title: Abnormal cortical growth in schizophrenia targets normative modules of synchronized development.
abstract: BACKGROUND
  Schizophrenia is a disorder of brain connectivity and altered neurodevelopmental processes. Cross-sectional case-control studies in different age groups have suggested that deficits in cortical thickness in childhood-onset schizophrenia may normalize over time, suggesting a disorder-related difference in cortical growth trajectories.
  
  
  METHODS
  We acquired magnetic resonance imaging scans repeated over several years for each subject, in a sample of 106 patients with childhood-onset schizophrenia and 102 age-matched healthy volunteers. Using semiparametric regression, we modeled the effect of schizophrenia on the growth curve of cortical thickness in ~80,000 locations across the cortex, in the age range 8 to 30 years. In addition, we derived normative developmental modules composed of cortical regions with similar maturational trajectories for cortical thickness in typical brain development.
  
  
  RESULTS
  We found abnormal nonlinear growth processes in prefrontal and temporal areas that have previously been implicated in schizophrenia, distinguishing for the first time between cortical areas with age-constant deficits in cortical thickness and areas whose maturational trajectories are altered in schizophrenia. In addition, we showed that when the brain is divided into five normative developmental modules, the areas with abnormal cortical growth overlap significantly only with the cingulo-fronto-temporal module.
  
  
  CONCLUSIONS
  These findings suggest that abnormal cortical development in schizophrenia may be modularized or constrained by the normal community structure of developmental modules of the human brain connectome.
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland; Brain Mapping Unit, Behavioural & Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address: aalexanderbloch@gmail.com.
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Alexander-Bloch
authors.affiliation: New York University School of Medicine, New York, New York; Nathan S. Kline Institute for Psychiatric Research, New York, New York.
authors.forename: Philip T
authors.initials: PT
authors.lastname: Reiss
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland.
authors.forename: Judith
authors.initials: J
authors.lastname: Rapoport
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland.
authors.forename: Harry
authors.initials: H
authors.lastname: McAdams
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland.
authors.forename: Jay N
authors.initials: JN
authors.lastname: Giedd
authors.affiliation: Brain Mapping Unit, Behavioural & Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; Cambridgeshire & Peterborough National Health Service Foundation Trust, Cambridge; ImmunoPsychiatry, Alternative Discovery & Development, GlaxoSmithKline, Stevenage, United Kingdom.
authors.forename: Ed T
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland.
authors.forename: Nitin
authors.initials: N
authors.lastname: Gogtay
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000002:abnormalities*; D002648:Child; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000473:pathology*; D012559:Schizophrenia / Q000473:pathology*; D055815:Young Adult
keywords: Neuroimaging; penalized splines; psychosis; system; topology