Hippocampal dysgenesis in mutant mouse and schizophrenic man: is there a relationship?

A rapidly growing body of data points to structural alterations of the temporal lobe in a significant number of schizophrenic patients. At the histological level, these changes are most frequently seen in the hippocampus and entorhinal cortex, and a strong case can be made for attributing them to disturbed neuroembryogenesis. Archicortical components of the temporal lobe are now known to follow an unusually complex course of embryological development, and we suggest that the process may be especially vulnerable to interference. A number of autosomal mutant mice express anomalies of hippocampal development, some of which resemble caricatures of the more subtle alterations in schizophrenic patients. We have suggested that at least some schizophrenias may result from the impact of maternal exposure to influenza virus during the period of neuroblast migration into the hippocampal primordium in the presence of as yet unspecified patterns of genetically transmitted immuno-incompetence. Although this putative interaction of genetic and epigenetic factors in humans probably differs from the factors involved in the mutant mouse, study of the murine model may reveal those mechanisms of embryogenesis that are most likely to be disturbed in the temporal lobe of schizophrenic patients.