Neural Substrates of Treatment Response to Cognitive-Behavioral Therapy in Panic Disorder With Agoraphobia
Publication: American Journal of Psychiatry
Abstract
Objective
Although exposure-based cognitive-behavioral therapy (CBT) is an effective treatment option for panic disorder with agoraphobia, the neural substrates of treatment response remain unknown. Evidence suggests that panic disorder with agoraphobia is characterized by dysfunctional safety signal processing. Using fear conditioning as a neurofunctional probe, the authors investigated neural baseline characteristics and neuroplastic changes after CBT that were associated with treatment outcome in patients with panic disorder with agoraphobia.
Method
Neural correlates of fear conditioning and extinction were measured using functional MRI before and after a manualized CBT program focusing on behavioral exposure in 49 medication-free patients with a primary diagnosis of panic disorder with agoraphobia. Treatment response was defined as a reduction exceeding 50% in Hamilton Anxiety Rating Scale scores.
Results
At baseline, nonresponders exhibited enhanced activation in the right pregenual anterior cingulate cortex, the hippocampus, and the amygdala in response to a safety signal. While this activation pattern partly resolved in nonresponders after CBT, successful treatment was characterized by increased right hippocampal activation when processing stimulus contingencies. Treatment response was associated with an inhibitory functional coupling between the anterior cingulate cortex and the amygdala that did not change over time.
Conclusions
This study identified brain activation patterns associated with treatment response in patients with panic disorder with agoraphobia. Altered safety signal processing and anterior cingulate cortex-amygdala coupling may indicate individual differences among these patients that determine the effectiveness of exposure-based CBT and associated neuroplastic changes. Findings point to brain networks by which successful CBT in this patient population is mediated.
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History
Received: 28 November 2012
Revision received: 27 February 2013
Accepted: 5 April 2013
Published online: 1 November 2013
Published in print: November 2013
Authors
Author Contributions
Profs. Jansen and Kircher contributed equally to this article as senior authors.
Funding Information
Dr. Konrad has received fees for educational programs from Aristo Pharma GmbH, Esparma GmbH, Lilly Deutschland GmbH, MagVenture GmbH, and Servier Deutschland GmbH. Dr. Wittchen has received research grants and travel funds from and served on the advisory boards of Lundbeck, Novartis, Pfizer, and Servier. Prof. Ströhle has received research grants from the European Commission (FP6), the German Federal Ministry of Education and Research, and Lundbeck, and he has received speaking honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Lundbeck, Pfizer, UCB, and Wyeth. Prof. Ströhle has received research funding from the German Federal Ministry of Education and Research, the European Commission (FP6), and Lundbeck; he has received speaker's honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Lundbeck, Pfizer, Wyeth, and UCB; and he has received educational grants from the Stifterverband für die Deutsche Wissenschaft, the Berlin Brandenburgische Akademie der Wissenschaften, the Boehringer Ingelheim Fonds, and the Eli Lilly International Foundation. Prof. Arolt has participated in CME activities for or served on the advisory boards of AstraZeneca, Eli Lilly, Janssen-Organon, Lundbeck, Pfizer, Servier, and Wyeth. Prof. Kircher has received fees for educational programs from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Pfizer, and Servier; he has also received travel sponsorship from Servier, speaking honoraria from Janssen-Cilag, and research grant support from Lundbeck and Pfizer. All other authors report no financial relationships with commercial interests.
Supplementary Material
Supported in part by the German multicenter trial Mechanisms of Action in CBT (MAC). The MAC study is funded by the German Federal Ministry of Education and Research (project number, 01GV0615; neuroimaging study: project number, 01GV0611) as part of the Federal Ministry of Education and Research Psychotherapy Research Funding Initiative.Metrics & Citations
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