Current gold-standard mental health questionnaires typically focus on one aspect of psychological functioning and are designed for adults. Over two studies, we co-designed and validated a youth-centric transdiagnostic mental health questionnaire. In Study 1, N=665 treatment-seeking and non-treatment-seeking youth (12-25 years) completed 15 mental health questionnaires. A factor analysis identified four transdiagnostic dimensions: ‘Uncontrollable Thinking Patterns’, ‘Re-experiencing Difficult Events’, ‘Rigid High Standards’, and ‘Emotional Agency’. A multi-target Lasso regression was used to reduce the measure to 34 items. This measure, co-designed with a Lived Experience Advisory Group, was named the Youth Mental Health Map. In Study 2, N=245 youth completed the measure twice, two weeks apart. The tool demonstrated moderate-to-good reliability, and correlations with scores on the K10 and PGI-S supported the construct and predictive validity of the tool. This tool holds clinical potential, allowing a more fine-grained and multidimensional measurement of psychological functioning in youth.

BACKGROUND:Reducing the duration of untreated psychosis (DUP) is a key aim of early intervention in psychosis (EIP) services. While DUP accounts for a proportion of the time individuals experience psychotic symptoms, the duration of active psychosis (DAP) concept provides a broader scope by including the duration of psychosis both before and after treatment initiation. This study aimed to describe DAP in a large naturalistic cohort of people with first-episode psychosis (FEP), and explore the relationship between DAP and early psychosis outcomes. METHODS:This study involved secondary analyses of an existing dataset of consecutive cases of FEP in young people aged 15 to 24 from an EIP service in Melbourne. The duration of active psychosis after treatment initiation (DAT), limited to the first year of care, was estimated using the short form Scale for the Assessment of Positive Symptoms measured repeatedly at regular intervals. This was combined with DUP to calculate DAP. DAP was divided into four groups according to quartiles and regression analysis was used to explore the relationship between DAP and outcomes at discharge. RESULTS:DAP was estimated for 749 individuals with FEP. The group with the longest DAP (>58 weeks) presented at a younger age (mean 18.6 vs mean 19.7) and had a higher proportion of females (49.7% vs 38.9%). Adjusted linear regression models demonstrated that longer DAP (>58 weeks) was a significant predictor of worse overall functioning (β = -7.07, p = .005) and negative symptom severity (β = 1.10, p = .006) at discharge from the EIP service. CONCLUSIONS:Time spent in active psychosis is an important consideration beyond the initial untreated period and further research is indicated to establish the relationship between DAP and outcomes in FEP.

AIMS:Negative symptoms are a core component of schizophrenia, affecting up to 60% of individuals with the disorder. They are categorised into primary negative symptoms (PNS), which are intrinsic to the illness, and secondary negative symptoms, which arise from external factors such as depression or medication side effects. They can also be divided into diminished expression and amotivation/anhedonia subtypes. While inflammation has been implicated in schizophrenia and linked to negative symptoms, little is known about whether inflammatory profiles differ between negative symptom subtypes in individuals at Ultra-High Risk (UHR) for psychosis. METHODS:We conducted a secondary analysis of 147 UHR participants from the Staged Treatment in Early Psychosis (STEP) study to examine whether inflammatory markers (Alpha-2-Macroglobulin, IL-6, CRP, sICAM-1, sVCAM-1, and suPAR) differed across negative symptom subgroups, using multinomial and binomial logistic regression models adjusted for age, sex, smoking, and BMI. RESULTS:Overall, most inflammatory markers were not significantly associated with negative symptom subgroups. However, higher sICAM-1 levels were asscoiated with lower odds of primary negative symptoms compared with no negative symptoms. Additionally, younger age was associated with increased odds of PNS and amotivation, while smoking was associated with higher odds of secondary negative symptoms compared with no negative symptoms. DISCUSSION:These findings suggest that inflammation may not broadly distinguish negative symptom subtypes at the UHR stage, although sICAM-1 may play a role in early illness processes. Limitations include sample ascertainment, potential misclassification of negative symptoms, and the relatively small number of participants with PNS. Future studies with larger samples and longitudinal designs are needed to clarify whether inflammatory changes contribute to the emergence of specific negative symptom subtypes.

