Matthew D Albaugh1, Catherine Orr2, Bader Chaarani2, Robert R Althoff2, Nicholas Allgaier2, Nicholas D'Alberto2, Kelsey Hudson2, Scott Mackey2, Philip A Spechler2, Tobias Banaschewski3, Rüdiger Brühl4, Arun L W Bokde5, Uli Bromberg6, Christian Büchel6, Anna Cattrell7, Patricia J Conrod8, Sylvane Desrivières7, Herta Flor9, Vincent Frouin10, Jürgen Gallinat11, Robert Goodman12, Penny Gowland13, Yvonne Grimmer9, Andreas Heinz14, Viola Kappel15, Jean-Luc Martinot16, Marie-Laure Paillère Martinot17, Frauke Nees9, Dimitri Papadopoulos Orfanos10, Jani Penttila18, Luise Poustka3, Tomáš Paus19, Michael N Smolka20, Maren Struve9, Henrik Walter14, Robert Whelan21, Gunter Schumann7, Hugh Garavan2, Alexandra S Potter2. 1. Department of Psychiatry, University of Vermont College of Medicine, Burlington, Vermont. Electronic address: malbaugh@uvm.edu. 2. Department of Psychiatry, University of Vermont College of Medicine, Burlington, Vermont. 3. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim. 4. Physikalisch-Technische Bundesanstalt, Psychosomatics and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin. 5. Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College Dublin, Dublin. 6. University Medical Center Hamburg-Eppendorf, Hamburg. 7. Medical Research Council Social, Genetic and Developmental Psychiatry Centre, University of Nottingham, Nottingham, United Kingdom. 8. Department of Psychological Medicine and Psychiatry, University of Nottingham, Nottingham, United Kingdom; Department of Psychiatry, Université de Montréal, Centre Hospitalier Universitaire Sainte-Justine Hospital, Montreal, Quebec. 9. Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Fac ulty Mannheim, Heidelberg University, Mannheim. 10. Neurospin, Commissariat à l'Energie Atomique, CEA Saclay Center, Paris, France. 11. Department of Psychiatry and Psychotherapy, Hamburg. 12. Institute of Psychiatry, Psychology and Neuroscience, King's College London, University of Nottingham, Nottingham, United Kingdom. 13. Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom. 14. Department of Psychiatry and Psychotherapy, Psychosomatics and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin. 15. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin. 16. Institut National de la Santé et de la Recherche Médicale Unit 1000 Neuroimaging and Psychiatry, University Paris Sud, University Paris Descartes-Sorbonne Paris Cité and Maison de Solenn, Paris, France. 17. Institut National de la Santé et de la Recherche Médicale Unit 1000 Neuroimaging and Psychiatry, Service Hospitalier Frédéric Joliot, Orsay, University Paris Sud, University Paris Saclay, Orsay, and Maison De Solenn, University Paris Descartes, Paris, France; Department of Adolescent Psychopathology and Medicine, Maison De Solenn, Cochin Hospital, Paris, France. 18. Medical School, University of Tampere, Tampere, Finland. 19. Rotman Research Institute, Baycrest, and Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada. 20. Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany. 21. Department of Psychology, University College Dublin, Dublin.
Abstract
BACKGROUND: Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. We investigated the relationship between dimensional measures of ADHD symptomatology, brain structure, and reaction time variability-an index of lapses in attention. We also tested for associations between brain structural correlates of ADHD symptomatology and maps of dopaminergic gene expression. METHODS: Psychopathology and imaging data were available for 1538 youths. Parent ratings of ADHD symptoms were obtained using the Development and Well-Being Assessment and the Strengths and Difficulties Questionnaire (SDQ). Self-reports of ADHD symptoms were assessed using the youth version of the SDQ. Reaction time variability was available in a subset of participants. For each measure, whole-brain voxelwise regressions with gray matter volume were calculated. RESULTS: Parent ratings of ADHD symptoms (Development and Well-Being Assessment and SDQ), adolescent self-reports of ADHD symptoms on the SDQ, and reaction time variability were each negatively associated with gray matter volume in an overlapping region of the ventromedial prefrontal cortex. Maps of DRD1 and DRD2 gene expression were associated with brain structural correlates of ADHD symptomatology. CONCLUSIONS: This is the first study to reveal relationships between ventromedial prefrontal cortex structure and multi-informant measures of ADHD symptoms in a large population-based sample of adolescents. Our results indicate that ventromedial prefrontal cortex structure is a biomarker for ADHD symptomatology. These findings extend previous research implicating the default mode network and dopaminergic dysfunction in ADHD.
BACKGROUND: Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. We investigated the relationship between dimensional measures of ADHD symptomatology, brain structure, and reaction time variability-an index of lapses in attention. We also tested for associations between brain structural correlates of ADHD symptomatology and maps of dopaminergic gene expression. METHODS: Psychopathology and imaging data were available for 1538 youths. Parent ratings of ADHD symptoms were obtained using the Development and Well-Being Assessment and the Strengths and Difficulties Questionnaire (SDQ). Self-reports of ADHD symptoms were assessed using the youth version of the SDQ. Reaction time variability was available in a subset of participants. For each measure, whole-brain voxelwise regressions with gray matter volume were calculated. RESULTS: Parent ratings of ADHD symptoms (Development and Well-Being Assessment and SDQ), adolescent self-reports of ADHD symptoms on the SDQ, and reaction time variability were each negatively associated with gray matter volume in an overlapping region of the ventromedial prefrontal cortex. Maps of DRD1 and DRD2 gene expression were associated with brain structural correlates of ADHD symptomatology. CONCLUSIONS: This is the first study to reveal relationships between ventromedial prefrontal cortex structure and multi-informant measures of ADHD symptoms in a large population-based sample of adolescents. Our results indicate that ventromedial prefrontal cortex structure is a biomarker for ADHD symptomatology. These findings extend previous research implicating the default mode network and dopaminergic dysfunction in ADHD.
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