvergente und diskriminante Validität sind ähnlich gut. Das ISR zeigt eine sehr gute faktorielle Validität, während die des BSI als ungenügend beurteilt wird. Von der störungsspezifischen Interpretation der Subskalen des Brief Symptom Inventory muss aufgrund der unklaren Faktorstruktur abgeraten werden. Insgesamt scheint das ISR als Maß für die generelle Symptombelastung eine gute Alternative zum BSI zu sein, da es ähnlich reliabel und messpräzise ist, aber hinsichtlich der Validität bessere Kennwerte aufweist und zeiteffizienter ist.

Zusammenfassung. Theoretischer Hintergrund: Obwohl Prüfungsangst ein häufiges Anliegen in psychologischen Beratungsstellen ist, wissen wir wenig über ihren zeitlichen Verlauf sowie über Risikofaktoren für hohe Prüfungsangst kurz vor den Prüfungen. Fragestellung: Diese Studie untersucht, ob sich die Intensität von Prüfungsangst während eines Semesters verändert und wie Personen mit hoher Belastung kurz vor der Prüfung früh identifiziert werden können. Methodik: Zu Beginn und kurz vor den Prüfungen des Wintersemesters 2014/15 wurden Prüfungsangst, Depressivität und Prokrastination bei 427 Studierenden (88.3 % Erstsemester; 68.4 % weiblich; Altersdurchschnitt 20.0 Jahre) erfasst. Ergebnisse: Die Analyse auf Einzelfallebene zeigte, dass sich die Prüfungsangst bei den meisten Studierenden nicht signifikant veränderte. Bei der Vorhersage der Prüfungsangst zum Semesterende stellten Prüfungsangst und Depressivität zu Semesterbeginn signifikante Prädiktoren dar. Diese wurden anhand von 80 % der Gesamtstichprobe ermittelt und an den anderen 20 % validiert. Schlussfolgerungen: Erhöhte Prüfungsangst und Depressivität zu Semesterbeginn können die frühe Identifikation von Studierenden mit bedeutsamer Prüfungsangst kurz vor Prüfungen ermöglichen.

Zusammenfassung. Theoretischer Hintergrund: Das BDI-II ist ein Selbstbeurteilungsinstrument zur Erfassung des Schweregrads einer Depression. Es liegen kaum Analysen mit Modellen aus der Item-Response-Theorie (IRT) vor. Fragestellung: Wie hoch ist die Messgenauigkeit des BDI-II über die unterschiedlichen Ausprägungen des latenten Traits (Depressivität) hinweg und sind die Kategorien der Items jeweils aufsteigend geordnet? Methode: Anhand von sechs großen Datensätzen aus verschiedenen klinischen Bereichen wurden psychometrische Analysen mit dem Graded Response Model durchgeführt. Ergebnisse: In allen Stichproben fand sich eine hohe interne Konsistenz. Die Schwellenwerte waren mit Ausnahme von Item 6 („Bestrafungsgefühle“) geordnet. Gemäß Testinformationsfunktion misst das BDI-II im mittleren bis hohen Depressionsbereich sehr gut (Reliabilität > .90) und im unteren Bereich gut. Schlussfolgerung: Für das BDI-II ergibt sich eine hohe und relativ gleichbleibende Messpräzision über einen weiten Bereich des latenten Traits, weshalb es insbesondere im klinischen, aber auch im nicht klinisch relevanten Wertebereich zur Erhebung des Schweregrades einer Depression gut geeignet ist., publishedVersion

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.

