Recent advances in research on schizophrenia have significantly changed the manner in which translational research is being conducted in this field. Although there is a lack of gross morphological change observed in the brains of schizophrenic patients, there is substantial evidence that this disorder is one of impaired synaptic connectivity, which has been observed in numerous humans postmortem as well as in functional and structural brain imaging studies. This chapter outlines the major neuropathological and behavioral abnormalities associated with schizophrenia. It discusses the risk genes most implicated in the pathophysiology of schizophrenia and outlines their roles in regulating aspects of neuroplasticity thought to be perturbed in this disease. The chapter describes the pharmacological and genetic animal models that are being used in translational research. It highlights novel therapeutic targets currently being investigated for treating schizophrenia.

The fact that risk genes for schizophrenia are salient for brain development or that fetal brain insults mimic the cortical and behavioral pathology of schizophrenia has led to a certain degree of pessimism that these deficits could be ameliorated in the mature brain. Animal models of disorders like schizophrenia that are manifest primarily by cognitive symptoms such as disorganized thinking and hallucinations are based on rather tenuous behavioral inferences such as hyperactivity and stereotypic behavior and are equivalent to psychosis because it is reduced by antipsychotic drugs. Although it has long been known that schizophrenia is associated with loss of cortical volume and increased size of the lateral ventricles, the pathology of the mood disorders was thought to be primarily functional. Biogenic amine neurotransmitters were the major focus of translational research, given their role in mediating the therapeutic effects of antipsychotic and antidepressant medications.