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