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

PLoS One. 2013 Nov 15;8(11):e79015. doi: 10.1371/journal.pone.0079015. eCollection 2013.

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.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Amygdala
  • Anxiety Disorders* / genetics
  • Anxiety Disorders* / therapy
  • Catechol O-Methyltransferase / genetics*
  • Cognitive Behavioral Therapy*
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Social Behavior Disorders* / genetics
  • Social Behavior Disorders* / therapy
  • Tryptophan Hydroxylase / genetics*

Substances

  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • TPH2 protein, human
  • Tryptophan Hydroxylase
  • COMT protein, human
  • Catechol O-Methyltransferase

Associated data

  • ClinicalTrials.gov/NCT00564967

Grants and funding

This study was sponsored by grants from the Swedish Research Council and the Stockholm County CouncilN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.