Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-25T03:58:15.042Z Has data issue: false hasContentIssue false

Anticipating agoraphobic situations: the neural correlates of panic disorder with agoraphobia

Published online by Cambridge University Press:  07 January 2014

A. Wittmann*
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany
F. Schlagenhauf
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany Max Planck Institute for Human Cognitive and Brain Science, Leipzig, Germany
A. Guhn
Affiliation:
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
U. Lueken
Affiliation:
Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany
C. Gaehlsdorf
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany
M. Stoy
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany
F. Bermpohl
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany Berlin School of Mind and Brain, Berlin, Germany
T. Fydrich
Affiliation:
Institute of Psychology, Psychotherapy and Somatopsychology – Humboldt Universität zu Berlin, Germany
B. Pfleiderer
Affiliation:
Department of Clinical Radiology, University of Münster, Münster, Germany
H. Bruhn
Affiliation:
Department of Radiology, University of Jena, Jena, Germany
A. L. Gerlach
Affiliation:
Department of Psychology, University of Cologne, Cologne, Germany
T. Kircher
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany
B. Straube
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany
H.-U. Wittchen
Affiliation:
Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany
V. Arolt
Affiliation:
Department of Psychiatry, University of Münster, Münster, Germany
A. Heinz
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany
A. Ströhle
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany
*
*Address for correspondence: Mr A. Wittmann, Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. (Email: [email protected])

Abstract

Background

Panic disorder with agoraphobia is characterized by panic attacks and anxiety in situations where escape might be difficult. However, neuroimaging studies specifically focusing on agoraphobia are rare. Here we used functional magnetic resonance imaging (fMRI) with disorder-specific stimuli to investigate the neural substrates of agoraphobia.

Method

We compared the neural activations of 72 patients suffering from panic disorder with agoraphobia with 72 matched healthy control subjects in a 3-T fMRI study. To isolate agoraphobia-specific alterations we tested the effects of the anticipation and perception of an agoraphobia-specific stimulus set. During fMRI, 48 agoraphobia-specific and 48 neutral pictures were randomly presented with and without anticipatory stimulus indicating the content of the subsequent pictures (Westphal paradigm).

Results

During the anticipation of agoraphobia-specific pictures, stronger activations were found in the bilateral ventral striatum and left insula in patients compared with controls. There were no group differences during the perception phase of agoraphobia-specific pictures.

