Association of the dopamine transporter gene (DAT1) with poor methylphenidate response

Objective: This study attempted to relate the alleles of the D-2 (DRD2), D-4 (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.