Abstract This chapter introduces clinical staging as a diagnostic model that bridges categorical and dimensional approaches to enhance early detection, intervention, and prevention in psychiatry. It critiques traditional diagnostic systems, such as the DSM and ICD, for neglecting early and transdiagnostic stages of illness and presents staging as a developmental and longitudinal framework that captures evolving symptoms from risk (Stage 0) to treatment resistance (Stage 4). The chapter outlines neurobiological and functional distinctions across these stages and emphasizes the model’s capacity to guide proportional, stage-specific treatment, particularly for young people. It details targeted interventions across stages—from preventive strategies to intensive and long-term treatments—demonstrating how staging aligns care with illness progression. Finally, the chapter concludes that clinical staging offers a valid, evolving, and transdiagnostic framework that advances personalized care, while future research must refine stage boundaries and identify biomarkers to strengthen its predictive and therapeutic precision.

Eating disorders (EDs) are serious mental health conditions with peak onset during adolescence and young adulthood. While early intervention services frequently encounter young people at-risk of EDs, little is known about the trajectories and factors associated with ED risk among those engaged in services over time. The sample includes 494 young people (aged 12–25 years) who presented to youth mental health services in Australia between 2011 and 12, primarily for emerging mood disorders. ED risk was assessed at baseline and 12-month follow-up using the SCOFF questionnaire, with scores ≥ 2 (range 0–5) indicating high risk status. Participants were classified into four trajectory groups: persistent (high risk at both timepoints; n = 92, 18.62

The impact of climate change on mental health is increasingly evident, particularly among young people (16-25 years old), ranging from acute distress after extreme weather events to more persistent feelings of anxiety, grief, and uncertainty regarding the future. This Viewpoint explores how mental health care for young people can be improved to more effectively respond to the psychological impacts of climate change. Rather than proposing a new treatment model, this Viewpoint provides a starting point for clinicians by examining how existing therapeutic approaches could be applied, adapted, or reconsidered in the context of climate change. Furthermore, a range of therapeutic approaches commonly used in youth mental health care, including cognitive behavioural therapy, acceptance and commitment therapy, dialectical behaviour therapy, schema therapy, mindfulness and resilience-based interventions, nature-based approaches, empowerment and activism engagement, community-based interventions, and pharmacological treatments, are discussed for their potential relevance. We highlight both the strengths and limitations of these approaches when addressing climate distress. Finally, we outline key priorities for clinical practice, service development, and future research to support the mental health of young people in a changing climate.

The clinical management of a complex disorder such as schizophrenia remains a significant challenge worldwide. This disorder requires a comprehensive, integrated and personalized care that blends multiple approaches, and the real-world availability of multiple resources. We present here the first recommendations addressing the real-world comprehensive care for people with schizophrenia-spectrum psychoses across different approaches, clinical stages, and levels of available resources. The recommendations are based on a critical review of the scientific literature and a collaborative appraisal by numerous clinical academics actively treating people with schizophrenia worldwide, representing various countries and clinical settings, including those in the Global South. Experts by experience were also involved. Our recommendations indicate that the comprehensive care of schizophrenia should involve: a) early detection; b) measurement-based monitoring; c) pharmacological treatments; d) psychological interventions; e) psychosocial interventions (including supported employment, housing and education); f) management of somatic conditions; g) community care; h) inpatient care; i) peer support, self-help, and alternative healing methods; j) population-level prevention, and l) societal-level support. The overarching core recommendation is to implement evidence-based care that addresses disparities across high- to middle/low-resource settings, emphasizing early intervention (and prevention when possible), culturally-sensitive paradigms that leverage the local existing resources, and task-sharing models that involve non-professional health care workers and, if possible, traditional healers. In the future, we expect that scalable and resource-saving, evidence-based digital solutions will help extend and improve care quality and efficiency across all resource settings. However, none of this can be achieved without adequately focusing on and strengthening mental health funding, improving access to care, addressing social determinants of health, and recognizing that care for people at risk for or living with schizophrenia is uneven and in need of improvement across all settings.

