Neurodevelopment and Schizophrenia
Broadening the Focus Elaine Walker,
Daniel Shapiro,
Michelle Esterberg and
Hanan Trotman + Author Affiliations Emory University Elaine Walker, Department of Psychology, 36 Eagle Row, Emory University, Atlanta, GA 30322 E-mail: psyefw@emory.edu
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Abstract 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. Conclusions It is important to emphasize that the neurodevelopmental model depicted in Figure 1 is speculative. It reflects a combination of empirical research findings and hypotheses about causal processes. Other elements and mechanisms are likely involved. Further, schizophrenia is varied in its clinical presentation, and it is generally assumed that there is variability in how it originates. As noted, genetic research indicates that many genes and genetic mechanisms are involved as are many prenatal complications. Finally, recent findings from genetic studies indicate that schizophrenia shares genetic risk factors with other forms of psychosis, such as bipolar disorder with psychotic features. In sum, the model depicted in Figure 1 is assumed to be highly oversimplified and unlikely to account for all cases. It does, however, incorporate many current views and can serve as a point of departure for future models. For example, future research is likely to reveal that interactions between genetic and environmental factors and dynamic epigenetic processes are key pieces of the puzzle, and these will certainly be elements in future neurodevelopmental models. We clearly have a long way to go in unraveling the complex etiological pathways to schizophrenia. But there has been significant progress. In part, our progress is our acceptance of two facts about the etiological process: (a) that it is extremely complicated, and (b) that it interacts with the development of the brain at critical periods.
Broadening the Focus Elaine Walker,
Daniel Shapiro,
Michelle Esterberg and
Hanan Trotman + Author Affiliations Emory University Elaine Walker, Department of Psychology, 36 Eagle Row, Emory University, Atlanta, GA 30322 E-mail: psyefw@emory.edu
Next Section
Abstract 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. Conclusions It is important to emphasize that the neurodevelopmental model depicted in Figure 1 is speculative. It reflects a combination of empirical research findings and hypotheses about causal processes. Other elements and mechanisms are likely involved. Further, schizophrenia is varied in its clinical presentation, and it is generally assumed that there is variability in how it originates. As noted, genetic research indicates that many genes and genetic mechanisms are involved as are many prenatal complications. Finally, recent findings from genetic studies indicate that schizophrenia shares genetic risk factors with other forms of psychosis, such as bipolar disorder with psychotic features. In sum, the model depicted in Figure 1 is assumed to be highly oversimplified and unlikely to account for all cases. It does, however, incorporate many current views and can serve as a point of departure for future models. For example, future research is likely to reveal that interactions between genetic and environmental factors and dynamic epigenetic processes are key pieces of the puzzle, and these will certainly be elements in future neurodevelopmental models. We clearly have a long way to go in unraveling the complex etiological pathways to schizophrenia. But there has been significant progress. In part, our progress is our acceptance of two facts about the etiological process: (a) that it is extremely complicated, and (b) that it interacts with the development of the brain at critical periods.
