Neurodevelopment and Schizophrenia

Developmental changes in the brain are now a central feature of most etiological theories of schizophrenia. From the fetal period, in which vulnerability is presumed to originate, to the emergence of clinical illness in adolescence, brain changes are setting the stage for the first episode of psychosis. A host of factors that have the ability to alter fetal brain development have been linked with schizophrenia. Heritable genetic factors may increase risk for aberrant fetal brain development, and molecular genetic studies are now revealing mutations and epigenetic events that can also derail normal developmental processes. Prenatal complications also are now known to be associated with vulnerability. Later, adolescence and early adulthood are the critical periods for the onset of the prodrome, the period of decline before illness onset, and then the clinical syndrome. Here we summarize hypothesized elements of the neurodevelopmental process in schizophrenia in a model that spans both the prenatal and adolescent/young-adult periods. It is likely that future models will be much more complex as epigenetic processes and gene–environment interactions are incorporated.