ZUSAMMENFASSUNGDie Agoraphobie ist eine häufige Angsterkrankung und kann durch die kognitive Verhaltenstherapie (KVT) effizient behandelt werden. Für Patienten, die aufgrund einer schweren Symptomausprägung die eigene Wohnumgebung nicht selbstständig verlassen können, ist jedoch häufig die Aufnahme einer ambulanten Psychotherapie unmöglich. Das Pilotprojekt der „aufsuchenden Psychotherapie“ bietet deshalb in Berlin eine manualbasierte KVT an, die im häuslichen Bereich der Betroffenen beginnt. Den Schwerpunkt der Behandlung bildet eine 5-wöchige Intensivphase, in der durch eine Expositionstherapie die Mobilität der Patienten zeitnah wieder hegestellt und so die Fortsetzung der KVT im Rahmen der ambulanten Regelversorgung ermöglicht werden soll. Das speziell für diese Patientengruppe konzipierte Therapiemanual wird im Verlauf des Projekts kontinuierlich weiterentwickelt, um es möglichst optimal auf die Bedürfnisse der Patienten zu adaptieren und so eine größtmögliche Behandlungssicherheit herzustellen. Ziel des Projekts ist es, dass eine aufsuchende Komponente bedarfsgerecht als Teil der ambulanten KVT etabliert und finanziell adäquat durch die Kostenträger kompensiert wird.

Patients with anxiety disorders have a lower heart rate variability (HRV) than healthy controls. Low HRV is associated with cardiovascular disease and dysfunction of the autonomic nervous system (ANS). The aim of the present study was to investigate if HRV in patients with agoraphobia with or without panic disorder can be influenced by cognitive behavioral therapy (CBT). 73 patients with agoraphobia with or without panic disorder were included in the study. Heart rate (HR) and HRV were recorded at rest before and after CBT and during in-vivo exposure. No changes in HR and HRV were observed throughout therapy. During in-vivo exposure HRV increased significantly and HR exhibited a tendency to decrease. Despite clinical improvement of anxiety symptoms, ANS activity at rest did not seem to be influenced by CBT. However, during in-vivo exposure, HRV changed significantly, indicating a higher parasympathetic activity at the end of exposure.

Background The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. Methods This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. Results Both treatments resulted in substantial improvements at post (PeEx-I: d\(_{within}\) = 1.50, PeEx-S: d\(_{within}\) = 1.78) and follow-up (PeEx-I: d\(_{within}\) = 2.34; PeEx-S: d\(_{within}\) = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR\(_{PeEx-I}\)-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse. Conclusions Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.

Theoretically, panic disorder and agoraphobia pathology can be conceptualized as a cascade of dynamically changing defensive responses to threat cues from inside the body. Guided by this trans-diagnostic model we tested the interaction between defensive activation and vagal control as a marker of prefrontal inhibition of subcortical defensive activation. We investigated ultra-short-term changes of vagally controlled high frequency heart rate variability (HRV) during a standardized threat challenge (entrapment) in n = 232 patients with panic disorder and agoraphobia, and its interaction with various indices of defensive activation. We found a strong inverse relationship between HRV and heart rate during threat, which was stronger at the beginning of exposure. Patients with a strong increase in heart rate showed a deactivation of prefrontal vagal control while patients showing less heart rate acceleration showed an increase in vagal control. Moreover, vagal control collapsed in case of imminent threat, i.e., when body symptoms increase and seem to get out of control. In these cases of defensive action patients either fled from the situation or experienced a panic attack. Active avoidance, panic attacks, and increased sympathetic arousal are associated with an inability to maintain vagal control over the heart suggesting that teaching such regulation strategies during exposure treatment might be helpful to keep prefrontal control, particularly during the transition zone from post-encounter to circa strike defense. Trial Registration Number: ISRCTN80046034. German Federal Ministry of Education and Research Universität Greifswald (1032)

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 × 10−4 were 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

