Pathogenesis of schizophrenia: Part II. Temporo-frontal two-step hypothesis.

The objective of the present study was to provide a pathophysiological model of the development of schizophrenia. The method used was the selective review of recent findings, including those of animal models from our own department, to clarify the relationship between morphological brain changes and dopamine metabolism, and the pathophysiology of schizophrenia. The results showed that entorhinal cortex-lesioned animals had increased concentrations of dopamine in the amygdala, and methamphetamine-induced dopamine release in the amygdala of lesioned rats was significantly enhanced compared with sham-operated rats. These results and the morphological findings in schizotypal disorder patients support the view that temporal lobe changes may underlie a vulnerability to schizophrenia. Latent dysfunction in these regions may become clinically apparent as positive psychotic symptoms due to additional frontal lobe changes in schizophrenia. For the emergence of positive Schneiderian symptoms, aberrant activity of sociality-related circuits, including the amygdala was postulated. In conclusion, a temporo-frontal two-step hypothesis for the development of schizophrenia was suggested.