The dysplastic net hypothesis: an integration of developmental and dysconnectivity theories of schizophrenia

Two separate theories that attempt to explain different aspects of schizophrenia have recently attracted much attention. The first, the neurodevelopmental hypothesis, postulates that deviations in early development establish a neuronal phenotype that predisposes to, or, in some versions, determines the later onset of schizophrenia. The second theory proposes that schizophrenic symptoms arise from abnormalities in neuronal connectivity. Here, we suggest that the findings from these two separate lines of inquiry can be integrated into a unitary framework: the dysplastic net hypothesis. In essence, this proposes that anatomical and physiological dysconnectivity of the adult schizophrenic brain is determined by dysplastic fetal brain development. We also indicate how abnormal connectivity between brain regions constituting large-scale neurocognitive networks is expressed in both the prepsychotic and psychotic phases of schizophrenia, and we examine possible risk factors (genetic and environmental) for dysplastic formation of these networks.