title: Distinguishing Adolescents With ADHD From Their Unaffected Siblings and Healthy Comparison Subjects by Neural Activation Patterns During Response Inhibition.
abstract: OBJECTIVE
  Dysfunctional response inhibition is a key executive function impairment in attention deficit hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate affected from unaffected individuals. The authors therefore investigated neural correlates of response inhibition and the familial nature of these neural correlates.
  
  
  METHODS
  Functional MRI measurements of neural activation during the stop-signal task and behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy comparison subjects (N=124).
  
  
  RESULTS
  Stop-signal task reaction times were longer and error rates were higher in participants with ADHD, but not in their unaffected siblings, while reaction time variability was higher in both groups than in comparison subjects. Relative to comparison subjects, participants with ADHD and unaffected siblings had neural hypoactivation in frontal-striatal and frontal-parietal networks, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between levels of participants with ADHD and comparison subjects. Furthermore, neural activation in inferior frontal nodes correlated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity.
  
  
  CONCLUSIONS
  Neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. Although only affected participants with ADHD have deficient response inhibition, hypoactivation in inferior frontal and temporal-parietal nodes in unaffected siblings supports the familial nature of the underlying neural process. Activation deficits in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family.
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Daan
authors.initials: D
authors.lastname: van Rooij
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Hoekstra
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Maarten
authors.initials: M
authors.lastname: Mennes
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Daniel
authors.initials: D
authors.lastname: von Rhein
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Andrieke J A M
authors.initials: AJ
authors.lastname: Thissen
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Dirk
authors.initials: D
authors.lastname: Heslenfeld
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Zwiers
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Jaap
authors.initials: J
authors.lastname: Oosterlaan
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Nanda
authors.initials: N
authors.lastname: Rommelse
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.affiliation: From the Department of Psychiatry, University Medical Center, University of Groningen, Groningen, the Netherlands; the Department of Cognitive Neuroscience, the Department of Psychiatry, and the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, the Netherlands; the Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands; and the Department of Psychiatry and the Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, N.Y.
authors.forename: Catharina A
authors.initials: CA
authors.lastname: Hartman
mesh_terms: D000293:Adolescent; D001288:Attention / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D056344:Executive Function; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology*; D012016:Reference Values