Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia

Arch Gen Psychiatry. 2000 Jan;57(1):65-73. doi: 10.1001/archpsyc.57.1.65.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Autopsy
  • Cognition Disorders / physiopathology
  • Coloring Agents
  • Dendrites / drug effects
  • Dendrites / physiology
  • Dendrites / ultrastructure*
  • Female
  • Humans
  • Male
  • Memory Disorders / physiopathology
  • Middle Aged
  • Neural Pathways / cytology
  • Neural Pathways / physiopathology
  • Prefrontal Cortex / cytology*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology
  • Pyramidal Cells / cytology*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiopathology
  • Schizophrenia / diagnosis*
  • Schizophrenia / drug therapy
  • Schizophrenia / physiopathology
  • Thalamus / cytology
  • Thalamus / physiopathology


  • Antipsychotic Agents
  • Coloring Agents