Transdiagnostic clinical staging in youth mental health: a first international consensus statement

Abstract

Recognizing that current frameworks for classification and treatment in psychiatry are inadequate, particularly for use in young people and early intervention services, transdiagnostic clinical staging models have gained prominence. These models aim to identify where individuals lie along a continuum of illness, to improve treatment selection and to better understand patterns of illness continuity, discontinuity and aetiopathogenesis. All of these factors are particularly relevant to help‐seeking and mental health needs experienced during the peak age range of onset, namely the adolescent and young adult developmental periods (i.e., ages 12‐25 years). To date, progressive stages in transdiagnostic models have typically been defined by traditional symptom sets that distinguish “sub‐threshold” from “threshold‐level” disorders, even though both require clinical assessment and potential interventions. Here, we argue that staging models must go beyond illness progression to capture additional dimensions of illness extension as evidenced by emergence of mental or physical comorbidity/complexity or a marked change in a linked biological construct. To develop further consensus in this nascent field, we articulate principles and assumptions underpinning transdiagnostic clinical staging in youth mental health, how these models can be operationalized, and the implications of these arguments for research and development of new service systems. We then propose an agenda for the coming decade, including knowledge gaps, the need for multi‐stakeholder input, and a collaborative international process for advancing both science and implementation.

In clinical practice, health professionals respond to presentations for care by individuals at variable points along an illness course. Even with careful history‐taking, assessments are frequently conducted without a consistent approach that allows incorporation of risk factors, earlier presentations, individual trajectories or projected illness course into initial treatment selection or secondary prevention strategies ¹ . Among other things, current approaches generally lack predictive validity for future course of illness ² .

The goal of understanding how initial symptoms, syndromes, physical and mental health comorbidities ³ , and related social and occupational impairment remit or evolve over time thus requires the development of more innovative clinical frameworks ⁴ . Critically, these frameworks need to integrate prior and ongoing risk factors and individual illness course into new models for personalized treatment selection and organization of ongoing health care ⁵ .

This goal is especially crucial for conditions that have their onset during times of major neurobiological and socio‐developmental transition, such as adolescence to young adulthood6, 7. In this developmental period, there is a need to delineate the patterns of continuity and discontinuity (at the individual level) between the earlier mental phenomena or overt disorders that emerge in childhood8, 9, 10 (dominated by fundamental cognitive, attentional and behavioural features) and the more adult‐like conditions that manifest during adolescence and young adulthood. The latter largely consist of mood, perceptual and complex cognitive features, which have an increased probability of becoming persistent, recurrent or chronically impairing11, 12.

Recent epidemiological studies ¹³ have vividly demonstrated complex patterns of emergence of psychopathology, along with their homotypic and heterotypic continuity14, 15 and the appearance of diagnostic instability ¹³ and artefactual comorbidity ¹⁶ at the individual level. This underscores the need to adopt a broad “transdiagnostic” approach – one that views the individual as located along a multidimensional and evolving continuum of illness – rather than a traditional narrow view based on the historical concept of risk for development of a single and categorically discrete adult‐type “disorder”15, 17.

Traditional clinical frameworks have prioritized the identification of discrete mental disorders, largely as the basis for proceeding to evidence‐based treatment decisions. Such “discrete” disorders, however, typically represent the fully‐formed, prototypical and relatively late‐stage syndromes that are managed in adult specialized or secondary mental health service systems internationally ¹⁸ . These disorders dominate the international classification systems, that are used not only for clinical practice but also for aetiological, pathophysiological, prediction and intervention research19, 20. Ironically, despite being framed as “pure” cases, these individuals often present with complex and comorbid conditions, requiring multiple and/or intensive therapeutic interventions.

There is thus an urgent need to generate clinical definitions that both recognize the fluid developmental course of mental illness and are suitable for use in services aiming to intervene “early” , during the initial phases of illness ²¹ . Such a shift also needs to differentiate earlier risk factors (e.g., childhood maltreatment, childhood‐onset neurodevelopmental disorder) – some of which may be addressed by broad population‐based health measures – from mild clinical states (with low probability of illness progression) that benefit from supportive but nonspecific interventions, and from attenuated syndromes (with higher probabilities of progression) that may require immediate active intervention or secondary prevention ²² .

