Pluripotential Risk and Clinical Staging: Theoretical Considerations and Preliminary Data From a Transdiagnostic Risk Identification Approach

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.

Demographic and Clinical Presentations of Youth using Enhanced Mental Health Services in Six Indigenous Communities from the ACCESS Open Minds Network

“…There is emerging recognition that mental health problems during adolescent and youth are relatively diffuse and pluripotent. 64 During consultation on the design of AOM services, youth and other stakeholders also expressed concerns with potential harm and stigma associated with early labelling of youth’s presenting concerns in terms of specific diagnoses, particularly in community settings. These various considerations guided our decision to rely instead on self- and clinician-rated measures of distress, SRMH, functioning and overall severity.…”

Transdiagnostic Clinical Staging for Childhood Mental Health: An Adjunctive Tool for Classifying Internalizing and Externalizing Syndromes that Emerge in Children Aged 5–11 Years

“…For instance, clinical staging criteria within the tripartite youth model specify illness subtypes and pathophysiological mechanisms in psychosis, anxiety, and mood syndromes emerging in adolescence (12–25 years; Hickie et al, 2019a ). The tripartite model describes the fluid course of unique and overlapping symptomatology that wax and wane in expression over time, allowing for a “pluripotent” approach to specifying illness subtypes and the identification of transdiagnostic and specific risk factors for major mental disorders (Carpenter et al, 2019 ; Hartmann et al, 2021 ). Evaluation of criteria have provided preliminary support for organizing biological, psychosocial, and neuroscientific research findings into a framework for treatment selection and outcome prediction (e.g., Hickie et al, 2019b ; McGorry et al, 2014 , 2018 ).…”

Clinical Risk Constellations for the Development of Bipolar Disorders

“…While many lessons have been learned from diagnosis-specific research on risk factors and prodromal symptoms, some have argued for a model of a broad high-risk syndrome, a pluripotential clinical state that may later differentiate into specific diagnostic entities [ 43 , 44 ]. Given the heterogeneity of presentations within diagnostic groups like schizophrenia-spectrum psychosis, affective disorders, personality disorders, anxiety, OCD and many others, as well as the overlap between these categories and frequent comorbidity, the attempt to class unspecific and attenuated symptoms as a distinct high-risk syndrome for a single diagnostic group appears arbitrary.…”