title: Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance.
abstract: Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by gray and white matter abnormalities in several brain areas. Considerably less is known about white matter microstructure in adults with ADHD and its relation with clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109 gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). Additionally, we studied the relation of FA and MD values with symptom severity and cognitive performance on tasks measuring working memory, attention, inhibition, and delay discounting. In comparison to controls, participants with ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic radiation. Higher MD and RD were found in overlapping and even more widespread areas in both hemispheres, also encompassing internal and external capsule, sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD were not associated with symptom severity. However, within some white matter clusters that distinguished patients from controls, worse inhibition performance was associated with reduced FA and more impulsive decision making was associated with increased MD. This study shows widespread differences in white matter integrity between adults with persistent ADHD and healthy individuals. Changes in RD suggest aberrant myelination as a pathophysiological factor in persistent ADHD. The microstructural differences in adult ADHD may contribute to poor inhibition and greater impulsivity but appear to be independent of disease severity.
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: A Marten H
authors.initials: AM
authors.lastname: Onnink
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Zwiers
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Martine
authors.initials: M
authors.lastname: Hoogman
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jeanette C
authors.initials: JC
authors.lastname: Mostert
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Dammers
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Cornelis C
authors.initials: CC
authors.lastname: Kan
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Cognitive Neurosciences, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Alejandro Arias
authors.initials: AA
authors.lastname: Vasquez
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Aart H
authors.initials: AH
authors.lastname: Schene
authors.affiliation: Department of Cognitive Neurosciences, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Karakter Child and Adolescent Psychiatric University Centre, Nijmegen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Buitelaar
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: barbara.franke@radboudumc.nl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
mesh_terms: D000328:Adult; D016880:Anisotropy; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology / Q000528:radiation effects; D007266:Inhibition, Psychological; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D013223:Statistics as Topic; D066127:White Matter / Q000473:pathology*
keywords: Adult ADHD; Cognitive performance; Corpus callosum; DTI; Radial diffusivity; Symptom severity