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

J Am Acad Child Adolesc Psychiatry. 1999 Dec;38(12):1474-7. doi: 10.1097/00004583-199912000-00006.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Attention Deficit Disorder with Hyperactivity / blood
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Black People / genetics
  • Carrier Proteins / genetics*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / blood
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Dopamine Agents / administration & dosage
  • Dopamine Agents / blood
  • Dopamine Agents / therapeutic use*
  • Dopamine Plasma Membrane Transport Proteins
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Homozygote
  • Humans
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Methylphenidate / administration & dosage
  • Methylphenidate / blood
  • Methylphenidate / therapeutic use*
  • Nerve Tissue Proteins*
  • Polymorphism, Genetic

Substances

  • Carrier Proteins
  • Central Nervous System Stimulants
  • Dopamine Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A3 protein, human
  • Methylphenidate