Impact of a common genetic variation associated with putamen volume on neural mechanisms of ADHD
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 whethe...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Elsiever
2010
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| Online Access: | https://eprints.nottingham.ac.uk/41233/ |
| _version_ | 1848796227490021376 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xu, Bing |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:44:38Z |
| format | Article |
| id | nottingham-41233 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:44:38Z |
| publishDate | 2010 |
| publisher | Elsiever |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-412332020-05-04T16:29:10Z https://eprints.nottingham.ac.uk/41233/ 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 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. Elsiever 2010-03-08 Article PeerReviewed 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 and Desrivières, Sylvane (2010) 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 . ISSN 1527-5418 (In Press) |
| spellingShingle | 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 Impact of a common genetic variation associated with putamen volume on neural mechanisms of ADHD |
| title | Impact of a common genetic variation associated with putamen volume on neural mechanisms of ADHD |
| title_full | Impact of a common genetic variation associated with putamen volume on neural mechanisms of ADHD |
| title_fullStr | Impact of a common genetic variation associated with putamen volume on neural mechanisms of ADHD |
| title_full_unstemmed | Impact of a common genetic variation associated with putamen volume on neural mechanisms of ADHD |
| title_short | Impact of a common genetic variation associated with putamen volume on neural mechanisms of ADHD |
| title_sort | impact of a common genetic variation associated with putamen volume on neural mechanisms of adhd |
| url | https://eprints.nottingham.ac.uk/41233/ |