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

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. 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). 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%). 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.