A Dynamical Systems View of Psychiatric Disorders-Theory: A Review.

Importance: Psychiatric disorders may come and go with symptoms changing over a lifetime. This suggests the need for a paradigm shift in diagnosis and treatment. Here we present a fresh look inspired by dynamical systems theory. This theory is used widely to explain tipping points, cycles, and chaos in complex systems ranging from the climate to ecosystems. Observations: In the dynamical systems view, we propose the healthy state has a basin of attraction representing its resilience, while disorders are alternative attractors in which the system can become trapped. Rather than an immutable trait, resilience in this approach is a dynamical property. Recent work has demonstrated the universality of generic dynamical indicators of resilience that are now employed globally to monitor the risks of collapse of complex systems, such as tropical rainforests and tipping elements of the climate system. Other dynamical systems tools are used in ecology and climate science to infer causality from time series. Moreover, experiences in ecological restoration confirm the theoretical prediction that under some conditions, short interventions may invoke long-term success when they flip the system into an alternative basin of attraction. All this implies practical applications for psychiatry, as are discussed in part 2 of this article. Conclusions and Relevance: Work in the field of dynamical systems points to novel ways of inferring causality and quantifying resilience from time series. Those approaches have now been tried and tested in a range of complex systems. The same tools may help monitoring and managing resilience of the healthy state as well as psychiatric disorders.

A Dynamical Systems View of Psychiatric Disorders-Practical Implications: A Review.

Importance: Dynamical systems theory is widely used to explain tipping points, cycles, and chaos in complex systems ranging from the climate to ecosystems. It has been suggested that the same theory may be used to explain the nature and dynamics of psychiatric disorders, which may come and go with symptoms changing over a lifetime. Here we review evidence for the practical applicability of this theory and its quantitative tools in psychiatry. Observations: Emerging results suggest that time series of mood and behavior may be used to monitor the resilience of patients using the same generic dynamical indicators that are now employed globally to monitor the risks of collapse of complex systems, such as tropical rainforest and tipping elements of the climate system. Other dynamical systems tools used in ecology and climate science open ways to infer personalized webs of causality for patients that may be used to identify targets for intervention. Meanwhile, experiences in ecological restoration help make sense of the occasional long-term success of short interventions. Conclusions and Relevance: Those observations, while promising, evoke follow-up questions on how best to collect dynamic data, infer informative timescales, construct mechanistic models, and measure the effect of interventions on resilience. Done well, monitoring resilience to inform well-timed interventions may be integrated into approaches that give patients an active role in the lifelong challenge of managing their resilience and knowing when to seek professional help.

Non-psychotic Outcomes in Young People at Ultra-High Risk of Developing a Psychotic Disorder: A Long-Term Follow-up Study.

BACKGROUND: The majority of individuals at ultra-high risk (UHR) for psychosis do not transition to a full threshold psychotic disorder. It is therefore important to understand their longer-term clinical and functional outcomes, particularly given the high prevalence of comorbid mental disorders in this population at baseline. AIMS: This study investigated the prevalence of non-psychotic disorders in the UHR population at entry and long-term follow-up and their association with functional outcomes. Persistence of UHR status was also investigated. STUDY DESIGN: The sample comprised 102 UHR young people from the Personal Assessment and Crisis Evaluation (PACE) Clinic who had not transitioned to psychosis by long-term follow-up (mean = 8.8 years, range = 6.8-12.1 years since baseline). RESULTS: Eighty-eight percent of participants at baseline were diagnosed with at least one mental disorder, the majority of which were mood disorders (78%), anxiety disorders (35%), and substance use disorders (SUDs) (18%). This pattern of disorder prevalence continued at follow-up, though prevalence was reduced, with 52% not meeting criteria for current non-psychotic mental disorder. However, 35% of participants developed a new non-psychotic mental disorder by follow-up. Presence of a continuous non-psychotic mental disorder was associated with poorer functional outcomes at follow-up. 28% of participants still met UHR criteria at follow-up. CONCLUSIONS: The study adds to the evidence base that a substantial proportion of UHR individuals who do not transition to psychosis experience persistent attenuated psychotic symptoms and persistent and incident non-psychotic disorders over the long term. Long-term treatment and re-entry into services is indicated.

The self, neuroscience and psychosis study: Testing a neurophenomenological model of the onset of psychosis.

