Centre for Youth Mental Health - Research Publications

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    Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study
    Byrne, JF ; Healy, C ; Focking, M ; Susai, SR ; Mongan, D ; Wynne, K ; Kodosaki, E ; Heurich, M ; de Haan, L ; Hickie, IB ; Smesny, S ; Thompson, A ; Markulev, C ; Young, AR ; Schafer, MR ; Riecher-Rossler, A ; Mossaheb, N ; Berger, G ; Schlogelhofer, M ; Nordentoft, M ; Chen, EYH ; Verma, S ; Nieman, DH ; Woods, SW ; Cornblatt, BA ; Stone, WS ; Mathalon, DH ; Bearden, CE ; Cadenhead, KS ; Addington, J ; Walker, EF ; Cannon, TD ; Cannon, M ; McGorry, P ; Amminger, P ; Cagney, G ; Nelson, B ; Jeffries, C ; Perkins, D ; Cotter, DR (OXFORD UNIV PRESS, 2024-01-19)
    Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.
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    Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.
    Belov, V ; Erwin-Grabner, T ; Aghajani, M ; Aleman, A ; Amod, AR ; Basgoze, Z ; Benedetti, F ; Besteher, B ; Bülow, R ; Ching, CRK ; Connolly, CG ; Cullen, K ; Davey, CG ; Dima, D ; Dols, A ; Evans, JW ; Fu, CHY ; Gonul, AS ; Gotlib, IH ; Grabe, HJ ; Groenewold, N ; Hamilton, JP ; Harrison, BJ ; Ho, TC ; Mwangi, B ; Jaworska, N ; Jahanshad, N ; Klimes-Dougan, B ; Koopowitz, S-M ; Lancaster, T ; Li, M ; Linden, DEJ ; MacMaster, FP ; Mehler, DMA ; Melloni, E ; Mueller, BA ; Ojha, A ; Oudega, ML ; Penninx, BWJH ; Poletti, S ; Pomarol-Clotet, E ; Portella, MJ ; Pozzi, E ; Reneman, L ; Sacchet, MD ; Sämann, PG ; Schrantee, A ; Sim, K ; Soares, JC ; Stein, DJ ; Thomopoulos, SI ; Uyar-Demir, A ; van der Wee, NJA ; van der Werff, SJA ; Völzke, H ; Whittle, S ; Wittfeld, K ; Wright, MJ ; Wu, M-J ; Yang, TT ; Zarate, C ; Veltman, DJ ; Schmaal, L ; Thompson, PM ; Goya-Maldonado, R ; ENIGMA Major Depressive Disorder working group, (Springer Science and Business Media LLC, 2024-01-11)
    Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
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    Best practice for integrating digital interventions into clinical care for young people at risk of suicide: a Delphi study
    Bailey, E ; Bellairs-Walsh, I ; Reavley, N ; Gooding, P ; Hetrick, S ; Rice, S ; Boland, A ; Robinson, J (BMC, 2024-01-24)
    BACKGROUND: Digital tools have the capacity to complement and enhance clinical care for young people at risk of suicide. Despite the rapid rise of digital tools, their rate of integration into clinical practice remains low. The poor uptake of digital tools may be in part due to the lack of best-practice guidelines for clinicians and services to safely apply them with this population. METHODS: A Delphi study was conducted to produce a set of best-practice guidelines for clinicians and services on integrating digital tools into clinical care for young people at risk of suicide. First, a questionnaire was developed incorporating action items derived from peer-reviewed and grey literature, and stakeholder interviews with 17 participants. Next, two independent expert panels comprising professionals (academics and clinical staff; n = 20) and young people with lived experience of using digital technology for support with suicidal thoughts and behaviours (n = 29) rated items across two consensus rounds. Items reaching consensus (rated as "essential" or "important" by at least 80% of panel members) at the end of round two were collated into a set of guidelines. RESULTS: Out of 326 individual items rated by the panels, 188 (57.7%) reached consensus for inclusion in the guidelines. The endorsed items provide guidance on important topics when working with young people, including when and for whom digital tools should be used, how to select a digital tool and identify potentially harmful content, and identifying and managing suicide risk conveyed via digital tools. Several items directed at services (rather than individual clinicians) were also endorsed. CONCLUSIONS: This study offers world-first evidence-informed guidelines for clinicians and services to integrate digital tools into clinical care for young people at risk of suicide. Implementation of the guidelines is an important next step and will hopefully lead to improved uptake of potentially helpful digital tools in clinical practice.
