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White Matter Changes in Schizophrenia: Evidence for Myelin-Related Dysfunction
Abstract
Numerous lines of inquiry implicate connectivity as a central abnormality in schizophrenia. Myelination and factors that affect myelination, such as the function of oligodendroglia, are critical processes that could profoundly affect neuronal connectivity, especially given the diffuse distribution of oligodendrocytes and the widespread distribution of brain regions that have been implicated in schizophrenia. Multiple lines of evidence now converge to implicate oligodendroglia and myelin in schizophrenia. Imaging and neurocytochemical evidence, similarities with demyelinating diseases, age-related changes in white matter, myelin-related gene abnormalities, and morphologic abnormalities in the oligodendroglia demonstrated in schizophrenic brains are all examined in light of the hypothesis that oligodendroglial dysfunction and even death, with subsequent abnormalities in myelin maintenance and repair, contribute to the schizophrenic syndrome.
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“In schizophrenia, a severe mental illness characterized by positive (e.g., hallucinations and delusions) and negative (e.g., anhedonia and flat affect) symptoms, axon disruption with concurrent reduced myelin levels and oligodendrocyte abnormalities has been postulated as a key pathology based on both imaging and postmortem studies (Davis et al., 2003;Vikhreva et al., 2016).”
From NODDI in clinical research (2020) · cites this paper as Davis et al., 2003
In the citing paper
“Oligodendrocytes and myelination are clearly impaired in schizophrenia (Chew et al., 2013; Davis et al., 2003; Takahashi et al., 2011).”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Davis et al., 2003
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Metadata
- Authors
- Davis, K. L., Stewart, D. G., Friedman, J. I., Buchsbaum, M., Harvey, P. D., Hof, P. R., Buxbaum, J., & Haroutunian, V.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2003-05-01
- Volume
- 60
- Issue
- 5
- Pages
- 443
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2049973822
- Cited by
- 793
- References
- 258
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 20 · 2023: 11 · 2022: 17 · 2021: 14 · 2020: 25 · 2019: 35 · 2018: 28 · 2017: 27 · 2016: 36 · 2015: 41 · 2014: 34 · 2013: 32 · 2012: 50
- FWCI
- 24.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- schizophrenia, white matter, myelination, oligodendrocytes, myelin, neuronal connectivity, demyelinating disease, oligodendrocyte dysfunction, age-related white matter changes, neuroimaging
- MeSH terms
- Age Factors, Brain, Demyelinating Diseases, Humans, Myelin Sheath, Nerve Fibers, Myelinated, Oligodendroglia, Schizophrenia, Anisotropy, Cell Death, Protein Array Analysis
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