Evidence for morphological alterations in prefrontal white matter glia in schizophrenia and bipolar disorder

• Published in: Journal of psychiatry & neuroscience Vol. 39; no. 6; pp. 376 - 385
• Main Authors: Hercher, Christa, MSc, Chopra, Vikramjit, PhD, Beasley, Clare L., PhD
• Format: Journal Article
• Language: English
• Published: Ottawa, ON Canadian Medical Association 01.11.2014; Joule Inc; CMA Impact, Inc
• Subjects: 2',3'-Cyclic-Nucleotide Phosphodiesterases - metabolism; Adult; Adult and adolescent clinical studies; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - metabolism; Bipolar Disorder - pathology; DNA-Binding Proteins - metabolism; Female; Fundamental and applied biological sciences. Psychology; Glial Fibrillary Acidic Protein - metabolism; Health aspects; Humans; Immunohistochemistry; Male; Medical Education; Medical sciences; Middle Aged; Neuroglia; Neuroglia - metabolism; Neuroglia - pathology; Pathology; Photomicrography; Physiological aspects; Prefrontal cortex; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Psychiatry; Psychoanalysis; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychoses; Research Papers; Schizophrenia; Schizophrenia - metabolism; Schizophrenia - pathology; Studies; White Matter - metabolism; White Matter - pathology; Psychosis; Mood disorder; Morphology; Psychology; Central nervous system; Schizophrenia; Bipolar disorder; Prefrontal cortex; Psychopathology; Psychiatry; White matter; Encephalon
• ISSN: 1180-4882; 1488-2434
• DOI: 10.1503/jpn.130277

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. Limitations Oligodendrocytes were identified using morphological criteria. Conclusion 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.