Does the genotype for schizophrenia often remain unexpressed because of canalization and stochastic events during development?

BACKGROUND: It has been well established in the literature that a strong genetic component exists for schizophrenia. Available data are compatible with the hypothesis that for most cases of schizophrenia, the genetic component consists of multiple genes acting in an additive manner with the genotype for schizophrenia being present when the number of genes is greater than a threshold number. Twin studies suggest that the genotype for schizophrenia is unexpressed in some individuals who carry it. This phenomenon of reduced penetrance has led to a diversity of hypotheses concerning the aetiology of schizophrenia. Based on a review of the literature a neurodevelopmental model is proposed for schizophrenia that involves the actions of the schizophrenia genotype, canalization and stochastic events. CONCLUSIONS: The schizophrenia genotype is programmed to disrupt the migration of neuronal cells in the developing cortex during the second trimester, resulting in impaired embryogenesis. The presence of a specific lesion is the reason for the onset of schizophrenia later in life. The genotype for schizophrenia often remains unexpressed, or demonstrates variable expressivity, because of the actions of canalization and stochastic events that may allow migrating neuronal cells to reach or approach the target data. Stochastic events also influence whether canalization will be successful, therefore, chance plays a major role under normal conditions in determining whether the schizophrenia genotype will be expressed. Certain environmental factors acting during early development, such as high temperature resulting from maternal illness, may increase the penetrance of the schizophrenia genotype.