Circumscribed malformation and nerve cell alterations in the entorhinal cortex of schizophrenics. Pathogenetic and clinical aspects.

A postmortem histological comparison of 5 selected cases of schizophrenia with 5 non-schizophrenic controls showed a circumscribed malformation of the entorhinal cortex. The cortical alterations consisted mainly of a lack or a change of the characteristic island formations in layer II pre-alpha. Further, there were atypical neurons in layers II and III showing a conspicuous decrease of volume, often a change of the shape. They lay either in clusters or in columnar formations. These cells were considered "young neurons". The changes varied considerably from case to case and sometimes extended to all entorhinal layers. In one case the extension of the changes is described by means of serial sections in steps which extend over the whole rostral entorhinal region. Here, the striking architectural changes were formed in an exactly circumscribed sector and did not extend to the rostral hippocampal formation. On the whole, the changes are regarded as local migrational disturbances that occur during the second trimester of brain development. Neuronal displacements like these could give rise to various aberrant connections within the limbic system and related structures (e.g. the central position of the entorhinal region in circuits such as the entorhino-hippocampal loop, entorhinol-insula and entorhino-orbitofrontal reciprocal connections). Whereas alterations of the genetic programming of cell migrations may be suspected, various environmental influences (e.g. viral infections during the months III-V of pregnancy) appear to play a significant role. The malformations may be a decisive vulnerability factor for the later manifestation of the illness.