title: Neuroanatomical abnormalities and cognitive impairments are shared by adults with attention-deficit/hyperactivity disorder and their unaffected first-degree relatives.
abstract: BACKGROUND
  Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder, yet the search for genes with a definitive role in its etiology has been elusive. Deconstructing the disorder in its endophenotypic traits, where the variance is thought to be associated with a fewer number of genes, should boost the statistical power of molecular genetic studies and clarify the pathophysiology of ADHD. In this study, we tested for neuroanatomical and cognitive endophenotypes in a group of adults with ADHD, their unaffected first-degree relatives, and typically developing control subjects.
  
  
  METHODS
  Sixty participants, comprising 20 adults with ADHD, 20 unaffected first-degree relatives, and 20 typically developing control subjects matched for age and gender undertook structural magnetic resonance imaging scans. Voxel-based morphometry with DARTEL was performed to obtain regional gray and white matter volumes. General linear analyses of the volumes of brain regions, adjusting for age and total intracranial volume, were used to compare groups. Sustained attention and response inhibition were also investigated as cognitive endophenotypes.
  
  
  RESULTS
  Neuroanatomical abnormalities in gray matter volume in the right inferior frontal gyrus and white matter volume in the caudal portion of the right inferior fronto-occipital fasciculus were shared between ADHD probands and their unaffected first-degree relatives. In addition, impairments in sustained attention were also found to be shared between ADHD patients and their relatives.
  
  
  CONCLUSIONS
  Cognitive impairments in sustained attention and neuroanatomical abnormalities in the right inferior frontal gyrus and the posterior part of right inferior fronto-occipital fasciculus are putative neurocognitive endophenotypes in adult ADHD.
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; Adult ADHD Clinic, Cambridgeshire & Peterborough National Health Service Foundation Trust, Cambridge, United Kingdom. Electronic address: vp271@cam.ac.uk.
authors.forename: Valentino Antonio
authors.initials: VA
authors.lastname: Pironti
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Lai
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Adult ADHD Clinic, Cambridgeshire & Peterborough National Health Service Foundation Trust, Cambridge, United Kingdom.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Müller
authors.affiliation: Department of Psychology, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Chris Martin
authors.initials: CM
authors.lastname: Dodds
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Edward Thomas
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; Adult ADHD Clinic, Cambridgeshire & Peterborough National Health Service Foundation Trust, Cambridge, United Kingdom.
authors.forename: Barbara Jacquelyn
authors.initials: BJ
authors.lastname: Sahakian
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000473:pathology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D002658:Developmental Disabilities / Q000473:pathology; D005190:Family; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D013223:Statistics as Topic; D066127:White Matter / Q000473:pathology; D055815:Young Adult
keywords: ADHD; VBM; biomarkers; endophenotypes; neuroimaging; neuropsychology