AIM: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self-disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12-month follow-up. METHODS: SNAP is a longitudinal observational study. Participants include 400 UHR individuals, 100 clinical controls with no attenuated psychotic symptoms, and 50 healthy controls. All participants complete baseline clinical and neurocognitive assessments and electroencephalography. The UHR sample are followed up for a total of 24 months, with clinical assessment completed every 6 months. RESULTS: This paper presents the protocol of the SNAP study, including background rationale, aims and hypotheses, design, and assessment procedures. CONCLUSIONS: The SNAP study will test whether neurophenomenological disturbances associated with basic self-disturbance predict persistence or intensification of UHR symptomatology over a 2-year follow up period, and how specific these disturbances are to a clinical population with attenuated psychotic symptoms. This may ultimately inform clinical care and pathoaetiological models of psychosis.

[Public mental health from an international perspective: from "shifting the curve" to inclusion of vulnerable populations]. / Public Mental Health in internationaler Perspektive: vom Shifting the Curve zur Inklusion vulnerabler Populationen.

In recent years, efforts in the field of public mental health have increased that seek to promote mental health and mental health literacy at population level and yield advances in the prevention, treatment and care of mental health conditions. This paper provides an overview of contemporary conceptualisations of indicators and determinants of public mental health as well as population-based intervention strategies from an international perspective. Current conceptual and methodological challenges of so-called high-risk, whole-population and vulnerable population strategies are critically discussed. Future efforts in research, policy and practice need to address fundamental causes of social and health inequalities, drawing on all societal fields, to contribute to improving population mental health.

Potential mechanisms underlying sleep disturbance in young people with borderline personality disorder features: an exploratory study.

BACKGROUND: Sleep disturbance is common among young people (15-25 years) with features of borderline personality disorder (BPD). However, the mechanisms underlying sleep disturbance in BPD remain unknown. Understanding these underlying processes is essential to guide the development of sleep-improvement interventions and to optimise their efficacy through identifying beneficial treatment targets. This exploratory study aimed to investigate potential underlying mechanisms to inform future hypotheses, research development, and provide insight into potential treatment targets to improve sleep in young people with BPD. This study explored the indirect roles of emotion regulation difficulties, depression, anxiety and stress in the relationship between BPD features and sleep disturbance in young people. METHODS: Sleep was measured subjectively (self-report questionnaires) and objectively (10 days wrist actigraphy) in 40 young people with BPD features and 38 healthy young people. Participants also completed the Difficulties in Emotion Regulation Scale and the Depression, Anxiety and Stress Scale. RESULTS: Mediation analyses revealed that impulse control difficulties, limited emotion regulation strategies and anxiety indirectly affected the relationship between group (BPD vs. healthy) and subjective sleep disturbance in young people. Lack of emotional awareness and anxiety contributed to associations between group and objectively longer time in bed and bedtime variability, respectively. CONCLUSIONS: These preliminary findings suggest that targeting emotional dysregulation (impulse control, strategies, emotional awareness) and anxiety might be beneficial for improving sleep in this population.

Baseline data of a sequential multiple assignment randomized trial (STEP study).

AIM: Research has shown that preventative intervention in individuals at ultra-high risk of psychosis (UHR) improves symptomatic and functional outcomes. The staged treatment in early psychosis (STEP) trial aims to determine the most effective type, timing and sequence of interventions in the UHR population by sequentially studying the effectiveness of (1) support and problem solving, (2) cognitive-behavioural case management and (3) antidepressant medication with an embedded fast-fail option of (4) omega-3 fatty acids or low-dose antipsychotic medication. This paper presents the recruitment flow and baseline clinical characteristics of the sample. METHODS: STEP is a sequential multiple assignment randomized trial. We present the baseline demographics, clinical characteristics and acceptability and feasibility of this treatment approach as indicated by the flow of participants from first contact up until enrolment into the trial. Recruitment took place between April 2016 and January 2019. RESULTS: Of 1343, help-seeking young people who were considered for participation, 402 participants were not eligible and 599 declined/disengaged, resulting in a total of 342 participants enrolled in the study. The most common reason for exclusion was an active prescription of antidepressant medication. Eighty-five percent of the enrolled sample had a non-psychotic DSM-5 diagnosis and symptomatic/functional measures showed a moderate level of clinical severity and functional impairment. DISCUSSION: The present study demonstrates the acceptability and participant's general positive appraisal of sequential treatment. It also shows, in line with other trials in UHR individuals, a significant level of psychiatric morbidity and impairment, demonstrating the clear need for care in this group and that treatment is appropriate.

Comparing GENEActiv against Actiwatch-2 over Seven Nights Using a Common Sleep Scoring Algorithm and Device-Specific Wake Thresholds.

