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Commentary: Chickens and eggs; carts and horses: an outsider's perspective on the study of the early stages and potential prevention of psychosis and schizophrenia.

Because schizophrenia is such a devastating illness, information regarding early detection and treatment has the potential to have a major benefit. Yet, prevention in schizophrenia has been a largely unfulfilled promise, and the early course of the illness is still a subject of controversy. The articles in this special issue of Schizophrenia Bulletin reflect the current state of the art in this area, and I have been invited to provide a commentary on the articles in this issue. My role as a commentator is to provide an outsider's perspective on the information presented in this issue, based on the fact that my research in schizophrenia has not been closely involved with this topic area. In this commentary, I will pose the questions that occur to me when thinking about the whole range of articles in this issue. These include the challenge of defining the earliest indicators of impending psychosis, understanding the underlying biological processes that may cause psychosis, and developing and implementing treatments to either eliminate the occurrence of the illness or reduce the severity and disability burden associated with the onset of psychosis. The problem of prediction of the full development of the illness from the earliest signs of impending psychosis (e.g., "the prodrome") is a complex issue and is the origin of the "chicken and egg" component of the title. It is important to be able to identify predictors of extremely high risk for subsequent development of psychosis that can be identified early enough so that the illness has not already developed. If the only good indicator of high risk for the development of schizophrenia is an early sign of signifying that illness is under way, prevention efforts will be challenged. Thus, I will evaluate the articles in this issue on that basis. Also critical is determining how much information about the early stages of the illness is needed before interventions can be meaningfully attempted. Current antipsychotic treatments (i.e., atypical or novel antipsychotic medications) have shown promise for reducing the psychotic symptoms of the illness and reducing relapse. They have also shown promise, although to a much lesser extent, at improving cognitive functioning and treating negative symptoms. They are not approved for the prevention of the first episode of psychosis, although we know that they are commonly prescribed for individuals who are not psychotic. We do not know if these medications prevent a first episode of psychosis or whether they are even the best medication to use in an individual who has not yet developed psychosis. Thus, their use in individuals who have not yet developed psychosis raises the issue of at what point is the cart before the horse in terms of treatment. There are a number of additional questions associated with each of these issues, and there is a potential hierarchy of importance of these questions as well. Inability to reliably identify the early signs of psychosis would eliminate the possibility of providing early intervention treatments. Offering treatments just because they are available and have previously been used to treat developed cases of psychosis would not necessarily be expected to prevent psychosis unless the biological processes that cause psychosis are the same that are operative after psychosis develops.