Fusar-Poli et al1 are to be congratulated on their landmark, authoritative review. Particularly welcome is the emphasis on recommendations for middle- and low-income countries, along with the comprehensive referencing of schizophrenia spectrum research emerging from these countries. The authors rightly include the clinical high-risk syndrome for psychosis (CHR-P) in their review. Here we extend some of their recommendations for this condition. The recommendation for CHR-P detection in high-income countries can be extended by suggesting further research into task-sharing models. As noted in the review, CHR-P is common in high-income countries among adolescent and young adult clinical samples when ascertained in epidemiologic studies, but the CHR-P state may go unrecognized by many clinical providers. Moreover, several years after the establishment of a comprehensive CHR-P service in a high-income country, only 5% of emerging first episode psychosis cases in the same community had been previously detected as at CHR-P by the service2. In addition, a recent analysis in two CHR-P observational cohorts from high-income settings raised the possibility that clinicians had under-recognized the attenuated positive symptoms characteristic of the condition3. Lastly, even in high-income settings, it may be challenging to create and staff a sufficient number of CHR-P specialty clinics to meet the goal of preventing schizophrenia. If supported by further research, task-sharing models could potentially enhance the recognition and detection of CHR-P in high-income settings as well as in middle/low-income ones. CHR-P specialty clinics could, for example, provide education, consultation and digital resources to practitioners in general youth mental health services. Ultimately, the best way for the CHR-P paradigm to realize its promise to prevent schizophrenia may be for every clinician to possess basic skills in recognizing and treating CHR-P. Such a development would be consistent with the trajectory of other specialty clinics in psychiatry (e.g., lithium clinics, tardive dyskinesia clinics, clozapine clinics). However, our field must provide better reasons for clinicians to invest their time to learn about detection of CHR-P. For example, identification of a patient as at CHR-P does not help a busy clinician to determine which, if any, medication to recommend when psychological or psychosocial therapies are ineffective or unavailable, since no medications for CHR-P are approved by regulatory authorities in any country. In the past, the first approval of a medication for a new indication has dramatically increased recognition of previously neglected conditions (e.g., panic disorder). The goal of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) programme – a partnership between the US National Institutes of Health, the US Food and Drug Administration, the European Medicines Agency, and other organizations – is to provide sufficient information about the heterogeneity of CHR-P and its determinants to encourage pharmaceutical investment in the condition. The AMP® SCZ Observational Study4 has recently met its recruitment goal of >2,000 CHR-P participants at 43 sites in 13 countries. In addition to potentially remediating under-recognition and under-detection of CHR-P, regulatory approval of a medication with a novel mechanism would help address reliance on traditional dopamine D2-blocking antipsychotics by offering an effective and safer alternative. The AMP® SCZ Proof of Principle Studies first project is investigating the effects of nicotinic mechanisms on cognition in CHR-P. CHR-P may also be detected by clinical evaluations of referrals from realms beyond individual clinicians, such as schools, social media, health-care system databases, and Internet/social media. A recent report from two CHR-P observational cohorts demonstrates the impact of referral source on CHR-P sample demographic and severity features5. More research focus on the effects of referral source would shed more light on where CHR-P should be detected. Standardization of methods for capturing referral source would facilitate those efforts and the comparison of effects across cohorts. Recommended interview detection of CHR-P should be extended to include – in addition to the tools mentioned by Fusar-Poli et al – the Positive SYmptoms and diagnostic criteria for the CAARMS Harmonized with the SIPS (PSYCHS) semi-structured interview6 and the Abbreviated Structured Interview for Psychosis-Risk Syndromes (Mini-SIPS)7. The PSYCHS ascertains both Structured Interview for Psychosis–Risk Syndromes (SIPS) and Comprehensive Assessment of At-Risk Mental States (CAARMS) CHR-P diagnostic criteria. The Mini-SIPS ascertains SIPS CHR-P diagnostic criteria in 30 min. Training and certification are conducted fully online and are freely accessible. As noted above, pharmaceutical company investment would likely substantially increase recognition and detection of CHR-P. Such investment in CHR-P, and consequently the public health benefit that comes with an approved treatment, has been hindered up to now by a lack of international agreement on CHR-P diagnostic criteria. Although the PSYCHS succeeded in fully harmonizing attenuated positive symptom assessment6, CAARMS and SIPS diagnostic criteria for CHR-P remain discordant. A recent Schizophrenia International Research Society award is aiming to promote diagnostic criteria harmonization. The methods of CHR-P detection mentioned by Fusar-Poli et al are all interview-based. Recently, progress has been made in designing and testing behavioral task batteries that can be self-administered online8. Sensitivity to the CHR-P diagnosis was excellent, suggesting that such methods can be employed for screening purposes; however, specificity was low, indicating that so far they are not yet ready for independent diagnostic use. In the future, similar digital innovations may be able to improve CHR-P detection in both high-resource and middle/low-resource settings. Suicide is well-known as a tragic outcome of schizophrenia spectrum disorders, and patients are at higher risk earlier in the course of illness. A recent study reported that persistence of the attenuated positive symptoms characteristic of CHR-P was significantly associated with persistence of suicidal ideation, even when controlling for depressive symptoms9. These findings suggest that development of accessible, safe and effective treatments for CHR-P could have the benefit of reducing the risk for suicide. Finally, although it has been argued that at-risk labelling may cause stigmatization, it is a fact that CHR-P individuals often already suffer from stigma related to their behaviors and symptoms, so that the timely identification and management of the at-risk condition may actually have a positive impact on stigma, including self-stigmatizing attitudes.
Scott W. Woods (Fri,) studied this question.