Conclusions

This study revealed stronger region-specific activations in patients suffering from panic disorder with agoraphobia in anticipation of agoraphobia-specific stimuli. Patients seem to process these stimuli more intensively based on individual salience. Hyperactivation of the ventral striatum and insula when anticipating agoraphobia-specific situations might be a central neurofunctional correlate of agoraphobia. Knowledge about the neural correlates of anticipatory and perceptual processes regarding agoraphobic situations will help to optimize and evaluate treatments, such as exposure therapy, in patients with panic disorder and agoraphobia.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Boshuisen, ML, Ter Horst, GJ, Paans, AM, Reinders, AA, den Boer, JA (2002). rCBF differences between panic disorder patients and control subjects during anticipatory anxiety and rest. Biological Psychiatry 52, 126135.Google Scholar
Bradley, MM, Lang, PJ (1994). Measuring emotion: the Self-Assessment Manikin and the Semantic Differential. Journal of Behavior Therapy and Experimental Psychiatry 25, 4959.Google Scholar
Chambless, DL, Caputo, GC, Jasin, SE, Gracely, EJ, Williams, C (1985). The Mobility Inventory for Agoraphobia. Behaviour Research and Therapy 23, 3544.CrossRefGoogle ScholarPubMed
Delgado, MR, Jou, RL, Ledoux, JE, Phelps, EA (2009). Avoiding negative outcomes: tracking the mechanisms of avoidance learning in humans during fear conditioning. Frontiers in Behavioral Neuroscience 3, 33.CrossRefGoogle ScholarPubMed
Dresler, T, Guhn, A, Tupak, SV, Ehlis, AC, Herrmann, MJ, Fallgatter, AJ, Deckert, J, Domschke, K (2012). Revise the revised? New dimensions of the neuroanatomical hypothesis of panic disorder. Journal of Neural Transmission 120, 329.Google Scholar
Etkin, A, Wager, TD (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry 164, 14761488.Google Scholar
Friedman, L, Glover, GH (2006). Reducing interscanner variability of activation in a multicenter fMRI study: controlling for signal-to-fluctuation-noise-ratio (SFNR) differences. NeuroImage 33, 471481.Google Scholar
Gloster, AT, Wittchen, HU, Einsle, F, Hofler, M, Lang, T, Helbig-Lang, S, Fydrich, T, Fehm, L, Hamm, AO, Richter, J, Alpers, GW, Gerlach, AL, Strohle, A, Kircher, T, Deckert, J, Zwanzger, P, Arolt, V (2009). Mechanism of action in CBT (MAC): methods of a multi-center randomized controlled trial in 369 patients with panic disorder and agoraphobia. European Archives of Psychiatry and Clinical Neuroscience 259 (Suppl. 2), S155S166.Google Scholar
Gloster, AT, Wittchen, HU, Einsle, F, Lang, T, Helbig-Lang, S, Fydrich, T, Fehm, L, Hamm, AO, Richter, J, Alpers, GW, Gerlach, AL, Strohle, A, Kircher, T, Deckert, J, Zwanzger, P, Hofler, M, Arolt, V (2011). Psychological treatment for panic disorder with agoraphobia: a randomized controlled trial to examine the role of therapist-guided exposure in situ in CBT. Journal of Consulting and Clinical Psychology 79, 406420.Google Scholar
Gorman, JM, Kent, JM, Sullivan, GM, Coplan, JD (2000). Neuroanatomical hypothesis of panic disorder, revised. American Journal of Psychiatry 157, 493505.CrossRefGoogle ScholarPubMed
Guy, W (1976). Clinical global impression. In ECDEU Assessment Manual for Psychopharmacology, Revised (ed. Guy, W.), pp. 217222. National Insitute of Mental Health: Rockville.Google Scholar
Guyer, AE, Choate, VR, Detloff, A, Benson, B, Nelson, EE, Perez-Edgar, K, Fox, NA, Pine, DS, Ernst, M (2012). Striatal functional alteration during incentive anticipation in pediatric anxiety disorders. American Journal of Psychiatry 169, 205212.Google Scholar
