title: Evidence for morphological alterations in prefrontal white matter glia in schizophrenia and bipolar disorder.
abstract: BACKGROUND
  Brain imaging studies suggest that volume reductions and compromised white matter integrity occur in schizophrenia and bipolar disorder (BD). However, the cellular correlates have not yet been identified. To address this issue we assessed oligodendrocyte, astrocyte and microglial populations in postmortem white matter from schizophrenia, BD and nonpsychiatric control samples.
  
  
  METHODS
  The density, areal fraction and spatial distribution of glial fibrillary acidic protein (GFAP)-expressing astrocytes and ionized calcium-binding adaptor molecule-1 (IBA-1)-expressing microglia as well as the density, nuclear size and spatial distribution of Nissl-stained oligodendrocytes were quantified in postmortem white matter adjacent to the dorsolateral prefrontal cortex (Brodmann area 9) in schizophrenia, BD and control samples (n = 20). In addition, the oligodendrocyte-associated proteins myelin basic protein and 2,3-cyclic-nucleotide 3-phosphodiesterase (CNPase) were quantified in the same samples by enzyme-linked immunosorbent assay and immunoblotting.
  
  
  RESULTS
  Oligodendrocyte density (p = 0.012) and CNPase protein levels (p = 0.038) differed between groups, being increased in BD compared with control samples. The GFAP area fraction (p = 0.05) and astrocyte spatial distribution (p = 0.040) also differed between groups, reflecting decreased area fraction and increased cell clustering in both schizophrenia and BD samples.
  
  
  CONCLUSIONS
  Oligodendrocytes were identified using morphological criteria.
  
  
  CONCLUSIONS
  This study provides evidence for glial pathology in prefrontal white matter in schizophrenia and BD. Changes in oligodendrocyte and astrocyte populations in white matter in the major psychiatric disorders may reflect disruptions in structural or metabolic support of axons.
authors.affiliation: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Christa
authors.initials: C
authors.lastname: Hercher
authors.affiliation: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Vikramjit
authors.initials: V
authors.lastname: Chopra
authors.affiliation: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Beasley
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000328:Adult; D001714:Bipolar Disorder / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D010784:Photomicrography; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology*; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology*; D066127:White Matter / Q000378:metabolism / Q000473:pathology*
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases