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This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.

BACKGROUND: Disruptions of axonal connectivity are thought to be a core pathophysiological feature of psychotic illness, but whether they are present early in the illness, prior to antipsychotic exposure, and whether they can predict clinical outcome remains unknown. METHODS: We acquired diffusion-weighted MRI to map structural connectivity between each pair of 319 parcellated brain regions in 61 antipsychotic-naive individuals with First Episode Psychosis (FEP; 15-25 years, 46% female) and a demographically matched sample of 27 control participants, along with clinical follow-up data in patients three months and 12 months after the scan. We used connectome-wide analyses to map disruptions of inter-regional pairwise connectivity and connectome-based predictive modelling to predict longitudinal change in symptoms and functioning. RESULTS: Individuals with FEP showed disrupted connectivity in a brain-wide network linking all brain regions when compared with controls (pFWE=.03). Baseline structural connectivity significantly predicted change in functioning over 12 months (r=.44;pFWE=.041), such that lower connectivity within fronto-striato-thalamic systems predicted worse functional outcomes. CONCLUSIONS: Brain-wide reductions of structural connectivity exist during the early stages of psychotic illness and cannot be attributed to antipsychotic medication. Moreover, baseline measures of structural connectivity can predict change in patient functional outcomes up to one year after engagement with treatment services.

BACKGROUND: Integrating innovative digital mental health interventions within specialist services is a promising strategy to address the shortcomings of both face-to-face and web-based mental health services. However, despite young people's preferences and calls for integration of these services, current mental health services rarely offer blended models of care. OBJECTIVE: This pilot study tested an integrated digital and face-to-face transdiagnostic intervention (eOrygen) as a blended model of care for youth psychosis and borderline personality disorder. The primary aim was to evaluate the feasibility, acceptability, and safety of eOrygen. The secondary aim was to assess pre-post changes in key clinical and psychosocial outcomes. An exploratory aim was to explore the barriers and facilitators identified by young people and clinicians in implementing a blended model of care into practice. METHODS: A total of 33 young people (aged 15-25 years) and 18 clinicians were recruited over 4 months from two youth mental health services in Melbourne, Victoria, Australia: (1) the Early Psychosis Prevention and Intervention Centre, an early intervention service for first-episode psychosis; and (2) the Helping Young People Early Clinic, an early intervention service for borderline personality disorder. The feasibility, acceptability, and safety of eOrygen were evaluated via an uncontrolled single-group study. Repeated measures 2-tailed t tests assessed changes in clinical and psychosocial outcomes between before and after the intervention (3 months). Eight semistructured qualitative interviews were conducted with the young people, and 3 focus groups, attended by 15 (83%) of the 18 clinicians, were conducted after the intervention. RESULTS: eOrygen was found to be feasible, acceptable, and safe. Feasibility was established owing to a low refusal rate of 25% (15/59) and by exceeding our goal of young people recruited to the study per clinician. Acceptability was established becaus

BACKGROUND: Family carers of youth recovering from early psychosis experience significant stress; however, access to effective family interventions is poor. Digital interventions provide a promising solution. OBJECTIVE: Our objective was to evaluate across multiple Australian early psychosis services the effectiveness of a novel, web-based early psychosis intervention for carers. METHODS: In this cluster randomized controlled trial conducted across multiple Australian early psychosis services, our digital moderated online social therapy for carers (Altitudes) plus enhanced family treatment as usual (TAU) was compared with TAU alone on the primary outcome of perceived stress and secondary outcomes including mental health symptoms and family variables at the 6-month follow-up. RESULTS: Eighty-six caregivers were randomized and data were available for 74 young people in their care. Our primary hypothesis that carers randomized to Altitudes+TAU would report greater improvements in perceived stress at follow-up compared with carers randomized to TAU alone was not supported, with the TAU alone group showing more improvement. For secondary outcomes, the TAU alone group showed improved mindfulness over time. Regardless of group assignment, we observed improvements in satisfaction with life, quality of life, emotional overinvolvement, and burden of care. In contrast, hair cortisol concentration increased. Post hoc analyses revealed more contact with early psychosis services in the intervention group compared to TAU alone and that improvements in perceived stress and social support were associated with use of the intervention in the Altitudes+TAU group. In this study, 80% (12/15) reported a positive experience with Altitudes and 93% (14/15) would recommend it to others. CONCLUSIONS: Our trial did not show a treatment effect for Altitudes in perceived stress. However, our post hoc analysis indicated that the amount of use of Altitudes related to improvements in stress and soci

OBJECTIVE: Integrating digital technologies with clinical practice promises to improve access and enhance care in the context of high service demand and constrained capacity. METHOD: We outline the emerging research in the integration of digital tools in clinical care, known as blended care, and provide case examples of mental health technology platforms currently in use, summarise findings regarding novel technologies such as virtual reality, and outline real-world implementation challenges and potential solutions. RESULTS: Recent evidence shows that blended care approaches are clinically effective and improve service efficiency. Youth-specific technologies such as moderated online social therapy (MOST) are achieving a range of positive clinical and functional outcomes, while emerging technologies like virtual reality have strong evidence in anxiety disorder, and accumulating evidence in psychotic conditions. Implementation science frameworks show promise in helping overcome the common challenges faced in real-world adoption and ongoing use. CONCLUSION: The integrated, blended use of digital mental health technologies with face-to-face clinical care has the potential to improve care quality for young people while helping overcome the growing challenges faced by youth mental health service providers.

