Development and Psychopathology

Neurodevelopmental abnormalities in schizophrenia: Insights from neuropathology

a1 Center for Neurobiology and Behavior, University of Pennsylvania


Growing epidemiological, genetic, and clinical neurobiological evidence indicates that abnormalities in brain development play determining roles in the pathobiology of schizophrenia. Neuropathological research has made significant progress in delineating cellular and molecular abnormalities in schizophrenia that have relevance to neurodevelopment. This paper reviews the neurodevelopmental processes of neurogenesis, neuronal migration, differentiation, synaptogenesis, neuron and synaptic pruning, and myelination and the reported neuropathological findings in schizophrenia that may be a consequence of disturbances in these processes. While many neuropathological findings in schizophrenia are controversial or await confirmation, reported abnormalities in neuron density, number and morphology, cytoarchitecture, dendritic arbors and spines, synapse-related proteins, and the well-established absence of gliosis or any other evidence of neurodegeneration or neural injury all provide support for the neurodevelopmental model of schizophrenia.

c1 Address correspondence and reprint requests to: Steven E. Arnold, M.D., 142 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104; E-mail: alveus