In our view, clearer definitions of each of these stages and the clinical or pathophysiological boundaries between them requires a concurrent understanding of principles that underpin clinical staging, an agreed‐upon framework for operationalizing staging and its implications, and a clinical research agenda to advance the field. We hope that, by articulating these elements and creating a roadmap for international research and collaboration, a solid empirical basis for enhanced youth‐focused clinical practice and research can be provided that in turn galvanizes stakeholders and generates further momentum.

CURRENT AND FUTURE FRAMEWORKS

Traditional psychiatric taxonomies have been unable to capture the complexities of emerging and early illness, continuity and comorbidity, largely as a consequence of our limited understanding of underlying pathophysiology23, 24. In other areas of medicine – such as oncology, rheumatology and cardiovascular medicine – clinical staging is routinely linked to disease progression (of the primary clinical syndrome or pathophysiology), disease extension (i.e., complications beyond the primary pathophysiology), prognosis, and stage‐informed treatment selection ²⁵ .

In cancer, evolving understandings of disease progression have allowed the development of the tumor‐node‐metastasis (TNM) model of staging, that differentiates between pathological stages (pTNM, based on microscopic examination of tumors after surgical removal) and clinical stages (cTNM, based on all available clinical and investigatory information) ²⁶ . Furthermore, recent advances regarding immunological mechanisms involved in cancer progression have led to increasingly refined treatment strategies ²⁷ . Here the ability to link clinical presentation to pathophysiology is drawn from detailed knowledge of aetiology and longitudinal biomarkers.

Personalizing care is similarly the ultimate objective of clinical staging in psychiatry. Largely as a consequence of the early intervention movement, and beginning with early psychosis, transdiagnostic clinical staging in youth mental health has the overt aim of enhancing clinical care for young people entering our health service systems ²⁸ . What is still lacking, however, is a consensus as to how best to define, test and then iteratively refine the key clinical boundaries of the concept.

Importantly, an individual's stage differs from his/her current clinical state. State‐based measures such as symptoms and functioning frequently undergo partial or even full remission, making clinical state reversible. However, the achievement of an improved state (e.g., functional recovery or symptom remission) at any given stage does not guarantee that the underlying disease process(es) have been reversed. For this reason, the concept of clinical staging in mental disorders is unidirectional: that is, an individual's stage can move from solely having risk factors to nonspecific clinical syndromes and then on to earlier or later stages of active illness, but not in the reverse direction. Indeed, knowledge of a person's highest clinical stage incorporates salient details regarding his/her own personal history (longitudinal course), which in turn contains information that may be relevant for predicting future trajectory, treatment selection and prognosis. Operationalizing staging and clinical states in a manner that conveys both will be an essential aspect of a future clinical research agenda.

Despite the unidirectionality of staging, it is critical to note that progression from early to later stages is probabilistic rather than inevitable. In other words, individuals most likely to progress to a given stage are those currently proximal to that stage, while those least likely to progress are those currently at the earliest stages. Staging, therefore, assertively promotes prevention and treatment aimed at full recovery or remission from acute presentations (states), regardless of the clinical stage at presentation for care.

Consistent with the principles of early intervention ⁴ , the ultimate goal of staging is clinical utility. Staging models in mental health have typically made a distinction between early clinical stages – which are assumed to have low rates of progression to severe, persistent or recurrent disorders, thereby making prevention a central focus – from later stages, which are characterized by higher rates of persistence, impairment and disease progression, thereby demanding intensive clinical intervention ²² . At all stages, the optimal choice, intensity and duration of active intervention or secondary prevention strategies needs to take account of the probability of progression to later stages. This implies that different intensity and duration of care packages may be required to achieve these goals, with more intensive, specialized and multimodal interventions (albeit with potentially greater risk and delivered over longer periods) more likely to be required at later stages.

Recent transdiagnostic, pluripotential staging models have also proposed dimensional boundaries for progressive stages, signified by changes or increases in the severity of primary clinical presentations (Table 1). Specifically, syndromes comprised of nonspecific (largely anxiety and depressive – stage 1a) symptoms, or more complex but still attenuated (stage 1b) symptom sets, are differentiated from syndromes that are characterized by more discrete and persisting phenomena (e.g., manic symptoms, perceptual disturbances, severe depressive symptoms – stage 2), recurrent/multi‐episode (stage 3) or persistent/unremitting syndromes (stage 4), with corresponding thresholds for changes in functioning or neurocognition2, 18, 29. The specifics of each stage differ slightly across models.