Our study compared the psychometric properties of two broad scope symptom questionnaires, the Brief Symptom Inventory [7] and the ICD-10 Symptom Rating Scale [8], in a naturalistic data set of 507 patients in outpatient psychotherapeutic treatment. Reliability of total scores and subscale scores were estimated via internal consistency coefficients Cronbach's α and McDonald's ω. Measurement precision was operationalized via the uncertainty interval. Validity of the total scores as measures of symptom load was operationalized via convergence analysis with measures similar and dissimilar to that concept. Validity of the internal structure of each scale was operationalized via confirmatory factor analysis of multiple models established in literature. Reliability and measurement precision were comparable for the two questionnaires. The convergent and discriminant validity of both instruments appear to be similarly sufficient. The ISR clearly showed good factorial validity, whereas the BSI was found to have poor factorial validity. Due to its uncertain factorial structure, interpretation of the BSI subscales is not advised. In sum, the ISR and BSI have comparable reliability and measurement precision, but ISR has superior validity and better time efficiency and therefore can be considered a valid alternative to the BSI.Die vorliegende Studie vergleicht in einer naturalistischen Stichprobe aus 507 ambulanten Psychotherapiepatienten ausgewählte psychometrische Eigenschaften zweier störungsübergreifender Fragebögen: des Brief Symptom Inventory 7 und des ICD-10 Symptom Rating 8. Die Reliabilität von Gesamt- und Subskalenmittelwerten wurde anhand der internen Konsistenzkoeffizienten Cronbachs α und McDonalds ω geschätzt. Messpräzision wurde mittels des Unsicherheitsbereichs operationalisiert. Zur Unterstützung der Validität der Interpretation der Gesamtmittelwerte als Maß für psychische Belastung wurden die Korrelationen mit inhaltsnahen und inhaltsfernen Maßen bestimmt. Die Validität der Skalenstruktur wurde über konfirmatorische Faktorenanalysen geprüft. Bezüglich der Reliabilitätsschätzungen weist der ISR eine zum BSI vergleichbare interne Konsistenz und Messpräzision auf. Konvergente und diskriminante Validität sind ähnlich gut. Das ISR zeigt eine sehr gute faktorielle Validität, während die des BSI als ungenügend beurteilt wird. Von der störungsspezifischen Interpretation der Subskalen des Brief Symptom Inventory muss aufgrund der unklaren Faktorstruktur abgeraten werden. Insgesamt scheint das ISR als Maß für die generelle Symptombelastung eine gute Alternative zum BSI zu sein, da es ähnlich reliabel und messpräzise ist, aber hinsichtlich der Validität bessere Kennwerte aufweist und zeiteffizienter ist.

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.

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation—DNA methyltransferases (DNMTs)—has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

Am Muster eines Ausbildungsinstituts im Verbund universitarer Ausbildungsinstitute fur Psychotherapie (unith) werden charakteristische Masnahmen zur Sicherung einer guten Qualitat der Ausbildung von Psychologischen Psychotherapeuten bzw. Kinder- und Jugentlichenpsychotherapeuten dargestellt. Dabei wird insbesondere auf die Auswahl von Teilnehmern, die Durchfuhrung der theoretischen und praktischen Ausbildung und die Selbsterfahrung eingegangen. Zudem wird dargestellt, wie eine hohe Qualitat bei der Durchfuhrung der Ausbildungstherapien durch Supervision und psychometrische Uberprufung der Behandlungsverlaufe erreicht wird. Abschliesend werden erste Befunde uber c.a. 4.500 in unith Instituten behandelte Patienten dargestellt.

The use of d-cycloserine (DCS) to augment exposure based therapy for anxiety disorders has shown mixed, although overall positive effects. Aim of the present study was to examine post-exposure administration of DCS in patients with agoraphobia with or without panic disorder. 73 patients with agoraphobia (with or without panic disorder) were treated with 12 sessions of cognitive behavioral therapy (CBT) including 3 exposures. Following successful exposure patients were given double blind either placebo or 50 mg of DCS. Primary outcome criterion was change in the Panic and Agoraphobia Scale (PAS) between CBT session t1, t4 (+∼2 months), t10 (+∼3 months) und t11 (+∼4 months). During the course of CBT the patients' symptomatology decreased significantly as measured by primary and secondary outcome criteria, however, without an additional benefit for DCS treated patients. Exploratory sub-group analyses for severely ill patients and patients with high anxiety and strong habituation during exposure showed that DCS administration was associated with increased improvement during the 1-month follow-up period (t10 - t11) with medium to large effect sizes (range in effect size η2p from .06 to .25). Our study results are consistent with recent research on DCS, indicating a beneficial augmentative effect for sub-groups of anxiety patients. The lack of an overall DCS effect for the whole patient sample might be explained by a dual mechanism in fear conditioning and extinction with different cognitive processes being involved during exposure depending on the degree of anxiety experienced by the patient.

