High sibling correlation on methylphenidate response but no association with DAT1-10R homozygosity in Dutch sibpairs with ADHD

• Published in: Journal of child psychology and psychiatry Vol. 46; no. 10; pp. 1074 - 1080
• Main Authors: van der Meulen, Emma M., Bakker, Steven C., Pauls, David L., Oteman, Nicole, Kruitwagen, Cas L.J.J., Pearson, Peter L., Sinke, Richard J., Buitelaar, Jan K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing 01.10.2005; Wiley-Blackwell; Blackwell Publishing Ltd
• Subjects: ADD/ADHD; Aetiology; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - epidemiology; Attention Deficit Disorder with Hyperactivity - genetics; Attention Deficit Disorders; Attention Deficit Hyperactivity Disorder; Child; Children; Comorbidity; Correlation; DAT1; Dopamine Agents - pharmacology; Dopamine Plasma Membrane Transport Proteins - genetics; DRD4; Drug Therapy; etiology; Female; Foreign Countries; Genetic research; Genetics; Homozygote; Humans; Intraclass Correlation; Male; Mental Disorders - epidemiology; Methylphenidate; Methylphenidate - pharmacology; Minisatellite Repeats; Netherlands; Netherlands - epidemiology; Outcomes of Treatment; Patients; Phenotypes; Polymorphism, Genetic; Receptors, Dopamine D4 - genetics; Regression (Statistics); Regression Analysis; Retrospective Studies; Risk; Siblings; Side effects; Netherlands
• ISSN: 0021-9630; 1469-7610
• DOI: 10.1111/j.1469-7610.2005.01521.x

Background:  A minority of patients with attention‐deficit hyperactivity disorder (ADHD) do not respond favorably to methylphenidate. This has been partially associated with homozygosity for the Dopamine transporter (DAT1) 10‐repeat allele and the presence of one or two Dopamine D4 receptor (DRD4) 7‐repeat alleles. This study examined the sibling correlation of methylphenidate response rate and the possible association between response rate and these risk alleles. Methods:  A sample of 82 Dutch children with ADHD, from 54 families, (including 30 singletons and 28 sib pairs), who used methylphenidate, was phenotyped according to DSM‐IV criteria. Patients were members of affected sib pairs and were genotyped for DAT1 and DRD4. The sibling Intraclass Correlation Coefficient for methylphenidate response rate was calculated. The association between individual response rates and the risk alleles was examined using linear regression techniques. Results:  The Intraclass Correlation Coefficient was significant (r = .563, p = .001). No evidence was found establishing an association between methylphenidate response and DAT1‐homozygosity. There was a positive trend towards association with the presence of one or two DRD4‐7R alleles. Conclusions:  The sibling correlation may indicate a familial clustering of methylphenidate response. This response is possibly associated with the presence of one or two alleles at the DRD4‐7R locus, but not with DAT1‐10R homozygosity in the Dutch population.