Schizophrenia and viral infection during neurodevelopment: a pathogenesis model?

Abstract

The neurodevelopmental hypothesis of schizophrenia proposes that a portion of schizophrenia is the result of an early brain insult which affects brain development and in which several types of virus might play an etiological role. The main arguments in favor of the neurodevelopmental hypothesis and the involvement of prenatal exposure to virus infection as a risk factor for adult schizophrenia are reviewed. Schizophrenia is associated with an increased incidence of craniofacial asymmetries and dermatoglyphic irregularities which might reflect an abnormal development of the ectoderm and the neural crest as a result of a viral infection between the first and second trimester of pregnancy. The brain histology of deceased schizophrenic patients shows disturbed neuronal migration and formations such as disorganized lamina strata or ectopic pyramidal cells, abnormal expression of the neural cell adhesion molecule, and absence of gliosis. The main epidemiological arguments are derived from studies of obstetrical complications and influenza virus infection during pregnancy, both considered to be early risk factors of schizophrenia. Because no virus has been consistently linked with the pathogenesis of schizophrenia, the most plausible hypothesis is that an endemic virus could initiate schizophrenia by direct brain lesion or by triggering an autoimmune response during the neurodevelopmental period on a genetically susceptible brain. In a neurodevelopmental model, the viral hypothesis is a step toward the goal of building a comprehensive theory that integrates the environmental, genetic, immune, and neuropsychological features of schizophrenia.