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A new paradigm (Westphal-Paradigm) to study the neural correlates of panic disorder with agoraphobia

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Abstract

Agoraphobia (with and without panic disorder) is a highly prevalent and disabling anxiety disorder. Its neural complexity can be characterized by specific cues in fMRI studies. Therefore, we developed a fMRI paradigm with agoraphobia-specific stimuli. Pictures of potential agoraphobic situations were generated. Twenty-six patients, suffering from panic disorder and agoraphobia, and 22 healthy controls rated the pictures with respect to arousal, valence, and agoraphobia-related anxiety. The 96 pictures, which discriminated best between groups were chosen, split into two parallel sets and supplemented with matched neutral pictures from the International Affective Picture System. Reliability, criterion, and construct validity of the picture set were determined in a second sample (44 patients, 28 controls). The resulting event-related “Westphal-Paradigm” with cued and uncued pictures was tested in a fMRI pilot study with 16 patients. Internal consistency of the sets was very high; parallelism was given. Positive correlations of picture ratings with Mobility Inventory and Hamilton anxiety scores support construct validity. FMRI data revealed activations in areas associated with the fear circuit including amygdala, insula, and hippocampal areas. Psychometric properties of the Westphal-Paradigm meet necessary quality requirements for further scientific use. The paradigm reliably produces behavioral and fMRI patterns in response to agoraphobia-specific stimuli. To our knowledge, it is the first fMRI paradigm with these properties. This paradigm can be used to further characterize the functional neuroanatomy of panic disorder and agoraphobia and might be useful to contribute data to the differentiation of panic disorder and agoraphobia as related, but conceptually different clinical disorders.

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Acknowledgments

We thank Hans-Ulrich Wittchen for his generous and helpful discussion of these results and Lorna Schlochtermeier for support and feedback. This work is part of the German multicenter trial ‘‘Mechanisms of Action in CBT (MAC)’’ [13] as associated fMRI project “Emotional processing and the fear circuit in the course of CBT intervention: a multicenter 3 Tesla fMRI study in panic disorder.” and funded by the German Federal Ministry of Education and Research (BMBF; project no. 01GV0612) as part of the BMBF Psychotherapy Research Funding Initiative.

Centers Principal investigators (PI) with respective areas of responsibility in the MAC study are V. Arolt (Münster: Overall MAC Program Coordination), H.U. Wittchen (Dresden: Principal Investigator (PI) for the Randomized Clinical Trial and Manual Development), A. Hamm (Greifswald: PI for Psychophysiology), A.L. Gerlach (Münster: PI for Psychophysiology and Panic subtypes), A. Ströhle (Berlin: PI for Experimental Pharmacology), T. Kircher (Marburg: PI for functional neuroimaging), and J. Deckert (Würzburg: PI for Genetics). Additional site directors in the RTC component of the program are G.W. Alpers (Würzburg), T. Fydrich and L. Fehm (Berlin-Adlershof), and T. Lang (Bremen).

Data Access and Responsibility All principle investigators take responsibility for the integrity of the respective study data and their components. All authors and co-authors had full access to all study data. Data analysis and manuscript preparation were completed by the authors and co-authors of this article, who take responsibility for its accuracy and content.

Acknowledgements and staff members by site Greifswald (coordinating site for Psychophysiology): Christiane Melzig, Jan Richter, Susan Richter, Matthias von Rad; Berlin-Charite (coordinating Center for Experimental Pharmacology): Harald Bruhn, Anja Siegmund, Meline Stoy, André Wittmann; Berlin-Adlershof: Irene Schulz; Münster (Overall MAC Program Coordination, Genetics and Functional Neuroimaging): Andreas Behnken, Katharina Domschke, Adrianna Ewert, Carsten Konrad, Bettina Pfleiderer, Peter Zwanzger Münster (coordinating site for psychophysiology and subtyping): Judith Eidecker, Swantje Koller, Fred Rist, Anna Vossbeck-Elsebusch; Marburg/Aachen (coordinating center for functional neuroimaging): Barbara Drüke, Sonja Eskens, Thomas Forkmann, Siegfried Gauggel, Susan Gruber, Andreas Jansen, Thilo Kellermann, Isabelle Reinhardt, Nina Vercamer-Fabri; Dresden (coordinating site for data collection, analysis, and the RCT): Franziska Einsle, Christine Fröhlich, Andrew T. Gloster, Christina Hauke, Simone Heinze, Michael Höfler, Ulrike Lueken, Peter Neudeck, Stephanie Preiß, Dorte Westphal; Würzburg Psychiatry Department (coordinating center for genetics): Andreas Reif; Würzburg Psychology Department: Julia Dürner, Hedwig Eisenbarth, Antje B. M. Gerdes, Harald Krebs, Paul Pauli, Silvia Schad, Nina Steinhäuser; Bremen: Veronika Bamann, Sylvia Helbig-Lang, Anne Kordt, Pia Ley, Franz Petermann, Eva-Maria Schröder. Additional support was provided by the coordinating center for clinical studies in Dresden (KKS Dresden): Xina Grählert and Marko Käppler.

The RTC project was approved by the Ethics Committee of the Medical Faculty of the Technical University of Dresden (EK 164082006). The neuroimaging components were approved by the Ethics Committee of the Medical Faculty of the Rheinisch-Westfälische Hochschule University Aachen (EK 073/07). The experimental pharmacology study was approved by the Ethics Committee of the state of Berlin (EudraCT: 2006-00-4860-29). The study was registered with the ISRCTN: ISRCTN80046034.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    A. Wittmann, F. Schlagenhauf, T. John, A. Guhn, A. Siegmund, M. Stoy, D. Held, A. Heinz & A. Ströhle

  2. Institute of Psychology, Psychotherapy and Somatopsychology, Humboldt Universität Berlin, Rudower Chaussee 18, 12489, Berlin, Germany

    I. Schulz, L. Fehm & T. Fydrich

  3. Department of Radiology, Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    H. Rehbein & H. Bruhn

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  1. A. Wittmann
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  2. F. Schlagenhauf
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  14. A. Ströhle
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Correspondence to A. Wittmann.

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Wittmann, A., Schlagenhauf, F., John, T. et al. A new paradigm (Westphal-Paradigm) to study the neural correlates of panic disorder with agoraphobia. Eur Arch Psychiatry Clin Neurosci 261, 185–194 (2011). https://doi.org/10.1007/s00406-010-0167-1

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  • DOI: https://doi.org/10.1007/s00406-010-0167-1

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