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Association of the dopamine transporter gene (DAT1) with poor methylphenidate response
1Division of Child Psychiatry and Pediatrics, Brookdale University Hospital and Medical Center, Brooklyn, NY 11212, USA.
Objective:
This study attempted to relate the alleles of the D2 (DRD2), D4 (DRD4), and dopamine transporter (DAT1) genes to the behavioral outcome of methylphenidate therapy.
Method:
African-American children with attention-deficit hyperactivity disorder were treated with methylphenidate in doses not in excess of 60 mg/day. The dosage was increased until behavioral change was achieved, using a decrement in scores of less than or equal to 1 on a commonly used rating scale or until the maximum tolerated dose was achieved. Blood samples were obtained at that point, and genotypes for polymorphism at the respective genes were identified.
Results:
Genotypes were then tested by chi 2 to assess the significance of any association with drug response. Only the dopamine transporter gene was found to be significant. Homozygosity of the 10-repeat allele was found to characterize nonresponse to methylphenidate therapy (p = .008).
Conclusions:
While the results suggest that alleles of the dopamine transporter gene play a role in methylphenidate response, replication in additional studies is needed.