Variations in oligodendrocyte-related gene expression across multiple cortical regions: implications for the pathophysiology of schizophrenia.
The disconnectivity syndrome hypothesis of schizophrenia suggests that communication between multiple brain circuits and regions may be disrupted. Microarray studies analysed gene expression in 15 different brain regions derived from 13 persons with schizophrenia and controls. The superior temporal gyrus, cingulate gyrus and hippocampus evidence the greatest numbers of abnormally expressed genes. Gene ontology categorization suggested that gene classes associated with oligodendrocytes and myelin function were among the most profoundly affected. qPCR and additional microarray studies have validated these oligodendrocyte- and myelin-associated findings in independent cohorts. At least some of the affected genes are associated with the regulation of axoglial contacts, axon calibre and the integrity of functional elements involved in signal propagation. The confluence of emerging evidence shows that myelination abnormalities are major components of the neurobiology of schizophrenia and suggest that re-evaluation of some long-held hypotheses and beliefs regarding the biological substrates of schizophrenia may be warranted.
Haroutunian
Vahram
V
Department of Psychiatry, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6575, USA. vahram.haroutunian@mssm.edu
Katsel
Pavel
P
Dracheva
Stella
S
Stewart
Daniel G
DG
Davis
Kenneth L
KL
D000368:Aged; D002102:Cadaver; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012565:Schizophrenic Psychology; D015398:Signal Transduction
D009419:Nerve Tissue Proteins