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Evidence for Myelin-Related Dysfunction

Kenneth L. Davis, MD; Daniel G. Stewart, MD; Joseph I. Friedman, MD; Monte Buchsbaum, MD; Philip D. Harvey, PhD; Patrick R. Hof, MD; Joseph Buxbaum, PhD; Vahram Haroutunian, PhD

Arch Gen Psychiatry. 2003;60:443-456.

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.

From the Department of Psychiatry (Drs Davis, Stewart, Friedman, Buchsbaum, Harvey, Hof, Buxbaum, and Haroutunian), Kastor Neurobiology of Aging Laboratories, Fishberg Research Center for Neurobiology, and Department of Geriatric Adult Development (Dr Hof), Mount Sinai School of Medicine, New York, NY; Mental Illness Research Education and Clinical Center, Bronx VA Medical Center, Bronx, NY (Dr Haroutunian); and Pilgrim Psychiatric Center, Brentwood, NY (Dr Friedman).

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