Pathophysiology of schizophrenia from the perspective of neuropathology

Abstract

Neuropathological investigation is a classic technique that has conducted for over 100 years in the study of the pathophysiology of schizophrenia. The findings from neuropathological investigations have indicated abnormalities in neurodevelopment, such as neuronal differentiation, neuronal migration, neurite branching, neurite elongation and synapse formation in schizophrenia, and have contributed to the elucidation of the pathogenesis of schizophrenia. However, it has been often difficult to clarify whether the observational findings are due to the disease itself, as the findings may be affected by lifetime events, including agonal factors. In addition, reproducibility may also be affected by biological heterogeneity in schizophrenia diagnosed based on operational diagnostic criteria. Therefore, we focus on schizophrenia with rare variants as one of the strategies, and conducted neuropathological investigations with consideration of the genomic background in order to reveal more disease‐specific neuropathological findings. In order to elucidate the pathology of schizophrenia, it is desirable not only to accumulate postmortem brains, but also to expand brain banks that have genome analysis information.