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Influence of DAT1 and COMT variants on neural activation during response inhibition in adolescents with attention-deficit/hyperactivity disorder and healthy controls

Published online by Cambridge University Press:  15 June 2015

D. van Rooij ,
P. J. Hoekstra ,
J. Bralten ,
M. Hakobjan ,
J. Oosterlaan ,
B. Franke ,
N. Rommelse ,
J. K. Buitelaar  and
C. A. Hartman
D. van Rooij*
Affiliation:
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
P. J. Hoekstra
Affiliation:
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
J. Bralten
Affiliation:
Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
M. Hakobjan
Affiliation:
Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
J. Oosterlaan
Affiliation:
Department of Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands
B. Franke
Affiliation:
Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
N. Rommelse
Affiliation:
Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands Karakter Child and Adolescent Psychiatry, Radboud University Center Nijmegen, Nijmegen, The Netherlands
J. K. Buitelaar
Affiliation:
Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands Karakter Child and Adolescent Psychiatry, Radboud University Center Nijmegen, Nijmegen, The Netherlands
C. A. Hartman
Affiliation:
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
*
*Address for correspondence: D. van Rooij, M.Sc., Department of Psychiatry, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. (Email: [email protected])
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Abstract

Background.

Impairment of response inhibition has been implicated in attention-deficit/hyperactivity disorder (ADHD). Dopamine neurotransmission has been linked to the behavioural and neural correlates of response inhibition. The current study aimed to investigate the relationship of polymorphisms in two dopamine-related genes, the catechol-O-methyltransferase gene (COMT) and the dopamine transporter gene (SLC6A3 or DAT1), with the neural and behavioural correlates of response inhibition.

Method.

Behavioural and neural measures of response inhibition were obtained in 185 adolescents with ADHD, 111 of their unaffected siblings and 124 healthy controls (mean age 16.9 years). We investigated the association of DAT1 and COMT variants on task performance and whole-brain neural activation during response inhibition in a hypothesis-free manner. Additionally, we attempted to explain variance in previously found ADHD effects on neural activation during response inhibition using these DAT1 and COMT polymorphisms.

Results.

The whole-brain analyses demonstrated large-scale neural activation changes in the medial and lateral prefrontal, subcortical and parietal regions of the response inhibition network in relation to DAT1 and COMT polymorphisms. Although these neural activation changes were associated with different task performance measures, no relationship was found between DAT1 or COMT variants and ADHD, nor did variants in these genes explain variance in the effects of ADHD on neural activation.

Conclusions.

These results suggest that dopamine-related genes play a role in the neurobiology of response inhibition. The limited associations between gene polymorphisms and task performance further indicate the added value of neural measures in linking genetic factors and behavioural measures.

Keywords

Attention-deficit/hyperactivity disorderCOMTDAT1dopamineresponse inhibition
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 15 , November 2015 , pp. 3159 - 3170
Copyright
Copyright © Cambridge University Press 2015 

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