The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial.

Early supports to enhance social development in children with autism are widely promoted. While oxytocin has a crucial role in mammalian social development, its potential role as a medication to enhance social development in humans remains unclear. We investigated the efficacy, tolerability, and safety of intranasal oxytocin in young children with autism using a double-blind, randomized, placebo-controlled, clinical trial, following a placebo lead-in phase. A total of 87 children (aged between 3 and 12 years) with autism received 16 International Units (IU) of oxytocin (n = 45) or placebo (n = 42) nasal spray, morning and night (32 IU per day) for twelve weeks, following a 3-week placebo lead-in phase. Overall, there was no effect of oxytocin treatment over time on the caregiver-rated Social Responsiveness Scale (SRS-2) (p = 0.686). However, a significant interaction with age (p = 0.028) showed that for younger children, aged 3-5 years, there was some indication of a treatment effect. Younger children who received oxytocin showed improvement on caregiver-rated social responsiveness ( SRS-2). There was no other evidence of benefit in the sample as a whole, or in the younger age group, on the clinician-rated Clinical Global Improvement Scale (CGI-S), or any secondary measure. Importantly, placebo effects in the lead-in phase were evident and there was support for washout of the placebo response in the randomised phase. Oxytocin was well tolerated, with more adverse side effects reported in the placebo group. This study suggests the need for further clinical trials to test the benefits of oxytocin treatment in younger populations with autism.Trial registration www.anzctr.org.au (ACTRN12617000441314).

Improving access to mental health care: a system dynamics model of direct access to specialist care and accelerated specialist service capacity growth.

OBJECTIVE: To simulate the impact on population mental health indicators of allowing people to book some Medicare-subsidised sessions with psychologists and other mental health care professionals without a referral (direct access), and of increasing the annual growth rate in specialist mental health care capacity (consultations). DESIGN: System dynamics model, calibrated using historical time series data from the Australian Bureau of Statistics, HealthStats NSW, the Australian Institute of Health and Welfare, and the Australian Early Development Census. Parameter values that could not be derived from these sources were estimated by constrained optimisation. SETTING: New South Wales, 1 September 2021 - 1 September 2028. MAIN OUTCOME MEASURES: Projected mental health-related emergency department presentations, hospitalisations following self-harm, and deaths by suicide, both overall and for people aged 15-24 years. RESULTS: Direct access (for 10-50% of people requiring specialist mental health care) would lead to increases in the numbers of mental health-related emergency department presentations (0.33-1.68% of baseline), hospitalisations with self-harm (0.16-0.77%), and deaths by suicide (0.19-0.90%), as waiting times for consultations would increase, leading to disengagement and consequently to increases in adverse outcomes. Increasing the annual rate of growth of mental health service capacity (two- to fivefold) would reduce the frequency of all three outcomes; combining direct access to a proportion of services with increased growth in capacity achieved substantially greater gains than an increase in service capacity alone. A fivefold increase in the annual service growth rate would increase capacity by 71.6% by the end of 2028, compared with current projections; combined with direct access to 50% of mental health consultations, 26 616 emergency department presentations (3.6%), 1199 hospitalisations following self-harm (1.9%), and 158 deaths by suicide (2.1%) could be averted. CONCLUSION: The optimal combination of increased service capacity growth (fivefold) and direct access (50% of consultations) would have double the impact over seven years of accelerated capacity growth alone. Our model highlights the risks of implementing individual reforms without knowledge of their overall system effect.

Strengthening mental health research outcomes through genuine partnerships with young people with lived or living experience: A pilot evaluation study.

