Studies of neurones

Various cytoarchitectural alterations have been described in schizophrenia, of which three have generated particular interest: abnormal neuronal organization (dysplasia) in the entorhinal cortex, disarray of hippocampal neurones, and an altered distribution of neurones in the subcortical white matter. These findings are important because they support the hypothesis of an early neurodevelopmental anomaly underlying schizophrenia. However, none have been unequivocally and independently replicated, and for each there is at least one non-replication. (31>

A less well known yet seemingly more robust cytoarchitectural feature of schizophrenia is that many neurones are smaller than expected. This has been shown in three studies of pyramidal neurones in the hippocampus, and has also been reported in dorsolateral prefrontal cortex and cerebellar Purkinje cells. Some studies find that the neurones are also more closely packed. Outside the cerebral cortex, good cytoarchitectural data are limited to the thalamus, with a replicated finding that the dorsomedial nucleus, which is part of a circuit involving the prefrontal cortex (see Chapter,l2^.3,!), contains significantly fewer neurones than in normal subjects.

In summary, a range of differences in neuronal structure and organization have been reported to occur in schizophrenia. The abnormalities most often taken to be characteristic of the disorder—disarray, displacement, and paucity of hippocampal and cortical neurones—are features which in fact have not been well demonstrated. This undermines attempts to date the pathology of schizophrenia to the second trimester in utero based on their presence (see below). In contrast, decreased neuronal size and loss of thalamic neurones have been shown fairly convincingly. Some of the discrepancies in the literature may reflect regional heterogeneity in the cytoarchitectural pathology of schizophrenia; notably, the cingulate gyrus may have a different pattern of changes. (32>

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