Entorhinal cortex pre-alpha cell clusters in schizophrenia: quantitative evidence of a developmental abnormality

Background: Previous studies using semiquantitative or qualitative techniques demonstrated abnormalities of positioning of clusters of neurons (pre-alpha cells) in the entorhinal cortex in schizophrenia, suggesting a developmental mechanism could contribute to the illness. Recent quantitative studies of laminar thickness and laminar cell counts have been less consistent, and several failed to replicate the finding. However, none of the quantitative studies focused on the position of the pre-alpha cell clusters. Methods: To study pre-alpha cell position in detail, we examined the entorhinal cortex in serial sections from 21 control and 19 schizophrenic brains. Cluster position relative to the gray–white matter junction and cluster size were measured. Results: Quantitative assessment of 1991 clusters indicated clusters were positioned relatively closer to the gray–white matter junction in the anterior half of schizophrenic entorhinal cortices. In addition, the size of clusters in males with schizophrenia was reduced. Conclusions: These results support the model of schizophrenia as an illness in which brain development is impaired. The findings in males with schizophrenia may indicate the presence of more severe pathology, or an additional pathogenic mechanism