Demonstrating inter-device reliability is essential to use devices interchangeably, and accurately integrate, interpret, or compare data from different actigraphs. Despite this, there is a paucity of comparative literature over a timeframe exceeding one night. The aims of this study were to determine an optimal wake threshold for GENEActiv and to evaluate the concordance between Actiwatch-2 and GENEActiv using a common algorithm (Phillips Respironics). Data were collected from 33 individuals (20 female) aged 20-35 years (M= 25.33, SD = 4.69) across a total 213 nights. Participants wore both devices simultaneously and continuously for seven days. The sleep parameters of interest were: total sleep time, sleep efficiency, sleep onset latency, and wake after sleep onset. Exploratory analyses of sensitivity, specificity, overall accuracy, mean bias, and paired samples t-tests indicated an optimal wake threshold of 115 for GENEActiv, compared with Actiwatch-2 at the 40 (medium, default) threshold. Using these thresholds, sensitivity, and overall accuracy of GENEActiv were both good (86% and 78%, respectively), however specificity was relatively low (40%). There were no significant inter-device differences for any sleep parameters, and all absolute mean biases were small. Overall, the findings from this study provide the first empirical evidence to support the reliability of GENEActiv against Actiwatch-2 over multiple nights using a common algorithm with device-specific wake thresholds.

Subjective and objective sleep in young people with borderline personality disorder features.

Characterising sleep in young people (aged 15-25 years) with borderline personality disorder (BPD) features is crucial given the association between BPD features and sleep disturbance, negative consequences of poor sleep, and normative developmental sleep changes that occur in this age group. The present study aimed to characterise the sleep profile of young people with BPD to determine whether this profile is non-normative and specific to BPD. Participants were 96 young people (40 with BPD features, 38 healthy individuals, and 18 young people seeking help for mental health difficulties without BPD). Sleep was measured subjectively (self-report questionnaires) and objectively (10 days of actigraphy). Young people with BPD features reported poorer subjective sleep quality, greater insomnia symptoms and later chronotype than same-age healthy and clinical comparison groups. Young people with BPD features also displayed irregular sleep timing, later rise times, greater time in bed and longer sleep durations than healthy young people. Those with BPD features had superior sleep quality (greater sleep efficiency, less wake after sleep onset) and longer sleep durations than the clinical comparison group. Sleep profiles were similar across young people with BPD features with and without co-occurring depression. Overall, the findings revealed a subjective-objective sleep discrepancy and suggest that sleep-improvement interventions might be beneficial to improve subjective sleep in young people with BPD features.

Patients', carers' and clinicians' attitudes towards alternative terms to describe the at-risk for psychosis state.

OBJECTIVE: Language used in psychiatry is important because it provides an understandable and accurate way of describing clinical and theoretical concepts. The use of labels in psychiatry has often been associated with stigma and reduced engagement with clinical services. This studys aims were to generate new terms for the 'at-risk mental state' (ARMS) concept and to investigate what young people, their caregivers and clinicians thought about them as well as terms commonly used in early intervention clinics. Another aim was to understand participants preference related to the best timing to introduce the at-risk concept and the extent and context of the information presented. METHODS: New terms illustrating the at-risk concept have been generated by a youth reference group with lived experience of mental illness: 'pre-diagnosis stage' (PDS), potential of developing a mental illness (PDMI) and disposition for developing a mental illness (DDMI). A specifically designed questionnaire was administered to 46 patients with ARMS, 24 caregivers and 52 clinicians to obtain their feedback on newly proposed terms and on the terms already used in clinical practice and research. RESULTS: The preferred terms were PDS, PDMI and ARMS. The least favoured terms were Ultra High Risk and Attenuated Psychosis Syndrome, which were thought to be associated with the most stigma. Most participants agreed that disclosure about diagnosis should be delivered early by the key clinician. CONCLUSIONS: Patients generated terms such as PDS, PDMI, alongside ARMS should be considered to be used in clinical practice. They present with low stigma and are illustrative of young peoples difficulties.

Greater preference for eveningness is associated with negative symptoms in an ultra-high risk for psychosis sample.

AIM: Investigating biological processes in at-risk individuals may help elucidate the aetiological mechanisms underlying psychosis development, refine prediction models and improve intervention strategies. This study examined the associations between sleep disturbances, chronotype, depressive and psychotic symptoms in individuals at ultra-high risk for psychosis. METHODS: A sample of 81 ultra-high risk patients completed clinical interviews and self-report assessments of chronotype and sleep during the Neurapro clinical trial. Mixed regression was used to investigate the cross-sectional associations between symptoms and sleep disturbances/chronotype. RESULTS: Sleep disturbances were significantly associated with increased depressive and attenuated positive psychotic symptoms. Greater preference for eveningness was significantly associated with increased negative symptoms, but not with depressive or attenuated positive psychotic symptoms. CONCLUSION: Sleep disturbances and chronotype may impact the emerging psychopathology experienced by ultra-high risk individuals. Further, the preliminary relationship observed between greater preference for eveningness and negative symptoms offers a unique opportunity to treat negative symptoms through chronobiological approaches.

