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J Am Acad Child Adolesc Psychiatry. 2017 May;56(5):436-444.e4. doi: 10.1016/j.jaac.2017.02.009. Epub 2017 Mar 8.

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

Author information

1
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
2
Clinical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Germany.
3
Discipline of Psychiatry, School of Medicine and the Trinity College Institute of Neurosciences, Trinity College Dublin, Ireland.
4
University Medical Centre Hamburg-Eppendorf, Germany.
5
Université de Montreal, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada.
6
Central Institute of Mental Health, Medical Faculty Mannheim, Germany.
7
Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France.
8
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
9
University of Vermont, Burlington.
10
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, UK.
11
Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Germany.
12
Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Germany.
13
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.
14
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; Maison de Solenn, Cochin Hospital, Paris.
15
Rotman Research Institute, Baycrest and the University of Toronto, Canada.
16
Technische Universität Dresden, Germany.
17
University College Dublin, Ireland.
18
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. Electronic address: sylvane.desrivieres@kcl.ac.uk.

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.

KEYWORDS:

attention-deficit/hyperactivity disorder; putamen; response control; reward anticipation; rs945270

PMID:
28433093
DOI:
10.1016/j.jaac.2017.02.009
[Indexed for MEDLINE]

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