Aaron F Alexander-Bloch1, Philip T Reiss2, Judith Rapoport3, Harry McAdams3, Jay N Giedd3, Ed T Bullmore4, Nitin Gogtay3. 1. 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. 2. New York University School of Medicine, New York, New York; Nathan S. Kline Institute for Psychiatric Research, New York, New York. 3. Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland. 4. 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.
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.
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: Armin Raznahan; Jason P Lerch; Nancy Lee; Dede Greenstein; Gregory L Wallace; Michael Stockman; Liv Clasen; Phillip W Shaw; Jay N Giedd Journal: Neuron Date: 2011-12-08 Impact factor: 17.173
Authors: Guusje Collin; Marcel A de Reus; Wiepke Cahn; Hilleke E Hulshoff Pol; René S Kahn; Martijn P van den Heuvel Journal: Eur Neuropsychopharmacol Date: 2012-10-01 Impact factor: 4.600
Authors: David C Glahn; Angela R Laird; Ian Ellison-Wright; Sarah M Thelen; Jennifer L Robinson; Jack L Lancaster; Edward Bullmore; Peter T Fox Journal: Biol Psychiatry Date: 2008-05-16 Impact factor: 13.382
Authors: Nitin Gogtay; Deanna Greenstein; Marge Lenane; Liv Clasen; Wendy Sharp; Pete Gochman; Philip Butler; Alan Evans; Judith Rapoport Journal: Arch Gen Psychiatry Date: 2007-07
Authors: Vincent W V Jaddoe; Cock M van Duijn; Albert J van der Heijden; Johan P Mackenbach; Henriëtte A Moll; Eric A P Steegers; Henning Tiemeier; Andre G Uitterlinden; Frank C Verhulst; Albert Hofman Journal: Eur J Epidemiol Date: 2010-10-22 Impact factor: 8.082
Authors: Jason P Lerch; André J W van der Kouwe; Armin Raznahan; Tomáš Paus; Heidi Johansen-Berg; Karla L Miller; Stephen M Smith; Bruce Fischl; Stamatios N Sotiropoulos Journal: Nat Neurosci Date: 2017-02-23 Impact factor: 24.884
Authors: Jie Song; Rasmus M Birn; Mélanie Boly; Timothy B Meier; Veena A Nair; Mary E Meyerand; Vivek Prabhakaran Journal: Brain Connect Date: 2014-10-06
Authors: Aaron F Alexander-Bloch; Samuel R Mathias; Peter T Fox; Rene L Olvera; Harold H H Göring; Ravi Duggirala; Joanne E Curran; John Blangero; David C Glahn Journal: Cereb Cortex Date: 2019-01-01 Impact factor: 5.357
Authors: Urs Braun; Axel Schaefer; Richard F Betzel; Heike Tost; Andreas Meyer-Lindenberg; Danielle S Bassett Journal: Neuron Date: 2018-01-03 Impact factor: 17.173