Animal models of obstetric complications in relation to schizophrenia

Epidemiological studies have provided strong evidence that exposure to obstetric complications is associated with an increased risk for later development of schizophrenia. These human studies have now begun to tease out which specific pregnancy, labor/delivery or neonatal complications might confer greatest risk for schizophrenia. Animal modeling can be a useful tool to directly ask if a particular obstetric complication can actually cause changes in brain function or behavior resembling changes in schizophrenia. This review describes currently available animal models for some of the obstetric complications with greatest effect size for schizophrenia, including maternal diabetes, preeclampsia, infection and stress during pregnancy, intrauterine growth retardation and fetal/neonatal hypoxia. Where available, evidence that these types of obstetric complications in animals produce alterations in CNS function or behavior, related to features of schizophrenic pathology, is presented. Animal models might provide insights into the mechanisms by which specific obstetric complications have long-term influence on brain development leading to increased risk for schizophrenia. Factors common to several obstetric complications associated with schizophrenia may also be discerned. In this way, animal modeling may provide the framework for human studies to ask further more refined questions concerning the role of specific obstetric factors contributing to schizophrenia, and may provide clues to prevention. (C) 2004 Elsevier B.V. All rights reserved.