Table 1.

Examples of recent staging models in youth mental health

Stage	Definition
	Symptoms	Functioning	Neurocognition
0	No current symptoms; increased risk of disorder	No historical change	Normal to mild deficits
1a	Mild or nonspecific symptoms (QIDS 0‐11)	Mild functional change/decline; GAF 70‐100	Mild neurocognitive deficits or relatively normal profile
1b	Moderate but sub‐threshold symptoms (QIDS 11‐20, YMRS >9, attenuated ­psychotic symptoms)	Functional decline to caseness (GAF <70)	Moderate neurocognitive changes, particularly in attention, learning, or executive ­function (e.g., 0.5‐1.0 SD decrement relative to premorbid IQ)
2	Full‐threshold disorder with moderate to severe symptoms (QIDS >20, YMRS >15, meets CAARMS/SIPS criteria)	Functional decline (GAF <50)	Neurocognitive deficits (1.0‐1.5 SD decrements relative to premorbid IQ)
3	Incomplete remission or relapse	Persistent functional decline (GAF <40)	Persistent decrement in neurocognition (>1.5 SD relative to premorbid IQ), ­including social cognition
4	Severe, unremitting or refractory illness	Poor treatment effectiveness despite persistently intensive interventions (GAF <30)	Similar to stage 3, with poor treatment ­effectiveness despite persistently intensive interventions

QIDS – Quick Inventory of Depressive Symptomatology, YMRS – Young Mania Rating Scale, CAARMS – Comprehensive Assessment of At Risk Mental States, SIPS – Structured Interview of Psychosis‐risk Syndromes, GAF – Global Assessment of Functioning

This “transdiagnostic” approach implies that staging can be applied to clinical presentations both within and across traditional diagnostic boundaries, and capturing both homotypic and heterotypic progression30, 31. Homotypic progression may be the development of a severe depression following a milder form, or development of a threshold‐level psychosis following a prior attenuated syndrome characterized by brief and non‐persistent psychotic‐like experiences. In contrast, heterotypic shifts might typically include new‐onset mania or new‐onset psychotic syndrome in individuals who had previously only experienced unipolar depressive episodes. A key advantage of the transdiagnostic, pluripotential approach is that its broader scope may better facilitate the prediction of future course of illness than those approaches that are organized within or around diagnostic ­silos ² .

TRANSDIAGNOSTIC CLINICAL STAGING: THE ROAD AHEAD

We argue that the further development of clinical staging for young people now needs to accomplish two critical tasks. First, it requires frameworks that can better capture the complexity of emerging mental health syndromes, moving beyond classical notions of “sub‐threshold” and “threshold” disorders ³² . The clinical features of “sub‐threshold” presentations rarely sit within one major diagnostic category: they are more often protean and ill‐defined, with admixtures of anxiety, depressive, sleep disturbance and other symptoms that frequently morph over time.

Notions of “threshold” are also inconsistent across the disorders that are most relevant to youth mental health. For example, rather than treating all “full‐threshold” disorders as comparable, anxiety disorders are frequently considered “at‐risk” states for depressive disorders. Depressive disorders are seen as at‐risk states to psychotic disorders, while full‐threshold unipolar depressive disorders have also been considered as at‐risk states to bipolar disorders. In this way, current “threshold” concepts remain grounded within existing diagnostic systems, creating the artefactual notion of diagnostic purity once a supra‐threshold “exit‐disorder” has emerged – whereas the reality is often one of more rather than less complexity and comorbidity over time.

Second, any research programme on clinical staging must differentiate more clearly the concept of illness progression from illness extension. While the idea of progression inherently involves a shift from categorical diagnoses to dimensionality, it is also tied to notions of meaningful step‐wise changes in clinical status (for example, from partial to full delusional conviction), not simple increases in symptom severity, intensity or duration. It implies that at any particular point along the illness path, further worsening is possible, especially if appropriate specific treatments or secondary prevention strategies are not provided.

