The 5-HTTLPR polymorphism of the serotonin transporter gene and short term behavioral response to methylphenidate in children with ADHD

BMC Psychiatry

Research Article

Norbert Schmitz¹  Natalie Grizenko¹  Sarojini M Sengupta²  Ridha Joober³  Geeta A Thakur⁴ 

[1] Department of Psychiatry, McGill University, (1033 Pine Avenue West), (H3A 1A1), Montreal, Canada;Douglas Mental Health University Institute, (6875 LaSalle Blvd.), (H4 H 1R3), Montreal, Canada;Douglas Mental Health University Institute, (6875 LaSalle Blvd.), (H4 H 1R3), Montreal, Canada;Integrated Program in Neuroscience, McGill University, (3801 University Street), (H3A 2B4), Montreal, Canada;Department of Psychiatry, McGill University, (1033 Pine Avenue West), (H3A 1A1), Montreal, Canada;Department of Human Genetics, McGill University, (1205 Dr Penfield Avenue), (H3A 1B1), Montreal, Canada;Douglas Mental Health University Institute, (6875 LaSalle Blvd.), (H4 H 1R3), Montreal, Canada;Integrated Program in Neuroscience, McGill University, (3801 University Street), (H3A 2B4), Montreal, Canada;Douglas Mental Health University Institute, (6875 LaSalle Blvd.), (H4 H 1R3), Montreal, Canada;

关键词: Behavioral Response;    Methylphenidate;    ADHD Symptom;    Dopamine Transporter;    Genotype Group;   

DOI  :  10.1186/1471-244X-10-50

 received in 2008-12-01, accepted in 2010-06-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAnimal 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.MethodsPatients 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.ResultsMixed 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 higher expressing allele (lA). No genotype main effects on either CGI-Parents or CGI-teachers were observed.ConclusionsA double blind placebo-controlled design was used to assess the behavioral effects of methylphenidate in relation to the triallelic 5-HTTLPR polymorphism of the SLC6A4 gene in children with ADHD. This polymorphism appears to modulate the behavioral response to methylphenidate in children with ADHD as assessed in the home environment by parents. Further investigation is needed to assess the clinical implications of this finding.Trial RegistrationClinicalTrials.gov NCT00483106

【 授权许可】

Unknown   
© Thakur et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.