Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological
Bung-Nyun Kim1, Jae-Won Kim, Tarrant D R Cummins
1Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University, College of Medicine, Seoul, Korea.
Journal of Clinical Psychopharmacology
|April 24, 2013
Summary
Genetic variations in norepinephrine-related genes (SLC6A2 and ADRA2A) are linked to attention deficits and response time variability in children with ADHD. These findings support response time variability as a key endophenotype for ADHD and a potential measure for treatment response.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Noradrenergic dysfunction is implicated in attention-deficit/hyperactivity disorder (ADHD) cognitive impairments.
- Increased response time variability (RTV) is a proposed endophenotype for ADHD.
- The role of specific gene polymorphisms in ADHD-related RTV requires further investigation.
Purpose of the Study:
- To investigate the association between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children.
- To examine these associations before and after pharmacological treatment with methylphenidate (MPH).
Main Methods:
- One hundred one medication-naive ADHD children were assessed.
- Subjects received methylphenidate (MPH)-OROS for 12 weeks.
- Computerized attention tests measured response time variability (RTV) at baseline and post-treatment.
- Regression analyses examined associations between RTV and ADRA2A/SLC6A2 gene polymorphisms, controlling for covariates.
Main Results:
- Increased A allele possession at SLC6A2 G1287A was linked to heightened baseline RTV in sustained and auditory selective attention tasks.
- Increased T allele possession at ADRA2A DraI polymorphism correlated with higher baseline RTV in the auditory selective attention task.
- Post-treatment, increased G allele possession at ADRA2A MspI was associated with greater MPH-related change in RTV in the flanker task.
Conclusions:
- Norepinephrine gene variants (SLC6A2, ADRA2A) are associated with RTV in children with ADHD, both at baseline and after MPH treatment.
- RTV is supported as a viable endophenotype for ADHD.
- RTV may serve as a useful surrogate endpoint for measuring stimulant response in pharmacogenetic studies of ADHD.
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