title: White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  A developmental improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental improvement of ADHD symptoms.
  
  
  METHODS
  A cross-sectional magnetic resonance imaging (MRI) analysis was embedded in a prospective follow-up of an adolescent cohort of ADHD and control subjects (NeuroIMAGE). Mean age at baseline was 11.9 years, mean interval of follow-up was 5.9 years. About 75.3% of the original cohort was retained successfully. Data of 101 participants with ADHD combined type at baseline and 40 healthy controls were analysed. ADHD symptoms were measured with semistructured, investigator-based interviews and Conners' questionnaires, on the basis of DSM-IV criteria. Fractional anisotropy (FA) and mean diffusivity (MD) indices of white matter microstructure were measured using whole brain diffusion tensor imaging at follow-up only. In a dimensional analysis FA and MD were related to change in ADHD symptoms. To link this analysis to DSM-IV diagnoses, a post hoc categorical group analysis was conducted comparing participants with persistent (n = 59) versus remittent (n = 42) ADHD and controls.
  
  
  RESULTS
  Over time, participants with ADHD showed improvement mainly in hyperactive/impulsive symptoms. This improvement was associated with lower FA and higher MD values in the left corticospinal tract at follow-up. Findings of the dimensional and the categorical analysis strongly converged. Changes in inattentive symptoms over time were minimal and not related to white matter microstructure.
  
  
  CONCLUSIONS
  The corticospinal tract is important in the control of voluntary movements, suggesting the importance of the motor system in the persistence of hyperactive/impulsive symptoms.
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Winke
authors.initials: W
authors.lastname: Francx
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.|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 Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Mennes
authors.affiliation: Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Oosterlaan
authors.affiliation: Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: Heslenfeld
authors.affiliation: Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Hoekstra
authors.affiliation: Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Catharina A
authors.initials: CA
authors.lastname: Hartman
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.|Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.|Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Laurence
authors.initials: L
authors.lastname: O'Dwyer
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.|Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
mesh_terms: D000293:Adolescent; D041923:Adolescent Development / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D002648:Child; D005500:Follow-Up Studies; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D011595:Psychomotor Agitation / Q000209:etiology / Q000503:physiopathology*; D011712:Pyramidal Tracts / Q000473:pathology*; D012075:Remission, Spontaneous; D066127:White Matter / Q000473:pathology*
keywords: Attention-deficit/hyperactivity disorder; development; diffusion tensor imaging; hyperactivity/impulsivity; recovery; white matter