Original Investigation


, Volume 187, Issue 1, pp 68-72

First online:

Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder

  • Murray B. SteinAffiliated withDepartments of Psychiatry and Family & Preventive Medicine, University of California Email author 
  • , Soraya SeedatAffiliated withDepartment of Psychiatry, Stellenbosch University
  • , Joel GelernterAffiliated withDepartment of Psychiatry, Yale University School of Medicine

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To determine whether variation in the serotonin transporter gene promoter (5HTTLPR) influences the efficacy of selective serotonin reuptake inhibitors (SSRIs) in generalized social anxiety disorder (GSAD).


Consecutive series of N=32 patients with DSM-IV GSAD for whom DNA and standardized outcome data from a 12-week SSRI trial were available. After ensuring that neither clinical response [clinical global impression of change scale (CGI-C)] nor 5HTTLPR genotype was confounded by ethnicity or sex, we determined whether the number of copies (0, 1, or 2) of hi-risk alleles using either the diallelic L–S system or the triallelic La–Lg–S system, predicted response and change in Liebowitz social anxiety scale (LSAS) and brief social phobia scale (BSPS) scores during SSRI treatment.


Twenty-one patients (66%) were responders to SSRI (i.e., CGI-C much or very much improved). A trend was seen for a linear association between 5HTTLPR genotype and likelihood of response to SSRI: diallelic classification L/L 7/8 (88%), L/S 12/18 (67%), S/S 2/6 (33%), p=0.051; triallelic classification L′/L′ 4/5 (80%), L′/S′ 14/19 (74%), S′/S′ 3/8 (38%), p=0.093. Reduction in LSAS (and BSPS) scores during SSRI treatment was significantly (p<0.02) associated with 5HTTLPR genotype using either the diallelic or triallelic classification.


Variation in a functional polymorphism known to influence serotonin reuptake is associated with SSRI response in patients with GSAD. Independent replication in larger samples is required before the predictive utility of this information can be confirmed and generalized to clinical settings.


Selective serotonin reuptake inhibitor (SSRI) Social anxiety disorder (SAD) Pharmacotherapy Genetics Polymorphism Pharmacogenomics