Abstract
Most psychiatric disorders develop during adolescence and young adulthood and are preceded by a phase during which attenuated or episodic symptoms and functional decline are apparent. The introduction of the ultra-high risk (UHR) criteria two decades ago created a new framework for identification of risk and for pre-emptive psychiatry, focusing on first episode psychosis as an outcome. Research in this paradigm demonstrated the comorbid, diffuse nature of emerging psychopathology and a high degree of developmental heterotopy, suggesting the need to adopt a broader, more agnostic approach to risk identification. Guided by the principles of clinical staging, we introduce the concept of a pluripotent at-risk mental state. The clinical high at risk mental state (CHARMS) approach broadens identification of risk beyond psychosis, encompassing multiple exit syndromes such as mania, severe depression, and personality disorder. It does not diagnostically differentiate the early stages of psychopathology, but adopts a “pluripotent” approach, allowing for overlapping and heterotypic trajectories and enabling the identification of both transdiagnostic and specific risk factors. As CHARMS is developed within the framework of clinical staging, clinical utility is maximized by acknowledging the dimensional nature of clinical phenotypes, while retaining thresholds for introducing specific interventions. Preliminary data from our ongoing CHARMS cohort study (N = 114) show that 34% of young people who completed the 12-month follow-up assessment (N = 78) transitioned from Stage 1b (attenuated syndrome) to Stage 2 (full disorder). While not without limitations, this broader risk identification approach might ultimately allow reliable, transdiagnostic identification of young people in the early stages of severe mental illness, presenting further opportunities for targeted early intervention and prevention strategies.
Highlights
Over the past decade, we have observed increased public awareness of the prevalence and debilitating consequences of severe mental illness
Only a small proportion of young people in first episode psychosis (FEP) programs linked to ultra-high risk (UHR) programs go through UHR clinics first [25], implying that there might be alternative early symptom trajectories leading to psychosis, which might be missed by services focusing exclusively on psychotic symptoms [21]
These observations, and the modest proportion of UHR young people transitioning to psychosis in research trials [∼20% over 2 years [26]] causing statistical challenges for the design of intervention studies [27], highlight the need for the development of a broader, transdiagnostic at-risk approach
Summary
We have observed increased public awareness of the prevalence and debilitating consequences of severe mental illness. Current diagnostic and research systems are less appropriate for these early approaches, as they are based on crosssectional features observed in entrenched or chronic mental illness, embodying the “end-state” of illness trajectories only, failing to represent the progressive and dynamic nature of (emerging) psychopathology [6, 7]. Only a small proportion of young people in FEP programs linked to UHR programs go through UHR clinics first [25], implying that there might be alternative early symptom trajectories leading to psychosis, which might be missed by services focusing exclusively on (attenuated) psychotic symptoms [21] These observations, and the modest proportion of UHR young people transitioning to psychosis in research trials [∼20% over 2 years [26]] causing statistical challenges for the design of intervention studies [27], highlight the need for the development of a broader, transdiagnostic at-risk approach. It is a diagnostic framework that increases clinical utility
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