PANIK-Netz: Teilprojekt P5b

Specificity in CBT treatment effects: Exploring the impact of psychophysiological subtypes of panic disorder and their relation to genotype

Principal Investigator:
PD Dr. Alexander L. Gerlach
Institute of Psychology
University of Münster
Fliednerstr. 21
D-48149 Münster
Tel.: +49 251 83 34132
Fax.: +49 251 83 31331

Duration applied for
3 years.

Project description:
Introduction / state of the art
Panic attack subtypes have been identified in a number of studies employing factor and cluster analytic methodology based on self-reports of attack symptoms (e.g. Seguí et al., 1998). More importantly, one such subtype reliably showed congruous physiological reactivity in a challenge paradigm (Beck, Shipherd, & Ohtake, 2000; Beck, Ohtake, & Shipherd, 1999). The identification of panic disorder subtypes is important both for genetic and for treatment outcome studies. Whereas twin and family studies clearly demonstrate genetic risk factors beyond doubt (e. g. van West & Claes, 2004), attempts to map the loci underlying these genetic factors have been mostly inconclusive (Gordon & Hen, 2004). On this background, it seems mandatory to analyze the association of PD phenotypes with patient groups identified in biological challenge paradigms. Two biological subtypes are especially promising: Respiratory Subtype: Respiratory irregularities are often reported by panic disorder patients and recent studies successfully identified biologically defined subgroups of panic patients with respiratory abnormalities (Beck, Shipherd, & Ohtake, 2000; Biber & Alkin, 1999; Hegel & Ferguson, 1997). However, they did not follow these patients during treatment. Vestibulary Subtype: There is a close association between balance control and anxiety (Sklare, Konrad, Maser, & Jacob, 2001). Dizziness and body sway are common symptoms in panic attacks and comorbidity of vestibular and anxiety disorders is high (Balaban & Jacob, 2001). Therefore, subclinical vestibular dysfunctions likely contribute to the onset and maintenance of panic disorder in a patient subgroup (Erez, Gordon, Sever, Sadeh, & Mintz, 2004).

The goal is to identify the above described biologically defined subtypes of PD and agoraphobia by means of specific challenges, relate the physiological reactions observed to self-report panic symptomatology (BSQ) and to follow these subtypes throughout treatment. Moreover, it will be investigated how anticipation of these different challenges might modulate autonomic responding and startle reactivity in anticipation of exposure (P5). This will clarify the impact of differential symptomatology on treatment efficacy and indicate to what extent treatment needs to be tailored specifically. In cooperation with Prof. Deckert, we will relate these biologically defined panic subtypes (phenotypes) to specific genotypes (see project P6). By following patients throughout treatment we will explore the relationship between subtypes and treatment response.

Previous work and resources:
Our group has extensive experience with psychophysiological measurements in anxiety disorders in general (e. g. Gerlach, Wilhelm, Gruber & Roth 2001; Gerlach et al. in press.) as well as specifically with respiratory challenges in panic disorder (e. g. Wilhelm, Gerlach, & Roth, 1999). Currently, e.g. a DFG-sponsored study in social phobia is being undertaken. Even more relevant to the present proposal, we have just completed an analysis of self-report panic symptomatology using probabilistic latent factor analysis in a sample of 517 panic/agoraphobia patients. The model identifying subgroups based on symptomatology was stable across several subsamples of these patients (Schneider, Gerlach, & Rist, 2005). Our large outpatient treatment center is treating ~1000 patients per year. All therapists are supervised by licensed and CBT trained supervisors. Finally, a productive collaboration has already been established with the research group of Professor Deckert (Gerlach et al.; in press).
Gerlach, A. L., Spellmeyer, G. Vögele, C., Huster, R. Stephens, S., Hetzel, G. & Deckert, J. (in press) Blood-injury phobia with and without a history of fainting: Disgust sensitivity does not explain the fainting response. Psychosomatic Medicine.
Gerlach, A. L., Mourlane, D., & Rist, F. (2004). Public and private heart rate feedback in social phobia: A manipulation of anxiety visibility. Cognitive Behaviour Therapy, 33, 36-45.
Gerlach, A. L., Wilhelm, F. H., Gruber, K., & Roth, W. T. (2001). Blushing and physiological arousability in social phobia. Journal of Abnormal Psychology, 110, 247-258.
Schneider, F., Gerlach, A. L., & Rist, F. (2004). Panik ist nicht gleich Panik: Identifikation von Subtypen des Panikanfalls. (Poster presented at the 22. Symposium für Klinisch-Psychologische Forschung, 6.-8. April 2004 in Halle, Germany).
Wilhelm, F. H., Gerlach, A. L., & Roth, W. T. (1999). Slow recovery from voluntary hyperventilation in panic disorder. Psychosomatic Medicine, 63, 638-649.

Work program:
We plan to examine 60 panic patients in two different types of challenges tailored to trigger the respective subtype-relevant symptomatology. Self report of panic symptomatology (dizziness and respiratory symptoms) will be used to preselect patients and will be related to the respective physiological reactions. Subsequent treatment will strictly follow the procedures outlined in the core clinical network project. Gender- and age-matched controls will also be assessed to control for not anxiety related activation during the tasks.
Procedures: The respiratory challenge will follow the protocol by Beck et. al. (1999, 2000) and the vestibular challenge will rely on a visual challenge to induce body sway (Redfern, Yardley, & Bronstein, 2001). We currently are establishing the set-up for both the vestibular challenge and the respiratory challenge, and we started to collect pilot data with healthy controls (approved by the local ethics committee). The patients will be tested (a) at the beginning of CBT, (b) after therapy, and (c) at 6 months follow up according to the core clinical network protocol (P2), allowing us to assess stability of the subtype typology as well as changes in their reactivity.
Measures: During the two panic provocation tests we will measure ECG, respiration (pneumotachography and petCO2) and skin conductance.

Cooperation and Add on
All 60 patients of the current study will also participate in the psychophysiological assessment during the anticipation of a behavioral avoidance task (narrow dark room). It will therefore be possible to relate the data of the anticipation of respiratory and vestibulatory challenge to the findings of the clinical assessment of anticipatory anxiety. DNA of all participating patients will be genotyped (P6) allowing to assess the contribution of genetic variation to interindividual responses.

Ethical and legal considerations
No unusual risks or ethical concerns involved.