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Does Glial Asthenia Predispose to Schizophrenia?

Does Glial Asthenia Predispose to Schizophrenia? Glial cells have been grossly neglected in schizophrenia research.1 Hopefully, the publication of the oligodendrocytehypothesis by Davis et al2 in the May 2003issue of the ARCHIVES and their excellent review of the supportingevidence will change the situation. Oligodendrocytes produce myelin and, togetherwith astrocytes and microglia, were formerly thought to be merely glia (“glue”)of the brain. Additional evidence from genetic and other studies supports the oligodendrocytehypothesis and further suggests a more general glial deficiency involvingastrocytes. (1) Pooled linkage data and the colocalization of genes relatedto glial growth suggest that glial asthenia is an important factor in theliability to schizophrenia.3 (2) Genetic associationsbetween schizophrenia and genes for neuregulin 1 and the rhesus factor havebeen reported. The gene product of neuregulin 1 is glial growth factor 2,suggesting a deficiency of glial growth in schizophrenia. In regard to therhesus factor, maternal rhesus factor incompatibility increases unconjugatedbilirubin, a neurotoxin that predominately inhibits astrocyte functioning.(3) The decrease of protein specific to astrocytes, the glial fibrillary acidicprotein, was found in 4 postmortem studies of schizophrenic brains. (4) Adecrease of astroglia has also been observed in lobotomized brains. (5) Functionalimaging studies of schizophrenia display hypofrontality that might reflectdisruption of astrocyte metabolism.1 (6) Asin brain damage, patients with acute schizophrenia have elevated serum andcerebrospinal fluid levels of S100B, a protein predominantly expressed inastrocytes. (7) Astrocytes play an important role in regulating glutamateconcentration, synaptic transmission (tripartite synapse), and synaptic stability. Davis and colleagues convincingly demonstrated that oligodendrocytesmatter in schizophrenia. An equal amount of evidence supports a role for astrocytes.In conclusion, glial deficiency below a certain threshold is expected to leadto synaptic destabilization, disconnectivity, and probably acute schizophrenia.Oligodendrocyte and astrocyte asthenia, whether caused by genetic or environmentalfactors, seem to predispose to the disorder. Correspondence: Dr Moises, Department ofPsychiatry, Kiel University Hospital, D-24105 Kiel, Germany (moises@psychiatry.uni-kiel.de). References 1. Coyle JTSchwarcz R Mind glue: implications of glial biology for psychiatry. Arch Gen Psychiatry 2000;5790- 93PubMedGoogle ScholarCrossref 2. Davis KLStewart DGFriedman JIBuchsbaum MHarvey PDHof PRBuxbaum JHaroutunian V White matter changes in schizophrenia: evidence for myelin-relateddysfunction. Arch Gen Psychiatry 2003;60443- 456PubMedGoogle ScholarCrossref 3. Moises HWZoega TGottesman II The glial growth factors deficiency and synaptic destabilization hypothesisof schizophrenia. BMC Psychiatry 2002;28PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Does Glial Asthenia Predispose to Schizophrenia?

Does Glial Asthenia Predispose to Schizophrenia?

Abstract

Glial cells have been grossly neglected in schizophrenia research.1 Hopefully, the publication of the oligodendrocytehypothesis by Davis et al2 in the May 2003issue of the ARCHIVES and their excellent review of the supportingevidence will change the situation. Oligodendrocytes produce myelin and, togetherwith astrocytes and microglia, were formerly thought to be merely glia (“glue”)of the brain. Additional evidence from genetic and other studies supports the...
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Publisher
American Medical Association
Copyright
Copyright © 2004 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.61.11.1170
Publisher site
See Article on Publisher Site

Abstract

Glial cells have been grossly neglected in schizophrenia research.1 Hopefully, the publication of the oligodendrocytehypothesis by Davis et al2 in the May 2003issue of the ARCHIVES and their excellent review of the supportingevidence will change the situation. Oligodendrocytes produce myelin and, togetherwith astrocytes and microglia, were formerly thought to be merely glia (“glue”)of the brain. Additional evidence from genetic and other studies supports the oligodendrocytehypothesis and further suggests a more general glial deficiency involvingastrocytes. (1) Pooled linkage data and the colocalization of genes relatedto glial growth suggest that glial asthenia is an important factor in theliability to schizophrenia.3 (2) Genetic associationsbetween schizophrenia and genes for neuregulin 1 and the rhesus factor havebeen reported. The gene product of neuregulin 1 is glial growth factor 2,suggesting a deficiency of glial growth in schizophrenia. In regard to therhesus factor, maternal rhesus factor incompatibility increases unconjugatedbilirubin, a neurotoxin that predominately inhibits astrocyte functioning.(3) The decrease of protein specific to astrocytes, the glial fibrillary acidicprotein, was found in 4 postmortem studies of schizophrenic brains. (4) Adecrease of astroglia has also been observed in lobotomized brains. (5) Functionalimaging studies of schizophrenia display hypofrontality that might reflectdisruption of astrocyte metabolism.1 (6) Asin brain damage, patients with acute schizophrenia have elevated serum andcerebrospinal fluid levels of S100B, a protein predominantly expressed inastrocytes. (7) Astrocytes play an important role in regulating glutamateconcentration, synaptic transmission (tripartite synapse), and synaptic stability. Davis and colleagues convincingly demonstrated that oligodendrocytesmatter in schizophrenia. An equal amount of evidence supports a role for astrocytes.In conclusion, glial deficiency below a certain threshold is expected to leadto synaptic destabilization, disconnectivity, and probably acute schizophrenia.Oligodendrocyte and astrocyte asthenia, whether caused by genetic or environmentalfactors, seem to predispose to the disorder. Correspondence: Dr Moises, Department ofPsychiatry, Kiel University Hospital, D-24105 Kiel, Germany (moises@psychiatry.uni-kiel.de). References 1. Coyle JTSchwarcz R Mind glue: implications of glial biology for psychiatry. Arch Gen Psychiatry 2000;5790- 93PubMedGoogle ScholarCrossref 2. Davis KLStewart DGFriedman JIBuchsbaum MHarvey PDHof PRBuxbaum JHaroutunian V White matter changes in schizophrenia: evidence for myelin-relateddysfunction. Arch Gen Psychiatry 2003;60443- 456PubMedGoogle ScholarCrossref 3. Moises HWZoega TGottesman II The glial growth factors deficiency and synaptic destabilization hypothesisof schizophrenia. BMC Psychiatry 2002;28PubMedGoogle ScholarCrossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Nov 1, 2004

References