BACKGROUND: Despite increasing support for stakeholder inclusion in research, there is limited evaluative research to guide safe (i.e., youth-friendly) and meaningful (i.e., non-tokenistic) partnerships with young people with lived experience of mental ill-health in research. This paper describes a pilot evaluation and iterative design of a Youth Lived Experience Working Group (LEWG) protocol that was established by the Youth Mental Health and Technology team at The University of Sydney's Brain and Mind Centre, based on the results of two studies. METHODS: Study one consisted of a pilot evaluation of the extent to which youth partners felt empowered to contribute, to qualitatively explore how LEWG processes could be improved. Youth partners completed online surveys, and results were shared over two LEWG meetings in 2021 to empower youth partners to collectively identify actions of positive change regarding LEWG processes. These meetings were audio-recorded and transcripts were subsequently coded using thematic analysis. Study two assessed whether LEWG processes and proposed improvements were acceptable and feasible from the perspective of academic researchers via an online survey in 2022. RESULTS: Quantitative and qualitative data collected from nine youth partners and 42 academic researchers uncovered initial learnings regarding facilitators, motivators, and barriers to partnering with young people with lived experience in research. Implementing clear processes for youth partners and academic researchers on effective partnership strategies, providing training opportunities for youth partners to develop research skills, and providing regular updates on how youth partner contributions led to research outcomes were identified as key facilitators. CONCLUSIONS: This pilot study provides insight into a growing international field on how to optimise participatory processes so that researchers and young people with lived experience can be better supported and engaged to make meaningful contributions to mental health research. We argue that more transparency is needed around participatory research processes so that partnerships with young people with lived experience are not merely tokenistic. CONSUMER CONTRIBUTIONS: Our study has also been approved by and reflects the concepts and priorities of our youth lived experience partners and lived experience researchers, all of whom are authors of this paper.

Dynamic modelling of the impact of community-based acute mental health services for children and adolescents.

OBJECTIVE: To evaluate the potential impact of the recently announced 'Safeguards' initiative on mental health-related emergency department presentation rates for children and adolescents (0-17 years). This state-funded initiative aims to establish 25 Child and Adolescent Acute Response Teams across New South Wales. METHODS: We estimated the effects of the 'Safeguards' initiative using a state-level dynamic model of child and adolescent acute mental health care. Potential reductions in total numbers of mental health-related emergency department presentations and re-presentations (i.e. presentations within 3 months of an initial presentation) were assessed via a series of simulation experiments in which we systematically varied the total number of Child and Adolescent Acute Response Teams and the mean duration of care per patient. RESULTS: Assuming a mean treatment duration of 6 weeks per patient, 25 Child and Adolescent Acute Response Teams are projected to reduce total numbers of mental health-related emergency department presentations and re-presentations over the period 2022-2031 by 15.0% (95% interval, 12.0-18.2%) and 31.7% (26.2-37.8%), respectively. Increasing the total number of Child and Adolescent Acute Response Teams above 25 has minimal additional impact on projected reductions in numbers of emergency department presentations and re-presentations, provided the mean duration of care is no more than 8 weeks. However, where the mean duration of care is greater than 4 weeks, a decrease in the number of Child and Adolescent Acute Response Teams below 25 reduces the potential effectiveness of the 'Safeguards' initiative significantly. CONCLUSION: Our simulation results indicate that full and timely implementation will be critical if the potentially substantial impact of the 'Safeguards' initiative on demand for hospital-based emergency mental health care is to be realised.

Population mental health improves with increasing access to treatment: evidence from a dynamic modelling analysis.

BACKGROUND: Multiple studies indicate that the prevalence of mental disorders in high-income countries has remained stable or increased despite substantial increases in the provision of care, leading some authors to question the effectiveness of increasing access to current treatments as a means of improving population mental health. METHODS: We developed a system dynamics model of mental disorder incidence and treatment-dependent recovery to assess two potential explanations for the apparent failure of increasing treatment provision to reduce mental disorder prevalence: 1) an increase in the individual-level risk of disorder onset; and 2) declining effectiveness of care resulting from insufficient services capacity growth. Bayesian Markov Chain Monte Carlo (MCMC) methods were used to fit the model to data on the prevalence of high to very high psychological distress in Australia for the period 2008-2019. RESULTS: Estimates of yearly rates of increase in the per capita incidence of high to very high psychological distress and the proportion of patients recovering when treated indicate that the individual-level risk of developing high to very high levels of distress increased between 2008 and 2019 (posterior probability > 0.999) but provide no evidence for declining treatment effectiveness. Simulation analyses suggest that the prevalence of high to very high psychological distress would have decreased from 14.4% in 2008 to 13.6% in 2019 if per capita incidence had not increased over this period (prevalence difference 0.0079, 95% credible interval 0.0015-0.0176). CONCLUSIONS: Our analyses indicate that a modest but significant effect of increasing access to mental health care in Australia between 2008 and 2019 was obscured by a concurrent increase in the incidence of high to very high psychological distress.

