Animal Models of Relevance to the Schizophrenia Prodrome

Patients with schizophrenia often undergo a prodromal phase prior to diagnosis. Given the absence of significant therapeutic improvements, attention has recently shifted to the possibility of intervention during this early stage to delay or diminish symptom severity or even prevent onset. Unfortunately, the 20 or so trials of intervention to date have not been successful in either preventing onset or improving long-term outcomes in subjects who are at risk of developing schizophrenia. One reason may be that the biological pathways an effective intervention must target are not static. The prodromal phase typically occurs during late adolescence, a period during which a number of brain circuits and structures are still maturing. We propose that developing a deeper understanding of which circuits/processes and brain structures are still maturing at this time and which processes drive the transition to schizophrenia will take us a step closer to developing better prophylactic interventions. Fortunately, such knowledge is now emerging from clinical studies, complemented by work in animal models. Our task here is to describe what would constitute an appropriate animal model to study and to potentially intervene in such processes. Such a model would allow invasive analysis of the cellular and molecular substrates of the progressive neurobiology that defines the schizophrenia prodrome and hopefully offer valuable insights into potential prophylactic targets.