title: Additive effects of 5-HTTLPR (serotonin transporter) and tryptophan hydroxylase 2 G-703T gene polymorphisms on the clinical response to citalopram among children and adolescents with depression and anxiety disorders.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the association between polymorphisms in two serotonin pathway genes and the clinical response to citalopram among children and adolescents with depression and/or anxiety disorders.
  
  
  METHODS
  Eighty-three children and adolescents with depression and/or anxiety disorders were treated with citalopram for 8 weeks. We assessed the association between the response to citalopram and polymorphisms in the tryptophan hydroxylase-2 (TPH2) and the serotonin transporter gene. The polymorphisms included single nucleotide polymorphisms (SNPs) in the transcriptional control region (G-703T) of the TPH2 gene and the serotonin transporter gene-linked promoter region (5-HTTLPR).
  
  
  RESULTS
  Fifty patients of the 83 (60.2%) achieved satisfactory response (Clinical Global Impressions - Improvement ≤2). We observed an additive effect of the two genes on the clinical response to citalopram. Patients carrying the combination of TPH2 -703G and the 5-HTTLPR L alleles were the most likely to respond (80%). In contrast, patients carrying the combination of TPH2 -703T and the 5-HTTLPR S alleles were least likely to respond (31%). The other patients (with -703G/5-HTTLPR S and -703T/5-HTTLPR L alleles) showed intermediate response (67%).
  
  
  CONCLUSIONS
  This finding suggests that 5-HTTLPR and TPH2 genes may act in concert to modulate the clinical response to citalopram among children and adolescents with depression and/or anxiety disorders.
authors.affiliation: Department of Child and Adolescent Psychiatry, Geha Mental Health Center, Petach Tikva, Israel. beni.rotberg@gmail.com
authors.forename: Benyamin
authors.initials: B
authors.lastname: Rotberg
authors.forename: Sefi
authors.initials: S
authors.lastname: Kronenberg
authors.forename: Miri
authors.initials: M
authors.lastname: Carmel
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.forename: David
authors.initials: D
authors.lastname: Brent
authors.forename: Gil
authors.initials: G
authors.lastname: Zalsman
authors.forename: Alan
authors.initials: A
authors.lastname: Apter
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D000293:Adolescent; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000235:genetics; D002648:Child; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: D015283:Citalopram; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase; C493230:SLC6A4 protein, human; C494784:TPH2 protein, human