Reduced dendritic spine density on cerebral cortical pyramidalneurons in schizophrenia

OBJECTIVE—A pilot study of the density ofdendritic spines on pyramidal neurons in layer III of human temporaland frontal cerebral neocortex in schizophrenia.
METHODS—Postmortem material from a groupof eight prospectively diagnosed schizophrenic patients,five archive schizophrenic patients, 11 non-schizophrenic controls,and one patient with schizophrenia-like psychosis, thought to be due tosubstance misuse, was impregnated with a rapid Golgi method. Spineswere counted on the dendrites of pyramidal neurons in temporaland frontal association areas, of which the soma was in layer III(which take part in corticocortical connectivity) and which met strictcriteria for impregnation quality. Altogether 25 blocks were studied inthe schizophrenic group and 21 in the controls. If more than one blockwas examined from a single area, the counts for that area wereaveraged. All measurements were made blind: diagnoses were onlydisclosed by a third party after measurements were completed. Possibleconfounding affects of coexisiting Alzheimer's disease were taken intoaccount, as were the effects of age at death and postmortem interval.
RESULTS—There was a significant (p<0.001)reduction in the numerical density of spines in schizophrenia (276/mmin control temporal cortex and 112/mm in schizophrenic patients, and299 and 101 respectively in the frontal cortex). An analysis ofvariance, taking out effects of age at death and postmortem interval,which might have explained the low spine density for some of theschizophrenic patients, did not affect the significance of the results.
CONCLUSION—The results support theconcept of there being a defect in the fine structure of dendritesof pyramidal neurons, involving loss of spines, in schizophreniaand may help to explain the loss of cortical volume without loss ofneurons in this condition, although the effect of neuroleptic drugscannot be ruled out.