Abstract
Neuronal circuitry relies to a large extent on the presence of functional myelin produced in the brain by oligodendrocytes. Schizophrenia has been proposed to arise partly from altered brain connectivity. Brain imaging and neuropathologic studies have revealed changes in white matter and reduction in myelin content in patients with schizophrenia. In particular, alterations in the directionality and alignment of axons have been documented in schizophrenia. Moreover, the expression levels of several myelin-related genes are decreased in postmortem brains obtained from patients with schizophrenia. These findings have led to the formulation of the oligodendrocyte/myelin dysfunction hypothesis of schizophrenia. In this review, we present a brief overview of the neuropathologic findings obtained on white matter and oligodendrocyte status observed in schizophrenia patients, and relate these changes to the processes of brain maturation and myelination. We also review recent data on oligodendrocyte/myelin genes, and present some recent mouse models of myelin deficiencies. The use of transgenic and mutant animal models offers a unique opportunity to analyze oligodendrocyte and neuronal changes that may have a clinical impact. Lastly, we present some recent morphological findings supporting possible causal involvement of white and grey matter abnormalities, in the aim of determining the morphologic characteristics of the circuits whose alteration leads to the cortical dysfunction that possibly underlies the pathogenesis of schizophrenia.
Highlights
Reviewed by: Andrew Dwork, Columbia University Medical Center, New York, NY, USA Alan Peters, Boston University School of Medicine, Boston, MA, USA Kathleen S
We present a brief overview of the neuropathologic findings obtained on white matter and oligodendrocyte status observed in schizophrenia patients, and relate these changes to the processes of brain maturation and myelination
Leukodystrophies and leukoencephalopathies, diseases characterized by progressive degeneration of the white matter, if diagnosed in late adolescence or early adulthood can present with psychotic symptoms sometimes indistinguishable from those of schizophrenia (Davis et al, 2003; Denier et al, 2007; Walterfang et al, 2005)
Summary
Reviewed by: Andrew Dwork, Columbia University Medical Center, New York, NY, USA Alan Peters, Boston University School of Medicine, Boston, MA, USA Kathleen S. Brain imaging and neuropathologic studies have revealed changes in white matter and reduction in myelin content in patients with schizophrenia.
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