Impact of a Common Genetic Variation Associated With Putamen Volume on Neural Mechanisms of Attention-Deficit/Hyperactivity Disorder - 06/10/17

Doi : 10.1016/j.jaac.2017.02.009

Bing Xu, PhD ^a, Tianye Jia, PhD ^a, Christine Macare, PhD ^a, Tobias Banaschewski, MD, PhD ^b, Arun L.W. Bokde, PhD ^c, Uli Bromberg, DiplPsych ^d, Christian Büchel, MD ^d, Anna Cattrell, PhD ^a, Patricia J. Conrod, PhD ^e, Herta Flor, PhD ^f, Vincent Frouin, PhD ^g, Jürgen Gallinat, MD ^h, Hugh Garavan, PhD ⁱ, Penny Gowland, PhD ^j, Andreas Heinz, MD, PhD ^k, Bernd Ittermann, PhD ^l, Jean-Luc Martinot, MD, PhD ^m, Marie-Laure Paillère Martinot, MD, PhD ^m,ⁿ, Frauke Nees, PhD ^f, Dimitri Papadopoulos Orfanos, PhD ^g, Tomáš Paus, MD, PhD ^o, Luise Poustka, PhD ^b, Michael N. Smolka, MD ^p, Henrik Walter, MD, PhD ^k, Robert Whelan, PhD ^q, Gunter Schumann, MD ^a, Sylvane Desrivières, PhD ^a,^⁎
and the
IMAGEN Consortium
Tobias Banaschewski, MD, PhD, Gareth Barker, PhD, Arun L.W. Bokde, PhD, Uli Bromberg, DiplPsych, Christian Büchel, MD, Erin Burke Quinlan, PhD, Sylvane Desrivières, PhD, Herta Flor, PhD, Vincent Frouin, PhD, Hugh Garavan, PhD, Penny Gowland, PhD, Andreas Heinz, MD, PhD, Bernd Ittermann, PhD, Jean-Luc Martinot, MD, PhD, Marie-Laure Paillère Martinot, MD, PhD, Eric Artiges, MD, PhD, Herve Lemaitre, PhD, Frauke Nees, PhD, Dimitri Papadopoulos Orfanos, PhD, Tomáš Paus, MD, PhD, Luise Poustka, MD, Michael N. Smolka, MD, Nora C. Vetter, PhD, Sarah Jurk, DiplPsych, Eva Mennigen, MD, Henrik Walter, MD, PhD, Robert Whelan, PhD, Gunter Schumann, MD

^a Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK
^b Clinical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Germany
^c Discipline of Psychiatry, School of Medicine and the Trinity College Institute of Neurosciences, Trinity College Dublin, Ireland
^d University Medical Centre Hamburg-Eppendorf, Germany
^e Université de Montreal, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada
^f Central Institute of Mental Health, Medical Faculty Mannheim, Germany
^g Neurospin, Commissariat à l’Energie Atomique, CEA-Saclay Center, Paris, France
^h University Medical Center Hamburg-Eppendorf, Hamburg, Germany
ⁱ University of Vermont, Burlington
^j Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, UK
^k Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Germany
^l Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Germany
^m Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 Neuroimaging and Psychiatry, University Paris Sud, University Paris Descartes, Sorbonne Paris Cité and Maison de Solenn, Paris
ⁿ Maison de Solenn, Cochin Hospital, Paris
^o Rotman Research Institute, Baycrest and the University of Toronto, Canada
^p Technische Universität Dresden, Germany
^q University College Dublin, Ireland

^∗Correspondence to Sylvane Desrivières, PhD, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 16 De Crespigny Park, SE5 8AF, London, UKMRC Social, Genetic and Developmental Psychiatry CentreInstitute of PsychiatryPsychology and NeuroscienceKing’s College London16 De Crespigny Park, SE5 8AFLondonUK

Abstract

Objective

In a recent genomewide association study of subcortical brain volumes, a common genetic variation at rs945270 was identified as having the strongest effect on putamen volume, a brain measurement linked to familial risk for attention-deficit/hyperactivity disorder (ADHD). To determine whether rs945270 might be a genetic determinant of ADHD, its effects on ADHD-related symptoms and neural mechanisms of ADHD, such as response inhibition and reward sensitivity, were explored.

