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 o f 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 chang e 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 achieve d. Blood samples were obtained at that point, and genotypes for polymorphis m at the respective genes were identified. Results: Genotypes were then tes ted by chi(2) to assess the significance of any association with drug respo nse. Only the dopamine transporter gene was found to be significant. Homozy gosity of the 10-repeat allele was found to characterize nonresponse to met hylphenidate therapy (p = .008). Conclusions: While the results suggest tha t alleles of the dopamine transporter gene play a role in methylphenidate r esponse, replication in additional studies is needed.