IMPORTANCE: Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown. OBJECTIVE: To test the hypothesis that brain network architecture constrains cross-sectional and longitudinal gray matter alterations across different stages of psychotic illness and to identify whether certain brain regions act as putative epicenters from which volume loss spreads. DESIGN, SETTINGS, AND PARTICIPANTS: This case-control study included 534 individuals from 4 cohorts, spanning early and late stages of psychotic illness. Early-stage cohorts included patients with antipsychotic-naive first-episode psychosis (n = 59) and a group of patients receiving medications within 3 years of psychosis onset (n = 121). Late-stage cohorts comprised 2 independent samples of people with established schizophrenia (n = 136). Each patient group had a corresponding matched control group (n = 218). A sample of healthy adults (n = 356) was used to derive representative structural and functional brain networks for modeling of network-based spreading processes. Longitudinal illness-related and antipsychotic-related gray matter changes over 3 and 12 months were examined using a triple-blind randomized placebo-control magnetic resonance imaging study of the antipsychotic-naive patients. All data were collected between April 29, 2008, and January 15, 2020, and analyses were performed between March 1, 2021, and January 14, 2023. MAIN OUTCOMES AND MEASURES: Coordinated deformation models were used to estimate the extent of gray matter volume (GMV) change in each of 332 parcellated areas by the volume changes observed in areas to which they were structurally or functionally coupled. To identify putative epicenters of volume loss, a network diffusion model was used to simulate the spread of pathology from different seed regions. Correlations between estimated

Gaining awareness of psychosis (i.e., insight) is linked to depression, particularly in the post-acute phase of psychosis. Informed by social rank theory, we examined whether the insight-depression relationship is explained by reduced social rank related to psychosis and whether self-compassion (including uncompassionate self-responding [UCS] and compassionate self-responding [CSR]) and mindfulness buffered the relationship between social rank and depression in individuals with first episode psychosis during the post-acute phase. Participants were 145 young people (Mage = 20.81; female = 66) with first episode psychosis approaching discharge from an early psychosis intervention centre. Questionnaires and interviews assessed insight, depressive symptoms, perceived social rank, self-compassion, mindfulness and illness severity. Results showed that insight was not significantly associated to depression and thus no mediation analysis was conducted. However, lower perceived social rank was related to higher depression, and this relationship was moderated by self-compassion and, more specifically, UCS. Mindfulness was related to depression but had no moderating effect on social rank and depression. Results supported previous findings that depressive symptoms are common during the post-acute phase. The role of insight in depression for this sample is unclear and may be less important during the post-acute phase than previously considered. Supporting social rank theory, the results suggest that low perceived social rank contributes to depression, and reducing UCS may ameliorate this effect. UCS, social rank and possibly mindfulness may be valuable intervention targets for depression intervention and prevention efforts in the recovery of psychosis.

BACKGROUND: Common challenges in the youth mental health system include low access, poor uptake, poor adherence, and limited overall effectiveness. Digital technologies offer promise, yet challenges in real-world integration and uptake persist. Moderated Online Social Therapy (MOST) aims to overcome these problems by integrating a comprehensive digital platform into existing youth mental health services. Theory of change (ToC) frameworks can help articulate how and why complex interventions work and what conditions are required for success. OBJECTIVE: The objective of this study is to create a ToC for MOST to explain how it works, why it works, who benefits and how, and what conditions are required for its success. METHODS: We used a multimethod approach to construct a ToC for MOST. The synthesis aimed to assess the real-world impact of MOST, a digital platform designed to enhance face-to-face youth mental health services, and to guide its iterative refinement. Data were gathered from 2 completed and 4 ongoing randomized controlled trials, 11 pilot studies, and over 1000 co-design sessions using MOST. Additionally, published qualitative findings from diverse clinical contexts and a review of related digital mental health literature were included. The study culminated in an updated ToC framework informed by expert feedback. The final ToC was produced in both narrative and table form and captured components common in program logic and ToC frameworks. RESULTS: The MOST ToC captured several assumptions about digital mental health adoption, including factors such as the readiness of young people and service providers to embrace digital platforms. External considerations included high service demand and a potential lack of infrastructure to support integration. Young people and service providers face several challenges and pain points MOST seeks to address, such as limited accessibility, high demand, poor engagement, and a lack of personalized support. Self-determination

BACKGROUND: Repetitive negative thinking (RNT) is a key transdiagnostic mechanism underpinning depression and anxiety. Using "just-in-time adaptive interventions" via smartphones may disrupt RNT in real time, providing targeted and personalized intervention. OBJECTIVE: This pilot randomized controlled trial evaluates the feasibility, acceptability, and preliminary clinical outcomes and mechanisms of Mello-a fully automated, personalized, transdiagnostic, and mechanistic smartphone intervention targeting RNT in young people with depression and anxiety. METHODS: Participants with heightened depression, anxiety, and RNT were recruited via social media and randomized to receive Mello or a nonactive control over a 6-week intervention period. Assessments were completed via Zoom sessions at baseline and at 3 and 6 weeks after baseline. RESULTS: The findings supported feasibility and acceptability, with high rates of recruitment (N=55), uptake (55/64, 86% of eligible participants), and retention (52/55, 95% at 6 weeks). Engagement was high, with 90% (26/29) and 59% (17/29) of the participants in the Mello condition still using the app during the third and sixth weeks, respectively. Greater reductions in depression (Cohen d=0.50), anxiety (Cohen d=0.61), and RNT (Cohen d=0.87) were observed for Mello users versus controls. Mediation analyses suggested that changes in depression and anxiety were accounted for by changes in RNT. CONCLUSIONS: The results indicate that mechanistic, targeted, and real-time technology-based solutions may provide scalable and effective interventions that advance the treatment of youth mental ill health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621001701819; http://tinyurl.com/4d3jfj9f.

