The brain in schizophrenia.

Schizophrenia has been the subject of intensive neuropsychologic, neuroradiologic, neuropathologic, and neurochemical investigations. The most consistent and reproducible result from all this effort has been the demonstration of a mild degree of enlargement of the cerebral ventricles. The existence of this finding is no longer a subject of controversy, and it clearly occurs independently of psychiatric treatment and chronicity of disease. This finding represents the strongest evidence to date that a structural lesion of the central nervous system underlies schizophrenia. The localization of the lesion responsible for ventricular enlargement and for the clinical findings in schizophrenia is not as clear. Pathologic alterations in the anteriomedial temporal lobe, particularly in the hippocampus, have been independently identified by several groups, using both in vivo neuroimaging and postmortem anatomic techniques. The details and etiology of temporal lobe-hippocampal pathologic states remain to be elucidated. Neuropsychologic and cerebral blood flow studies suggest that the frontal lobe is dysfunctional in schizophrenics. However, there is little known about the neuropathologic basis and neurochemical correlates of this deficit. One of the intriguing new hypotheses about the neurologic findings in schizophrenia is that they are the result of an abnormality in the early development of the brain. The possibility that the clinical illness is a delayed manifestation of this process, perhaps because of an interaction between the early developmental deficit and later maturing functional neural systems, is a subject of speculation. While much study has been devoted to the structural and functional abnormalities underlying schizophrenia, much remains to be discovered. In the past 20 years, the development and application of new techniques, including CT, MRI, rCBF, and PET, have revolutionized the study of schizophrenia, and have produced the first consistent neuropathologic findings in this disorder. The pace of discovery has been gradually accelerating. Application of new techniques and careful use of patient selection criteria will help further decipher the neurologic basis of this disorder. There is reasonable hope that by the end of this century, the pathology and pathophysiology of this common but baffling illness will be revealed.