the 5-httlpr polymorphism of the serotonin transporter gene and short term behavioral response to methylphenidate in children with adhd5 - httlpr羟色胺转运体基因多态性的和短期行为反应与adhd儿童哌醋甲酯.pdf

Thakur et al. BMC Psychiatry 2010, 10:50 /1471-244X/10/50 R E S E A R C H A R T I C L E Open Access Research article The 5-HTTLPR polymorphism of the serotonin transporter gene and short term behavioral response to methylphenidate in children with ADHD 1,4 2,4 4 2,4 1,2,3,4 Geeta A Thakur , Natalie Grizenko , Sarojini M Sengupta , Norbert Schmitz and Ridha Joober* Abstract Background: Animal models of ADHD suggest that the paradoxical calming effect of methylphenidate on motor activity could be mediated through its action on serotonin transmission. In this study, we have investigated the relationship between the 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4) and the response of ADHD relevant behaviors with methylphenidate treatment. Methods: Patients between ages 6-12 (n = 157) were assessed with regard to their behavioral response to methylphenidate (0.5 mg/kg/day) using a 2-week prospective within-subject, placebo-controlled (crossover) trial. The children were then genotyped with regard to the triallelic 5-HTTLPR polymorphism in the SLC6A4 gene. Main outcome measure: Conners Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) at baseline and at the end of each week of treatment with placebo and methylphenidate. For both outcome measurements, we used a mixed model analysis of variance to determine gene, treatment and gene × treatment interaction effects. Results: Mixed model analysis of variance revealed a gene × treatment interaction for CGI-Parents but not for CGI- Teachers. Children homozygous for the lower expressing alleles (s+lG = s) responded well to placebo and did not derive additional improvement with methylphenidate compared to children carrying a hi