A qualitative and quantitative analysis of the entorhinal cortex in schizophrenia

The entorhinal cortex (ERC) has been implicated in schizophrenia by anumber of studies. There is anatomical observation of neuronal heterotopiasin the rostral ERC, which is consistent with a hypothesis ofneurodevelopmental abnormalities in this disease. In view of thesignificant cytoarchitectonic variation of the ERC throughout itsrostro-caudal extent, we performed a detailed subareal analysis of therostral two-thirds of the entorhinal cortex (ERCr) in 14 postmortemschizophrenic brains and 14 matched controls (mean ages of 48 and 47respectively). This systematic evaluation included both a qualitativemicroscopic analysis of morphogenetic anomalies that would be consistentwith neurodevelopmental pathology and quantitative measurements of totalneuronal number, average neuronal density, laminar volume and laminar depthfrom the cortical surface in cytoarchitectonically matched subareas ofschizophrenic and control brains. Parcellation of the entire ERC on thebasis of cytoarchitectonic criteria identified five distinct regions,similar to those described in the macaque, except that in the human brainthree of the regions were further divisible into two or three subareas,yielding nine distinct cellular compartments. Five rostral areas, prorhinal(Pr), lateral (28L), intermediate rostral and caudal (281r and 281c), andsulcal (28S), comprise the ERCr. Gross and microscopic examination of thesesubdivisions throughout the ERCr failed to reveal laminar disorganizationin any of the schizophrenic brains. The brains also did not differsignificantly with respect to total neuronal number, total volume andneuronal density per laminar and subareal subdivision, or laminar thicknessper entorhinal subarea. However, neuronal number and density were reducedby 12-18% in Pr and 28L, suggesting that mild quantitative abnormalitiesmay exist in the ERCr and might possibly be revealed in a larger sample ofschizophrenic brains. We have failed to confirm previous reports of laminardisorganization in the ERCr in brains of patients with schizophrenia; tothe extent that this region is implicated in schizophrenia, the structuralchanges are likely to consist of more subtle cellular disturbances.