Genetic polymorphisms in monoamine systems and outcome of cognitive behavior therapy for social anxiety disorder

Evelyn Andersson, Christian Rück, Catharina Lavebratt, Erik Hedman, Martin Schalling, Nils Lindefors, Elias Eriksson, Per Carlbring, Gerhard Andersson, Tomas Furmark, Evelyn Andersson, Christian Rück, Catharina Lavebratt, Erik Hedman, Martin Schalling, Nils Lindefors, Elias Eriksson, Per Carlbring, Gerhard Andersson, Tomas Furmark

Abstract

Objective: The role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703T polymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients.

Method: Participants were recruited from two separate randomized controlled CBT trials (trial 1: n = 112, trial 2: n = 202). Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment) for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report.

Results: At long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials.

Conclusions: None of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD.

Trial registration: ClinicalTrials.gov (ID-NCT0056496).

Trial registration: ClinicalTrials.gov NCT00564967.

Conflict of interest statement

Competing Interests: Gerhard Andersson is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Liebowitz Social Anxiety Scale self-rated…
Figure 1. Liebowitz Social Anxiety Scale self-rated score (LSAS-SR) by TPH2 G-703T genotype before and after cognitive behavior therapy (CBT) in social anxiety disorder (SAD) patients.
Mean LSAS-SR score in G homozygotes (light grey bars) and T carriers (dark grey bars).

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