Zusammenfassung. Theoretischer Hintergrund: Im Jahr 2013 entstand die Initiative, Daten der universitären Psychotherapieambulanzen zusammenzuführen, um so eine deutschlandweite Forschungsdatenplattform zu schaffen. Der Forschungsverbund KODAP (Koordination der Datenerhebung und -auswertung an Forschungs-‍, Lehr- und Ausbildungsambulanzen für psychologische Psychotherapie) organisiert dieses komplexe Vorhaben. Fragestellung / Methode: In der vorliegenden Studie wird die technische und organisatorische Machbarkeit einer solchen Forschungskooperation im Hinblick auf die Übermittlung und Zusammenführung der Daten dargestellt. Gleichzeitig wird die im Jahr 2016 in den Ambulanzen behandelte Patient_innenpopulation beschrieben und es werden erste Vergleichsdaten zur Häufigkeit ICD-10-basierter Diagnosen in diesem Versorgungssegment generiert. Ergebnisse: Insgesamt stellten 16 Ambulanzen Daten von 4504 Patientinnen und Patienten (MAlter = 37.87; SD = 13.47; Range = 15 bis 86; 65.3 % weiblich) aus dem Jahr 2016 zur Verfügung. Trotz der unterschiedlichen Systeme und Formate, in denen Patient_innen- und therapiebezogene Forschungsdaten verwaltet werden, erwies sich die Übermittlung und Zusammenführung der Datensätze als machbar. Affektive Störungen (F3) und Neurotische, Belastungs- und Somatoforme Störungen (F4) machten den Großteil der vergebenen Diagnosen aus. Bei mehr als der Hälfte der Patient_innen lag mehr als eine Störungsdiagnose vor (M = 1.84; SD = 0.99; Range = 0 bis 7). Schlussfolgerungen: Diese Studie konnte zeigen, dass die Aufbereitung, Zusammenführung und Auswertung von Forschungsdaten über Ambulanzen hinweg möglich ist. Der Forderung nach einer stärkeren Ausrichtung der Psychologie in Richtung kumulativer und kooperativer Forschungsprojekte kommt das KODAP-Projekt in besonderem Maße nach.

Psychotherapie ist in ihrer zeitlichen und raumlichen Intensitat stark eingeschrankt: Im Regelfall finden ein bis zwei Therapiesitzungen pro Woche statt – im Alltag muss sich der Patient auch wahrend einer Behandlung meist allein mit kritischen Situationen und Reaktionen auseinandersetzen. Um Effektivitat und Wirkungsgrad der Therapie zu erhohen, werden gezielt therapeutische Vereinbarungen, Absprachen und Aufgaben eingesetzt. Diese helfen das gemeinsame Arbeiten zu strukturieren und zu intensivieren, klare Ziel- und Erfolgskriterien festzulegen sowie neue Verhaltensweisen systematisch einzufuhren und im Alltag zu etablieren.

The gene coding for glycine receptor β subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk») in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment.

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

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.

The availability of large-scale datasets and sophisticated machine learning tools enables developing models that predict treatment outcomes for individual patients. However, few studies used routinely available sociodemographic and clinical data for this task, and many previous investigations used highly selected samples. This study aimed to investigate cognitive behavioral therapy (CBT) outcomes in a large, naturalistic and longitudinal dataset. Routine data from a university-based outpatient center with n = 2.147 patients was analyzed. Only baseline data including sociodemographics, symptom measures and functional impairment ratings was used for prediction. Different competing classification and regression models were compared to each other; the best models were then applied to previously unseen validation data. Applied on the validation set, the best performing classification model for remission achieved a balanced accuracy of 59% (p 0.001) and the best performing regression model for dimensional change achieved r = 0.27 (p 0.001). Age, sex, functional impairment, symptom severity, and axis II comorbidity were among the most important features. Predictor performances significantly exceeded chance level but were far from clinical utility. Neither applying more sophisticated approaches nor restricting the sample to homogeneous subgroups resulted in considerable performance gains. Adding hypotheses-based, more specific clinical constructs and deep (e.g. neurobiological) to digital phenotypes may increase prediction performance.