Neuroticism and the Overlap Between Autistic and ADHD Traits: Findings From a Population Sample of Young Adult Australian Twins.

Neuroticism, a 'Big Five' personality trait, has been associated with sub-clinical traits of both autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The objective of the current study was to examine whether causal overlap between ASD and ADHD traits can be accounted for by genetic and environmental risk factors that are shared with neuroticism. We performed twin-based structural equation modeling using self-report data from 12 items of the Neo Five-Factor Inventory Neuroticism domain, 11 Social Responsiveness Scale items, and 12 Adult ADHD Self-Report Scale items obtained from 3,170 young adult Australian individual twins (1,081 complete pairs). Univariate analysis for neuroticism, ASD, and ADHD traits suggested that the most parsimonious models were those with additive genetic and unique environmental components, without sex limitation effects. Heritability of neuroticism, ASD, and ADHD traits, as measured by these methods, was moderate (between 40% and 45% for each respective trait). In a trivariate model, we observed moderate phenotypic (between 0.45 and 0.62), genetic (between 0.56 and 0.71), and unique environmental correlations (between 0.37and 0.55) among neuroticism, ASD, and ADHD traits, with the highest value for the shared genetic influence between neuroticism and self-reported ASD traits (r g = 0.71). Together, our results suggest that in young adults, genetic, and unique environmental risk factors indexed by neuroticism overlap with those that are shared by ASD and ADHD.

Diffusion tensor imaging predictors of treatment outcomes in major depressive disorder.

BACKGROUND: Functional neuroimaging studies implicate anterior cingulate and limbic dysfunction in major depressive disorder (MDD) and responsiveness to antidepressants. Diffusion tensor imaging (DTI) enables characterisation of white matter tracts that relate to these regions. AIMS: To examine whether DTI measures of anterior cingulate and limbic white matter are useful prognostic biomarkers for MDD. METHOD: Of the 102 MDD out-patients from the International Study to Predict Optimized Treatment for Depression (iSPOT-D) who provided baseline magnetic resonance imaging (MRI) data, 74 completed an 8-week course of antidepressant medication (randomised to escitalopram, sertraline or extended-release venlafaxine) and were included in the present analyses. Thirty-four matched controls also provided DTI data. Fractional anisotropy was measured for five anterior cingulate-limbic white matter tracts: cingulum cingulate and hippocampus bundle, fornix, stria terminalis and uncinate fasciculus. (Trial registered at ClinicalTrials.gov: NCT00693849.) RESULTS: A cross-validated logistic regression model demonstrated that altered connectivity for the cingulum part of the cingulate and stria terminalis tracts significantly predicted remission independent of demographic and clinical measures with 62% accuracy. Prediction improved to 74% when age was added to this model. CONCLUSIONS: Anterior cingulate-limbic white matter is a useful predictor of antidepressant treatment outcome in MDD.

Mental health impacts of COVID-19: A retrospective analysis of dynamic modelling projections for Australia.

Background: In early 2020, we developed a dynamic model to support policy responses aimed at mitigating the adverse mental health effects of the COVID-19 pandemic in Australia. As the pandemic has progressed, it has become clear that our initial model forecasts overestimated the impacts of infection control measures (lockdowns, physical distancing, etc.) on suicide, intentional self-harm hospitalisation, and mental health-related emergency department (ED) presentation rates. Methods: Potential explanations for the divergence of our model predictions from observed outcomes were assessed by comparing simulation results for a set of progressively more refined models with data on the prevalence of moderate to very high psychological distress and numbers of suicides, intentional self-harm hospitalisations, and mental health-related ED presentations published after our modelling was released in July 2020. Results: Allowing per capita rates of spontaneous recovery and intentional self-harm to differ between people experiencing moderate to very high psychological distress prior to the pandemic and those developing comparable levels of psychological distress only as a consequence of infection control measures substantially improves the fit of our model to empirical estimates of the prevalence of psychological distress and leads to significantly lower predicted effects of COVID-19 on suicide, intentional self-harm hospitalisation, and mental health-related ED presentation rates. Conclusion: Accommodating the influence of prior mental health on the psychological effects of population-wide social and economic disruption is likely to be critical for accurately forecasting the mental health impacts of future public health crises as they inevitably arise.

