Cellular and molecular neuropathology of schizophrenia: new directions from developmental neurobiology

Schizophrenia is in essence a developmental disorder, but an unusual one in that the onset of symptoms is markedly delayed. Neuropathologic studies of the brain in schizophrenia have revealed subtle abnormalities that may reflect abnormal neuronal development. A more detailed examination of the cellular and molecular pathology of schizophrenia has been limited by the lack of informative markers that might allow a more complete understanding of the brain defects that characterize this disorder. Recent advances in molecular biology have made available a growing number of probes for examining the expression of specific gene products in brain tissue by using in situ hybridization and immunohistochemistry using antibodies to recombinant antigens. Several recently cloned neural genes are expressed in the forebrain regions which have been implicated in schizophrenia, and may have significant roles in brain development or function. Selected neurotransmitter receptors, neurotrophins and their receptors, and transcription factors of the POU and MADS families are promising candidates for future studies of the cellular and molecular neuropathology of schizophrenia.