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    Global prevalence of psychosocial assessment following hospital-treated self-harm: systematic review and meta-analysis
    Witt, K ; McGill, K ; Leckning, B ; Hill, NTM ; Davies, BM ; Robinson, J ; Carter, G (CAMBRIDGE UNIV PRESS, 2024-01-11)
    BACKGROUND: Hospital-treated self-harm is common, costly and associated with repeated self-harm and suicide. Providing a comprehensive psychosocial assessment following self-harm is recommended by professional bodies and may improve outcomes. AIMS: To review the provision of psychosocial assessments after hospital-presenting self-harm and the extent to which macro-level factors indicative of service provision explain variability in these estimates. METHOD: We searched five electronic databases to 3 January 2023 for studies reporting data on the proportion of patients and/or events that were provided a psychosocial assessment. Pooled weighted prevalence estimates were calculated with the random-effects model. Random-effects meta-regression was used to investigate between-study variability. RESULTS: 119 publications (69 unique samples) were included. Across ages, two-thirds of patients had a psychosocial assessment (0.67, 95% CI 0.58-0.76). The proportion was higher for young people and older adults (0.75, 95% CI 0.36-0.99 and 0.83, 95% CI 0.48-1.00, respectively) compared with adults (0.64, 95% CI 0.54-0.73). For events, around half of all presentations had these assessments across the age range. No macro-level factor explained between-study heterogeneity. CONCLUSIONS: There is room for improvement in the universal provision of psychosocial assessments for self-harm. This represents a missed opportunity to review and tailor aftercare supports for those at risk. Given the marked unexplained heterogeneity between studies, the person- and system-level factors that influence provision of psychosocial assessments after self-harm should be studied further.
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    Developing a Theory of Change for a Digital Youth Mental Health Service (Moderated Online Social Therapy): Mixed Methods Knowledge Synthesis Study
    Cross, S ; Nicholas, J ; Mangelsdorf, S ; Valentine, L ; Baker, S ; McGorry, P ; Gleeson, J ; Alvarez-Jimenez, M (JMIR PUBLICATIONS, INC, 2023)
    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 theory, transdiagnostic psychological treatment approaches, and evidence-based implementation theories and their associated mechanisms are drawn upon to frame the intervention components that make up the platform. Platform usage data are captured and linked to short-, medium-, and long-term intended outcomes, such as reductions in mental health symptoms, improvements in functioning and quality of life, reductions in hospital visits, and reduced overall mental health care costs. CONCLUSIONS: The MOST ToC serves as a strategic framework for refining MOST over time. The creation of the ToC helped guide the development of therapeutic content personalization, user engagement enhancement, and clinician adoption through specialized implementation frameworks. While powerful, the ToC approach has its limitations, such as a lack of standardized methodology and the amount of resourcing required for its development. Nonetheless, it provides an invaluable roadmap for iterative development, evaluation, and scaling of MOST and offers a replicable model for other digital health interventions aiming for targeted, evidence-based impact.
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    Non-psychotic Outcomes in Young People at Ultra-High Risk of Developing a Psychotic Disorder: A Long-Term Follow-up Study
    Spiteri-Staines, AE ; Yung, AR ; Lin, A ; Hartmann, JA ; Amminger, P ; Mcgorry, PD ; Thompson, A ; Wood, SJ ; Nelson, B (OXFORD UNIV PRESS, 2024-02-16)
    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.