Cost-effectiveness of system-level mental health strategies for young people in the Australian Capital Territory: a dynamic simulation modelling study.

BACKGROUND: Regional mental health planning is a key challenge for decision makers because mental health care is a complex, dynamic system. Economic evaluation using a system dynamics modelling approach presents an opportunity for more sophisticated planning and important evidence on the value of alternative investments. We aimed to investigate the cost-effectiveness of eight systems-based interventions targeted at improving the mental health and wellbeing of children, adolescents, and young adults in the Australian Capital Territory (ACT). METHODS: We assessed eight interventions for children and young people (aged ≤25 years) with low, moderate, and high-to-very-high psychological distress: technology-enabled integrated care, emergency department-based suicide prevention, crisis response service, family education programme, online parenting programme, school-based suicide prevention programme, trauma service for youths, and multicultural-informed care. We developed a system dynamics model for the ACT through a participatory process and calibrated the model with historical data, including population demographics, the prevalence of psychological distress, and mental health services provision. We calculated incremental cost-effectiveness ratios compared with business as usual for cost (AU$) per: quality-adjusted life-year (QALY), suicide death avoided, self-harm related hospital admissions avoided, and mental health-related emergency department presentation, using a 10-year time horizon for health-care and societal perspectives. We investigated uncertainty through probabilistic sensitivity analysis and deterministic sensitivity analysis, including using a 30-year timeframe. FINDINGS: From a societal perspective, increased investment in technology-enabled integrated care, family education, an online parenting programme, and multicultural-informed care were expected to improve health outcomes (incremental QALYs 4517 [95% UI -3135 to 14 507] for technology-enabled integrated care; 339 [91 to 661] for family education; 724 [114 to 1149] for the online parenting programme; and 137 [88 to 194] for multicultural-informed care) and reduce costs ($-91·4 million [-382·7 to 100·7]; $-12·8 million [-21·0 to -6·6]; $-3·6 million  [-6·3 to 0·2]; and $-3·1 million [-4·5 to -1·8], respectively) compared with business as usual using a 10-year time horizon. The incremental net monetary benefit for the societal perspective for these four interventions was $452 million (-351 to 1555), $40 million (14 to 74), $61 million (9 to 98), and $14 million (9 to 20), respectively, compared with business as usual, when QALYs were monetised using a willingness to pay of $79 930 per QALY. Synergistic effects are anticipated if these interventions were to be implemented concurrently. The univariate and probabilistic sensitivity analyses indicated a high level of certainty in the results. Although emergency department-based suicide prevention and school-based suicide prevention were not cost effective in the base case (41 QALYs [0 to 48], incremental cost $4·1 million [1·2 to 8·2] for emergency department-based suicide prevention; -234 QALYs [-764 to 12], incremental cost $90·3 million [72·2 to 111·0] for school-based suicide prevention) compared with business as usual, there were scenarios for which these interventions could be considered cost effective. A dedicated trauma service for young people (9 QALYs gained [4 to 16], incremental cost $8·3 million [6·8 to 10·0]) and a crisis response service (-11 QALYs gained [-12 to -10], incremental cost $7·8 million [5·1 to 11·0]) were unlikely to be cost effective in terms of QALYs. INTERPRETATION: Synergistic effects were identified, supporting the combined implementation of technology-enabled integrated care, family education, an online parenting programme, and multicultural-informed care. Synergistic effects, emergent outcomes in the form of unintended consequences, the capability to account for service capacity constraints, and ease of use by stakeholders are unique attributes of a system dynamics modelling approach to economic evaluation. FUNDING: BHP Foundation.

Quantifying the interrelationships between physical, social, and cognitive-emotional components of mental fitness using digital technology.

