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Impact of a common genetic variation associated with putamen volume on neural mechanisms of ADHD

Xu, Bing; Jia, Tianye; Macare, Christine; Banaschewski, Tobias; Bokde, Arun L.W.; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J.; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny A.; Heinz, Andreas; Ittermann, Bernd; Martinot, Jean-Luc; Martinot, Marie-Laure Paillère; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Paus, Tomáš; Poustka, Luise; Smolka, Michael N.; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Desrivières, Sylvane

Authors

Bing Xu

Tianye Jia

Christine Macare

Tobias Banaschewski

Arun L.W. Bokde

Uli Bromberg

Christian Büchel

Anna Cattrell

Patricia J. Conrod

Herta Flor

Vincent Frouin

Jürgen Gallinat

Hugh Garavan

Penny A. Gowland

Andreas Heinz

Bernd Ittermann

Jean-Luc Martinot

Marie-Laure Paillère Martinot

Frauke Nees

Dimitri Papadopoulos Orfanos

Tomáš Paus

Luise Poustka

Michael N. Smolka

Henrik Walter

Robert Whelan

Gunter Schumann

Sylvane Desrivières

Abstract

Objective: In a recent genome-wide association study of subcortical brain volumes, we have identified common genetic variation at rs945270 as having the strongest effect on putamen volume, a brain measure linked to familial risk for attentiondeficit/hyperactivity disorder (ADHD). To determine whether rs945270 is a genetic determinant of ADHD, we now explored it impacts on ADHD related symptoms and on neural mechanisms of ADHD, such as response inhibition and reward sensitivity.
Method: We used a large population sample of 1,834 14 years old adolescents to test the effects of rs945270 on (i) ADHD symptoms accessed through the Strengths and Difficulties Questionnaire (SDQ) and (ii) Region-of interest (ROI) analyses of putamen activation by functional magnetic resonance imaging (fMRI) using the Stop Signal (SST) and monetary incentive delay (MID) tasks, assessing response inhibition and rewards sensitivity, respectively.
Results: We found a significant link between rs945270 and ADHD symptoms scores, the C-allele being associated with lower symptoms scores, most notably hyperactivity. We also observed sex-specific effects of this variant on the brain. In boys, the C-allele associated with lower putamen activity during successful response inhibition, a brain response that was not associated with ADHD symptoms. In girls, putamen activation during reward anticipation increased with the number of C-alleles, most significantly in the right putamen. Remarkably, right putamen activation during reward anticipation tended to negatively correlate with ADHD symptoms.
Conclusions: Our results indicate that rs945270 may contribute to the genetic risk of ADHD partly through its effects on hyperactivity and reward processing in girls.

Journal Article Type Article
Publication Date May 31, 2017
Journal Journal of the American Academy of Child and Adolescent Psychiatry
Print ISSN 0890-8567
Electronic ISSN 1527-5418
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 56
Issue 5
Institution Citation Xu, B., Jia, T., Macare, C., Banaschewski, T., Bokde, A. L., Bromberg, U., …Desrivières, S. (2017). Impact of a common genetic variation associated with putamen volume on neural mechanisms of ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 56(5), doi:10.1016/j.jaac.2017.02.009. ISSN 0890-8567
DOI https://doi.org/10.1016/j.jaac.2017.02.009
Publisher URL https://www.sciencedirect.com/science/article/pii/S0890856717301028
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information This study was presented as a poster presentation at the 22nd Annual Meeting of the Organization for Human Brain Mapping; Geneva, Switzerland; June 26–30, 2016.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf




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