Lamina-specific reductions in dendritic spine density in the prefrontal cortex of subjects with schizophrenia.

OBJECTIVE In a previous study the authors found that dendritic spine density was reduced on prefrontal pyramidal neurons in layer 3 of subjects with schizophrenia. From a neural circuitry perspective, understanding the pathophysiological significance of this finding requires knowledge of whether pyramidal neurons in other cortical layers are similarly affected. The authors' goal was to determine whether their finding in layer 3 was also present in other cortical layers in the same group of subjects with schizophrenia. METHOD Spine density and other dendritic measures were made for pyramidal neurons in layers 5 and 6 of prefrontal area 46 in the brains of deceased subjects with schizophrenia, subjects with other psychiatric disorders, and normal comparison subjects. RESULTS None of the dendritic measures for layer 5 or 6 pyramidal neurons differed across the subject groups, but the within-subject differences in spine density between deep layer 3 and layer 5 or 6 pyramidal neurons were significantly greater in the patients with schizophrenia than in the comparison subjects. CONCLUSIONS These findings are consistent with the idea that prefrontal pyramidal neurons involved in corticocortical and/or thalamocortical connections are preferentially affected in schizophrenia.

[1]  David A Lewis,et al.  Cortical connections of the lateral mediodorsal thalamus in cynomolgus monkeys , 2004, The Journal of comparative neurology.

[2]  P S Goldman-Rakic,et al.  Synaptogenesis in the prefrontal cortex of rhesus monkeys. , 1994, Cerebral cortex.

[3]  P. Goldman-Rakic,et al.  Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. , 1998, Archives of general psychiatry.

[4]  A. Sampson,et al.  Decreased somal size of deep layer 3 pyramidal neurons in the prefrontal cortex of subjects with schizophrenia. , 2001, Archives of general psychiatry.

[5]  A. Sampson,et al.  Stereological analysis of the mediodorsal thalamic nucleus in schizophrenia: Volume, neuron number, and cell types , 2004, The Journal of comparative neurology.

[6]  I. Feinberg,et al.  Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? , 1982, Journal of psychiatric research.

[7]  Pat Levitt,et al.  Analysis of complex brain disorders with gene expression microarrays: schizophrenia as a disease of the synapse , 2001, Trends in Neurosciences.

[8]  P. Goldman-Rakic,et al.  The reduced neuropil hypothesis: a circuit based model of schizophrenia , 1999, Biological Psychiatry.

[9]  S. Hirsch,et al.  Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia , 1998, Journal of neurology, neurosurgery, and psychiatry.

[10]  D. Lewis,et al.  Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. , 2000, Archives of general psychiatry.