Extension, by contrast, is fundamentally multidimensional and potentially independent of progression (Figure 1). Extension signifies that the illness process has taken on new and more complex features. This can be operationalized as one or more of: a) the emergence of mental or physical health comorbidities (e.g., onset of substance dependence alongside mental health symptoms or dysfunction; onset of metabolic or autoimmune complications); b) a marked change in a linked biological construct (e.g., emergence of an objective marker of circadian dysfunction in an individual with bipolar disorder ⁷ ). Finally, previous staging models have lumped neurocognition together with symptoms and functioning18, 29. While there may be some evidence for this in conditions such as psychosis33, 34 and bipolar disorder35, 36, this is unlikely to occur in synchronized decrements across all disorders ³⁷ . Thus, extension may also be marked by c) an independent neuropsychological construct (e.g., marked deterioration in objective measures of cognitive function, such as verbal memory or executive function).

Figure 1.

A revised multidimensional staging model for youth mental health incorporating elements of progression and extension

STAGING AND CLINICAL UTILITY

Since illness progression or extension implies a step‐wise increase in severity or complexity, along with increased risk of persistence or recurrence, it should be accompanied by a corresponding need to instigate a categorical change in immediate treatment or indicated prevention strategies. The distinction between progression and extension means that interventions should become more intensive in the case of the former, or may need to broaden and expand in the case of the latter. Examples of response to progressive changes in core clinical symptoms and functioning would be the use of lithium following a first manic episode or the initiation of antipsychotic agents in association with a clear first‐onset psychotic illness. Examples of response to the extension of illness would be dietary modifications and/or metformin for individuals whose illness now includes varying degrees of metabolic dysregulation, or addition of a psychosocial therapy targeting self‐harm and suicidal ideation for individuals in which these elements develop.

For cardiovascular disease, staging is grounded in individually‐focused reductions in known risk factors that can be clinically assessed (e.g., cessation of smoking, or reduction in blood pressure or cholesterol in individuals at high familial risk), followed by initiation of secondary prevention strategies or immediate intervention based on changes in clinical stage ²³ . Similarly, preventive interventions aimed at addressing the earliest stages of mental health difficulties may be more effective at the population rather than the individual level. Further along, “indicated” prevention may take place at the individual level ³⁸ .

At still higher stages, the emphasis should first be on examining which novel, combined or alternative treatment strategies are required to improve immediate outcomes or prevent progression or extension of illness – and “reverse translating” this to identify the critical transitions, junctures or step‐wise discontinuities in illness course (which might distinguish between putative stages) that such interventions address. The extent to which clinical transitions correspond to objective or neurobiological “markers” is also the subject of active clinical research6, 37; maintaining a central focus on clinical utility may allow staging to address recent critiques regarding psychiatry's thus far futile search for disorder‐specific biomarkers39, 40, 41.

Finally, we recognize that there are other models either under development or articulated that also appreciate the transdiagnostic nature of mental illness, especially for research purposes41, 42, 43, 44. We do not see these as competing approaches: clinical staging is designed principally to enhance the delivery of highly personalized care, with its appeal being that it is explicitly meant for clinical practice. And staging is particularly well poised to contribute to youth mental health, given that it is in synchrony with the momentum already established towards broader early intervention and services development2, 4, 45.

INTERNATIONAL CONSENSUS STATEMENT

Despite much promise ⁴⁶ , clinical staging has yet to be embraced widely in clinical practice, mental health services or health systems research. In order to accelerate its study and refinement, and following input from international experts in youth mental health, we propose a coordinated approach that: a) focuses on transdiagnostic clinical staging in youth mental health (onset age 12‐25 years); b) draws from principles underlying the utility of clinical staging in general medicine; and c) sets a proposed agenda for coordinating future collaborative and comparative work in this area.

Principles and assumptions

Transdiagnostic clinical staging in youth mental health:

• relates to those mental health problems that typically have their onset at ages 12‐25, and their putative resolution, progression or extension (which may continue through to the adult years);

• is an approach to clinical staging; that is, it is most relevant for individuals entering health service systems. As such, it should draw from and be applied to broadly defined help‐seekers rather than non‐clinical, community or other population‐based samples. While important, the application of the model to the latter groups presents many other challenges and is beyond the scope of this consensus statement;

• is not only about redefining illness course or trajectory within or across traditional diagnoses such as major depression, bipolar disorder or psychotic disorder, but also about characterizing these beyond diagnostic silos;