Physiological mechanisms of an anti-depressive effect of physical exercise in major depressive disorder (MDD) seem to involve alterations in brain-derived neurotrophic factor (BDNF) level. However, previous studies which investigated this effect in a single bout of exercise, did not control for confounding peripheral factors that contribute to BDNF-alterations. Therefore, the underlying cause of exercise-induced BDNF-changes remains unclear. The current study aims to investigate serum BDNF (sBDNF)-changes due to a single-bout of graded aerobic exercise in a group of 30 outpatients with MDD, suggesting a more precise analysis method by taking plasma volume shift and number of platelets into account. Results show that exercise-induced increases in sBDNF remain significant (p .001) when adjusting for plasma volume shift and controlling for number of platelets. The interaction of sBDNF change and number of platelets was also significant (p = .001) indicating larger sBDNF-increase in participants with smaller number of platelets. Thus, findings of this study suggest an involvement of peripheral as well as additional - possibly brain-derived - mechanisms explaining exercise-related BDNF release in MDD. For future studies in the field of exercise-related BDNF research, the importance of controlling for peripheral parameters is emphasized.

Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.

Exposure therapy is considered an effective treatment strategy for phobic anxiety, however, it is rarely applied in clinical practice. The under-usage might be due to various factors of which heightened stress levels not only in patients but also in therapists are presumed to be of particular relevance. The present study aimed to investigate whether different forms of exposure might lead to varying physiological and psychological stress responses in therapists and phobic patients. 25 patients with specific phobia underwent individual cognitive behavioural therapy, performed by 25 psychotherapist trainees, applying exposure sessions in graduated form or the flooding technique. Patients and therapists provided subjective evaluations of stress and five saliva samples for analysis of salivary cortisol and alpha-amylase either during two graduated exposure sessions or during one flooding session, while a regular therapy session served as control condition. Therapists displayed heightened salivary alpha-amylase release during exposure of the flooding, but not the graduated, type. Patients showed elevated salivary cortisol during flooding exposure numerically, however, not on a statistically significant level. Therapists reported more pronounced subjective stress during flooding compared to graduated exposure. Elevated stress levels should be addressed in clinical training in order to improve application of exposure in routine practice.

This work is part of the German multicenter trial ‘Mechanisms of Action in CBT (MAC)’. The MAC study is funded by the German Federal Ministry of Education and Research (BMBF; project no. 01GV0615) as part of the BMBF Psychotherapy Research Funding Initiative. The study was further supported by the DFG (Grant RE1632/5-1 and KFO 125 to AR; SFB TRR 58 Z02 to JD, PP and AR; C02 to JD and KD; DE357/4-1 to JD, AR, JR and AH; RTG 1256 to AR, JD and PP; IZKF-Würzburg Z-6 to HW). Corticotropin releasing hormone (CRH) is a major regulator of the hypothalamicpituitary-adrenal (HPA) axis. Binding to its receptor CRHR1 triggers the downstream release of cortisol, a hormone needed for regulation of stress responses. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here, we aimed to evaluate CRHR1 as a candidate molecule in panic disorder (PD). Allelic variation throughout the CRHR1 gene was captured by 9 selected single nucleotide polymorphisms (SNPs); these were genotyped in 531 matched case/control pairs (discovery sample (n=239); replication sample (n=292)). Four SNPs were found to be associated with PD, in at least one sub-sample. The minor alleles of rs17689918 and rs17689966 were found to significantly increase risk for PD in females of the discovery, the replication and the combined sample, both withstanding correction for multiple testing (prs17689918=1.3*10-4; prs17689966=0.042). Expressional analysis demonstrated that both minor alleles of rs17689918 and rs17689966 significantly decreased CRHR1 mRNA in the forebrain and amygdala. Bioinformatical analysis revealed a high proportion of differential neuro-relevant transcription factor binding possibly underlying expression changes. When investigating the neural correlates underlying this association, risk allele carriers of rs17689918 and rs17689966 showed aberrant differential conditioning and safety signal processing arguing for predominant generalization of fear and hence anxious apprehension. Furthermore, the minor risk (A) 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 CRHR1 expression driven by CRHR1 risk allele leads to a phenotype characterized by a fear bias and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder. Postprint

