The hippocampus in schizophrenia: lateralized increase in neuronal density and altered cytoarchitectural asymmetry

The histological basis of schizophrenia is unknown, but it appears to affect the hippocampal and neocortical cytoarchitecture. Some cytoarchitectural parameters normally differ between the two cerebral hemispheres. Moreover, schizophrenia is associated with altered structural cerebral asymmetry. However, few cytoarchitectural studies of schizophrenia have taken the question of asymmetry fully into account.

We performed a morphometric post mortem study of neuronal density in sections from the left and right hippocampus (dentate gyrus, CA4, CA3, CA1 and subiculum) of 22 schizophrenics and 18 normal subjects. We also determined the correlations of neuronal density between pairs of subfields as an index of their inter-relationship; a previous study had found correlations in the left but not the right hippocampus of normal subjects.

There were three differences in the schizophrenics compared to the controls. (1) neuronal density was increased in right CA3 (by 25%) and right CA1 (by 22%); (2) neuronal density correlated strongly between homologous left and right subfields (i.e. inter-hippocampally) for CA4, CA3, CA1 and subiculum, in normals this occurs only for dentate gyrus and CA4; and (3) intrahippocampal correlations of neuronal density between pairs of subfields were similar in both hippocampi of the schizophrenia cases, unlike their asymmetrical distribution in controls.

The alterations may be part of the histological substrate of schizophrenia. The nature of the findings is consistent with a neurodevelopmental origin, and with a disease process that affects cerebral asymmetry and leaves its imprint upon the hippocampal cytoarchitecture.