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signalling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state functional MRI to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia and 100 controls. We also investigated the association between FST effective connectivity and striatal 18F-DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent functional MRI and PET. Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy 18F-DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients. Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signalling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.

BACKGROUND: Family members, who provide the majority of informal care during the recovery period from first-episode psychosis (FEP), experience high levels of psychological distress. However, there is a lack of effective and accessible interventions for FEP carers. OBJECTIVE: To determine the effectiveness of an online intervention ("Altitudes") in relation to the primary outcome of FEP-carer stress at 6 months follow-up. METHODS: We conducted a cluster randomized controlled trial in which FEP carers were randomized to Altitudes combined with specialized treatment as usual (STAU) or STAU alone. In addition to questionnaires, we included multiple waves of intensive ecological momentary assessment (EMA) to measure carer stress and family outcomes in 164 carers of young (15-27 years) FEP patients. RESULTS: Both groups improved over time on stress and a range of secondary outcomes, including mental health symptoms, self-efficacy, and expressed emotion with no group by time interactions. At 12 months there were significantly fewer visits to emergency departments by FEP patients in the Altitudes group (p = 0.022). Modelling of multiple EMA waves revealed that more time spent by carers with FEP patients predicted greater worry, expressed emotion, and adaptive coping. CONCLUSIONS: Engagement and usability findings for Altitudes were positive. Further refinements to our online carer interventions may be needed to engage carers in purposeful skill development for improved management of stress and communication with the young person compared with existing specialist family interventions. TRIAL REGISTRATION: ACTRN12616000968471.

BACKGROUND: Depression and anxiety are prevalent in youth populations and typically emerge during adolescence. Repetitive negative thinking (RNT) is a putative transdiagnostic mechanism with consistent associations with depression and anxiety. Targeting transdiagnostic processes like RNT for youth depression and anxiety may offer more targeted, personalised and effective treatment. METHODS: A meta-analysis was conducted to examine the effect of psychological treatments on RNT, depression and anxiety symptoms in young people with depression or anxiety, and a meta-regression to examine relationships between outcomes. RESULTS: Twenty-eight randomised controlled trials examining 17 different psychological interventions were included. Effect sizes were small to moderate across all outcomes (Hedge's g depression = -0.47, CI -0.77 to -0.17; anxiety = -0.42, CI -0.65 to -0.20; RNT = -0.45, CI -0.67 to -0.23). RNT-focused and non-RNT focused approaches had comparable effects; however, those focusing on modifying the process of RNT had significantly larger effects on RNT than those focusing on modifying negative thought content. Meta-regression revealed a significant relationship between RNT and depression outcomes only across all intervention types and with both depression and anxiety for RNT focused interventions only. CONCLUSION: Consistent with findings in adults, this review provides evidence that reducing RNT with psychological treatment is associated with improvements in depression and anxiety in youth. Targeting RNT specifically may not lead to better outcomes compared to general approaches; however, focusing on modifying the process of RNT may be more effective than targeting content. Further research is needed to determine causal pathways.

Both psychotic illness and subclinical psychosis-like experiences (PLEs) have been associated with cortico-striatal dysfunction. This work has largely relied on a discrete parcellation of the striatum into distinct functional areas, but recent evidence suggests that the striatum comprises multiple overlapping and smoothly varying gradients (i.e., modes) of functional organization. Here, we investigated two of these functional connectivity modes, previously associated with variations in the topographic patterning of cortico-striatal connectivity (first-order gradient), and dopaminergic innervation of the striatum (second-order gradient), and assessed continuities in striatal function from subclinical to clinical domains. We applied connectopic mapping to resting-state fMRI data to obtain the first-order and second-order striatal connectivity modes in two distinct samples: (1) 56 antipsychotic-free patients (26 females) with first-episode psychosis (FEP) and 27 healthy controls (17 females); and (2) a community-based cohort of 377 healthy individuals (213 females) comprehensively assessed for subclinical PLEs and schizotypy. The first-order "cortico-striatal" and second-order "dopaminergic" connectivity gradients were significantly different in FEP patients compared to controls bilaterally. In the independent sample of healthy individuals, variations in the left first-order "cortico-striatal" connectivity gradient were associated with inter-individual differences in a factor capturing general schizotypy and PLE severity. The presumed cortico-striatal connectivity gradient was implicated in both subclinical and clinical cohorts, suggesting that variations in its organization may represent a neurobiological trait marker across the psychosis continuum. Disruption of the presumed dopaminergic gradient was only noticeable in patients, suggesting that neurotransmitter dysfunction may be more apparent to clinical illness.

