Sylvia Helbig-Lang

Mechanism of action in CBT (MAC): methods of a multi-center randomized controlled trial in 369 patients with panic disorder and agoraphobia

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.

MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy.

Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.

Dynamics of Defensive Reactivity in Patients with Panic Disorder and Agoraphobia: Implications for the Etiology of Panic Disorder

BACKGROUND The learning perspective of panic disorder distinguishes between acute panic and anxious apprehension as distinct emotional states. Following animal models, these clinical entities reflect different stages of defensive reactivity depending upon the imminence of interoceptive or exteroceptive threat cues. The current study tested this model by investigating the dynamics of defensive reactivity in a large group of patients with panic disorder and agoraphobia (PD/AG). METHODS Three hundred forty-five PD/AG patients participated in a standardized behavioral avoidance test (being entrapped in a small, dark chamber for 10 minutes). Defense reactivity was assessed measuring avoidance and escape behavior, self-reports of anxiety and panic symptoms, autonomic arousal (heart rate and skin conductance), and potentiation of the startle reflex before and during exposure of the behavioral avoidance test. RESULTS Panic disorder and agoraphobia patients differed substantially in their defensive reactivity. While 31.6% of the patients showed strong anxious apprehension during this task (as indexed by increased reports of anxiety, elevated physiological arousal, and startle potentiation), 20.9% of the patients escaped from the test chamber. Active escape was initiated at the peak of the autonomic surge accompanied by an inhibition of the startle response as predicted by the animal model. These physiological responses resembled the pattern observed during the 34 reported panic attacks. CONCLUSIONS We found evidence that defensive reactivity in PD/AG patients is dynamically organized ranging from anxious apprehension to panic with increasing proximity of interoceptive threat. These data support the learning perspective of panic disorder.

Specificity of Homework Compliance Effects on Treatment Outcome in CBT: Evidence from a Controlled Trial on Panic Disorder and Agoraphobia

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.

The role of safety behaviors in exposure-based treatment for panic disorder and agoraphobia: associations to symptom severity, treatment course, and outcome

The potentially detrimental effects of safety behaviors during exposure therapy are still subject to debate. Empirical findings are inconsistent, and few studies have investigated effects of idiosyncratic safety behavior manifestations during exposure or in everyday life. These limitations might be due to a lack of appropriate measures that address individual safety behaviors. We examined psychometric properties and predictive value of the Texas Safety Maneuver Scale (TSMS), a questionnaire specifically targeting safety behaviors in panic disorder and agoraphobia. Effects of safety behavior use, both during everyday life and during therapy, were examined using data from a multicenter RCT of N=268 patients that aimed at evaluating efficacy and mechanisms of action of two variants of an exposure-based therapy. The TSMS total score demonstrated good internal consistency (α=0.89), and it showed significant correlations with selected measures of baseline anxiety and impairment. The proposed factor structure could not be replicated. Frequent safety behavior use at baseline was associated with actual safety behavior during exposure exercises. Pronounced in-situ safety behavior, but not baseline safety behavior was associated to detrimental treatment outcome. The results underline the relevance of a rigorous safety behavior assessment in therapy. The actual relationship between safety behavior use and treatment outcome is yet to determine.

Was wirkt in der Kognitiven Verhaltenstherapie der Panikstörung mit Agoraphobie? Ein systematisches Review

Zusammenfassung. Die kognitive Verhaltenstherapie (KVT) hat sich in empirischen Studien als wirksame Behandlungsform von Pa- nikstorungen mit Agoraphobie erwiesen. Zu den zentralen Behandlungskomponenten gehoren a) Psychoedukation uber Angst und Panik, b) kognitive Interventionen, um die Tendenz zu Missinterpretationen korperlicher Wahrnehmungen zu vermindern, c) interozeptive und in vivo Exposition sowie d) Bewaltigungskompetenzen zur Beeinflussung von korperlichen Symptomen, wie beispielsweise Entspan- nungs- und Atemtechniken. Empirische Befunde zur Effektivitat dieser Interventionen werden vorgestellt und abschliesend hinsichtlich ihrer Bedeutung im Rahmen einer evidenzbasierten Therapie der Panikstorung mit und ohne Agoraphobie in der Praxis diskutiert. Schlusselworter: Panikstorung, Agoraphobie, kognitive Verhaltenstherapie, Exposition, Entspannungsverfahren, Atemtraining Abstract. Cognitive-behavioral therapy can be regarded as gold standard in treating panic disorder and agoraphobia. Frequently endorsed intervention techniques are a) psychoeducation about anxiety and panic, b) cognitive restructuring regarding the tendency to catastrophize perceived bodily symptoms, c) exposure to internal as well as external cues, and d) training of coping strategies for dealing with bodily symptoms, e.g., relaxation techniques and breathing retraining. Empirical findings on these interventions are reviewed and discussed regarding their importance within the frame of evidence-based CBT treatment for panic disorder and agoraphobia.

