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Schizophrenia is a pervasive neuropsychiatric disorder with worldwide prevalence. Family and adoption studies indicate a strong genetic component of disease susceptibility. However, epidemiological studies also point to a role for infections and other environmental factors in disease etiology. We review the evidence for a role for infectious agents in the etiopathogenesis of schizophrenia and related disorders, focusing on the apicomplexan parasite Toxoplasma gondii. We discuss the epidemiological evidence for a role for this agent, as well as potential mechanisms of gene-environmental interactions which are consistent with the genetic components of disease susceptibility. We describe how the potential role of infections as causative agents of complex disorders such as schizophrenia are not consistent with classical postulates of causation such as the Koch Postulates, but may be consistent with more modern concepts of how infectious agents can interact with genetic determinants to result in disease in susceptible individuals. We outline the research approaches which are necessary to define associations between infectious agents and complex disorders. The successful association between infectious agents and diseases such as schizophrenia might lead to new methods for treatment and prevention of these devastating disorders. (C) 2006 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved.