title: Gray Matter Neuritic Microstructure Deficits in Schizophrenia and Bipolar Disorder.
abstract: BACKGROUND
  Postmortem studies have demonstrated considerable dendritic pathologies among persons with schizophrenia and to some extent among those with bipolar I disorder. Modeling gray matter (GM) microstructural properties is now possible with a recently proposed diffusion-weighted magnetic resonance imaging modeling technique: neurite orientation dispersion and density imaging. This technique may bridge the gap between neuroimaging and histopathological findings.
  
  
  METHODS
  We performed an extended series of multishell diffusion-weighted imaging and other structural imaging series using 3T magnetic resonance imaging. Participants scanned included individuals with schizophrenia (n = 36), bipolar I disorder (n = 29), and healthy controls (n = 35). GM-based spatial statistics was used to compare neurite orientation dispersion and density imaging-driven microstructural measures (orientation dispersion index and neurite density index [NDI]) among groups and to assess their relationship with neurocognitive performance. We also investigated the accuracy of these measures in the prediction of group membership, and whether combining them with cortical thickness and white matter fractional anisotropy further improved accuracy.
  
  
  RESULTS
  The GM-NDI was significantly lower in temporal pole, anterior parahippocampal gyrus, and hippocampus of the schizophrenia patients than the healthy controls. The GM-NDI of patients with bipolar I disorder did not differ significantly from either schizophrenia patients or healthy controls, and it was intermediate between the two groups in the post hoc analysis. Regardless of diagnosis, higher performance in spatial working memory was significantly associated with higher GM-NDI mainly in the frontotemporal areas. The addition of GM-NDI to cortical thickness resulted in higher accuracy to predict group membership.
  
  
  CONCLUSIONS
  GM-NDI captures brain differences in the major psychoses that are not accessible with other structural magnetic resonance imaging methods. Given the strong association of GM-NDI with disease state and neurocognitive performance, its potential utility for biological subtyping should be further explored.
authors.affiliation: Kimel Family Translational Imaging-Genetics Laboratory, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Arash
authors.initials: A
authors.lastname: Nazeri
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.affiliation: Kimel Family Translational Imaging-Genetics Laboratory, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Levesque
authors.affiliation: Kimel Family Translational Imaging-Genetics Laboratory, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Jon
authors.initials: J
authors.lastname: Pipitone
authors.affiliation: Kimel Family Translational Imaging-Genetics Laboratory, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Stefanik
authors.affiliation: Kimel Family Translational Imaging-Genetics Laboratory, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Saba
authors.initials: S
authors.lastname: Shahab
authors.affiliation: Kimel Family Translational Imaging-Genetics Laboratory, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tina
authors.initials: T
authors.lastname: Roostaei
authors.affiliation: Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Wheeler
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Sofia
authors.initials: S
authors.lastname: Chavez
authors.affiliation: Kimel Family Translational Imaging-Genetics Laboratory, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: Aristotle.Voineskos@camh.ca.
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
mesh_terms: D000328:Adult; D016880:Anisotropy; D001714:Bipolar Disorder / Q000150:complications / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology; D060825:Cognitive Dysfunction / Q000150:complications / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016501:Neurites / Q000473:pathology*; D059906:Neuroimaging; D009483:Neuropsychological Tests; D012559:Schizophrenia / Q000150:complications / Q000473:pathology*; D066127:White Matter / Q000473:pathology; D055815:Young Adult
keywords: Bipolar disorder; GBSS; Gray matter microstructure; NODDI; Neuritic density; Schizophrenia