BACKGROUND AND HYPOTHESIS:The requirement for hospital admission to initiate clozapine presents a health-systems-related barrier to clozapine prescription and contributes to its underutilization in treatment-resistant schizophrenia (TRS). This study aimed to examine the clinicodemographic characteristics associated with treatment settings for clozapine initiation within a first-episode psychosis (FEP) cohort attending an early intervention in psychosis service. STUDY DESIGN:Secondary analysis of a retrospective cohort study of 1220 young people presenting with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne between 2011 - 2017. STUDY RESULTS:Ninety-one cases of TRS were identified and included in the analysis, with 70 commencing clozapine, of whom 67 had a commencement setting identified. Over half (n = 36, 53.7%) commenced clozapine in the community. When compared to the hospital initiation group, the community initiation group were less likely to have had a hospital admission at baseline (odds ratio (OR) 0.26, 95%CI, 0.09-0.87) or an involuntary admission during the 2 year episode of care with EPPIC (OR 0.25, 95%CI, 0.09-0.70). The community initiated group had presented with less severe delusion scores on short form Scale for Assessment of Positive Symptoms at baseline (mean 3.08 vs 3.94, P = .031). First generation migrants were less likely to initiate clozapine in the community (OR 0.29, 95%CI, 0.09-0.97). The community initiation group also had reduced odds of clozapine discontinuation until discharge from EPPIC (OR 0.22, 95%CI, 0.06-0.76). CONCLUSION:Community initiation provides an alternative route to clozapine treatment and may be associated with a reduced rate of clozapine discontinuation.

OBJECTIVE:This paper evaluated the impact of expanding the intake criteria at the Personal Assessment and Crisis Evaluation (PACE) clinic, a Melbourne based specialized early psychosis service, on its clinical governance, by including young people with complex mental health presentations. METHODS:Electronic medical records of 80 consecutive individuals aged 15-25 enrolled at PACE in 2020 were audited. A typical episode of care at PACE lasts six months. Service users were classified into three groups: At-Risk Mental State (ARMS), First Episode Psychosis (FEP), and Complex Presentations (CP). Demographic, clinical, and treatment characteristics were compared. Outcomes included clinical characteristics, comorbidities, length of care, and transition to psychosis during clinical care. RESULTS:Of 80 people, 56 % met ARMS criteria, 14 % FEP, and 31 % CP at Youth Access Team assessment, the port of entry of Orygen Specialist Program. Among the Complex group, 40 % later met ARMS criteria at entry into PACE. 12-month psychosis transition rate for ARMS was 20 % whilst none in the CP transitioned. Despite not meeting threshold for psychosis, 91 % of the CP had an episodes of care of more than 12 months. There were high rates of comorbidity including major depression (39 %), autism spectrum disorder (21 %), and substance use (39 %). CONCLUSIONS:Expanding PACE's intake criteria to include CP allowed for the engagement of young people with substantial unmet care needs. Importantly, 40 % of individuals with CP also met criteria for ARMS. Furthermore, over 90 % of those with CP required treatment for more than one year, highlighting a persistent need for long-term care. The study also highlighted challenges in applying evidence-based evaluation tools to systematically identify young people presenting with an at-risk syndrome, impacting the provision of stage-based care. Inclusion of CP in an ARMS clinic increased heterogeneity in an already diverse ARMS population and potentially undermined the consistency of the ARMS construct. Therefore, ARMS clinics should focus primarily on assessing and supporting people with ARMS only. There remains an ongoing need for professional development to maintain standards of care in early intervention, and consistent efforts should be made to successfully integrate evidence into clinical practice.

OBJECTIVE:To prepare evidence-based guidelines on psychosis prevention. METHODS:We reviewed evidence on risk factors for/age at onset of psychosis, tools to assess clinical high-risk of psychosis (CHR-P), transition rates, risk calculation/ethical considerations around risk communication, CHR-P biological/clinical correlates, efficacy/cost-effectiveness of interventions/psychosis prevention services. The World Federation of Societies of Biological Psychiatry framework was used to grade evidence regarding interventions/services, elaborating guidelines with evidence-/consensus-based clinical recommendations to prevent psychosis in CHR-P subjects. RESULTS:At the service organisation level, (i) psychosis indicated prevention services might be implemented in close collaboration with early intervention services for psychosis to minimise duration of untreated illness, (ii) intake age criteria should be between 14 to 35, (iii) services should allow access to persons with cannabis use disorder. At the assessment and risk communication level, in clinical settings: (iv) staff in mental health services should be trained in administering/rating CHR-P assessment tools, (v) administer them, (vi) be trained in using/interpreting risk calculators, and (vii) in communicating risk, (viii) only use validated risk calculators, keeping a human-to-human interaction. Also, (ix) prevention services should assess comorbid mental disorders. At the intervention level: (x) staff should offer treatment for abstinence from cannabis, (xi) offer evidence-based treatment for comorbid mental disorders, and (xii) offer treatment for CHR-P based on patient preference, following the 'first do no harm' principle. CONCLUSIONS:Prevention services should be implemented, including interventions for cannabis use, reducing the duration of untreated psychosis, and treating comorbid mental disorders.