• is not simply a way of arranging our existing narrow categorical diagnoses in a sequential manner based on conventional features of severity, duration, persistence or recurrence: earlier stages of the common anxiety, mood or psychotic disorders are not equivalent to current criteria for sub‐threshold or threshold‐level DSM or ICD common (anxiety or depressive) disorders, and later stages are not simply equivalent to threshold‐level severe (mood, bipolar, psychotic or personality) disorders;

• acknowledges the fluid, heterotypic nature of the evolution of emerging mental disorders, and the pluripotentiality of later outcomes for those who present at earlier stages. Thus, transdiagnostic clinical staging for young people includes the broader admixture of clinical syndromes and associated complexities that dominate attenuated and full‐threshold, as well as highly comorbid, mental health and substance misuse disorders;

• offers advantages over current nosology, diagnostic systems and cross‐sectional clinical practice (including treatment selection, prognostic statements and secondary prevention) in youth mental health, that are increasingly acknowledged as inadequate ⁴⁷ ;

• is fundamentally based on the idea, consistent with staging in other areas of health care, that any transition from an earlier to a later stage (disease progression or extension) is associated with a step‐wise or meaningful deterioration in a relevant clinical, health, neurobiological or social factor, or leads to consideration of a new specific treatment or secondary prevention intervention;

• is tied to clinical interventions whose goals at each stage are to relieve current symptoms, reduce risk and prevent progression to later stages. In other words, it aims to both address the illness at the stage at which the individual is presenting (reducing prevalence), and to arrest its clinical and pathophysiological progression or elaboration (reducing future incidence);

• carries with it the concept that transitions across stages are probabilistic, not inevitable. Those who are at stage 0 have risk factors, but are not presenting for care: the goal through community or population‐based interventions is to prevent transition to “a need for care”. For those at subsequent clinical stages, it is to prevent transition to the next downward step in illness course;

• posits that likelihood of progression to a given stage is associated with prior proximity to that stage, meaning that those at later stages are at greater risk of progression to further stages. Similarly, illness progression (severity, persistence, recurrence, functioning) or extension (involvement of other physical/mental systems or comorbidity) within a stage may also predict increased risk of transition to a later stage. In both cases, these individuals are also at higher risk of illness extension to other poor health or social outcomes than those who are at earlier stages;

• should have the capacity to evolve iteratively based on emerging evidence. Specifically, a well‐operationalized staging approach should generate testable clinical, neurobiological and psychosocial hypotheses. In turn, these can be studied systematically, and refined or refuted, on the basis of relevant data;

• can be used in an iterative manner to complement other formal diagnostic systems. Initially, the aim is to use staging for improved clinical prediction of risk and selection of the most personalized and appropriate treatments early in the course of illness;

• recognizes, as its archetypal methodological approach, longitudinal and multidimensional data collection from broad clinical cohorts, beginning at the earliest stages of illness and need for care. This may be complemented by a range of analytic techniques;

• must embody (and assemble knowledge with) the values of hope, optimism, respect and transparency that have served as cornerstones for the youth mental health community.

Operationalization of staging

Fully operationalized, transdiagnostic clinical staging in youth mental health:

• should be based on systems that operate across the full course of illness(es) or syndrome(s). As such, these systems need to specify distinctions – based on clear criteria and independent validation – between:

  1. population‐based, but individually‐applicable, risk factors (e.g., family history of bipolar disorder; exposure to childhood trauma; persistent cannabis use);
  2. non‐specific symptom sets, where the individual already displays relevant emotional, cognitive or behavioural symptoms, but has no clearly persisting syndrome;
  3. onset of illness syndromes (i.e., persisting and associated with functional impairment), whether these are “sub‐ “or supra “threshold” according to current diagnostic systems;
  4. need for care, where local context may strongly influence both presentations to, and willingness to provide, appropriate health care;

• envisions a multi‐stage system, from risk factors (non‐symptomatic, non‐impaired) to early symptomatic states (symptoms but minimal impairment) to those with more overt clinical syndromes with significant impairment and on to more severe and persistent illness. However, it is based on help‐seeking and corresponding clinical case identification. Its applicability in wider population‐based and epidemiological studies, where the base rate of specific disorders varies and differentiation from normal deviations in development remains unclear, is problematic;

• must fundamentally integrate the course of clinical presentation (including disease progression and extension) into comprehensive assessments, which would in turn facilitate an assignment of stage. Multidimensional assessments should take into account core presenting phenomena (symptom type, severity and frequency, along with functioning) as well as components of extension: severity of distress, substance use, neurocognition, physical and mental health comorbidities, and other clinically apparent features;

