Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia

TLDR

The study aimed to quantify dendritic spine density on layer III pyramidal neurons in temporal and frontal cortex of schizophrenia patients. Postmortem cortical tissue from 24 schizophrenia cases and 11 controls was processed with a rapid Golgi method, and dendritic spines on layer III pyramidal neurons in temporal and frontal association areas were blindly counted across 25 and 21 blocks, respectively, controlling for age, post‑mortem interval, and Alzheimer’s pathology. Schizophrenia patients exhibited a markedly lower spine density (≈112–101/mm) compared to controls (≈276–299/mm) in both temporal and frontal cortex, a difference that remained significant after adjusting for age and post‑mortem interval, supporting a dendritic spine loss underlying cortical volume reduction.

Abstract

<h3>OBJECTIVE</h3> A pilot study of the density of dendritic spines on pyramidal neurons in layer III of human temporal and frontal cerebral neocortex in schizophrenia. <h3>METHODS</h3> Postmortem material from a group of eight prospectively diagnosed schizophrenic patients, five archive schizophrenic patients, 11 non-schizophrenic controls, and one patient with schizophrenia-like psychosis, thought to be due to substance misuse, was impregnated with a rapid Golgi method. Spines were counted on the dendrites of pyramidal neurons in temporal and frontal association areas, of which the soma was in layer III (which take part in corticocortical connectivity) and which met strict criteria for impregnation quality. Altogether 25 blocks were studied in the schizophrenic group and 21 in the controls. If more than one block was examined from a single area, the counts for that area were averaged. All measurements were made blind: diagnoses were only disclosed by a third party after measurements were completed. Possible confounding affects of coexisiting Alzheimer’s disease were taken into account, as were the effects of age at death and postmortem interval. <h3>RESULTS</h3> There was a significant (p&lt;0.001) reduction in the numerical density of spines in schizophrenia (276/mm in control temporal cortex and 112/mm in schizophrenic patients, and 299 and 101 respectively in the frontal cortex). An analysis of variance, taking out effects of age at death and postmortem interval, which might have explained the low spine density for some of the schizophrenic patients, did not affect the significance of the results. <h3>CONCLUSION</h3> The results support the concept of there being a defect in the fine structure of dendrites of pyramidal neurons, involving loss of spines, in schizophrenia and may help to explain the loss of cortical volume without loss of neurons in this condition, although the effect of neuroleptic drugs cannot be ruled out.