Differential associations of dopamine-related polymorphisms with discrete components of reaction time variability: relevance for attention deficit/hyperactivity disorder.

Abstract

BACKGROUND:

Reaction time variability (RTV) is considered a valid endophenotype of attention deficit/hyperactivity disorder (ADHD). It is also often used to examine the efficacy of drug treatment or individual patients' treatment responses and has been furthermore suggested to significantly reduce the potential number of false-positive diagnoses. Among the most commonly investigated candidate genes for ADHD are DRD2, SLC6A3 (DAT), COMT and MAOA. Genetic associations have, however, proven inconclusive or inconsistent.

METHODS:

Due to the complexity of dopaminergic neurotransmission in the two distinct prosencephalic dopamine pathways, we examined whether the effects of dopamine-related candidate polymorphisms in the genes DRD2, SLC6A3, COMT and MAOA may be differentially associated with discrete subcomponents of RTV, rather than global RTV. A total of 260 healthy volunteers were genotyped for the aforementioned polymorphisms and performed a reaction time paradigm able to distinguish between sensory and motor reaction time.

RESULTS:

We found that functional polymorphisms in the genes encoding for dopamine-catabolizing enzymes (i.e. COMT and MAOA) are associated with motor RTV but not with sensory RTV, whereas vice versa the gene DRD2 influences sensory but not motor RTV. No significant associations for the gene SLC6A3 (DAT) were found.

CONCLUSIONS:

Our results give new insight into the inconsistent state of the literature regarding genetic associations of RTV and clearly show that the examination of subcomponents thereof explains far more variance compared to global RTV. This could be of great relevance to the use of RTV in basic research, clinical diagnostics and pharmacological studies examining the efficacy of novel drug treatments.

• Authors: Phillip Grant, Yvonne Kuepper, Catrin Wielpuetz, Jürgen Hennig
• Journal: Neuropsychobiology (Neuropsychobiology) Vol. 69 Issue 4 Pg. 220-6 ( 2014) ISSN: 1423-0224 [Electronic] Switzerland
• PMID: 24942140 (Publication Type: Journal Article)

Chemical References

• DRD2 protein, human
• Dopamine Plasma Membrane Transport Proteins
• Receptors, Dopamine D2
• SLC6A3 protein, human
• Monoamine Oxidase
• monoamine oxidase A, human
• COMT protein, human
• Catechol O-Methyltransferase

Topics

• Age Factors
• Attention Deficit Disorder with Hyperactivity (genetics, physiopathology)
• Catechol O-Methyltransferase (genetics)
• Dopamine Plasma Membrane Transport Proteins (genetics)
• Endophenotypes
• Genetic Association Studies
• Genotyping Techniques
• Humans
• Male
• Monoamine Oxidase (genetics)
• Neuropsychological Tests
• Polymorphism, Genetic
• Reaction Time (genetics)
• Receptors, Dopamine D2 (genetics)
• Sex Factors
• Young Adult