BACKGROUND: Low engagement rates with digital mental health interventions are a major challenge in the field. Multicomponent digital interventions aim to improve engagement by adding components such as social networks. Although social networks may be engaging, they may not be sufficient to improve clinical outcomes or lead users to engage with key therapeutic components. Therefore, we need to understand what components drive engagement with digital mental health interventions overall and what drives engagement with key therapeutic components. OBJECTIVE: Horyzons was an 18-month digital mental health intervention for young people recovering from first-episode psychosis, incorporating therapeutic content and a private social network. However, it is unclear whether use of the social network leads to subsequent use of therapeutic content or vice versa. This study aimed to determine the causal relationship between the social networking and therapeutic components of Horyzons. METHODS: Participants comprised 82 young people (16-27 years) recovering from first-episode psychosis. Multiple convergent cross mapping was used to test causality, as a secondary analysis of the Horyzons intervention. Multiple convergent cross mapping tested the direction of the relationship between each pair of social and therapeutic system usage variables on Horyzons, using longitudinal usage data. RESULTS: Results indicated that the social networking aspects of Horyzons were most engaging. Posting on the social network drove engagement with all therapeutic components (r=0.06-0.36). Reacting to social network posts drove engagement with all therapeutic components (r=0.39-0.65). Commenting on social network posts drove engagement with most therapeutic components (r=0.11-0.18). Liking social network posts drove engagement with most therapeutic components (r=0.09-0.17). However, starting a therapy pathway led to commenting on social network posts (r=0.05) and liking social network posts (r=0.06), and

Digital health innovations may help to improve access to psychosocial therapy and peer support; however, the existence of evidence-based digital health interventions for individuals recovering from a first-episode psychosis (FEP) remains limited. This study aims to investigate the feasibility, acceptability, safety, and pre-post outcomes of Horyzons-Canada (HoryzonsCa), a Canadian adaptation of a digital mental health intervention consisting of psychosocial interventions, online social networking, and clinical and peer support moderation. Using a convergent mixed-methods research design, we recruited participants from a specialized early intervention clinic for FEP in Montreal, Canada. Twenty-three participants (mean age = 26.8) completed baseline assessments, and 20 completed follow-up assessments after 8 weeks of intervention access. Most participants provided positive feedback on general experience (85%, 17/20) and the utility of Horyzons for identifying their strengths (70%, 14/20). Almost all perceived the platform as easy to use (95%, 19/20) and felt safe using it (90%, 18/20). There were no adverse events related to the intervention. Participants used HoryzonsCa to learn about their illness and how to get better (65%, 13/20), receive support (60%, 12/20), and access social networking (35%, 7/20) and peer support (30%, 6/20). Regarding adoption, 65% (13/20) logged in at least 4 times over 8 weeks. There was a nonsignificant increase in social functioning and no deterioration on the Clinical Global Impression Scale. Overall, HoryzonsCa was feasible to implement and perceived as safe and acceptable. More research is needed with larger sample sizes and using in-depth qualitative methods to better understand the implementation and impact of HoryzonsCa.

UNLABELLED: Horyzons is a digital health intervention designed to support recovery in young people receiving specialized early intervention services for first-episode psychosis (FEP). Horyzons was developed in Australia and adapted for implementation in Canada based on input from clinicians and patients (Horyzons-Canada Phase 1) and subsequently pilot-tested with 20 young people with FEP (Horyzons-Canada Phase 2). OBJECTIVE: To understand the experiences of young adults with FEP who participated in the pilot study based on focus group data. METHODS: Among the twenty individuals that accessed the intervention, nine participated across four focus groups. Three team members were involved in data management and analysis, informed by a thematic analysis approach. A coding framework was created by adapting the Phase 1 framework to current study objectives, then revised iteratively by applying it to the current data. Once the coding framework was finalized, it was systematically applied to the entire dataset. RESULTS: Four themes were identified: (1) Perceiving Horyzons-Canada as helpful for recovery; (2) Appreciating core intervention components (i.e., peer networking; therapeutic content; moderation) and ease of use; (3) Being unaware of its features; and (4) Expressing concerns, suggestions, and future directions. CONCLUSIONS: Horyzons-Canada was well received, with participants wanting it to grow in scale, accessibility, and functionality.

INTRODUCTION: Over 25% of Dutch young people are psychologically unhealthy. Individual and societal consequences that follow from having mental health complaints at this age are substantial. Young people need care which is often unavailable. ENgage YOung people earlY (ENYOY) is a moderated digital social therapy-platform that aims to help youngsters with emerging mental health complaints. Comprehensive research is being conducted into the effects and to optimize and implement the ENYOY-platform throughout the Netherlands. The aim of this study is to explore the usability and user experience of the ENYOY-platform. METHODS: A user-centered mixed-method design was chosen. 26 young people aged 16-25 with emerging mental health complaints participated. Semi-structured interviews were conducted to explore usability, user-friendliness, impact, accessibility, inclusivity, and connection (Phase 1). Phase 2 assessed usability problems using the concurrent and retrospective Think Aloud-method. User experience and perceived helpfulness were assessed using a 10-point rating scale and semi-structured interviews (Phase 3). The Health Information Technology Usability Evaluation Scale (Health-ITUES; Phase 1) and System Usability Scale (SUS; Phase 2 and 3) were administered. Qualitative data was analyzed using thematic analysis. Task completion rate and time were tracked and usability problems were categorized using the Nielsen's rating scale (Phase 2). RESULTS: Adequate to high usability was found (Phase 1 Health-ITUES 4.0(0.34); Phase 2 SUS 69,5(13,70); Phase 3 SUS 71,6(5,63)). Findings from Phase 1 (N = 10) indicated that users viewed ENYOY as a user-friendly, safe, accessible, and inclusive initiative which helped them reduce their mental health complaints and improve quality of life. Phase 2 (N = 10) uncovered 18 usability problems of which 5 of major severity (e.g. troubles accessing the platform). Findings from Phase 3 (N = 6) suggested that users perceived the coaching calls

