DeLisi correctly points out that our study does not establish that the brain abnormalities found in schizophrenia are neurodevelopmental in origin or due to a fixed lesion. We cannot, however, agree with the suggestion made by DeLisi that "reduction in gray matter was probably a continuous process since it was not as great as that seen when similar patients were scanned in the chronic phase of illness." First, it is not at all clear that our first episode subjects from Toronto, Ontario, were similar to chronically ill subjects recruited from a veterans' hospital in California1; for this reason, we highlighted the possibility that the smaller effect size found in first episode patients might be due to a selection bias. Second, the structural brain abnormalities found in schizophrenia have not generally been found to be associated with the duration of illness in studies of either chronic1-3 or first episode patients.4,5 Third, despite recent evidence that progression of ventricular enlargement may take place over some part of the course of the illness,6 there is no evidence that this is a process that is continuous over the entire course of the illness. Finally, there is no reason to assume that all structural brain findings in schizophrenia relate to a single pathophysiology. Woods et al7 have suggested that the brain abnormalities found in schizophrenia might be best explained by a 2-process model involving both static and progressive abnormalities. Progressive ventricular enlargement during the course of schizophrenia might also be due to the effects of aging, alcohol, nutrition, medication, or an impoverished environment.8
Zipursky RB, Kapur S. Structural Brain Changes in Schizophrenia—Reply. Arch Gen Psychiatry. 1999;56(2):195–196. doi:
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