Method

A large population sample of 1,834 14-year-old adolescents was used to test the effects of rs945270 on ADHD symptoms assessed through the Strengths and Difficulties Questionnaire and region-of-interest analyses of putamen activation by functional magnetic resonance imaging using the stop signal and monetary incentive delay tasks, assessing response inhibition and reward sensitivity, respectively.

Results

There was a significant link between rs945270 and ADHD symptom scores, with the C allele associated with lower symptom scores, most notably hyperactivity. In addition, there were sex-specific effects of this variant on the brain. In boys, the C allele was 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.

Conclusion

These results indicate that rs945270 might contribute to the genetic risk of ADHD partly through its effects on hyperactivity and reward processing in girls.

Le texte complet de cet article est disponible en PDF.

Key words : rs945270, putamen, attention-deficit/hyperactivity disorder, reward anticipation, response control

Plan

Method

Participants

ADHD Symptoms (Strengths and Difficulties Questionnaire)

Genotyping and Quality Control

MRI Data Acquisition and Preprocessing

Monetary Incentive Delay Task

Stop Signal Task

Statistical Analyses

Results

Relation of rs945270 to ADHD Symptoms

Response Inhibition

Reward Anticipation

Discussion

	This work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-Related Behaviour in Normal Brain Function and Psychopathology; LSHM-CT-2007-037286), the FP7 projects IMAGEMEND (602450; IMAging GEnetics for MENtal Disorders), AGGRESSOTYPE (602805) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300-2), the Medical Research Council grants “Developmental Pathways Into Adolescent Substance Abuse” (93558) and the Consortium on Vulnerability to Externalizing Disorders and Addictions (c-VEDA; MR/N000390/1), the Swedish funding agencies VR, FORTE and FORMAS, the Medical Research Council and the Wellcome Trust (Behavioural and Clinical Neuroscience Institute, University of Cambridge), the National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-1, SM 80/7-2, SFB 940/1), the National Institutes of Health (NIH), Bethesda, MD (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and by the NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence.
	Dr. Jia served as the statistical expert for this research.
	Disclosure: Dr. Banaschewski has served as an advisor or consultant to Bristol-Myers Squibb, Desitin Arzneimittel, Eli Lilly and Co., Medice, Novartis, Pfizer, Shire, UCB, and Vifor Pharma. He has received conference attendance support, conference support, or speaking fees from Eli Lilly and Co., Janssen McNeil, Medice, Novartis, Shire, and UCB. He is involved in clinical trials conducted by Eli Lilly and Co., Novartis, and Shire; the present work is unrelated to these relationships. Dr. Gallinat has received research funding from the German Federal Ministry of Education and Research, AstraZeneca, Eli Lilly and Co., Janssen-Cilag, and Bristol-Myers Squibb. He has received speaking fees from AstraZeneca, Janssen-Cilag, and Bristol-Myers Squibb. Dr. Paillère-Martinot has received compensation from Janssen-Cilag for CME activities. Prof. Poustka has received speaking fees from Shire, Eli Lilly and Co., and Medice. Drs. Xu, Jia, Macare, Bokde, Bromberg, Büchel, Cattrell, Conrod, Flor, Frouin, Garavan, Gowland, Heinz, Ittermann, Martinot, Nees, Orfanos, Paus, Smolka, Walter, Whelan, Schumann, and Desrivières report no biomedical financial interests or potential conflicts of interest.

Export

Vol 56 - N° 5

P. 436 - mai 2017 Retour au numéro

Article précédent

Behavioral and Neural Sustained Attention Deficits in Disruptive Mood Dysregulation Disorder and Attention-Deficit/Hyperactivity Disorder
David Pagliaccio, Jillian Lee Wiggins, Nancy E. Adleman, Alexa Curhan, Susan Zhang, Kenneth E. Towbin, Melissa A. Brotman, Daniel S. Pine, Ellen Leibenluft

| Article suivant

Trouble
Schuyler W. Henderson

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

Impact of a Common Genetic Variation Associated With Putamen Volume on Neural Mechanisms of Attention-Deficit/Hyperactivity Disorder - 06/10/17

Abstract

Objective

Method

Results

Conclusion

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL