Abstract
It has been proposed that schizophrenia results partly from altered brain connectivity. Gene microarray analyses performed in gray matter have indicated that several myelin-related genes normally expressed in oligodendrocytes have decreased expression levels in schizophrenia. These data suggest that oligodendrocytes may be involved in the deficits of schizophrenia and may be decreased in number in the case of disease. The anterior cingulate cortex in particular has been demonstrated to be affected in schizophrenia, with studies reporting altered neuronal arrangement, decreased anisotropy in diffusion tensor images, and hypometabolism. We used a stereologic nearest-neighbor estimator of spatial distribution to investigate oligodendrocytes in the anterior cingulum bundle using postmortem tissue from 13 chronic schizophrenics and 13 age-matched controls. Using a spatial point pattern analysis, we measured the degree of oligodendrocyte clustering by comparing the probability of finding a nearest-neighbor at a given distance in schizophrenics and controls. At the same time, we also estimated the number and density of oligodendrocytes in the region of interest. In the present study, we found no significant differences in the oligodendrocyte distribution or density in the cingulum bundle between the two groups, in contrast to earlier data from the prefrontal subcortical white matter. These results suggest that a subtler oligodendrocyte or myelin anomaly may underlie the structural deficits observed by brain imaging in the cingulum bundle in schizophrenia.
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Acknowledgments
Supported by NIH grants MH66392 and MH82286 and by the Stanley Medical Research Institute. The authors would like to thank W.G.M. Janssen and B. Wicinski for expert technical assistance, Dr. V. Haroutunian for helpful discussion, Dr. D.P. Purohit for expert neuropathological assessments, and L. White and M. Kundu for review of neuropsychological and medical records.
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Segal, D., Schmitz, C. & Hof, P.R. Spatial distribution and density of oligodendrocytes in the cingulum bundle are unaltered in schizophrenia. Acta Neuropathol 117, 385–394 (2009). https://doi.org/10.1007/s00401-008-0379-x
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DOI: https://doi.org/10.1007/s00401-008-0379-x