• is based on a convention that, while clinical state is reversible, staging itself is unidirectional. Thus, while an individual may remit or recover fully at any stage, he/she still retains the original stage classification – but can be assigned a further designation regarding current state, such as “in remission” or “responded to treatment”. This convention recognizes that individuals who have made these step‐wise stage progressions may have key differences compared to those who never progressed to the same stage, are at substantive increased lifetime risk of recurrence or future illness progression, and may benefit from additional interventions or different combination of them. For example:

  1. stages can be used concurrently with detailed modifiers of longitudinal clinical course to indicate grades of response to treatment, degrees of remission from an episode, number and frequency of relapses, and short or longer‐term functional recovery;
  2. stages can contain indices of within‐stage stratification based on key clinical, neurobiological, neuropsychological or psychosocial features, or response to treatment. A key consideration is whether such factors predict response to treatment or prognosis (notably transition rates to later stages);

• recognizes earlier or concurrent risk exposures (e.g., exposure to cannabis misuse, psychosocial trauma) known to increase risk for a staging transition, and risk indicators (e.g., traits that may suggest higher risk for a stage transition but may not themselves have a causal relationship), both of which may provide valuable information regarding prognosis and treatment response;

• begins with an initial stage (stage 0) comprised of known risk factors (e.g., prior history of childhood trauma, central nervous system infection, remitted childhood‐onset mental or neurodevelopmental disorder, significant family history) for a new adolescent‐onset mental disorder (i.e., syndrome) or impairment, but not currently help‐seeking;

• requires the creation of an ongoing, collaborative and international clinical research process to create, refine and test the validity of criteria used to define stages and to distinguish between successive stages;

• acknowledges that those with youth presentations of mental disorders may have had childhood‐onset disorders that may have persisted or remitted, or are associated with increased risk of new‐onset adolescent disorders – e.g., childhood anxiety increasing the risk of adolescent‐onset depression, childhood‐onset attention‐deficit/hyperactivity disorder (ADHD) increasing the risk of other adolescent‐onset mood, cognitive or behavioural syndromes. Childhood‐onset anxiety or depression that persists into adolescence needs to be assessed appropriately in terms of adult‐type disease progression or extension;

• should be designed to assist the earliest provision of specific early intervention and secondary prevention efforts that not only offer a better risk/benefit ratio, but also target the underlying pathophysiology. Consequently, this approach has the potential to prevent the development of chronic illness states (neurobiologically and psychosocially);

• proposes specific clinical or clinicopathological ¹⁸ “cut‐points” that may represent thresholds for major changes in treatment strategies – particularly where there are no specific independent markers available to guide such clinical decision‐making. Typically, the benefit‐risk ratio is anticipated to shift towards more intensive and higher‐risk interventions in later stages;

• is designed to be dynamic, in that understanding of an individual's clinical trajectory should change as more clinical and neurobiological information is acquired. Thus, the adoption and application of staging should itself encourage more individualized assessment and systematic longitudinal tracking over time;

• promotes the measurement‐based tracking of individual trajectories. However, individual trajectories need to be differentiated from the broader concept of clinical stages, with the step‐wise nature of the latter being quite distinct.

Implications for research and service systems

Transdiagnostic staging in youth mental health:

• needs to formally test the assumption that multidimensional staging models are an advance over simpler unidimensional models of illness course (which track severity, duration, persistence or recurrence);

• is best developed in naturalistic clinical cohorts that are recruited from services with broad (non‐exclusive) entry criteria, in order to ensure inclusion of subjects with typically variable clinical courses, complex comorbidities, mixed risk factors, and multiple underlying pathophysiologies;

• is not simply focused on preventing one DSM/ICD‐defined exit disorder18, 48. As illness processes develop, they rarely result in one simple or single outcome. In fact, disorders often gain complexity, due to secondary complications of the initial illness processes (biologically and socially), and comorbidities with other conditions. Studies should, therefore, be designed to measure and record outcomes against a multidimensional framework that includes multiple forms of potential disease extension. These factors should be captured and documented independently of the primary diagnosis assigned by clinicians ¹ ;

