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Neuropsychopharmacology. 2019 Aug;44(9):1597-1603. doi: 10.1038/s41386-019-0383-y. Epub 2019 Apr 6.

White matter microstructure is associated with hyperactive/inattentive symptomatology and polygenic risk for attention-deficit/hyperactivity disorder in a population-based sample of adolescents.

Author information

1
Department of Psychiatry, Vermont Center for Children, Youth, and Families, University of Vermont College of Medicine, Burlington, VT, USA. malbaugh@uvm.edu.
2
Department of Psychiatry, Vermont Center for Children, Youth, and Families, University of Vermont College of Medicine, Burlington, VT, USA.
3
Medical Research Council - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
4
Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT, USA.
5
Institut National de la Santé et de la Recherche Médicale, UMR 992 INSERM, CEA, Faculté de médecine, Université Paris-Sud, Université Paris-Saclay, NeuroSpin, F-91191, Gif-sur-Yvette, France.
6
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
7
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
8
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
9
University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistrasse 52, 20246, Hamburg, Germany.
10
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany.
11
Department of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany.
12
NeuroSpin, CEA, Université Paris-Saclay, 91191, Gif-sur-Yvette, France.
13
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
14
Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charitéplatz 1, Berlin, Germany.
15
Physikalisch-Technische Bundesanstalt (PTB), Abbestrasse 2 - 12, Berlin, Germany.
16
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud, University Paris Descartes - Sorbonne Paris Cité; and Maison de Solenn, Paris, France.
17
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, M6A 2E1, Canada.
18
Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Strasse 5, 37075, Göttingen, Germany.
19
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
20
School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.

Abstract

Few studies have investigated the link between putative biomarkers of attention-deficit/hyperactivity disorder (ADHD) symptomatology and genetic risk for ADHD. To address this, we investigate the degree to which ADHD symptomatology is associated with white matter microstructure and cerebral cortical thickness in a large population-based sample of adolescents. Critically, we then test the extent to which multimodal correlates of ADHD symptomatology are related to ADHD polygenic risk score (PRS). Neuroimaging, genetic, and behavioral data were obtained from the IMAGEN study. A dimensional ADHD composite score was derived from multi-informant ratings of ADHD symptomatology. Using tract-based spatial statistics, whole brain voxel-wise regressions between fractional anisotropy (FA) and ADHD composite score were calculated. Local cortical thickness was regressed on ADHD composite score. ADHD PRS was based on a very recent genome-wide association study, and calculated using PRSice. ADHD composite score was negatively associated with FA in several white matter pathways, including bilateral superior and inferior longitudinal fasciculi (p < 0.05, corrected). ADHD composite score was negatively associated with orbitofrontal cortical thickness (p < 0.05, corrected). The ADHD composite score was correlated with ADHD PRS (p < 0.001). FA correlates of ADHD symptomatology were significantly associated with ADHD PRS, whereas cortical thickness correlates of ADHD symptomatology were unrelated to ADHD PRS. Variation in hyperactive/inattentive symptomatology was associated with white matter microstructure, which, in turn, was related to ADHD PRS. Results suggest that genetic risk for ADHD symptomatology may be tied to biological processes affecting white matter microstructure.

PMID:
30952157
DOI:
10.1038/s41386-019-0383-y

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