Guyer, AE, Lau, JY, McClure-Tone, EB, Parrish, J, Shiffrin, ND, Reynolds, RC, Chen, G, Blair, RJ, Leibenluft, E, Fox, NA, Ernst, M, Pine, DS, Nelson, EE (2008). Amygdala and ventrolateral prefrontal cortex function during anticipated peer evaluation in pediatric social anxiety. Archives of General Psychiatry 65, 13031312.Google Scholar
Heinz, A, Schlagenhauf, F (2010). Dopaminergic dysfunction in schizophrenia: salience attribution revisited. Schizophrenia Bulletin 36, 472485.Google Scholar
Helbig-Lang, S, Lang, T, Petermann, F, Hoyer, J (2012). Anticipatory anxiety as a function of panic attacks and panic-related self-efficacy: an ambulatory assessment study in panic disorder. Behavioural and Cognitive Psychotherapy 40, 590604.Google Scholar
Herwig, U, Abler, B, Walter, H, Erk, S (2007). Expecting unpleasant stimuli – an fMRI study. Psychiatry Research 154, 112.CrossRefGoogle ScholarPubMed
Holzschneider, K, Mulert, C (2011). Neuroimaging in anxiety disorders. Dialogues in Clinical Neuroscience 13, 453461.CrossRefGoogle ScholarPubMed
Horvitz, JC (2002). Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum. Behavioural Brain Research 137, 6574.Google Scholar
Ishihara, S (1917). Tests for Colour-Blindness. Hongo Harukicho Handaya: Tokyo.Google Scholar
Jensen, J, McIntosh, AR, Crawley, AP, Mikulis, DJ, Remington, G, Kapur, S (2003). Direct activation of the ventral striatum in anticipation of aversive stimuli. Neuron 40, 12511257.Google Scholar
Kessler, RC, Chiu, WT, Jin, R, Ruscio, AM, Shear, K, Walters, EE (2006). The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication. Archives of General Psychiatry 63, 415424.Google Scholar
Kircher, T, Arolt, V, Jansen, A, Pyka, M, Reinhardt, I, Kellermann, T, Konrad, C, Lueken, U, Gloster, AT, Gerlach, AL, Strohle, A, Wittmann, A, Pfleiderer, B, Wittchen, HU, Straube, B (2013). Effect of cognitive-behavioral therapy on neural correlates of fear conditioning in panic disorder. Biological Psychiatry 73, 93101.Google Scholar
Lang, PJ, Bradley, MM, Cuthbert, BN (1997). International Affective Picture System (IAPS): Technical Manual and Affective Ratings. NIMH Center for the Study of Emotion and Attention, University of Florida: Gainesville, FL.Google Scholar
Liu, X, Hairston, J, Schrier, M, Fan, J (2011). Common and distinct networks underlying reward valence and processing stages: a meta-analysis of functional neuroimaging studies. Neuroscience and Biobehavioral Reviews 35, 12191236.CrossRefGoogle ScholarPubMed
Lorberbaum, JP, Kose, S, Johnson, MR, Arana, GW, Sullivan, LK, Hamner, MB, Ballenger, JC, Lydiard, RB, Brodrick, PS, Bohning, DE, George, MS (2004). Neural correlates of speech anticipatory anxiety in generalized social phobia. Neuroreport 15, 27012705.Google Scholar
Maldjian, JA, Laurienti, PJ, Kraft, RA, Burdette, JH (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19, 12331239.CrossRefGoogle ScholarPubMed
Menon, V, Uddin, LQ (2010). Saliency, switching, attention and control: a network model of insula function. Brain Structure and Function 214, 655667.Google Scholar
Nagai, M, Kishi, K, Kato, S (2007). Insular cortex and neuropsychiatric disorders: a review of recent literature. European Psychiatry 22, 387394.CrossRefGoogle ScholarPubMed
Oldfield, RC (1971). The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia 9, 97113.Google Scholar
Paulus, MP, Stein, MB (2006). An insular view of anxiety. Biological Psychiatry 60, 383387.CrossRefGoogle ScholarPubMed
Phillips, ML, Drevets, WC, Rauch, SL, Lane, R (2003). Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biological Psychiatry 54, 504514.Google Scholar
Sakai, Y, Kumano, H, Nishikawa, M, Sakano, Y, Kaiya, H, Imabayashi, E, Ohnishi, T, Matsuda, H, Yasuda, A, Sato, A, Diksic, M, Kuboki, T (2005). Cerebral glucose metabolism associated with a fear network in panic disorder. Neuroreport 16, 927931.CrossRefGoogle ScholarPubMed
