Harmony at last: Overcoming arbitrary variation in clinical high risk (CHR) for psychosis assessment

The concept of the prodrome, imported from the infectious disease field, was a hallmark of the deterministic and pessimistic mindsets that had characterized the field of schizophrenia since the time of Kraepe-lin. It was a clinical perspective dependent on the benefit of hindsight and hence reinforced the illusion of inevitability of onset and deterioration in people ‘ destined ’ to develop schizophrenia. In the early 1990s, the emergence of the early psychosis paradigm challenged this sense of destiny and inevitability and shifted the clinical gaze from hindsight to foresight and future. In the context of implementing the EPPIC program (McGorry, 1993; McGorry et al., 1996) and greatly reduced treat-ment delay, our formulation of the ‘ at risk mental state ’ or ‘ ARMS ’ (McGorry & Singh, 1995) and subsequently the more specific and operationally defined Ultra High Risk (UHR) state (Yung & McGorry, 1996) transformed the field of schizophrenia and psychosis research and, subsequently, systems of clinical care. This prototypical approach has also evolved into a transdiagnostic clinical staging model, which is adding heuristic value to research and clinical care, particularly in young people with emerging mental disorders (McGorry & Hickie, 2019). The operational definition of this initial stage of psychotic illness and the development of assessment instruments to measure and monitor this have been outlined in Addington et al. (2024). A seminal event in this process was the visit of Dr Thomas McGlashan to Mel-bourne in 1994 to the PACE clinic in Melbourne where he was exposed to the development of the Comprehensive Assessment of

The concept of the prodrome, imported from the infectious disease field, was a hallmark of the deterministic and pessimistic mindsets that had characterized the field of schizophrenia since the time of Kraepelin.It was a clinical perspective dependent on the benefit of hindsight and hence reinforced the illusion of inevitability of onset and deterioration in people 'destined' to develop schizophrenia.In the early 1990s, the emergence of the early psychosis paradigm challenged this sense of destiny and inevitability and shifted the clinical gaze from hindsight to foresight and future.In the context of implementing the EPPIC program (McGorry, 1993;McGorry et al., 1996) and greatly reduced treatment delay, our formulation of the 'at risk mental state' or 'ARMS' (McGorry & Singh, 1995) and subsequently the more specific and operationally defined Ultra High Risk (UHR) state (Yung & McGorry, 1996) transformed the field of schizophrenia and psychosis research and, subsequently, systems of clinical care.This prototypical approach has also evolved into a transdiagnostic clinical staging model, which is adding heuristic value to research and clinical care, particularly in young people with emerging mental disorders (McGorry & Hickie, 2019).
The operational definition of this initial stage of psychotic illness and the development of assessment instruments to measure and monitor this have been outlined in Addington et al. (2024).A seminal event in this process was the visit of Dr Thomas McGlashan to Melbourne in 1994 to the PACE clinic in Melbourne where he was exposed to the development of the Comprehensive Assessment of At Risk Mental States (CAARMS) by Yung et al. (2005).He successfully introduced these new ideas into North American psychiatry and, with colleagues Scott Woods and Tandy Miller, developed a very similar set of criteria and instruments (the Structured Interview for Psychosis-Risk Syndromes (SIPS) (McGlashan et al., 2010) and Scale of Psychosis-risk Symptoms (SOPS)) (Miller et al., 2002;Miller et al., 2003).These evolved to align more closely with the North American ecosystem, being influenced by the DSM system and the structure of the Positive and Negative Symptom Scale (Kay et al., 1987).The CAARMS by contrast was more agnostic to standard classification systems such as the DSM and ICD and more empirical.This all resulted in a modest yet potentially significant divergence in some areas, which are covered in the papers in this special issue.Terminology shifted as well with North America adopting the term 'clinical high risk' (CHR) rather than 'ultra high risk' for this stage of illness and two sets of instruments became embedded with North America scale.The decision to employ common criteria and a common instrument across all sites involved in AMP SCZ, rather than allow choice of CAARMS or SIPS, more or less resulted in a deadline for harmonization to be achieved.The paper by Woods et al. (2024) describes in detail how, and to what extent, harmonization has been realized.The process was protracted and exhaustive requiring compromises on both sides but possible, at least in part, due to the preexisting goodwill between all involved.AMP SCZ will enable the practical significance of the decisions made during the harmonization process, and of the residual differences that could not be harmonized, to be studied and a final fully harmonized PSYCHS to be produced.
One of the harmonization effects that is unfortunate is the dominant focus on positive psychotic features, admittedly central to entry and exit criteria for this stage of illness with a corresponding loss of emphasis on a range of psychopathology which forms part of this early stage of illness.The latter include affective features, basic symptoms and negative symptoms, which were all featured in the CAARMS.It will be important to ensure that these features continue to be measured in research studies from here, and most importantly, their impact on functioning and recovery of young people is not overlooked.Another concern is that the new instrument in use in AMP SCZ appears to be more time consuming and complex for research staff and participants to use and therefore potentially burdensome.
The perfect may have become the enemy of the good.Time will tell.
There is an agreed need to achieve international agreement on streamlining and harmonizing assessment instruments across the whole field of mental health science (Farber et al., 2023;Krause et al., 2021;Wolpert, 2020).Observing how labour intensive and protracted the process of harmonizing two instruments, which were already close relatives (cousins at least, if not siblings), suggests this will not be an easy process.Instrument development and validation has a long pedigree and a sound scientific basis and this must be respected.Perhaps equally important is ensuring that such instruments are culturally and developmentally appropriate for the key age ranges and stages of life and illness.There is a genuine need for new instruments to focus on this transitional or emerging adult stage.The paediatric-adult divide at 18 years is just as problematic for research as it is for the provision of clinical care.This is no more important than in the assessment and follow up of emerging psychosis and other trajectories in adolescents and emerging adults.
broadly going with the SIPS and Australia, Asia and Europe mostly sticking with the CAARMS.Generally speaking, this has not held back research, which has flourished in this space for nearly 30 years, and the results of research conducted with these alternative tools have been able to be compared and blended within systematic reviews and meta-analyses (Fusar-Poli et al., 2017; Salazar de Pablo et al., 2021), albeit with certain assumptions being made.Throughout this time, researchers have created a collegial and collaborative environment despite these differences in terminology and measures.As outlined by Addington et al. (2024), the National Institute of Mental Health's (NIMH) Harmonization of At-Risk Multisite Observational Networks for Youth (HARMONY) consortium was established to develop a new assessment tool with common linked criteria for the UHR/CHR state and for full threshold psychosis.The need for this work was hastened by the advent of the Accelerating Medicines Partnership Schizophrenia Project (AMP SCZ) funded by NIH, a global predictive study of CHR for psychosis with unprecedented funding and

ACKNOWLEDGEMENT
None.Open access publishing facilitated by The University of Melbourne, as part of the Wiley -The University of Melbourne agreement via the Council of Australian University Librarians.ORCIDLisa Phillipshttps://orcid.org/0000-0003-1060-6068