Background: Neurosteroids are synthesized both in brain and peripheral steroidogenic tissue from cholesterol or steroidal precursors. Neurosteroids have been shown to be implicated in neural proliferation, differentiation, and activity. Preclinical and clinical studies also suggest a modulatory role of neurosteroids in anxiety-related phenotypes. However, little is known about the contribution of genetic variants in genes relevant for the neurosteroidogenesis to anxiety disorders. Methods: We performed an association analysis of single nucleotide polymorphisms (SNPs) in five genes related to the neurosteroidal pathway with emphasis on progesterone and allopregnanolone biosynthesis (steroid-5-alpha-reductase 1A (SRD5A1), aldo-keto reductase family 1 C1-C3 (AKR1C1-AKR1C3) and translocator protein 18 kDA (TSPO) with panic disorder (PD) and dimensional anxietyintwoGermanPDsamples(casesN =522,controlsN =1,115).Results: Case–control analysis for PD and SNPs in the five selected genes was negative

Objectives: Although homework assignments are an integral component of cognitive-behavioral therapy (CBT) and relate to positive therapy outcomes, it is unclear whether specific homework types and their completion have specific effects on outcome. Method: Data from N = 292 patients (75% female, mean age 36 years) with panic disorder and agoraphobia and treated with standardized CBT were analyzed with homework compliance quality and quantity for different types of homework serving as predictors for different outcome variables. Results: Quality ratings of homework completion were stronger outcome predictors than quantitative compliance ratings. Exposure homework was a better outcome predictor than homework relating to psychoeducation and self-monitoring. Conclusion: Different aspects of homework compliance and specific homework types might differentially relate to CBT outcome.

Contains fulltext : 177350.pdf (Publisher’s version ) (Closed access) 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 GLRB gene (rs78726293, P=3.3 x 10-8; rs191260602, P=3.9 x 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 GLRB single-nucleotide variants rs17035816 (P=3.8 x 10-4) and rs7688285 (P=7.6 x 10-5). GLRB gene 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 GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout mice demonstrated an agoraphobic phenotype. In conjunction with the clinical observation that rare coding GLRB gene 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.

Objectives For characterizing the association between parenting and offspring social phobia (SP), contrasting maternal vs. paternal contributions, putative predictors of unfavorable parenting behaviors and its specificity for SP are warranted to delineate targeted prevention and intervention strategies. Methods A population-based sample of 1053 adolescents was followed-up using the M-CIDI. Parenting was assessed via questionnaire in offspring passing the high risk period for SP-onset. Natal complications and childhood serious health problems as assessed by maternal reports were hypothesized to relate to unfavorable parenting. Results The pattern of maternal overprotection, paternal rejection and lower emotional warmth was associated with SP, but not with other offspring anxiety disorders. Natal complications were related to overprotection and lower emotional warmth; trend-level associations emerged for serious health problems and unfavorable parenting. Conclusions Paternal behavior appears particularly relevant for SP. The pattern of maternal overprotection, paternal rejection and lower emotional warmth was observed in SP only, suggesting that its detailed assessment provides a promising opportunity for targeted prevention and intervention in SP.

Beesdo-Baum K, Knappe S, Fehm L, Hofler M, Lieb R, Hofmann SG, Wittchen H-U. The natural course of social anxiety disorder among adolescents and young adults. Objective: To examine the natural course of social anxiety disorder (SAD) in the community and to explore predictors for adverse long-term outcomes. Method: A community sample of N = 3021 subjects aged 14–24 was followed-up over 10 years using the DSM-IV/M-CIDI. Persistence of SAD is based on a composite score reflecting the proportion of years affected since onset. Diagnostic stability is the proportion of SAD subjects still affected at follow-up. Results: SAD reveals considerable persistence with more than half of the years observed since onset spent with symptoms. 56.7% of SAD cases revealed stability with at least symptomatic expressions at follow-up; 15.5% met SAD threshold criteria again. 15.1% were completely remitted (no SAD symptoms and no other mental disorders during follow-up). Several clinical features (early onset, generalized subtype, more anxiety cognitions, severe avoidance and impairment, co-occurring panic) and vulnerability characteristics (parental SAD and depression, behavioural inhibition, harm avoidance) predicted higher SAD persistence and – less impressively – diagnostic stability. Conclusion: A persistent course with a considerable degree of fluctuations in symptom severity is characteristic for SAD. Both consistently meeting full threshold diagnostic criteria and complete remissions are rare. Vulnerability and clinical severity indicators predict poor prognosis and might be helpful markers for intervention needs.

