Schizophrenia and the normal functional development of the prefrontal cortex

Schizophrenia is being increasingly viewed as a neurodevelopmental disorder, that is, one in which early, fixed pathology becomes manifest clinically during the normal course of maturation of the brain. Evidence for this position comes first from neuroimaging research, such as (1) studies that demonstrate morphologic brain changes (such as ventriculomegaly on CT scans) even in first break patients; and (2) a lack of correlation between these morphologic changes and duration of illness. Another source of evidence is studies of normal brain development in rodents and primates, including research that shows (1) the prefrontal cortex is a late maturing part of the brain, and (2) lesions of the prefrontal cortex may be initially silent and show delayed onset of dysfunction as the brain matures. A neurodevelopmental approach to schizophrenia, in turn, has stimulated further work into the normal development of brain regions implicated in the illness, such as the frontal cortex. Thus, the fields of neuropsychiatry and neurodevelopment have been mutually stimulated during the course of this work. In addition, viewing schizophrenia in developmental terms may have implications for the understanding of changes in cognition and behavior during normal adolescence.