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Leisa A. Glantz, PhD; David A. Lewis, MD

Arch Gen Psychiatry. 2000;57:65-73.

Background  The pathophysiological characteristics of schizophrenia appear to involve altered synaptic connectivity in the dorsolateral prefrontal cortex. Given the central role that layer 3 pyramidal neurons play in corticocortical and thalamocortical connectivity, we hypothesized that the excitatory inputs to these neurons are altered in subjects with schizophrenia.

Methods  To test this hypothesis, we determined the density of dendritic spines, markers of excitatory inputs, on the basilar dendrites of Golgi-impregnated pyramidal neurons in the superficial and deep portions of layer 3 in the dorsolateral prefrontal cortex (area 46) and in layer 3 of the primary visual cortex (area 17) of 15 schizophrenic subjects, 15 normal control subjects, and 15 nonschizophrenic subjects with a psychiatric illness (referred to as psychiatric subjects).

Results  There was a significant effect of diagnosis on spine density only for deep layer 3 pyramidal neurons in area 46 (P = .006). In the schizophrenic subjects, spine density on these neurons was decreased by 23% and 16% compared with the normal control (P = .004) and psychiatric (P = .08) subjects, respectively. In contrast, spine density on neurons in superficial layer 3 in area 46 (P = .09) or in area 17 (P = .08) did not significantly differ across the 3 subject groups. Furthermore, spine density on deep layer 3 neurons in area 46 did not significantly (P = .81) differ between psychiatric subjects treated with antipsychotic agents and normal controls.

Conclusion  This region- and disease-specific decrease in dendritic spine density on dorsolateral prefrontal cortex layer 3 pyramidal cells is consistent with the hypothesis that the number of cortical and/or thalamic excitatory inputs to these neurons is altered in subjects with schizophrenia.

From the Departments of Neuroscience (Drs Glantz and Lewis) and Psychiatry (Dr Lewis), University of Pittsburgh, Pittsburgh, Pa.

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