Schiller, D, Levy, I, Niv, Y, LeDoux, JE, Phelps, EA (2008). From fear to safety and back: reversal of fear in the human brain. Journal of Neuroscience 28, 1151711525.CrossRefGoogle ScholarPubMed
Schubert, R, Ritter, P, Wustenberg, T, Preuschhof, C, Curio, G, Sommer, W, Villringer, A (2008). Spatial attention related SEP amplitude modulations covary with BOLD signal in S1 – a simultaneous EEG–fMRI study. Cerebral Cortex 18, 26862700.Google Scholar
Shear, MK, Vander Bilt, J, Rucci, P, Endicott, J, Lydiard, B, Otto, MW, Pollack, MH, Chandler, L, Williams, J, Ali, A, Frank, DM (2001). Reliability and validity of a structured interview guide for the Hamilton Anxiety Rating Scale (SIGH-A). Depression and Anxiety 13, 166178.Google Scholar
Simmons, A, Strigo, I, Matthews, SC, Paulus, MP, Stein, MB (2006). Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects. Biological Psychiatry 60, 402409.Google Scholar
Stocker, T, Schneider, F, Klein, M, Habel, U, Kellermann, T, Zilles, K, Shah, NJ (2005). Automated quality assurance routines for fMRI data applied to a multicenter study. Human Brain Mapping 25, 237246.CrossRefGoogle ScholarPubMed
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273289.Google Scholar
Ueda, K, Okamoto, Y, Okada, G, Yamashita, H, Hori, T, Yamawaki, S (2003). Brain activity during expectancy of emotional stimuli: an fMRI study. Neuroreport 14, 5155.CrossRefGoogle ScholarPubMed
van den Heuvel, OA, Mataix-Cols, D, Zwitser, G, Cath, DC, van der Werf, YD, Groenewegen, HJ, van Balkom, AJ, Veltman, DJ (2011). Common limbic and frontal-striatal disturbances in patients with obsessive compulsive disorder, panic disorder and hypochondriasis. Psychological Medicine 41, 23992410.CrossRefGoogle ScholarPubMed
van den Heuvel, OA, Veltman, DJ, Groenewegen, HJ, Witter, MP, Merkelbach, J, Cath, DC, van Balkom, AJ, van Oppen, P, van Dyck, R (2005). Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis. Archives of General Psychiatry 62, 922933.CrossRefGoogle ScholarPubMed
Westphal, C (1871). Agoraphobia, a neuropathological phenomenon [in German]. Archiv für Psychiatrie und Nervenkrankheiten 72, 138161.Google Scholar
Wittchen, HU, Jacobi, F, Rehm, J, Gustavsson, A, Svensson, M, Jonsson, B, Olesen, J, Allgulander, C, Alonso, J, Faravelli, C, Fratiglioni, L, Jennum, P, Lieb, R, Maercker, A, van Os, J, Preisig, M, Salvador-Carulla, L, Simon, R, Steinhausen, HC (2011). The size and burden of mental disorders and other disorders of the brain in Europe 2010. European Neuropsychopharmacology 21, 655679.Google Scholar
Wittchen, HU, Pfister, H (1997). DIA-X Interview. Instruktionsmanual zur Durchführung von DIA-X-Interviews (Instruction Manual for the DIA-X-Interview). Swets and Zeitlinger: Frankfurt.Google Scholar
Wittmann, A, Schlagenhauf, F, John, T, Guhn, A, Rehbein, H, Siegmund, A, Stoy, M, Held, D, Schulz, I, Fehm, L, Fydrich, T, Heinz, A, Bruhn, H, Strohle, A (2011). A new paradigm (Westphal-paradigm) to study the neural correlates of panic disorder with agoraphobia. European Archives of Psychiatry and Clinical Neuroscience 261, 185194.CrossRefGoogle Scholar
Yang, H, Spence, JS, Devous Sr, MD, Briggs, RW, Goyal, A, Xiao, H, Yadav, H, Adinoff, B (2012). Striatal-limbic activation is associated with intensity of anticipatory anxiety. Psychiatry Research 204, 123131.CrossRefGoogle ScholarPubMed
Zwanzger, P, Fallgatter, AJ, Zavorotnyy, M, Padberg, F (2009). Anxiolytic effects of transcranial magnetic stimulation – an alternative treatment option in anxiety disorders? Journal of Neural Transmission 116, 767775.Google Scholar
Supplementary material: File

Wittmann Supplementary Material

Table

Download Wittmann Supplementary Material(File)
File 37.4 KB