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Altered top-down and bottom-up processing of fear conditioning in panic disorder with agoraphobia

Published online by Cambridge University Press:  23 April 2013

U. Lueken ,
B. Straube ,
I. Reinhardt ,
N. I. Maslowski ,
H.-U. Wittchen ,
A. Ströhle ,
A. Wittmann ,
B. Pfleiderer ,
C. Konrad  and
A. Ewert
...Show all authors
U. Lueken
Affiliation:
Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Germany
B. Straube
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps University Marburg, Germany
I. Reinhardt
Affiliation:
Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Germany
N. I. Maslowski
Affiliation:
Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Germany
H.-U. Wittchen
Affiliation:
Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Germany
A. Ströhle
Affiliation:
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Germany
A. Wittmann
Affiliation:
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – Universitätsmedizin Berlin, Germany
B. Pfleiderer
Affiliation:
Department of Clinical Radiology, University of Münster, Germany
C. Konrad
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps University Marburg, Germany
A. Ewert
Affiliation:
Department of Clinical Radiology, University of Münster, Germany
C. Uhlmann
Affiliation:
Department of Psychiatry and Psychotherapy, University of Münster, Germany
V. Arolt
Affiliation:
Department of Psychiatry and Psychotherapy, University of Münster, Germany
A. Jansen
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps University Marburg, Germany
T. Kircher*
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps University Marburg, Germany
*
* Address for correspondence: Prof. Dr. T. Kircher, Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Straße 8, D-35039 Marburg, Germany. (Email: kircher@med.uni-marburg.de)
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Abstract

Background

Although several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients.

Method

The blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls.

Results

Differential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation.

Conclusions

The results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder.

Keywords

Agoraphobiadefensive reactionfear conditioningfMRIfrontal cortexmidbrainpanic disorder
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 2 , January 2014 , pp. 381 - 394
Copyright
Copyright © Cambridge University Press 2013 

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