Background: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. Objective: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? Design: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. Settings: Glasgow, UK, and Melbourne, Australia. Participants: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. Interventions: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. Main outcome measures: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. Results: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use an

Background: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. Methods: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). Findings: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Au

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naive first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia patients and 100 controls. We also investigated the association between FST effective connectivity and striatal [18F]DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent fMRI and positron emission tomography. Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy [18F]DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients. Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.Copyright © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors

BACKGROUND: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. METHODS: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). FINDINGS: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Au

BACKGROUND: Multicomponent digital interventions offer the potential for tailored and flexible interventions that aim to address high attrition rates and increase engagement, an area of concern in digital mental health. However, increased flexibility in use makes it difficult to determine which components lead to improved treatment outcomes. OBJECTIVE: This study aims to identify user profiles on Horyzons, an 18-month digital relapse prevention intervention for first-episode psychosis that incorporates therapeutic content and social networking, along with clinical, vocational, and peer support, and to examine the predictive value of these user profiles for treatment outcomes. A secondary objective is to compare each user profile with young people receiving treatment as usual (TAU). METHODS: Participants comprised 82 young people (aged 16-27 years) with access to Horyzons and 84 receiving TAU, recovering from first-episode psychosis. In addition, 6-month use data from the therapy and social networking components of Horyzons were used as features for K-means clustering for joint trajectories to identify user profiles. Social functioning, psychotic symptoms, depression, and anxiety were assessed at baseline and 6-month follow-up. General linear mixed models were used to examine the predictive value of user profiles for treatment outcomes and between each user profile with TAU. RESULTS: A total of 3 user profiles were identified based on the following system use metrics: low use, maintained use of social components, and maintained use of both therapy and social components. The maintained therapy and social group showed improvements in social functioning (F2,51=3.58; P=.04), negative symptoms (F2,51=4.45; P=.02), and overall psychiatric symptom severity (F2,50=3.23; P=.048) compared with the other user profiles. This group also showed improvements in social functioning (F1,62=4.68; P=.03), negative symptoms (F1,62=14.61; P<.001), and overall psychiatric symptom severity

Nearly all young people use the internet daily. Many youth with mental health concerns, especially since the Covid-19 pandemic, are using this route to seek help, whether through digital mental health treatment, illness prevention tools, or supports for mental wellbeing. Videogames also have wide appeal among young people, including those who receive mental health services. This review identifies the literature on videogame interventions for young people, ages 12-29, and maps the data on game use by those with mental health and substance use problems, focusing on evidence for the capacity of games to support treatment in youth mental health services; how stakeholders are involved in developing or evaluating games; and any potential harms and ethical remedies identified. A systematic scoping review methodology was used to identify and assess relevant studies. A search of multiple databases identified a total of 8,733 articles. They were screened, and 49 studies testing 32 digital games retained. An adapted stepped care model, including four levels, or steps, based on illness manifestation and severity, was used as a conceptual framework for organizing target populations, mental health conditions and corresponding digital games, and study results. The 49 selected studies included: 10 studies (20.4%) on mental health promotion/prevention or education for undiagnosed youth (Step 0: 7 games); 6 studies (12.2%) on at-risk groups or suspected mental problems (Step 1: 5 games); 24 studies (49.0%) on mild to moderate mental conditions (Steps 2-3: 16 games); and 9 studies (18.4%) focused on severe and complex mental conditions (Step 4: 7 games). Two interventions were played by youth at more than one level of illness severity: the SPARX game (Steps 1, 2-3, 4) and Dojo (Steps 2-3 and 4), bringing the total game count to 35 with these repetitions. Findings support the potential integration of digital games in youth services based on study outcomes, user satisfaction, relatively

Cognitive impairments in psychosis negatively impact functional recovery and quality of life. Existing interventions for improving cognitive impairment in recent-onset psychosis show inconsistent treatment efficacy, small effects, suboptimal engagement and limited generalizability to daily life functioning. In this perspective we explore how digital technology has the potential to address these limitations in order to improve cognitive and functional outcomes in recent-onset psychosis. Computer programs can be used for standardized, automated delivery of cognitive remediation training. Virtual reality provides the opportunity for learning and practicing cognitive skills in real-world scenarios within a virtual environment. Smartphone apps could be used for notification reminders for everyday tasks to compensate for cognitive difficulties. Internet-based technologies can offer psychoeducation and training materials for enhancing cognitive skills. Early findings indicate some forms of digital interventions for cognitive enhancement can be effective, with well-established evidence for human-supported computer-based cognitive remediation in recent-onset psychosis. Emerging evidence regarding virtual reality is favorable for improving social cognition. Overall, blending digital interventions with human support improves engagement and effectiveness. Despite the potential of digital interventions for enhancing cognition in recent-onset psychosis, few studies have been conducted to date. Implementation challenges affecting application of digital technologies for cognitive impairment in recent-onset psychosis are sustained engagement, clinical integration, and lack of quality in the commercial marketplace. Future opportunities lie in including motivational frameworks and behavioral change interventions, increasing service engagement in young people and lived experience involvement in digital intervention development.