Distinguishing schizophrenia spectrum from non-spectrum disorders among young patients with first episode psychosis and at high clinical risk: The role of basic self-disturbance and neurocognition.

INTRODUCTION: The distinction between the schizophrenia spectrum and other types of disorders may be clinically relevant in terms of its predictive validity as suggested by studies showing schizophrenia spectrum patients have more unfavourable outcomes compared to other psychotic disorders. The present study aimed to investigate whether basic self-disturbances and neurocognitive processes that have been linked to psychosis risk have discriminative power for schizophrenia spectrum disorders in patients presenting with first episode psychosis (FEP) and at ultra-high risk for psychosis (UHR). METHODS: 38 FEP patients, 48 UHR patients, and 33 healthy controls were assessed for basic self-disturbances (using the Examination of Anomalous Self-Experience, EASE, interview), source monitoring and aberrant salience (behavioural tasks to measure neurocognitive constructs). Clinical groups were divided into patients with schizophrenia spectrum disorders and those with other non-spectrum disorders and were further compared on measures controlling for symptom severity and age. RESULTS: Basic self-disturbances distinguished schizophrenia spectrum from non-spectrum disorders in the 'FEP only' sample, F = 19.76, p < 0.001, η2partial = 0.37, and also in the combined UHR/FEP sample, F = 23.56, p < 0.001, η2partial = 0.22. Additionally, some processes related to source monitoring deficits were elevated in schizophrenia spectrum disorders. In contrast, the two groups (schizophrenia spectrum vs other diagnoses) performed similarly in aberrant salience tasks. Comparable results were obtained for analyses performed with an FEP/UHR combined sample and the 'FEP only' sample. DISCUSSION: Basic self-disturbances at the phenomenological level and source monitoring deficits on the neurocognitive level may be useful in identifying risk of schizophrenia spectrum disorders at the earliest clinical presentation.

The association between migrant status and transition in an ultra-high risk for psychosis population.

PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.

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

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.

The relation of basic self-disturbance to self-harm, eating disorder symptomatology and other clinical features: Exploration in an early psychosis sample.

BACKGROUND AND AIMS: The notion of basic self-disturbance has been proposed as a core feature of schizophrenia-spectrum disorders and as an indicator of future transition to psychosis in high-risk populations. However, the relation of this notion to many clinical characteristics has not been explored. The aim of this study was: (a) to investigate the distribution of self-disturbance and other symptoms dimensions in ultra-high risk (UHR), first-episode psychosis (FEP) and healthy control groups; and (b) to explore the association of self-disturbance with a history of self-harm, suicidal attempt, eating disorder symptomatology, school bullying victimization and sexual or physical abuse. METHODS: Patients with UHR status (n = 38) or FEP (n = 26) and healthy controls (n = 33) were assessed with the Examination of Anomalous Self-Experience (EASE) and the Comprehensive Assessment of at Risk Mental States (CAARMS). The clinical-historical variables were assessed through medical records. RESULTS: The FEP group scored significantly higher on the EASE than the UHR group, which scored significantly higher than the healthy control group, which had a very low score. Multivariate logistic regression analyses revealed that higher EASE score was significantly associated with a history of self-harm, disordered eating and bullying victimization (but not with suicide attempts or sexual/physical abuse) after controlling for positive, negative and depressive symptoms. CONCLUSION: These novel findings suggest that self-disturbance may be related to a history of school bullying victimization, self-harm and eating disorder symptomatology in patients with or at-risk of psychosis. If further confirmed, these findings are potentially relevant to clinical risk assessment and therapy.

Physical health assistance in early recovery of psychosis: Study protocol for a randomized controlled trial.

AIM: Young people with psychotic disorders have poorer physical health compared to their healthy peers, a state compounded by the metabolic side-effects of antipsychotic medications. To address this, Orygen Youth Health has introduced physical health services including exercise physiologists and dieticians. These services are typically coordinated by the case manager and doctor. It is not yet known whether a treating team member dedicated to physical health will improve engagement, adherence and outcomes with these services. Hence, the protocol is presented here for a trial to evaluate the effect of including a physical health nurse in the care of young people with first-episode psychosis. METHODS: This will be a single-blind randomized controlled trial that includes 15- to 24-year-olds with first-episode psychosis who have just commenced (within 30 days) antipsychotic medication. The primary outcome will be the event of clinically significant weight gain (≥7% body weight). Participants will be assigned either a physical health nurse in their treating team (in addition to the case manager and doctor) for a 12-week period, or treatment as usual (case manager and doctor). Research assessments will be conducted at baseline, 12 and 26 weeks. Activity trackers worn by participants for the study's duration will measure sleep and physical activity. CONCLUSION: The present study will determine whether a physical health nurse will facilitate participants in attending and engaging in physical health interventions and whether this will be associated with physical health improvements or the prevention of worsening physical health.

