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

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• 作者：Geeta A Thakur (1) (4)
  Natalie Grizenko (2) (4)
  Sarojini M Sengupta (4)
  Norbert Schmitz (2) (4)
  Ridha Joober (1) (2) (3) (4)
  
• 刊名：BMC Psychiatry
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：10
• 期：1
• 全文大小：609KB
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  51. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/10/50/prepub
  
• 作者单位：Geeta A Thakur (1) (4)
  Natalie Grizenko (2) (4)
  Sarojini M Sengupta (4)
  Norbert Schmitz (2) (4)
  Ridha Joober (1) (2) (3) (4)
  
  1. Integrated Program in Neuroscience, McGill University, (3801 University Street), Montreal, (H3A 2B4), Canada
  4. Douglas Mental Health University Institute, (6875 LaSalle Blvd.), Montreal, (H4 H 1R3), Canada
  2. Department of Psychiatry, McGill University, (1033 Pine Avenue West), Montreal, (H3A 1A1), Canada
  3. Department of Human Genetics, McGill University, (1205 Dr Penfield Avenue), Montreal, (H3A 1B1), Canada
  

文摘

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+l G = s') responded well to placebo and did not derive additional improvement with methylphenidate compared to children carrying a higher expressing allele (l A ). No genotype main effects on either CGI-Parents or CGI-teachers were observed. Conclusions A 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 Registration ClinicalTrials.gov NCT00483106