OBJECTIVES: This study aimed to understand how young people with first-episode psychosis experienced online therapy on a Moderated Online Social Therapy (MOST) platform known as Horyzons. METHODS: Semi-structured in-depth qualitative interviews were conducted with 12 young people who had previously participated in Horyzons, a randomized controlled trial (RCT) of a long-term digital intervention for first-episode psychosis. Interviews were analysed using a phenomenological approach. RESULTS: This study found that the online therapy experience for first-episode psychosis was idiosyncratic, taking on different meaning for different users. The relatively fixed therapeutic content led to experiences that included on-demand help-seeking, positive distraction, revision, generalization and translation, and normalization. We also found that although the experience of online therapy was motivating to some, it was overwhelming for others. CONCLUSIONS: The self-directed and flexible nature of the Horyzons online therapy gave some young people a sense of welcomed control over their mental health journey, and others felt overwhelmed by the high level of choice. Feeling overwhelmed by the level of choice appeared to interrupt their engagement with the platform, and thus their overall ability to use the intervention meaningfully. We also found that on-demand help-seeking and positive distraction were two functions unique to young people through online therapy and may have been related to the significant reduction in the number of overall presentations by young people to emergency departments and a non-significant trend for lower hospitalizations due to psychosis in the intervention group of the Horyzons RCT. PRACTITIONER POINTS: Young people used online therapy for on-demand support to help deal with distress. Young people used online therapy to distract themselves from distress in a positive way. Some young people valued the flexibility of online therapy, which increased their mot

BACKGROUND: Young people present high rates of cannabis use, abuse, and dependence. The United Nations estimates that roughly 3.8% of the global population aged 15-64 years used cannabis at least once in 2017. Cannabis use in young people may impair cognitive skills, interfere with learning, impact relationships, and lead to long term behavioural and psychological consequences. Online cannabis interventions (OCI) are increasingly popular, but their dissemination is not often supported by empirical evidence. AIM: To systematically compile and analyse the effectiveness of OCI for the reduction of cannabis use among adolescents and young adults (AYA). METHODS: Pooled effect sizes of cannabis use between treatment and control groups were estimated. For each comparison, Hedge's g was calculated using a random effects model. RESULTS: The search strategy yielded 4531 articles. Of those, a total of 411 articles were retrieved for detailed evaluation resulting in 17 eligible studies (n = 3525). Analyses revealed that online interventions did not significantly reduce cannabis consumption (Hedge's g = -0.061, 95% CI [-0.363] to [-0.242], p = .695) and high heterogeneity was noted (Q = 191.290). More recent studies using structured interventions, daily feedback, AYA centred designs, and peer support, specifically targeting CU seemed to have positive effects to address CU in this population. CONCLUSIONS: The lack of positive outcomes suggests that more specific and targeted interventions may be necessary to promote cannabis-related behavioural change among young people. These targeted interventions may include structured CU modules, daily feedback, peer support for increased adherence, user-centred design procedures, and input from key stakeholders such as families and service providers.

OBJECTIVE: Comorbid social anxiety is common in psychotic disorders and is associated with multiple negative consequences. However, the long-term effects of persistent social anxiety versus fluctuating or no anxiety on social functioning and health-related quality of life (HR-QoL) have received scant attention. Therefore, we aimed to examine the prevalence of persistent social anxiety to determine its effect on social functioning and HR-QoL in first-episode psychosis (FEP). METHODS: One hundred and eight individuals with remitted FEP were classified into three groups (persistent, fluctuating or no social anxiety) according to the Social Interaction Anxiety Scale over an 18-month follow-up period. The three groups were then compared at 18 months follow-up to assess the influence of social anxiety on social functioning and HR-QoL before and after controlling for confounders. RESULTS: Of the 108 individuals with FEP, 25 (23.1%) had persistent social anxiety. This group presented lower social functioning and HR-QoL levels compared to the groups with fluctuating or no anxiety symptoms. The effect on HR-QoL remained significant after controlling for positive psychotic and depressive symptoms. CONCLUSIONS: In this study, nearly one-quarter of young people with remitted FEP experienced persistent social anxiety symptoms, which had a negative impact on HR-QoL. Thus, individuals with persistent social anxiety constitute a highly vulnerable group and may require targeted interventions to improve their social functioning and HR-QoL.