Kann man chronische Depression effektiv psychotherapeutisch behandeln

Chronische Depression gilt in der klinischen Praxis als besonders schwer behandelbar. Die Befundlage zu dieser Annahme ist jedoch unbefriedigend. Die wenigen existierenden Effektivitatsstudien zu verschiedenen Formen von Psychotherapie bei chronischen Depressionen (z. B. KVT, IPT, CBASP) zeigen tatsachlich, dass die Wirksamkeit eines rein psychotherapeutischen Vorgehens bei chronischen Depressionen begrenzt zu sein scheint; es gibt jedoch Hinweise auf additive Effekte im Rahmen einer Kombinationsbehandlung mit Psychopharmaka. Welchen spezifischen Nutzen neue oder modifizierte Behandlungsverfahren gegenuber klassischen Behandlungsverfahren haben, ist offen, da bislang keine Studien existieren, die diese Verfahren direkt mit klassischen Behandlungsansatzen vergleichen. Weiterhin offen bleibt, inwieweit die schlechten Behandlungsergebnisse tatsachlich der Chronizitat der depressiven Storung geschuldet sind, oder ob andere Faktoren, wie eine hohe Achse-II-Komorbiditat, den Ausschlag dafur geben.

Expositionsbasierte Therapie der Panikstörung mit Agoraphobie

Die Wirksamkeit von kognitiv-verhaltenstherapeutischen Programmen bei Panikstorung und Agoraphobie wurde vielfach nachgewiesen. Diese Programme bestehen in der Regel aus verschiedensten Interventionen, wobei Exposition eine der wirksamsten Strategien darstellt. In der therapeutischen Praxis gestaltet sich die Durchfuhrung der Expositionsubungen aus organisatorischen und inhaltlichen Grunden jedoch haufig schwierig. Das vorliegende Manual stellt die Expositionskomponente in den Mittelpunkt der Behandlung und beschreibt zwei Anwendungsvarianten: Exposition mit Therapeutenbegleitung in der Situation sowie ausfuhrliche Vor- und Nachbereitung von Expositionsubungen ohne explizite Therapeutenbegleitung. Nach einer Beschreibung des Storungsbildes und des diagnostischen Vorgehens werden die 12 Sitzungen des Therapieprogrammes praxisorientiert dargestellt. Zu Beginn der Behandlung werden im Rahmen der Psychoedukation die individuellen Entstehungs- und Aufrechterhaltungsbedingungen der Storung gemeinsam erarbeitet. Mit Hilfe strukturierter Therapiematerialien wird der Patient Schritt fur Schritt an die Expositionsdurchfuhrung herangefuhrt. Zunachst werden Expositionsubungen zur Reduktion der Angst vor Korpersymptomen gemeinsam durchgefuhrt, bevor anschliesend Ubungen zur Reduktion der Angst in Situationen geplant werden. Fur die Ubungsbesprechung und die Durchfuhrung von Hausaufgaben stehen Expositionsprotokolle zur Verfugung. Ausfuhrlich wird auch auf den Umgang mit Problemen bei der Durchfuhrung der Ubungen eingegangen. Das Programm beinhaltet ferner zwei Auffrischungssitzungen zur Ruckfallprophylaxe. Die zahlreichen Arbeitsmaterialien liegen auf einer CD-ROM vor. Die Wirksamkeit des Behandlungsprogramms wurde in einer kontrollierten Studie an 369 Patienten mit Panikstorung und Agoraphobie nachgewiesen.

Zum empirischen Aussagegehalt des Konzepts «Chronische Depression»

Bei der chronischen Depression handelt es sich um ein am Storungsverlauf orientiertes Konstrukt, dessen empirische Fundierung bislang nur als unzureichend charakterisiert werden kann. Vor diesem Hintergrund werden die bisher gangigen Definitionen chronischer Depression empirischen Befunden zur Abgrenzung von akuten bzw. episodischen Depressionen gegenubergestellt. Aus empirischer Sicht gibt es bislang nur begrenzt Evidenz fur eine inhaltsvalide Abgrenzung chronischer und akuter Depression, wenngleich einzelne Hinweise auf Unterschiede in der Entwicklungspsychopathologie dieser Depressionsformen existieren. Die bisherige Klassifikation von Subtypen chronischer Depression scheint dagegen empirisch nicht haltbar zu sein. In der Diagnostik und Fruherkennung chronischer Depression sollte verstarkt auf eine Familienanamnese affektiver Storungen geachtet werden. Weitere Studien sollten modifizierte, z. B. dimensionale Definitionen der Chronizitat mit einbeziehen.

How Well Can We Measure Visual Attention? Psychometric Properties of Manual Response Times and First Fixation Latencies in a Visual Search Paradigm

Attentional biases are considered to be important for the development and maintenance of anxiety disorders, but despite widespread research in this area, the psychometric properties of measures targeting attentional allocation processes have rarely been evaluated. The current study assessed the reliability and validity of manual response times and first fixation latencies within a visual search paradigm, including data from one hundred twenty-two participants (n = sixty-two participants with social anxiety disorder). We found raw manual response times to be highly reliable, while raw first fixation latencies, in most cases, were not. Bias scores were neither reliable for manual responses nor for first fixation latencies. However, we found indicators of convergent validity, as raw values and also bias scores of both measures were significantly correlated. These results raise doubts about our ability to accurately measure visual attention, especially via eye-tracking procedures.