Regional neuropathology in schizophrenia: where are we? Where are we going?

This paper presents a neurologic formulation for the clinical features of the schizophrenic syndrome, and tests it against a systematic, region by region review of available postmortem neuroanatomical and neuropharmacological data. Based on this review a model is proposed that postulates a developmental lesion affecting the midline neurotransmitter-specific ascending projection systems. Due to the facilitatory role these systems play in the development of the brain regions to which they project, such a lesion is one parsimonious, and testable, explanation for virtually all the clinical, laboratory, and pathological findings reported to date in schizophrenia research. A case is made for establishing a global antemortem-postmortem collaboration using a Latin square design; the alternative may be that, as has happened in the past, the best efforts of dilligent researchers around the world may lead to little improvement in our understanding of schizophrenia.