Mental fitness is a construct that goes beyond a simple focus on subjective emotional wellbeing to encompass more broadly our ability to think, feel, and act to achieve what we want in our daily lives. The measurement and monitoring of multiple (often interacting) domains is crucial to gain a holistic and complete insight into an individual's mental fitness. We aimed to demonstrate the capability of a new mobile app to characterise the mental fitness of a general population of Australians and to quantify the interrelationships among different domains of mental fitness. Cross-sectional data were collected from 4901 adults from the general population of Australians engaged in work or education who used a mobile app (Innowell) between September 2021 and November 2022. Individuals completed a baseline questionnaire comprised of 26 questions across seven domains of mental fitness (i.e., physical activity, sleep and circadian rhythms, nutrition, substance use, daily activities, social connection, psychological distress). Network analysis was applied at both a domain-level (e.g., 7 nodes representing each cluster of items) and an individual item-level (i.e., 26 nodes representing all questionnaire items). Only 612 people (12%) were functioning well across all domains. One quarter (n = 1204, 25%) had only one problem domain and most (n = 3085, 63%) had multiple problem domains. The two most problematic domains were physical activity (n = 2631, 54%) and social connection (n = 2151, 44%), followed closely by daily activity (n = 1914, 39%). At the domain-level, the strongest association emerged between psychological distress and daily activity (r = 0.301). Psychological distress was the most central node in the network (as measured by strength and expected influence), followed closely by daily activity, sleep and circadian rhythms and then social connection. The item-level network revealed that the nodes with the highest centrality in the network were: hopelessness, depression, functional impairment, effortfulness, subjective energy, worthlessness, and social connectedness. Social connection, sleep and circadian rhythms, and daily activities may be critical targets for intervention due to their widespread associations in the overall network. While psychological distress was not among the most common problems, its centrality may indicate its importance for indicated prevention and early intervention. We showcase the capability of a new mobile app to monitor mental fitness and identify the interrelationships among multiple domains, which may help people develop more personalised insights and approaches.

Feasibility and effectiveness of an evidence-based asthma service in Australian community pharmacies: a pragmatic cluster randomized trial.

OBJECTIVE: To test the feasibility, effectiveness, and sustainability of a pharmacy asthma service in primary care. METHODS: A pragmatic cluster randomized trial in community pharmacies in four Australian states/territories in 2009. Specially trained pharmacists were randomized to deliver an asthma service in two groups, providing three versus four consultations over 6 months. People with poorly controlled asthma or no recent asthma review were included. Follow-up for 12 months after service completion occurred in 30% of randomly selected completing patients. Outcomes included change in asthma control (poor and fair/good) and Asthma Control Questionnaire (ACQ) score, inhaler technique, quality of life, perceived control, adherence, asthma knowledge, and asthma action plan ownership. RESULTS: Ninety-six pharmacists enrolled 570 patients, with 398 (70%) completing. Asthma control significantly improved with both the three- and four-visit service, with no significant difference between groups (good/fair control 29% and 21% at baseline, 61% and 59% at end, p = .791). Significant improvements were also evident in the ACQ (mean change 0.56), inhaler technique (17-33% correct baseline, 57-72% end), asthma action plan ownership (19% baseline, 56% end), quality of life, adherence, perceived control, and asthma knowledge, with no significant difference between groups for any variable. Outcomes were sustained at 12 months post-service. CONCLUSIONS: The pharmacy asthma service delivered clinically important improvements in both a three-visit and four-visit service. Pharmacists were able to recruit and deliver the service with minimal intervention, suggesting it is practical to implement in practice. The three-visit service would be feasible and effective to implement, with a review at 12 months.

Population-level effectiveness of alternative approaches to preventing mental disorders in adolescents and young adults.

Preventive interventions that are effective in reducing the incidence of mental disorders in adolescence and early adulthood may impact substantially on lifetime economic, educational, and health outcomes; however, relatively few studies have examined the capacity of alternative approaches to preventing youth mental disorders (specifically, universal, selective, and indicated prevention) to reduce disorder incidence at a population level. Using a dynamic model of the onset of non-specific, relatively mild symptoms and progression to more severe disease, we show that: (1) indicated preventive interventions, targeting adolescents and young adults experiencing subthreshold symptoms, may often be more effective in reducing mental disorder prevalence than universal interventions delivered to the general population (contrary to the widely accepted view that a 'high risk' prevention strategy, focussing on those individuals with the greatest risk of developing a disorder, will generally be less effective than a whole-population strategy); and (2) the ability of selective preventive interventions (targeting vulnerable, asymptomatic youth) to alter the prevalence of mental disorders is severely restricted by an inverse relationship between the prevalence of significant risk factors for mental illness and the relative risk of developing symptoms.