Trajectories of symptom severity and functioning over a three-year period in a psychosis high-risk sample: A secondary analysis of the Neurapro trial.

The Ultra-High Risk (UHR) for psychosis group is known to be heterogeneous with diverse outcomes. This study aimed to: 1. Identify subclasses of UHR individuals based on trajectories of symptomatic and functional change over time, 2. Identify predictors of these trajectories. A sample of 304 UHR individuals participating in the Neurapro trial were followed over an average of 40 months. All participants received cognitive-behavioural case management (CBCM). Symptomatic and functional profiles were investigated using latent class growth analysis. Multinomial regression was employed to investigate predictors of classes. Identified trajectories showed mostly parallel slopes (i.e. improving symptoms/functioning over time), which were primarily distinct regarding the severity of symptomatology/level of functioning at baseline (i.e. the intercept). Higher symptomatic/lower functioning classes were predicted by higher substance use, older age, female gender, and lower cognitive functioning. No divergent trajectories were identified as all classes improved over time. This may reflect effective treatment through CBCM, natural illness course, or effective engagement with mental health services. Nonetheless, classes highest in symptoms/lowest in functioning still showed considerable impairment during follow-up, highlighting the need for targeted intervention in these subgroups. The study emphasizes the need for more clinical attention directed towards UHR patients being female or using substances.

Capturing the risk of persisting depressive symptoms: A dynamic network investigation of patients' daily symptom experiences.

What drives the large differences across patients in terms of treatment efficacy of major depressive disorder (MDD) is unclear. A network approach to psychopathology may help to reveal underlying mechanisms determining patients' capacity for recovery. We used daily diary MDD symptom data and six-month follow-up data on depression to examine how dynamic associations between symptoms relate to the future course of MDD. Daily experiences of depressive symptoms of 69 participants were assessed by means of the SCL-90-R depression subscale, three days a week for a period of six weeks, as part of a larger intervention study. Multilevel vector autoregressive modelling was used to estimate networks of dynamic symptom connections. Long-term outcome was determined by the percentage change in Hamilton Depression Rating Scale (HDRS) score between pre-intervention and six-month follow-up. For patients with more persisting symptoms, the symptom 'feeling everything is an effort' most strongly predicted other symptoms. The networks of the two groups did not significantly differ in overall connectivity. Findings suggest that future research should not solely focus on the presence or intensity of individual symptoms when predicting long-term outcomes, but should also examine the role of a specific symptom in the larger network of dynamic symptom-to-symptom interactions.

Broad clinical high-risk mental state (CHARMS): Methodology of a cohort study validating criteria for pluripotent risk.

AIM: The development of the ultra-high risk (UHR) criteria for psychosis created a new paradigm for the prevention research in psychiatry. Since (1) prevention research faces the challenge of achieving adequate statistical power when focusing on single low-incidence syndromes and (2) early clinical phenotypes are overlapping and non-specific, this study broadens the UHR state beyond psychosis as an outcome. The CHARMS (clinical high at-risk mental state) study aims to prospectively validate a set of trans-diagnostic criteria to identify help-seeking young people at risk of developing a range of serious mental illnesses. METHODS: This paper describes the methodology of the CHARMS study, which involves applying the CHARMS criteria to a cohort of help-seeking young people aged 12 to 25 attending youth mental health services in Melbourne. New referrals meeting the CHARMS criteria are allocated to the CHARMS+ group; referrals not meeting CHARMS threshold are allocated to CHARMS- group (control group); referrals meeting criteria for a full-threshold disorder are excluded. Transition status and clinical and functional outcomes are re-assessed at 6 and 12 months. CONCLUSIONS: This study will be the first to introduce and validate clinical criteria to identify a broader at-risk patient population, which may facilitate young people's access to clinical services and early treatment by reducing the reliance on "caseness" defined according to current diagnostic categories being required for service entry. These criteria may introduce a new, trans-diagnostic approach for understanding risk factors and pathogenic mechanisms that drive the onset of severe mental illness and the next generation of preventive intervention trials.