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    The role of identity in anorexia nervosa: A narrative review
    Croce, SR ; Malcolm, AC ; Ralph-Nearman, C ; Phillipou, A (Elsevier BV, 2024-01-01)
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    Diversity, equity, and inclusivity in observational ambulatory assessment: Recommendations from two decades of Electronically Activated Recorder (EAR) research.
    Kaplan, DM ; Tidwell, CA ; Chung, JM ; Alisic, E ; Demiray, B ; Bruni, M ; Evora, S ; Gajewski-Nemes, JA ; Macbeth, A ; Mangelsdorf, SN ; Mascaro, JS ; Minor, KS ; Noga, RN ; Nugent, NR ; Polsinelli, AJ ; Rentscher, KE ; Resnikoff, AW ; Robbins, ML ; Slatcher, RB ; Tejeda-Padron, AB ; Mehl, MR (Springer Science and Business Media LLC, 2023-12-08)
    Ambient audio sampling methods such as the Electronically Activated Recorder (EAR) have become increasingly prominent in clinical and social sciences research. These methods record snippets of naturalistically assessed audio from participants' daily lives, enabling novel observational research about the daily social interactions, identities, environments, behaviors, and speech of populations of interest. In practice, these scientific opportunities are equaled by methodological challenges: researchers' own cultural backgrounds and identities can easily and unknowingly permeate the collection, coding, analysis, and interpretation of social data from daily life. Ambient audio sampling poses unique and significant challenges to cultural humility, diversity, equity, and inclusivity (DEI) in scientific research that require systematized attention. Motivated by this observation, an international consortium of 21 researchers who have used ambient audio sampling methodologies created a workgroup with the aim of improving upon existing published guidelines. We pooled formally and informally documented challenges pertaining to DEI in ambient audio sampling from our collective experience on 40+ studies (most of which used the EAR app) in clinical and healthy populations ranging from children to older adults. This article presents our resultant recommendations and argues for the incorporation of community-engaged research methods in observational ambulatory assessment designs looking forward. We provide concrete recommendations across each stage typical of an ambient audio sampling study (recruiting and enrolling participants, developing coding systems, training coders, handling multi-linguistic participants, data analysis and interpretation, and dissemination of results) as well as guiding questions that can be used to adapt these recommendations to project-specific constraints and needs.
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    What do Australian consumers with lived experience of bipolar disorder want from early intervention services?
    Gates, J ; Bendall, S ; Tremain, H ; Shelton, C ; Hammond, D ; Macneil, C ; McGorry, P ; Berk, M ; Cotton, S ; Murray, G ; Ratheesh, A (SAGE PUBLICATIONS LTD, 2024-03)
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    An analysis of real-time suicidal ideation and its relationship with retrospective reports among young people with borderline personality disorder
    Andrewes, HE ; Cavelti, M ; Hulbert, C ; Cotton, SM ; Betts, JK ; Jackson, HJ ; McCutcheon, L ; Gleeson, J ; Davey, CG ; Chanen, AM (WILEY, 2024-02-20)
    INTRODUCTION: This study aimed to analyze the real-time variability of suicidal ideation intensity and the relationship between real-time and retrospective reports of suicidal ideation made on the Beck Scale for Suicidal Ideation (BSS), among young people with borderline personality disorder (BPD). METHODS: Young people (15-25-year olds) with BPD (N = 46), recruited from two government-funded mental health services, rated the intensity of their suicidal ideation six times per day for 7 days before completing the BSS. RESULTS: For 70% of participants, suicidal ideation changed in intensity approximately five times across the week, both within and between days. BSS ratings were most highly correlated with the highest real-time ratings of suicidal ideation. However, this was not significantly different from the relationship between the BSS and both the average and most recent ratings. Median ratings of suicidal ideation intensity were higher on the BSS compared with an equivalent question asked in real time. CONCLUSION: Findings suggest that young people with BPD experience high levels of fluctuation in their intensity of suicidal ideation across a week and that retrospective reports of suicidal ideation might be more reflective of the most intense experience of suicidal ideation across the week.