Dopamine transporter genotype and stimulant dose-response in youth with attention-deficit/hyperactivity disorder

Mark A. Stein; Irwin Waldman; Jeffrey Newcorn; Jeffrey Bishop; Rick Kittles; Edwin H. Cook

doi:10.1089/cap.2013.0102

Dopamine transporter genotype and stimulant dose-response in youth with attention-deficit/hyperactivity disorder

Mark A. Stein
, Irwin Waldman
, Jeffrey Newcorn
, Jeffrey Bishop
, Rick Kittles
, Edwin H. Cook

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

OBJECTIVES: This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD).

METHODS: Fifty-six children and adolescents (mean age=11.7±2.2) participated in a double-blind, two period crossover, dose-response study with a randomized placebo week in each 4 week drug period. Each period consisted of sequential week-long exposures to three dose levels (10, 20, 25-30 mg, depending upon weight) of D-MPH or MAS.

RESULTS: Doses of 10-20 mg of either D-MPH or MAS had little to no effect on hyperactivity-impulsivity and total ADHD symptom scores in subjects with the 9/9 genotype; this was in contrast to the dose-response curves of subjects with either the 10/10 or 10/9 genotype.

CONCLUSIONS: ADHD youth with the 9/9 genotype may require higher stimulant doses to achieve adequate symptom control.

Original language	English (US)
Pages (from-to)	238-244
Number of pages	7
Journal	Journal of child and adolescent psychopharmacology
Volume	24
Issue number	5
DOIs	https://doi.org/10.1089/cap.2013.0102
State	Published - Jun 1 2014
Externally published	Yes

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Psychiatry and Mental health
Pharmacology (medical)

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10.1089/cap.2013.0102

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title = "Dopamine transporter genotype and stimulant dose-response in youth with attention-deficit/hyperactivity disorder",

abstract = "OBJECTIVES: This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD).METHODS: Fifty-six children and adolescents (mean age=11.7±2.2) participated in a double-blind, two period crossover, dose-response study with a randomized placebo week in each 4 week drug period. Each period consisted of sequential week-long exposures to three dose levels (10, 20, 25-30 mg, depending upon weight) of D-MPH or MAS.RESULTS: Doses of 10-20 mg of either D-MPH or MAS had little to no effect on hyperactivity-impulsivity and total ADHD symptom scores in subjects with the 9/9 genotype; this was in contrast to the dose-response curves of subjects with either the 10/10 or 10/9 genotype.CONCLUSIONS: ADHD youth with the 9/9 genotype may require higher stimulant doses to achieve adequate symptom control.",

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doi = "10.1089/cap.2013.0102",

language = "English (US)",

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AU - Stein, Mark A.

AU - Waldman, Irwin

AU - Newcorn, Jeffrey

AU - Bishop, Jeffrey

AU - Kittles, Rick

AU - Cook, Edwin H.

PY - 2014/6/1

Y1 - 2014/6/1

N2 - OBJECTIVES: This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD).METHODS: Fifty-six children and adolescents (mean age=11.7±2.2) participated in a double-blind, two period crossover, dose-response study with a randomized placebo week in each 4 week drug period. Each period consisted of sequential week-long exposures to three dose levels (10, 20, 25-30 mg, depending upon weight) of D-MPH or MAS.RESULTS: Doses of 10-20 mg of either D-MPH or MAS had little to no effect on hyperactivity-impulsivity and total ADHD symptom scores in subjects with the 9/9 genotype; this was in contrast to the dose-response curves of subjects with either the 10/10 or 10/9 genotype.CONCLUSIONS: ADHD youth with the 9/9 genotype may require higher stimulant doses to achieve adequate symptom control.

AB - OBJECTIVES: This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD).METHODS: Fifty-six children and adolescents (mean age=11.7±2.2) participated in a double-blind, two period crossover, dose-response study with a randomized placebo week in each 4 week drug period. Each period consisted of sequential week-long exposures to three dose levels (10, 20, 25-30 mg, depending upon weight) of D-MPH or MAS.RESULTS: Doses of 10-20 mg of either D-MPH or MAS had little to no effect on hyperactivity-impulsivity and total ADHD symptom scores in subjects with the 9/9 genotype; this was in contrast to the dose-response curves of subjects with either the 10/10 or 10/9 genotype.CONCLUSIONS: ADHD youth with the 9/9 genotype may require higher stimulant doses to achieve adequate symptom control.

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Dopamine transporter genotype and stimulant dose-response in youth with attention-deficit/hyperactivity disorder

Abstract

ASJC Scopus subject areas

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