BACKGROUND: Online searches about anxiety and depression are recorded every 3-5 s. As such, information and communication technologies (ICT) have enormous potential to enable or impair help-seeking and patient-professional interactions. Youth studies indicate that ICT searches are undertaken before initial mental health consultations, but no publications have considered how this online activity affects the first steps of the patient journey in youth mental health settings. METHODS: State-of-the-art review using an iterative, evidence mapping approach to identify key literature and expert consensus to synthesize and prioritise clinical and research issues. RESULTS: Adolescents and young adults are more likely to seek health advice via online search engines or social media platforms than from a health professional. Young people not only search user-generated content and social media to obtain advice and support from online communities but increasingly contribute personal information online. CONCLUSIONS: A major clinical challenge is to raise professional awareness of the likely impact of this activity on mental health consultations. Potential strategies range from modifying the structure of clinical consultations to ensure young people are able to disclose ICT activities related to mental health, through to the development and implementation of 'internet prescriptions' and a youth-focused 'toolkit'.

AIM: Interpersonal trauma exposures are associated with anxiety, depression, and substance use in youth populations (aged 12-25 years). This meta-analysis reports on the efficacy of psychological interventions on these symptom domains in addition to post-traumatic stress. METHODS: Following PRISMA guidelines, a search of electronic databases was performed for randomized controlled trials (RCTs) assessing interventions for young people following interpersonal trauma exposure. Risk of bias was assessed using the Cochrane Risk of Bias tool. Data were analysed using random-effects meta-analyses. RESULTS: Of the 4832 records screened, 78 studies were reviewed, and 10 RCTs, involving 679 participants (mean age 15.6 years), were analysed. There was a large pooled effect size for post-traumatic stress (7 studies, g = 1.43, 95% CI [0.37, 2.15], p = .002) and substance use (2 studies, g = 0.70, 95% CI [-0.11, 1.22], p < .001) and small effect sizes for anxiety (4 studies, g = 0.30, 95% CI [0.10, 0.49], p = .003), and trend-level effect for depression (10 studies, g = 0.27, 95% CI [0.00, 0.54], p = .052). Heterogeneity was significant for post-traumatic stress and moderate for depression. CONCLUSIONS: High-quality RCTs of psychological interventions for anxiety, depression, substance use, and post-traumatic stress symptoms in young people exposed to interpersonal trauma are scarce. While available studies show either statistically significant or trend-level efficacy for psychological interventions in reducing these symptoms, wide confidence intervals, heterogeneity and small sample size mean that results need to be interpreted with caution.

BACKGROUND: Life at university provides important opportunities for personal growth; however, this developmental phase also coincides with the peak period of risk for the onset of mental health disorders. In addition, specific university lifestyle factors, including impaired sleep and academic and financial stress, are known to exacerbate psychological distress in students. As a result, university students have been identified as a vulnerable population who often experience significant barriers to accessing psychological treatment. Digital psychological interventions are emerging as a promising solution for this population, but their effectiveness remains unclear. OBJECTIVE: This systematic review and meta-analysis aimed to assess digital interventions targeting psychological well-being among university students. METHODS: Database searches were conducted on December 2, 2021, via Embase, MEDLINE, PsycINFO, and Web of Science. RESULTS: A total of 13 eligible studies were identified, 10 (77%) of which were included in the meta-analysis. Mean pre-post effect sizes indicated that such interventions led to small and significant improvement in psychological well-being (Hedges g=0.32, 95% CI 0.23-0.4; P<.001). These effects remained, albeit smaller, when studies that included a wait-list control group were excluded (Hedges g=0.22, 95% CI 0.08-0.35; P=.002). An analysis of acceptance and commitment therapy approaches revealed small and significant effects (k=6; Hedges g=0.35, 95% CI 0.25-0.45; P<.001). CONCLUSIONS: Digital psychological interventions hold considerable promise for university students, although features that optimize service delivery and outcomes require further assessment. TRIAL REGISTRATION: PROSPERO CRD42020196654; https:/www.crd.york.ac.uk/prospero/display_record.php?RecordID=196654.

OBJECTIVE: Elevations in distress, self-harm, and suicidal ideation or behavior are of significant concern in clinical practice. We examined these in a pilot trial of Trauma Focused-Cognitive Behavioral Therapy (TF-CBT) for transitional age youth (aged 15-25 years) with histories of interpersonal trauma and symptoms of posttraumatic stress disorder. METHOD: Participants were 20 young people (13 females, M = 19.5 years) from a pilot study of TF-CBT. Frequencies of elevated distress, self-harm, and suicidal ideation or behavior were measured throughout treatment sessions and across the treatment phases of TF-CBT. RESULTS: Across the 279 sessions of TF-CBT (m = 15.5 sessions), there were 16 incidents of elevated distress in seven participants (i.e., six in Phase I and five each in Phases II and III); 15 incidents of self-harming behavior in seven participants (five incidents in each of the three phases) and one incident of both elevated distress and suicide ideation (Phase I). CONCLUSION: Findings indicate that there may be a relationship between the experience of in session distress and self-harming behaviors. The importance of safety planning and coping skills (acquired in Phase 1) is stressed to ensure the effective implementation of TF-CBT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cognitive behavioral therapy (CBT) represents one of the major treatment options for depressive disorders besides pharmacological interventions. While newly developed digital CBT approaches hold important advantages due to higher accessibility, their relative effectiveness compared to traditional CBT remains unclear. We conducted a systematic literature search to identify all studies that conducted a CBT-based intervention (face-to-face or digital) in patients with major depression. Random-effects meta-analytic models of the standardized mean change using raw score standardization (SMCR) were computed. In 106 studies including n = 11854 patients face-to-face CBT shows superior clinical effectiveness compared to digital CBT when investigating depressive symptoms (p < 0.001, face-to-face CBT: SMCR = 1.97, 95%-CI: 1.74-2.13, digital CBT: SMCR = 1.20, 95%-CI: 1.08-1.32) and adherence (p = 0.014, face-to-face CBT: 82.4%, digital CBT: 72.9%). However, after accounting for differences between face-to-face and digital CBT studies, both approaches indicate similar effectiveness. Important variables with significant moderation effects include duration of the intervention, baseline severity, adherence and the level of human guidance in digital CBT interventions. After accounting for potential confounders our analysis indicates comparable effectiveness of face-to-face and digital CBT approaches. These findings underline the importance of moderators of clinical effects and provide a basis for the future personalization of CBT treatment in depression.

