A qualitative and quantitative analysis of the entorhinal cortex in schizophrenia |
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Authors: | Krimer LS; Herman MM; Saunders RC; Boyd JC; Hyde TM; Carter JM; Kleinman JE; Weinberger DR |
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Affiliation: | Clinical Brain Disorders Branch, IRP, NIMH, NIH Neuroscience Center at St Elizabeths, Washington, DC 20032, USA. |
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Abstract: | The entorhinal cortex (ERC) has been implicated in schizophrenia by a
number of studies. There is anatomical observation of neuronal heterotopias
in the rostral ERC, which is consistent with a hypothesis of
neurodevelopmental abnormalities in this disease. In view of the
significant cytoarchitectonic variation of the ERC throughout its
rostro-caudal extent, we performed a detailed subareal analysis of the
rostral two-thirds of the entorhinal cortex (ERCr) in 14 postmortem
schizophrenic brains and 14 matched controls (mean ages of 48 and 47
respectively). This systematic evaluation included both a qualitative
microscopic analysis of morphogenetic anomalies that would be consistent
with neurodevelopmental pathology and quantitative measurements of total
neuronal number, average neuronal density, laminar volume and laminar depth
from the cortical surface in cytoarchitectonically matched subareas of
schizophrenic and control brains. Parcellation of the entire ERC on the
basis of cytoarchitectonic criteria identified five distinct regions,
similar to those described in the macaque, except that in the human brain
three 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), and
sulcal (28S), comprise the ERCr. Gross and microscopic examination of these
subdivisions throughout the ERCr failed to reveal laminar disorganization
in any of the schizophrenic brains. The brains also did not differ
significantly with respect to total neuronal number, total volume and
neuronal density per laminar and subareal subdivision, or laminar thickness
per entorhinal subarea. However, neuronal number and density were reduced
by 12-18% in Pr and 28L, suggesting that mild quantitative abnormalities
may exist in the ERCr and might possibly be revealed in a larger sample of
schizophrenic brains. We have failed to confirm previous reports of laminar
disorganization in the ERCr in brains of patients with schizophrenia; to
the extent that this region is implicated in schizophrenia, the structural
changes are likely to consist of more subtle cellular disturbances.
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