Association Between a Functional Serotonin Transporter Promoter Polymorphism and Citalopram Treatment in Adult Outpatients With Major Depression

• DOI: 10.1001/archpsyc.64.7.783
• Publication Date: 2007-07-02T20:03:46Z
• Authors: Xian-Zhang Hu; A. John Rush; Dennis Charney; Alexander F. Wilson; Alexa J. M. Sorant; George J. Papanic...; Maurizio Fava; Madhukar H. Trivedi; Stephen R. Wisnie...; Gonzalo Laje; Silvia Paddock; Francis J. McMahon; Husseini Manji; Robert H. Lipsky
• Keywords: Citalopram; 5-HTTLPR

The HTTLPR, a functional polymorphism of the serotonin transporter gene solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4), promoter, affects transcription and may be involved in antidepressant drug treatment outcome, although response rates with antidepressants can lower patients who experience adverse effects.To test hypothesis that HTTLPR is associated outcome to citalopram.A clinical effectiveness trial, Sequenced Treatment Alternatives Relieve Depression, collected DNA samples from outpatients nonpsychotic major depressive disorder received citalopram first step. triallelic locus was genotyped 1775 discriminate between long (L) short (S) alleles, followed by A > G substitution. low-expression S L(G) alleles were grouped together compared high-expression L(A) allele.Eighteen primary care 23 psychiatric sites across United States.Ages 18 75 years, meeting criteria for single or recurrent depression.Categorical response, remission, tolerance, effect burden.Expression-based grouping produced significant finding association allele burden entire sample (P = .004 [genotype frequency]; P < .001 [allele frequency]). To control bias population stratification, white American subsample analyzed. lesser L(A)L(A) genotype frequency .03) .007). These findings did not hold when L undifferentiated. No observed phenotypes HTTLPR. Development diarrhea presence strongest risk factors burden.The effects. Because confers increased SLC6A4 transcription, levels brain other tissues lead fewer effects medications target transporter.