Pathophysiology in the clinical course of schizophrenia

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Abstract
Almost all patients recover from a first psychotic episode of schizophrenia but most suffer one or more subsequent relapses that leave them with persistent positive and negative symptoms and associated functional impairment. The decline in response to treatment could reflect either the development of tolerance to neuroleptic medication or an active pathophysiological process underlying progression of the illness. In a 10-year prospective study of first-episode, largely treatment-naive patients, treatment outcome and biological and clinical variables were assessed in an attempt to identify prognostic factors of the degenerative process. The duration of psychosis before treatment was strongly negatively correlated with treatment outcome. Magnetic resonance imaging revealed anomalies at the onset of illness, including reduction in volume and abnormalities in the shape of the cerebral cortices, enlargement of the lateral and third ventricles and reduction in the volume of the hippocampus; 30–40% of patients had a cavum septum pallucidum. In the first 2 years after onset of the illness, ventricular volumes increased and cerebral cortical volumes decreased in patients with a poor outcome, while there was no change in these dimensions in patients with good outcome. These results are evidence of neuropathological progression, reflecting the more deteriorative course of schizophrenia.

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