Abnormal patterns of cortical synaptic connectivity in schizophrenia

Electron microscopic morphometric study of postmortem prefrontal cortex (area 10) and visual cortex (area 17) was performed to estimate the numeric density (Nv) of synapses in layers I and II, neurons in layer 11 and the number of synapses per neuron in layer 11 in 20 cases of chronic schizophrenia and 16 healthy controls using stereological physical dissector method. In the prefrontal cortex the Nv of axospinous synapses was significantly lower in layer I (-20%, p < 0.05) in schizophrenia group and in the subgroup with predominantly positive symptoms as compared to controls (p < 0.05). On the contrary, a significantly higher Nv of synapses (+2495, p < 0.05) and the number of synapses per neuron were found in layer II (+4296, p < 0.05) in schizophrenia group and in the subgroups of cases with predominantly negative symptoms and a continuous course of schizophrenia (p < 0.001) as compared to the control group. The subgroup of cases with predominantly negative symptoms displayed a significantly lower number of neurons in layer II of the prefrontal cortex compared to controls (p < 0.05) and the subgroup of cases with predominantly positive symptoms (p < 0.01). In the visual cortex the number of axodendritic synapses per neuron in layer II was significantly higher in schizophrenia, but the other parameters did not differ from those in the control group. These prominent abnormalities of synaptic connectivity might be the structural basis for altered cognitive functions associated with changes in intracortical, cortico-cortical, and cortico-subcortical pathways, and could contribute to the formation of positive and negative symptoms and altered neuronal plasticity in patients with schizophrenia.