The impact of depressive comorbidity on neural plasticity following cognitive-behavioral therapy in panic disorder with agoraphobia

Stefanie L Kunas; Yunbo Yang; Benjamin Straube; Tilo Kircher; Alexander L Gerlach; Bettina Pfleiderer; Volker Arolt; André Wittmann; Andreas Stroehle; Hans-Ulrich Wittchen; Ulrike Lueken

doi:10.1016/j.jad.2018.11.026

The impact of depressive comorbidity on neural plasticity following cognitive-behavioral therapy in panic disorder with agoraphobia

J Affect Disord. 2019 Feb 15:245:451-460. doi: 10.1016/j.jad.2018.11.026. Epub 2018 Nov 4.

Authors

Affiliations

¹ Center of Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital Würzburg, Würzburg, Germany; Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany. Electronic address: stefanie.kunas@hu-berlin.de.
² Department of Psychiatry and Psychotherapy, Phillipps-University Marburg, Marburg, Germany.
³ Department of Psychology, University of Cologne, Cologne, Germany.
⁴ Department of Clinical Radiology, University Hospital Münster, Münster, Germany.
⁵ Department of Psychiatry and Psychotherapy, University Hospital Münster, Münster, Germany.
⁶ Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁷ Institute of Clinical Psychology and Psychotherapy, Department of Psychology, Technische Universität Dresden, Dresden, Germany.
⁸ Center of Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital Würzburg, Würzburg, Germany; Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.

PMID: 30428445
DOI: 10.1016/j.jad.2018.11.026

Abstract

Background: Depressive disorders are a frequent comorbidity of panic disorder with agoraphobia (PD/AG). Cognitive-behavioral therapy (CBT) for PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbidities. However, as depressive comorbidities can confound fear circuitry activation (i.e. amygdalae, insulae, anterior cingulate cortex) in PD/AG, we investigated whether comorbid depressive disorders alter neural plasticity following CBT.

Methods: Within a randomized, controlled clinical trial on exposure-based CBT, forty-two PD/AG patients including fifteen (35.7%) with a comorbid depressive disorder (PD/AG + DEP) participated in a longitudinal functional magnetic resonance imaging (fMRI) study. A differential fear conditioning task was used as probe of interest. A generalized psycho-physiological interaction analysis (gPPI) served to study functional connectivity patterns.

Results: After CBT, only PD/AG patients without comorbid depressive disorders (PD/AG-DEP) showed reduced activation in the left inferior frontal gyrus (IFG) extending to the insula. While PD/AG-DEP patients showed enhanced functional connectivity (FC) between the left IFG and subcortical structures (anterior cingulate cortex, thalamus and midbrain), PD/AG + DEP patients exhibited increased FC between the left IFG and cortical structures (prefrontal, parietal regions). In both groups, FC decreased following CBT.

Limitations: Primary depressed and medicated patients were excluded. Major depression and dysthymia were collapsed.

Conclusions: Reduced activation in the left IFG, as previously shown in PD/AG, appears to be a specific substrate of CBT effects in PD/AG-DEP patients only. Differential patterns of FC pertaining to fear circuitry networks in patients without depression vs. cognitive networks in patients with comorbid depression may point towards different pathways recruited by CBT as a function of comorbidity.

Keywords: CBT; Depressive disorder; FMRI; Fear conditioning; Functional connectivity; Panic disorder.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Agoraphobia / diagnostic imaging
Agoraphobia / physiopathology*
Agoraphobia / psychology
Agoraphobia / therapy
Amygdala / diagnostic imaging
Amygdala / physiopathology
Cerebral Cortex / diagnostic imaging
Cerebral Cortex / physiopathology
Cognition
Cognitive Behavioral Therapy
Comorbidity
Depressive Disorder / diagnostic imaging
Depressive Disorder / physiopathology*
Depressive Disorder / psychology
Fear / psychology
Female
Gyrus Cinguli / diagnostic imaging
Gyrus Cinguli / physiopathology
Humans
Longitudinal Studies
Magnetic Resonance Imaging / methods*
Male
Middle Aged
Neuronal Plasticity*
Panic Disorder / diagnostic imaging
Panic Disorder / physiopathology*
Panic Disorder / psychology
Panic Disorder / therapy