The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder

Tina B Lonsdorf,Christian Rück,Nils Lindefors,Jan Bergström,Gerhard Andersson,Martin Schalling,Arne Öhman

doi:10.1186/1471-244x-10-99

Abstract

BackgroundCognitive behavioral therapy (CBT) represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. We have recently demonstrated that the ability to extinguish learned fear responses is associated with a functional genetic polymorphism (COMTval158met) in the COMT gene and this study was aimed at transferring the experimental results on the COMTval158met polymorphism on extinction into a clinical setting.MethodsWe tested a possible effect of the COMTval158met polymorphism on the efficacy of CBT, in particular exposure-based treatment modules, in a sample of 69 panic disorder patients.ResultsWe present evidence that panic patients with the COMTval158met met/met genotype may profit less from (exposure-based) CBT treatment methods as compared to patients carrying at least one val-allele. No association was found with the 5-HTTLPR/rs25531 genotypes which is presented as additional material.ConclusionsWe were thus able to transfer findings on the effect of the COMTval158met polymorphism from an experimental extinction study obtained using healthy subjects to a clinical setting. Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype. Limitations of the study as well as possible clinical implications are discussed.Trial registrationClinical Trial Registry name: Internet-Versus Group-Administered Cognitive Behavior Therapy for Panic Disorder (IP2). Registration Identification number: NCT00845260, http://www.clinicaltrials.gov/ct2/show/NCT00845260

Highlights

Cognitive behavioral therapy (CBT) represents a learning process leading to symptom relief and resulting in long-term changes in behavior
This study aimed at transfering the experimental results of the COMTval158met polymorphism on extinction into a clinical setting by investigating the efficacy of CBT in a sample of panic disorder (PD) patients, genotyped for the COMTval158met
Patient population Patients were recruited from a randomized clinical equivalence trial (CET) of regular cognitive-behavioral group therapy vs. internet-based CBT for PD [13](see additional file 1)

Summary

Introduction

Cognitive behavioral therapy (CBT) represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. Cognitive behavioral therapy (CBT) represents a learning process leading to symptom relief It results in longterm changes in behavior, which have their correlates in altered neural activity [for a review see e.g., [1]], gene expression as well as synaptic connectivity in the brain [2]. CBT for anxiety disorders generally, and panic disorder (PD) is based on exposure These exposure-based processes can be studied in the laboratory as the extinction of experimentally acquired fear. The val-allele is associated with a three- to four-fold higher COMT activity as compared to the thermolabile met-allele [5,6]

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