• does not simply identify a threshold at which “discrete” , traditionally diagnosed disorders appear (see Figure 1, thick horizontal line). Instead, this stage signals the developed need for intensive clinical care (based on severity and functional impairment) in addition to secondary prevention measures. Over time, improved data quality and analyses will better indicate the clinical profiles, and neurobiological characteristics, of transdiagnostic illnesses at this stage and later;

• is likely to be of more limited utility in narrow cohorts that are pre‐selected based on:

  1. specific symptomatic or syndromal characteristics that are used to define current illness outcomes (e.g., psychotic or manic‐like experiences);
  2. risk factors that are likely to limit the breadth of outcomes (i.e., family history of major psychotic or mood disorder, offspring of parent with major psychotic or mood disorder);
  3. prior childhood‐onset neurodevelopmental disorders;
  4. specific patterns of comorbidity (e.g., alcohol or other substance misuse).

• should attempt to validate hypothesized boundaries (i.e., pathophysiologically, neurobiologically, socially) independently of the clinical criteria (symptoms and signs) used to define membership of any specified clinical syndrome. For example, specific brain imaging, circadian, immune, metabolic or objective neuropsychological tests may differentiate one stage from another;

• can be used to assist in health system developments, particularly in early intervention and youth mental health. Here, the concept is clearly designed to assist with the process of appropriate allocation of care intensity, matched to current need and potential for progression to later stages;

• also needs to explore whether cohorts of young people, and their families and carers, experience higher quality, satisfaction and safety of care provision as a result of its application;

• requires a multidisciplinary youth mental health workforce to undertake clinical training and professional development in the understanding of the clinical staging framework, and its skill‐based implications for assessment, intervention and care delivery.

KNOWLEDGE GAPS AND A FUTURE RESEARCH AGENDA

In the preceding text, we have provided background justification for the study and application of transdiagnostic clinical staging in youth mental health; described a multidimensional matrix including progression and extension that could catalyze further advances in this area; outlined principles and core operational parameters around which transdiagnostic staging can be organized; and argued for the close collaboration between research, service design and provision, and implementation science.

Indeed, this articulation of an approach to clinical staging that captures the key dimensions of disease progression and extension emerges alongside a new wave of clinical research infrastructures that combine reduced‐barrier services ⁴⁹ , an appreciation of the transdiagnostic course of mental illness in youth ⁵ , and acknowledgment of the need for both traditional research projects ⁵⁰ as well as attempts at implementation51, 52. We now chart key issues that a coordinated agenda for transdiagnostic clinical staging in youth mental health can tackle over the coming decade, and how the community can work together to achieve this (Table 2).

Table 2.

Cross‐cutting issues in transdiagnostic clinical staging for youth mental health

	Principle/Assumption	Operationalization	Implications
Service infrastructures	Transdiagnostic clinical staging does not simply aim to stage within or across traditional, symptom‐ or impairment‐based diagnoses.	Clinical infrastructures undertaking transdiagnostic staging need to have broad intake and exit points and provide continuity of care for those with ongoing need.	Research and service systems need the ability to follow individuals longitudinally and across current diagnostic silos. This may also require the ability to reach across service silos in more complex systems of care with multiple layers.
Cohort design	Clinical staging is based on the ­tracking of help‐seeking rather than ­community‐based cohorts.	Non‐help seeking (i.e., community‐ or population‐based) subjects may not experience or receive clinical ­interventions and are unlikely to ­reflect actual help‐seeking populations.	Studies of staging need to be tightly linked with functioning clinical services and systems.
Stage assessment and review	Assignment of stage is linked to disease progression and extension.	Infrastructures that purport to undertake transdiagnostic clinical staging need to capture multidimensional outcome measures in order to determine stage at the point of assessment and at regular points throughout care.	Youth mental health service structures must more effectively embed routine outcome monitoring using standard assessments and apparatus within their infrastructures.
Defining stages	Transitions from one stage to ­another are associated with a step‐wise ­deterioration in a relevant indicator.	Agreement must be established as to what constitutes a sufficient change or threshold for deterioration that is recognizable as a change in stage or a cut‐point.	For alignment and (ideally) collaborative research studies to be undertaken, a process is required to generate and agree on clear criteria and validation.

