What Have We Learned From the New Generation of Prospective Studies on First-Episode Psychosis?

It could be argued that every instance of psychotic illness, of whatever prior history or none, has involved a first episode that resulted in an individual’s adversities coming to the attention of a third party, whether family, friend, health professional, or judicial figure. In these terms, first-episode psychosis has been studied for as long as we have had a concept of psychotic illness. However, it is only over the past 2 decades that the potential of systematic studies has been fully realized, to result in a new generation of important studies that have specifically identified and investigated patients presenting with their first episode of psychosis. The nature of these studies has 2 consequences: we are projected forward prospectively, to study the clinical and biological course of psychotic illness in relation to treatmentandlong-termoutcome;yetwearealsoledbackward, to study the early evolution of illness and putative predictors of the transition to the first psychotic episode, with a view to understanding the lifetime trajectory and identifying preventive strategies. The latter is the controversial area of prodromal or ‘‘high-risk’’ studies, which are still in an early phase and require careful evaluation in their own right. While they are touched on here, it is the study of first-episode psychosis in its prospective context that is the primary topic of consideration. The challenges include the following: 1. Have we gained new, fundamental knowledge on schizophrenia from these prospective first-episode studies, and, if so, what is that knowledge? 2. Towhatextenthavefirst-episodestudiesprovidedspecial insights not attainable through other approaches? 3. To what extenthavenewtechnologiesadvancedknowledge in relation to the above issues? 4. Can we provide clear and firm answers to fundamental questions of diagnostic boundaries, stability of diagnosis, static versus progressive disease process, the meaning of recovery, predictors of outcome, and effects of treatment? 5. To what extent does increased understanding of schizophrenia generalize to and inform on the broader spectrum of psychotic illness? 6. What is the status of mania in this context? 7. What is the current place of prospective first-episode studies vis-a`-vis the new wave of prodromal/‘‘highrisk’’ studies? 8. What have we learned about how to improve health care provision? To help answer these fundamental questions, presented here is a series of 6 articles that will each review the new generation of prospective first-episode studies from 6 differing perspectives, namely: