Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia.
BACKGROUND
Brain imaging, molecular genetic, and ultrastructural evidence indicate the existence of pathologic alterations in the cortical and subcortical white matter of schizophrenic patients.


METHODS
We performed a stereologic analysis of numbers, densities, and spatial distribution of oligodendrocytes in layer III and in the gyral white matter of Brodmann's area 9 in the superior frontal gyrus to assess whether these cells are affected in schizophrenia. Counts were obtained on Nissl-stained materials and on sections immunolabeled for the oligodendrocyte marker 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in seven schizophrenic and seven age-matched control cases.


RESULTS
A 28% decrease in total numbers (or densities) of cortical layer III oligodendrocytes and a 27% decrease in the white matter were detected in schizophrenic compared with control cases based on CNPase immunostaining. Nissl and CNPase immunohistochemistry yielded comparable results. The spatial distribution of oligodendrocytes in area 9 white matter exhibited a less clustered arrangement in schizophrenic cases.


CONCLUSIONS
These results suggest a severe pathology of oligodendrocytes in schizophrenia and provide a quantitative cellular correlate of the white matter changes observed by brain imaging in vivo, showing reduced fractional anisotropy in schizophrenia. The data support recent evidence that several genes encoding myelin-related proteins consistently exhibit reduced expression in schizophrenia.
Hof
Patrick R
PR
Kastor Neurobiology of Aging Laboratories, Fishberg Research Center for Neurobiology and Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York 10029, USA.
Haroutunian
Vahram
V
Friedrich
Victor L
VL
Byne
William
W
Buitron
Cristian
C
Perl
Daniel P
DP
Davis
Kenneth L
KL
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000032:analysis; D001344:Autopsy; D016022:Case-Control Studies; D002452:Cell Count; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009836:Oligodendroglia / Q000201:enzymology / Q000473:pathology*; D012559:Schizophrenia / Q000473:pathology*
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases