Modeling psychotic disorders: Environment x environment interaction

Schizophrenia is a major psychotic disorder with multifactorial etiology that includes interactions between genetic vulnerability and environmental risk factors. In addition, interplay of multiple environmental adversities affects neurodevelopment and may increase the individual risk of developing schizophrenia. Consistent with the two-hit hypothesis of schizophrenia, we review rodent models that combine maternal immune activation as the first hit with other adverse environmental exposures as the second hit. We discuss the strengths and pitfalls of the current animal models of environment x environment interplay and propose some future directions to advance the field.