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

Matthew D Albaugh; James J Hudziak; Alex Ing; Bader Chaarani; Edward Barker; Tianye Jia; Herve Lemaitre; Richard Watts; Catherine Orr; Philip A Spechler; Claude Lepage; Vladimir Fonov; Louis Collins; Pierre Rioux; Alan C Evans; Tobias Banaschewski; Arun L W Bokde; Uli Bromberg; Christian Büchel; Erin Burke Quinlan; Sylvane Desrivières; Herta Flor; Vincent Frouin; Penny Gowland; Andreas Heinz; Bernd Ittermann; Jean-Luc Martinot; Frauke Nees; Dimitri Papadopoulos Orfanos; Tomáš Paus; Luise Poustka; Juliane H Fröhner; Michael N Smolka; Henrik Walter; Robert Whelan; Gunter Schumann; Hugh Garavan; Alexandra Potter

doi:10.1038/s41386-019-0383-y

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

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

Authors

Matthew D Albaugh¹, James J Hudziak², Alex Ing³, Bader Chaarani⁴, Edward Barker³, Tianye Jia³, Herve Lemaitre⁵, Richard Watts⁴, Catherine Orr⁴, Philip A Spechler⁴, Claude Lepage⁶, Vladimir Fonov⁶, Louis Collins⁶, Pierre Rioux⁶, Alan C Evans⁶, Tobias Banaschewski⁷, Arun L W Bokde⁸, Uli Bromberg⁹, Christian Büchel⁹, Erin Burke Quinlan³, Sylvane Desrivières³, Herta Flor^{10

11}, Vincent Frouin¹², Penny Gowland¹³, Andreas Heinz¹⁴, Bernd Ittermann¹⁵, Jean-Luc Martinot¹⁶, Frauke Nees^{7

10}, Dimitri Papadopoulos Orfanos¹², Tomáš Paus¹⁷, Luise Poustka¹⁸, Juliane H Fröhner¹⁹, Michael N Smolka¹⁹, Henrik Walter¹², Robert Whelan²⁰, Gunter Schumann³, Hugh Garavan⁴, Alexandra Potter⁴

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Anisotropy
Attention
Attention Deficit Disorder with Hyperactivity / diagnostic imaging*
Attention Deficit Disorder with Hyperactivity / genetics
Attention Deficit Disorder with Hyperactivity / physiopathology
Attention Deficit Disorder with Hyperactivity / psychology
Brain / diagnostic imaging
Brain / pathology
Cerebral Cortex / diagnostic imaging*
Cerebral Cortex / pathology
Child
Female
Humans
Male
Multifactorial Inheritance
Neural Pathways / diagnostic imaging
Organ Size
Prefrontal Cortex / diagnostic imaging
Prefrontal Cortex / pathology
Risk Assessment
White Matter / diagnostic imaging*
White Matter / pathology
White People / genetics

Abstract

Publication types

MeSH terms

Grants and funding