INTRODUCTION: To optimize treatment, it is of utmost importance to take into account the myriad of biological, social, and psychological changes that young people go through during adolescence which make them more vulnerable for developing mental health problems. Biocueing, a non-invasive method to transform physiological parameters into an observable signal, could strengthen stress- and emotion regulation by cueing physiologically unusual values in daily life. The aim of this study is to investigate the usability, feasibility, and exploratory effect of biocueing in addition to ENgage YOung people earlY (ENYOY), a moderated digital social therapy-platform, in young people with emerging mental health complaints. METHODS: A user-centered mixed-method design was used. A focus group was conducted to optimize the ENYOY-platform and biocueing intervention. Biocueing was operationalized by a smartwatch and the Sense-IT app. A within-subjects design was used; 10 days for all participants 'biofeedback off' (control), followed by 10 days 'biofeedback on' (experimental). Emotional awareness and perceived stress were measured using ecological momentary assessment. Eight individuals participated. User-friendliness, usability, and acceptance were assessed using a qualitative design. RESULTS: Findings from the focus group resulted in several adaptations of the biocueing intervention to the ENYOY-platform and vice versa. The average measurement compliance rate was 78.8%. Level-one findings showed different individual effects on perceived stress and emotional awareness. Level-two analyses showed no overall effects on perceived stress (B = -0.020, p = 0.562) and overall positive effects on emotional awareness (B = 0.030, p = 0.048) with small effect sizes (Improvement Rate Difference = 0.05-0.35). The intervention was found to be acceptable and showed moderate usability. Participants indicated they experienced improvements in reflection on feelings and changes in behavior, such as pa

OBJECTIVE: Caregivers of individuals with severe mental illness often experience significant negative experiences of care, which can be associated with higher levels of expressed emotion. Expressed emotion is potentially a modifiable target early in the course of illness, which might improve outcomes for caregivers and patients. However, expressed emotion and caregiver experiences in the early stages of disorders might be moderated by the type of severe mental illness. The aim was to determine whether experiences of the caregiver role and expressed emotion differ in caregivers of young people with first-episode psychosis versus young people with 'first-presentation' borderline personality disorder features. METHOD: Secondary analysis of baseline (pre-treatment) data from three clinical trials focused on improving caregiver outcomes for young people with first-episode psychosis and young people with borderline personality disorder features was conducted (ACTRN12616000968471, ACTRN12616000304437, ACTRN12618000616279). Caregivers completed self-report measures of experiences of the caregiver role and expressed emotion. Multivariate generalised linear models and moderation analyses were used to determine group differences. RESULTS: Data were available for 265 caregivers. Higher levels of negative experiences and expressed emotion, and stronger correlations between negative experiences and expressed emotion domains, were found in caregivers of young people with borderline personality disorder than first-episode psychosis. Caregiver group (borderline personality disorder, first-episode psychosis) moderated the relationship between expressed emotion and caregiver experiences in the domains of need to provide backup and positive personal experiences. CONCLUSION: Caregivers of young people with borderline personality disorder experience higher levels of negative experiences related to their role and expressed emotion compared with caregivers of young people with first-episod

Background: Identifying cognitive strengths may be one avenue for enhancing functional recovery in people with first-episode psychosis (FEP). This study explored the perspectives of young people with FEP on the conceptualisation of cognitive strengths and the perceived risks and benefits, and pragmatic considerations, of a cognitive strengths-based approach to assessment and treatment. Methods: Ten participants, aged 18 to 26 (Mage = 21.44 years, SD = 2.70), were recruited from an early psychosis assessment and treatment service. Data were collected using a semi-structured interview and analyzed using thematic analysis. Results: Four overarching themes emerged, related to: 1) Understanding cognitive strengths in FEP; 2) Potential benefits; 3) Barriers and risks; and 4) Considerations for development and implementation. Young people held positive views toward assessment and treatment methods focused on cognitive strengths, suggesting that identifying strengths and building confidence beliefs may promote greater functioning. Potential barriers, including harms related to being unable to identify cognitive strengths or neglecting deficits, were areas requiring further consideration. Discussion: A cognitive strengths-based approach to assessment and treatment in FEP is a promising area of investigation, according to young people with FEP. The results provide insight regarding a cognitive strengths definition and the ways that these could be measured in future.