Cognitive Behavioural Therapy (CBT) is the primary evidence-based treatment for major depressive disorder, with behavioural activation and cognitive restructuring skill acquisition proposed as key mechanisms. The relationship between CBT skill acquisition and reductions in depressive symptoms and suicidal ideation in young people remains unclear. Data were drawn from the Youth Depression Alleviation–Combined (YoDA-C) trial, a randomised controlled trial comparing CBT with fluoxetine or placebo in 15–25-year-olds diagnosed with major depressive disorder. Group-based trajectory modelling identified patterns of skill acquisition over 12 weeks. Demographic and clinical predictors of skill development were examined. Generalised linear mixed models (GLMMs) assessed associations between skill trajectories and changes in Montgomery–Åsberg Depression Rating Scale (MADRS) and Suicidal Ideation Questionnaire (SIQ) scores. Three trajectories emerged: Low-Stable (47.6

Europe is facing a mental health crisis that will last for decades, impacting the long-term health outcomes, wellbeing and economic productivity of our current generation of young people. Yet, large-scale, comparative research of youth-friendly mental health interventions is lacking. The YOUTHreach consortium aims to bridge this gap and provide a comprehensive European strategy. For this purpose, YOUTHreach will evaluate the clinical effectiveness and cost-effectiveness of three existing and accessible innovative interventions for prevention and early intervention of mental ill-health in youth, developed and tested in co-creation with youth: 1) YEAH, walk-in youth mental health support centres; 2) SELFIE, a transdiagnostic blended ecological momentary intervention; and 3) MOST, a clinical and peer-moderated digital youth mental health platform. In addition, feasibility and acceptability at new sites across Europe will be tested. Furthermore, in partnership with young people, best practice recommendations will be developed based on existing and new data and built into an integrated European youth mental health framework. Finally, awareness and accessibility of these interventions among policymakers, healthcare professionals, the general public, and youth—the target group—will be raised. YOUTHreach aims to contribute towards transformation of the present traditional mental healthcare system and providing the next generation with a better perspective in terms of health, wellbeing and productivity.

Public health monitoring based on the presence or absence of discrete health diagnoses helps to mitigate the burden associated with some health conditions, such as infectious diseases. However, this binary approach to disease monitoring misses opportunities for the prevention and effective care of mental health disorders, which are characterized by fluid boundaries between diagnoses and dimensional symptoms that vary over time. In this Review, we consider the staging model as an alternative to guide public mental health monitoring. This model situates individuals on a continuum covering six stages: asymptomatic individuals who have not experienced burdensome symptoms (stage 0); individuals with mixed symptoms not meeting criteria for full-threshold disorders (stage 1a); individuals with subthreshold presentations (stage 1b); individuals with a diagnosis of full-threshold disorders (stage 2); individuals with recurrent conditions (stage 3); and individuals with treatment-resistant conditions (stage 4). We integrate the staging model into public mental health monitoring by identifying possible indicators of mental health status at each stage. On the basis of identified gaps in monitoring the risk of progression across stages, we discuss how existing indicators can be reframed to improve the logic, intensity and timing of public health interventions and therefore the estimation of service and resource needs. Public mental health monitoring requires a nuanced approach that reflects the dimensional nature of mental health disorders. In this Review, Kieling and colleagues describe a staged monitoring approach that could improve the logic, intensity and timing of public mental health decision-making.

