Most at‐risk individuals will not develop a mental disorder: the limited predictive strength of risk factors

Abstract

World Psychiatry 20:2 June 2021 vehicle for indicated prevention of psychosis, one of the recent criticisms of the approach, echoed by Fusar-Poli et al, derives from the NEMESIS-2 cohort report that antecedent mood disorders account for more of the incidence of clinical psychosis than do psychotic-like symptoms. We see three important limitations of the NEMESIS-2 data that have received little attention. First, psychotic-like experiences gauged through questionnaires or non-clinical interviews in the general population are not comparable to clinician-assessed CHR syndromes. Second, the time-points in NEMESIS-2 were spaced three years apart. Partly-prospective data show that the average duration of CHR symptoms is two years or less in two-thirds of patients converting to psychosis, suggesting that the development of psychotic-like symptoms prior to psychosis may have been missed by the NEMESIS-2 design in as many as half the cases. Third and most crucially, the average age of cohort members at the second time point was 47.7 years, far older than the 12-to-early 30s range where CHR has been reported to predict psychosis and where the incidence of psychosis is known to be highest. As a consequence of these limitations, in our view the NEMESIS-2 data are only partially relevant to the value of CHR as a vehicle for indicated prevention. With regard to evidence for the success of preventive interventions for CHR, FusarPoli et al rightly point out that meta-analytic evidence so far is contradictory and that clinical trials featuring conversion to psychosis as their primary outcome require very large sample sizes. We do, however, see hope on the horizon. This past fall the US National Institute of Mental Health and the Foundation for the National Institutes of Health announced the Accelerated Medicines Partnership in Schizophrenia (AMP SCZ), a collaborative effort to advance early intervention for CHR individuals. This initiative seeks to identify parameters for future clinical trials on alternate outcomes of CHR such as social functioning or attenuated positive symptoms. These alternate endpoints can also potentially serve as surrogate outcomes for reducing the incidence of psychopathology, which can then be investigated directly after entry of the new treatments into clinical practice through epidemiologic methods. In conclusion, our view is not only that a combined universal and indicated approach is likely to be the best way to prevent psychosis in the future, but also that the CHR syndrome for psychosis continues to provide the most promising option for the indicated prevention component. We acknowledge a potential bias, working as we do in the CHR field, but we like to think we chose this field because it offers the best opportunities in psychiatry for improving public health rather than that we believe it offers the best opportunities for public health because we have chosen it.