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. Theoretical background: There is a paucity of studies examining the role of therapist guidance during in-vivo exposure for panic disorder with agoraphobia (PD/AG). A recent study (MAC-study) suggested superior effects of therapist-guided exposure compared to programmed practice. Objectives: Examining potential mechanisms of therapist-guided exposure. Methods: Data from 301 patients with PD/AG who received either CBT with therapist guidance during in-vivo exposure (T+), or CBT with programmed exposure practice (T–) were analysed in regard to effects of initial symptom severity, subtle avoidance behaviours, reductions in fear of fear, and frequency of exposure homework. Results: There were no interaction effects between symptom severity or subtle avoidance and outcome. T+ was associated with higher reductions in fear of fear as well as with higher frequency of exposure homework. Frequency of exposure homework mediated the effect of group on outcome. Conclusion: Advantages of therapist-guided exposure as well as frequency of self-exposure might be attributed to higher reductions in fear of fear.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is a first-line treatment for panic disorder with agoraphobia (PD/AG). Nevertheless, an understanding of its mechanisms and particularly the role of therapist-guided exposure is lacking. This study was aimed to evaluate whether therapist-guided exposure in situ is associated with more pervasive and long-lasting effects than therapist-prescribed exposure in situ. METHOD: A multicenter randomized controlled trial, in which 369 PD/AG patients were treated and followed up for 6 months. Patients were randomized to 2 manual-based variants of CBT (T+/T-) or a wait-list control group (WL; n = 68) and were treated twice weekly for 12 sessions. CBT variants were identical in content, structure, and length, except for implementation of exposure in situ: In the T+ variant (n = 163), therapists planned and supervised exposure in situ exercises outside the therapy room; in the T- group (n = 138), therapists planned and discussed patients' in situ exposure exercises but did not accompany them. Primary outcome measures were (a) Hamilton Anxiety Scale, (b) Clinical Global Impression, (c) number of panic attacks, and (d) agoraphobic avoidance (Mobility Inventory). RESULTS: For T+ and T- compared with WL, all outcome measures improved significantly with large effect sizes from baseline to post (range = -0.5 to -2.5) and from post to follow-up (range = -0.02 to -1.0). T+ improved more than T- on the Clinical Global Impression and Mobility Inventory at post and follow-up and had greater reduction in panic attacks during the follow-up period. Reduction in agoraphobic avoidance accelerated after exposure was introduced. A dose-response relation was found for Time × Frequency of Exposure and reduction in agoraphobic avoidance. CONCLUSIONS: Therapist-guided exposure is more effective for agoraphobic avoidance, overall functioning, and panic attacks in the follow-up period than is CBT without therapist-guided exposure. Therapist-guided exposure promotes additional therapeutic improvement--possibly mediated by increased physical engagement in feared situations--beyond the effects of a CBT treatment in which exposure is simply instructed.

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn 107 Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case–control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli. Molecular Psychiatry (2011) 16, 938–948; doi:10.1038/mp.2010.81; published online 6 July 2010

Cognitive behavioral therapy (CBT) is efficacious for panic disorder with agoraphobia (PD/A). Nevertheless, the active ingredients of treatment and the mechanisms through which CBT achieves its effects remain largely unknown. The mechanisms of action in CBT (MAC) study was established to investigate these questions in 369 patients diagnosed with PD/A. The MAC study utilized a multi-center, randomized controlled design, with two active treatment conditions in which the administration of exposure was varied, and a wait-list control group. The special feature of MAC is the way in which imbedded experimental, psychophysiological, and neurobiological paradigms were included to elucidate therapeutic and psychopathological processes. This paper describes the aims and goals of the MAC study and the methods utilized to achieve them. All aspects of the research design (e.g., assessments, treatment, experimental procedures) were implemented so as to facilitate the detection of active therapeutic components, and the mediators and moderators of therapeutic change. To this end, clinical, behavioral, physiological, experimental, and genetic data were collected and will be integrated.