BACKGROUND:The prognosis for early onset psychosis (EOP) is poor for a broad range of outcomes. Early intervention services (EIS) have proven beneficial for adult-onset first-episode psychosis, but no randomized trials have investigated EIS in samples of patients aged <18 years. We will examine benefits and harms of a new integrated intervention OPUS YOUNG for EOP. The primary objective is to compare the effect of the OPUS YOUNG intervention versus treatment as usual (TAU) on change in social functioning at end-of-treatment after two years. METHODS:This investigator-initiated, single-center, pragmatic randomized clinical trial with blinded outcome assessment takes place in child- and adolescent mental health services in Copenhagen, Denmark. We randomize 290 participants aged 12 to 17 years with first-onset psychosis in a 1:1 ratio to a two-year intervention with OPUS YOUNG versus TAU. The OPUS YOUNG manual builds on the Danish evidence-based intervention for young adults (OPUS) adjusted to meet the specific needs of youths. The primary outcome is social functioning (Personal and Social Performance Scale [PSP] total score). Key secondary outcomes include measures of psychotic, negative, and disorganized symptom dimensions, client satisfaction, and health-related quality of life. Analyses will follow the intention-to-treat principle and use mixed-effects repeated measures models. DISCUSSION:In a rigorous research design, we address the urgent need for evidence-based interventions integrating psychosocial and pharmacological treatments in an age-appropriate manualized program for EOP. The primary trial limitations are the risk of attrition during follow-up, and the inherent inability to mask for allocation in trials with psychosocial interventions. TRIAL REGISTRATION:ClinicalTrials.gov: NCT04916626, registered June 2021. Protocol and modifications is presented here: https://classic. CLINICALTRIALS:gov/ct2/show/NCT04916626.

BACKGROUND AND HYPOTHESIS:Processing speed and verbal learning are linked to functioning in people at clinical high-risk for psychosis (CHR-P). However, a clear understanding of these relationships has been limited by the use of single-value assessor ratings of functioning and limited incorporation of self-report and longitudinal functional assessments. This study aims to examine the effect of processing speed and verbal learning on longitudinal assessor-rated and self-reported functioning. STUDY DESIGN:Individuals at CHR-P (n = 1282) and community controls (n = 425) who participated in Accelerating Medicines Partnership-Schizophrenia were examined. Processing speed and verbal learning abilities were ascertained using the Penn Computerized Neurocognitive Battery. Assessor-rated functioning was measured using the Global Functioning Scales. Self-reported functioning was collected using Ecological Momentary Assessment. Analyses were linear models and mixed-effects models. STUDY RESULTS:Both processing speed and verbal learning were associated with assessor-rated functioning at baseline and through 2 months (Ps < 0.001). Processing speed abilities predicted changes in self-reported ability to function (P = .036), motivation (P = .040), and concentration (P = .020) over time. Verbal learning abilities predicted changes in self-reported loneliness (P = .044) over time. Processing speed and verbal learning were associated with assessor-rated and self-reported functioning over and above estimated intelligence quotient and positive symptoms. CONCLUSIONS:Processing speed and verbal learning are important predictors of short-term longitudinal functioning, and may be important targets for early recognition and mitigation of psychosis risk.

The Clinical High Risk (CHR) state for psychosis is consistently associated with widespread cortical thinning. However, the underlying mechanisms driving this neuroanatomical phenotype remain poorly understood. Here, we integrated the ENIGMA CHR Working Group's large pooled dataset (N = 1782 CHR, N = 1333 healthy controls) with an open-source PET molecular atlas to identify, for the first time, potential neurochemical drivers of cortical thinning associated with psychosis risk, transition, and its core symptoms. Using multilinear model analysis, we show that local chemoarchitecture significantly explains CT differences associated with CHR case-control status, the severity of negative symptoms, and future psychosis transition after excluding medication confounds. PET-based maps of dopamine, GABA, glutamate, serotonin, and norepinephrine consistently emerged as the strongest predictors of lower CT in CHR and psychosis transition (total dominance range: 62-69% and 58-87%, respectively), with contributions of monoamine systems being especially sensitive to medication exposure (8-23% change in dominance range). Negative symptom-associated cortical thinning was best explained by PET-based maps of dopamine, histamine, serotonin and opioid systems (total dominance range: 60-81%), with contributions of histamine being sensitive to medication exposure (9-19% change in dominance range). Combined, these results uniquely identify specific neurochemical systems - particularly monoaminergic, glutamatergic, and GABAergic pathways - as key molecular mechanisms associated with cortical thinning in people at high risk of developing psychosis.