Association of the Dopamine Transporter Gene (DAT1) With Poor Methylphenidate Response

Author/s: Bertrand G. Winsberg
Issue: Dec, 1999

ABSTRACT

Objective: This study attempted to relate the alleles of the [D.sub.2] (DRD2), [D.sub.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 [X.sup.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 transpor ter gene play a role in methyiphenidate response, replication in additional studies is needed.

J. Am. Acad. Child Adolesc. Psychiatry 1999, 38(12):1474-1 477. KeyWords: attention-deficit hyperactivity disorder, drug response, dopamine transporter, molecular genetics.