Centre for Youth Mental Health - Research Publications
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ItemAn open label pilot trial of low-dose lithium for young people at ultra-high risk for psychosis(WILEY, 2024-04-10)AIM: Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side-effect profile) of lithium in a sample of young people identified at ultra-high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical efficacy in reducing transition to psychosis compared with treatment as usual (TAU). METHODS: Young people attending the PACE clinic at Orygen, Melbourne, were prescribed a fixed dose (450 mg) of lithium (n = 25) or received TAU (n = 78). The primary outcome examined side-effects, with transition to psychosis, functioning and measures of psychopathology assessed as secondary outcomes. RESULTS: Participants in both groups were functionally compromised (lithium group GAF = 56.6; monitoring group GAF = 56.9). Side-effect assessment indicated that lithium was well-tolerated. 64% (n = 16) of participants in the lithium group were lithium-adherent to week 12. Few cases transitioned to psychosis across the study period; lithium group 4% (n = 1); monitoring group 7.7% (n = 6). There was no difference in time to transition to psychosis between the groups. No group differences were observed in other functioning and symptom domains, although all outcomes improved over time. CONCLUSIONS: With a side-effect profile either comparable to, or better than UHR antipsychotic trials, lithium might be explored for further research with UHR young people. A definitive larger trial is needed to determine the efficacy of lithium in this cohort.
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ItemDevelopment of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS(Wiley, 2024-04)AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSIONS: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.
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ItemAccelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis(OXFORD UNIV PRESS, 2024-04-30)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.
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ItemNo Preview AvailableDevelopment of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS.( 2023-05-02)AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and partial harmonization for CHR-P criteria. The semi-structured interview, named P ositive SY mptoms and Diagnostic Criteria for the C AARMS H armonized with the S IPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSION: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.
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ItemProteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study(OXFORD UNIV PRESS, 2024-04-30)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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ItemNo Preview AvailableNon-psychotic Outcomes in Young People at Ultra-High Risk of Developing a Psychotic Disorder: A Long-Term Follow-up Study(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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ItemNo Preview AvailableDeveloping a Theory of Change for a Digital Youth Mental Health Service (Moderated Online Social Therapy): Mixed Methods Knowledge Synthesis Study(JMIR Publications, 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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ItemNo Preview AvailableWhat do Australian consumers with lived experience of bipolar disorder want from early intervention services?(SAGE PUBLICATIONS LTD, 2024-03)
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ItemJohan Christoffer Cullberg (6th January 1934-14th June 2022)1.(Wiley, 2023-01)
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ItemNo Preview AvailableClimate change concerns impact on young Australians' psychological distress and outlook for the future(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2024-02)