First, other frameworks, including emerging empirically‐derived or research systems53, 54, have also recognized challenges with prevailing diagnostic systems (DSM‐5 and ICD‐10/11, with their accepted course specifiers). Advances commonly promoted by these frameworks (in addition to staging) include: a) recognition of the dimensional and/or transdiagnostic nature of characteristic (e.g., psychotic, manic or depressive) symptoms; b) use of agnostic clustering methods; or c) testing and subsequent inclusion of specific pathophysiological hypotheses (e.g., neurodevelopmental disorders, circadian‐based disorders, immune‐metabolic disorders).

Moving forward, the focus for staging models should be to demonstrate that this framework can produce genuine advances in clinical practice and service organization: specifically, its ability to identify and promote improved clinical outcomes, enhanced choice of treatments, personalization of care and prognostic predictions. We also believe that this further development of clinical staging in young people can eventually be extended to other developmental stages along the life course (e.g., early childhood, late‐life emotional and cognitive disorders). In doing so, this elaboration would need to incorporate other key features, such as age and developmentally‐dependent cognitive capacities. In children, these would include neural, social and communication development, while in older adults this would include classical neurocognitive abilities.

Second, even while some degree of predictive validity for clinical staging exists for illness paths such as early phases of psychosis ⁵⁵ , the evidence relevant to other possible paths remains limited. Additionally, while various cohorts have generally been followed for illness progression (measured by symptom severity, persistence or impairment), only rarely have they included elements of illness extension (within or across stages). New studies need to incorporate a multi‐dimensional framework that captures additional outcomes of interest, including neurocognition, social and occupational functioning, and neurobiological mea­sures (see Figure 1).

A longer‐term goal is to develop methods for studying staging models that have the capacity to evolve and to integrate emerging evidence from across these many dimensions. If staging is to have utility for treatment selection, data collection regarding the effectiveness of interventions and secondary prevention should include information regarding both the population being studied as well as indicators of relative risk and benefit.

Third, the complex relationships between mental health conditions that emerge in youth (adolescence or young adulthood) and those that emerge in childhood remain open to further examination. For example, it is still unclear whether childhood‐onset disorders (e.g., separation anxiety, ADHD, conduct disorder, autism spectrum disorder, or childhood‐onset bipolar disorder) should be treated as a separate track of early life neurodevelopmental conditions in their own right, whether they are better thought of as risk states for youth‐onset conditions, or both. Studies that aim to demonstrate advantages and disadvantages of such approaches are urgently required.

Fourth, staging and its application in research settings and service systems will undoubtedly benefit from the perspectives of multiple stakeholders – particularly those who are directly affected, such as youth and their families and carers. Such input could range from issues as broad as diagnostic terminology (e.g., the impact of telling individuals that they are experiencing “non‐specific symptom sets” , “risk states” or “risk syndromes”) to the effectiveness and tolerability of specific interventions or service platforms. This will enable researchers and practitioners to better understand and adapt the acceptability of this approach to the needs of people with lived experience, including awareness of relevant factors such as gender, age and ethnicity. Given the early stage of development of clinical staging, and the goal of accelerating its integration into real‐world practice settings and overarching clinical infrastructures, the involvement of such stakeholders, as well as research and implementation evaluation in this area, is critically needed.

Fifth, the rapid spread of digital (mobile and communications) technologies in mental health can be harnessed. These technologies now include a wide range of highly‐personalized (passive and active) mobile sensors and apps that can capture subjective and objective data on repeated occasions. Along with relevant e‐assessments, these technologies can now be integrated within more sophisticated clinical research infrastructures56, 57, 58. International collaboration around definitions and nomenclature involved in staging is urgently needed in order to design studies that capture such data (using novel technologies and sensors) that can facilitate comparing and contrasting findings59, 60, 61.

Sixth, it is highly likely that data from prior, ongoing or completed studies can be used to address priority areas or research questions around clinical staging. Funding agencies may choose to support this as a short‐term goal, while attempting to organize the research community around the longer‐term agenda described above.

Finally, building on this first international consensus statement, we propose the creation of an International Working Group on Transdiagnostic Clinical Staging in Youth Mental Health. In an effort to promote clinical staging, to determine clear criteria for transitions from one stage to another, to ensure consistency in their application, and to facilitate a base of research‐service collaboration around transdiagnostic clinical staging, this Working Group will convene – beginning in 2021 – workshops and satellite meetings at the International Association of Youth Mental Health and Intervention in Early Psychosis Association conferences, which run in alternating years. The development of staging models will also require the continuing engagement of young people and their families and carers.