Parental psychopathology and unfavorable family environment are established risk factors for onset of offspring social phobia (SP), but their associations with the further course, e.g., persistence of the disorder, remain understudied. A community cohort of 1395 adolescents and their parents was followed-up over almost 10 years using the DIA-X/M-CIDI. Parental diagnostic interviews were supplemented by family history data. Parental rearing was retrospectively assessed by the Questionnaire of Recalled Parental Rearing Behavior in offspring, and family functioning by the Family Assessment Device in parents. Persistence measures (proportion of years affected since onset) were derived from diagnostic interviews, using age of onset, age of recency, and course information. Lack of emotional warmth and dysfunctional family functioning characteristics were associated with higher SP persistence, particularly in interaction with parental psychopathology. Predictors for SP persistence differ from those predicting SP onset. Unfavorable family environment alone and in interaction with parental disorders predict higher SP persistence.

Hausaufgabenvereinbarungen zahlen zum Standardrepertoire psychotherapeutischer Interventionen. Wie kaum eine andere Intervention bieten therapeutische Hausaufgaben die Moglichkeit, die Eigenverantwortlichkeit des Patienten im Veranderungsprozess zu starken sowie die Therapie zu vertiefen und zu intensivieren. Ungeachtet dieses hohen Potenzials werden Hausaufgaben in der Psychotherapie noch viel zu selten systematisch eingesetzt. Auch vonseiten der Psychotherapieforschung wurden Hausaufgaben erst spat als eine wirksame therapeutische Methode aufgegriffen und untersucht. Mittlerweile kann als belegt gelten, dass der Einsatz von Hausaufgaben die Therapieergebnisse verbessert. Wenig ist jedoch daruber bekannt, welches therapeutische Vorgehen diese Effekte optimal fordert. Im vorliegenden Beitrag werden wichtige Funktionen von Hausaufgaben im therapeutischen Prozess im Zusammenhang mit den theoretisch angenommenen Wirkmechanismen vorgestellt und Empfehlungen fur den effektiven Einsatz von Hausaufgaben sowohl aus empirischer als auch aus praktischer Sicht gegeben.

Background: To examine the role of parental psychopathology and family environment for the risk of social phobia (SP) in off spring from childhood to early adulthood, encompassing the high risk period for SP Methods: A community sample of 1,395 adolescents was prospectively followed-up over 10 years. Offspring and parental pychopathology were assessed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV using the Munich Composite International Diagnostic Interview (M-CIDI), and direct diagnostic interviews in parents were supplemented by family history reports. Parental rearing was assessed by the Questionnaire of Recalled Rearing Behavior administered to offspring. Family functioning was assessed by the McMaster Family Assessment Device administered to parents. Results: Parental SP was associated with offspring's risk to develop SP (OR = 3.3, 95% CI 1.4-8.0). Other parental anxiety disorders (OR=2.9, 95% CI: 1.4-6.1), depression (OR=2.6, 95% CI: 1.2-5.4), and alcohol use disorders (OR = 2.8, 95% CI. 1.3-6.1) were also associated with offspring SP Parental rearing styles of overprotection, rejection, and lack of emotional warmth, were associated with offspring SP Family functioning measures were not associated with off spring SP Analyses of interaction of parental psychopathology and parental rearing indicated combined effects oil the risk for offspring SP Conclusions: Parental psychopathology and rearing were associated with offspring SP, independently as well as in their interaction. Further delineation of these associations is warranted as malleable components of these risk factors may provide potential targets for prevention programs. In addition, parent-to-offspring transmission of other internalizing disorders should be considered to examine the degree of diagnostic specificity. Depression and Anxiety 26:363-370, 2009.