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Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder.
J Clin Psychopharmacol 2013; 33(3):356-62JC

Abstract

Noradrenergic dysfunction may be associated with cognitive impairments in attention-deficit/hyperactivity disorder (ADHD), including increased response time variability, which has been proposed as a leading endophenotype for ADHD. The aim of this study was to examine the relationship between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children before and after pharmacological treatment.One hundred one medication-naive ADHD children were included. All subjects were administered methylphenidate (MPH)-OROS for 12 weeks. The subjects underwent a computerized comprehensive attention test to measure the response time variability at baseline before MPH treatment and after 12 weeks. Additive regression analyses controlling for ADHD symptom severity, age, sex, IQ, and final dose of MPH examined the association between response time variability on the comprehensive attention test measures and allelic variations in single-nucleotide polymorphisms of the ADRA2A and SLC6A2 before and after MPH treatment.Increasing possession of an A allele at the G1287A polymorphism of SLC6A2 was significantly related to heightened response time variability at baseline in the sustained (P = 2.0 × 10) and auditory selective attention (P = 1.0 × 10) tasks. Response time variability at baseline increased additively with possession of the T allele at the DraI polymorphism of the ADRA2A gene in the auditory selective attention task (P = 2.0 × 10). After medication, increasing possession of a G allele at the MspI polymorphism of the ADRA2A gene was associated with increased MPH-related change in response time variability in the flanker task (P = 1.0 × 10).Our study suggested an association between norepinephrine gene variants and response time variability measured at baseline and after MPH treatment in children with ADHD. Our results add to a growing body of evidence, suggesting that response time variability is a viable endophenotype for ADHD and suggesting its utility as a surrogate end point for measuring stimulant response in pharmacogenetic studies.

Authors+Show Affiliations

Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University, College of Medicine, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23609393

Citation

Kim, Bung-Nyun, et al. "Norepinephrine Genes Predict Response Time Variability and Methylphenidate-induced Changes in Neuropsychological Function in Attention Deficit Hyperactivity Disorder." Journal of Clinical Psychopharmacology, vol. 33, no. 3, 2013, pp. 356-62.
Kim BN, Kim JW, Cummins TD, et al. Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder. J Clin Psychopharmacol. 2013;33(3):356-62.
Kim, B. N., Kim, J. W., Cummins, T. D., Bellgrove, M. A., Hawi, Z., Hong, S. B., ... Han, D. H. (2013). Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder. Journal of Clinical Psychopharmacology, 33(3), pp. 356-62. doi:10.1097/JCP.0b013e31828f9fc3.
Kim BN, et al. Norepinephrine Genes Predict Response Time Variability and Methylphenidate-induced Changes in Neuropsychological Function in Attention Deficit Hyperactivity Disorder. J Clin Psychopharmacol. 2013;33(3):356-62. PubMed PMID: 23609393.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder. AU - Kim,Bung-Nyun, AU - Kim,Jae-Won, AU - Cummins,Tarrant D R, AU - Bellgrove,Mark A, AU - Hawi,Ziarih, AU - Hong,Soon-Beom, AU - Yang,Young-Hui, AU - Kim,Hyo-Jin, AU - Shin,Min-Sup, AU - Cho,Soo-Churl, AU - Kim,Ji-Hoon, AU - Son,Jung-Woo, AU - Shin,Yun-Mi, AU - Chung,Un-Sun, AU - Han,Doug-Hyun, PY - 2013/4/24/entrez PY - 2013/4/24/pubmed PY - 2013/11/8/medline SP - 356 EP - 62 JF - Journal of clinical psychopharmacology JO - J Clin Psychopharmacol VL - 33 IS - 3 N2 - Noradrenergic dysfunction may be associated with cognitive impairments in attention-deficit/hyperactivity disorder (ADHD), including increased response time variability, which has been proposed as a leading endophenotype for ADHD. The aim of this study was to examine the relationship between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children before and after pharmacological treatment.One hundred one medication-naive ADHD children were included. All subjects were administered methylphenidate (MPH)-OROS for 12 weeks. The subjects underwent a computerized comprehensive attention test to measure the response time variability at baseline before MPH treatment and after 12 weeks. Additive regression analyses controlling for ADHD symptom severity, age, sex, IQ, and final dose of MPH examined the association between response time variability on the comprehensive attention test measures and allelic variations in single-nucleotide polymorphisms of the ADRA2A and SLC6A2 before and after MPH treatment.Increasing possession of an A allele at the G1287A polymorphism of SLC6A2 was significantly related to heightened response time variability at baseline in the sustained (P = 2.0 × 10) and auditory selective attention (P = 1.0 × 10) tasks. Response time variability at baseline increased additively with possession of the T allele at the DraI polymorphism of the ADRA2A gene in the auditory selective attention task (P = 2.0 × 10). After medication, increasing possession of a G allele at the MspI polymorphism of the ADRA2A gene was associated with increased MPH-related change in response time variability in the flanker task (P = 1.0 × 10).Our study suggested an association between norepinephrine gene variants and response time variability measured at baseline and after MPH treatment in children with ADHD. Our results add to a growing body of evidence, suggesting that response time variability is a viable endophenotype for ADHD and suggesting its utility as a surrogate end point for measuring stimulant response in pharmacogenetic studies. SN - 1533-712X UR - https://www.unboundmedicine.com/medline/citation/23609393/Norepinephrine_genes_predict_response_time_variability_and_methylphenidate_induced_changes_in_neuropsychological_function_in_attention_deficit_hyperactivity_disorder_ L2 - http://Insights.ovid.com/pubmed?pmid=23609393 DB - PRIME DP - Unbound Medicine ER -