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Secondary prevention in schizophrenia is still not good enough, and the authors of the articles in this issue of Schizophrenia Bulletin present important new knowledge that may increase earlier detection and treatment. This final article discusses some of their main findings in relation to clinical consequences and new research. We need more knowledge about the clinical characteristics of the prodromal phase and about the factors that influence the help-seeking behavior of patients and families in the early phases of schizophrenia. The new models presented for early detection and treatment are promising and should be replicated in other countries and on other continents. Because we still lack an effective primary prevention of schizophrenia, we need to make great efforts to improve our secondary prevention. As long as this disorder persists as one of our most costly medical disorders -- economically as well as in terms of human suffering - any clinically significant reduction in the severity and/or duration of schizophrenia is surely worth any investment. Theoretically, secondary prevention is improved if we can apply a more effective treatment at an earlier point in the course of most disorders. For schizophrenia, there is some empirical evidence, although inconclusive, that this is the case. The work to improve the secondary prevention of schizophrenia will therefore have two aims: to find strategies and methods for earlier detection and to develop treatment methods and programs that are tailor-made for patients in the early phases of schizophrenia. What kind of knowledge do we skill need to reach these aims? Concerning earlier detection, we obviously need to know more about the very early signs and symptoms indicating the development of a schizophrenic disorder with a reasonably high degree of probability. We also need to know the biological, psychological, and social factors that influence the treatment-seeking behavior of subjects in the earlier phases of schizophrenia. Although the earliest signs and symptoms of schizophrenia may be universal and thereby easily generalizable, treatment-seeking behavior may be differently influenced by individual, family, social, and health service factors in different cultures and countries. Therefore, general knowledge about the most influential factors on treatment seeking must be based on studies from different countries and continents. Concerning early treatment intervention, we need to know whether the treatment modalities that have a significant impact on schizophrenia patients under the usual treatment-seeking situation, such as psychopharmacological, psychoeducational, and assertive outreach programs (Lehman et al. 1995), can be applied with the same or better results and without modifications to an earlier detected group. We should also explore whether patients detected earlier may benefit even more from other interventions. It is also important to prove empirically that an early intervention by itself is more beneficial for the patients and their families than a later one. These questions should be explored by comparing earlier and later detected patients who receive the same treatment program, at least concerning the core elements. We are in fact initiating such a prospective study in Norway in collaboration with Danish and American groups. Several of the research questions mentioned here are addressed by the contributors to this issue of the Schizophrenia Bulletin. In this final article, I will summarize and discuss some of the answers that these authors have given to these questions. I will also indicate some clinical consequences of the findings, and some research questions that should be studied further. What Are the Earliest Signs and Symptoms of Schizophrenia? The time interval from the onset of a schizophrenic disorder to the establishment of an adequate therapy is often several years (Larsen et al. 1996b, this issue), even if we estimate this time from the point when the patient fulfills the DSM-III-R (American Psychiatric Association 1987) criteria for schizophrenia and not from the (retrospectively estimated) beginning of the prodromal phase. Because most of our efforts to identify and treat patients in the prodromal phase will also influence the identification and treatment of patients in the early manifest psychotic phase, I will focus mostly on early detection and treatment in the prodromal phase. Schizophrenia usually starts with a prodromal phase in which the patient does not fulfill all the criteria of the disorder, but in which observable and experiential changes in behavior, thinking, and feelings occur. An early treatment should be established to identify (and treat) these patients in the prodromal phase. To accomplish this we need to know the "true" symptoms and signs of the prodromal phase. Most of our knowledge, as reflected in the DSM-III-R criteria, has been collected retrospectively by interviewing patients and families about the history of the psychotic development. These investigations, like the study reported here by Yung et al. (1996, this issue), have found that the length of the prodromal phase may vary from days to many years, and that most of the reported symptoms and signs seem to be rather nonspecific, even for psychosis. These findings also indicate that not all schizophrenia patients will have a long enough prodromal phase to be identified as such within this phase, and that cross-sectionally it is very difficult to pick out those who will eventually develop schizophrenia among persons having more moderate problems like anxiety, depression, or sleeping disorders. Even among persons with a substantial vulnerability for schizophrenia, some will fail to proceed from the prodromal phase to a full-blown syndrome even without treatment. Furthermore, the prodromal phase may be more or less the same for many types of psychoses (Yung et al. 1996, this issue). We need to know which features in the prodromal phase can predict the type and course of the subsequent psychosis. Ideally this should be studied prospectively, but it can also be explored retrospectively by comparing patient groups that each have a different first-onset psychosis. Some authors propose that attenuated psychotic symptoms like attentional or perceptual distortions may increase the low specificity of the prodromal signs and symptoms (see Yung et al. 1996, this issue). Based on their own clinical experiences and the findings from research on vulnerability markers, Olin and Mednick (1996, this issue) and Yung et al. (1996, this issue) propose that in the 16-30 year-old cohort population we can use a combination of different predictors of schizophrenia to identify persons with moderate psychopathological disturbances who should get early treatment for schizophrenia. McGorry et al. (1996, this issue) and Yung et al. (1996, this issue) are now exploring the value of combining risk factors such as family history of psychosis, prodromal symptoms from the DSM-III-R list, history of transient psychotic symptoms, and other neurobiological and neuropsychological predictors of schizophrenia. This is based on the notion that persons with prodromal symptoms of psychosis run an increased risk for advancing further into manifest schizophrenia if the above characteristics are present. The extensive list of predictors of schizophrenia (Olin and Mednick 1996, this issue) could be used to decide whether a person has a preschizophrenic prodromal syndrome. However, in clinical practice, subjecting patients with only vague prodromal symptoms to extensive biological and neuropsychological examinations may not be feasible. Therefore, we need to explore further which predictors best indicate a forthcoming schizophrenic syndrome among prodromal subjects. The ongoing study in Australia (Yung et al. 1996, this issue; McGorry et al. 1996, this issue) may give us new answers to this question. Prodromal symptoms for relapses have been studied in several follow-along studies of schizophrenia cohorts. As reviewed by Falloon et al. (1996, this issue), these prodromal symptoms are often idiosyncratic for each patient. If this is also the case in the first prodromal phase, we should focus more on the specificity of individual changes (e.g., degree, type, speed, stress relation) than on the symptom state to identify the important differences between a prodromal phase of psychosis and other changes that may occur in adolescence and young adulthood. In general, it might be best to follow the advice from McGorry et al. (1996, this issue) to study different phases of the psychotic process more separately with regard to clinical picture -- influencing biological, psychological, and social factors -- and therapeutic interventions. As in substance abuse disorders, different factors may be important for the prodromal, the active psychotic, the relapsing, and the chronic phases.
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