Unemployment and underemployment are causes of suicide.

Epidemiological studies indicate that labor underutilization and suicide are associated, yet it remains unclear whether this association is causal. We applied convergent cross mapping to test for causal effects of unemployment and underemployment on suicidal behavior, using monthly data on labor underutilization and suicide rates in Australia for the period 2004-2016. Our analyses provide evidence that rates of unemployment and underemployment were significant drivers of suicide mortality in Australia over the 13-year study period. Predictive modeling indicates that 9.5% of the ~32,000 suicides reported between 2004 and 2016 resulted directly from labor underutilization, including 1575 suicides attributable to unemployment and 1496 suicides attributable to underemployment. We conclude that economic policies prioritizing full employment should be considered integral to any comprehensive national suicide prevention strategy.

Bi-stability and critical transitions in mental health care systems: a model-based analysis.

BACKGROUND: Delayed initiation and early discontinuation of treatment due to limited availability and accessibility of services may often result in people with mild or moderate mental disorders developing more severe disorders, leading to an increase in demand for specialised care that would be expected to further restrict service availability and accessibility (due to increased waiting times, higher out-of-pocket costs, etc.). METHODS: We developed a simple system dynamics model of the interaction of specialised services capacity and disease progression to examine the impact of service availability and accessibility on the effectiveness and efficiency of mental health care systems. RESULTS: Model analysis indicates that, under certain conditions, increasing services capacity can precipitate an abrupt, step-like transition from a state of persistently high unmet need for specialised services to an alternative, stable state in which people presenting for care receive immediate and effective treatment. This qualitative shift in services system functioning results from a 'virtuous cycle' in which increasing treatment-dependent recovery among patients with mild to moderate disorders reduces the number of severely ill patients requiring intensive and/or prolonged treatment, effectively 'releasing' services capacity that can be used to further reduce the disease progression rate. We present an empirical case study of tertiary-level child and adolescent mental health services in the Australian state of South Australia demonstrating that the conditions under which such critical transitions can occur apply in real-world services systems. CONCLUSIONS: Policy and planning decisions aimed at increasing specialised services capacity have the potential to dramatically increase the effectiveness and efficiency of mental health care systems, promoting long-term sustainability and resilience in the face of future threats to population mental health (e.g., economic crises, natural disasters, global pandemics).

Premature mortality in young people accessing early intervention youth mental healthcare: data-linkage cohort study.

BACKGROUND: Understanding premature mortality risk from suicide and other causes in youth mental health cohorts is essential for delivering effective clinical interventions and secondary prevention strategies. AIMS: To establish premature mortality risk in young people accessing early intervention mental health services and identify predictors of mortality. METHOD: State-wide data registers of emergency departments, hospital admissions and mortality were linked to the Brain and Mind Research Register, a longitudinal cohort of 7081 young people accessing early intervention care, between 2008 and 2020. Outcomes were mortality rates and age-standardised mortality ratios (SMR). Cox regression was used to identify predictors of all-cause mortality and deaths due to suicide or accident. RESULTS: There were 60 deaths (male 63.3%) during the study period, 25 (42%) due to suicide, 19 (32%) from accident or injury and eight (13.3%) where cause was under investigation. All-cause SMR was 2.0 (95% CI 1.6-2.6) but higher for males (5.3, 95% CI 3.8-7.0). The mortality rate from suicide and accidental deaths was 101.56 per 100 000 person-years. Poisoning, whether intentional or accidental, was the single greatest primary cause of death (26.7%). Prior emergency department presentation for poisoning (hazard ratio (HR) 4.40, 95% CI 2.13-9.09) and psychiatric admission (HR 4.01, 95% CI 1.81-8.88) were the strongest predictors of mortality. CONCLUSION: Premature mortality in young people accessing early intervention mental health services is greatly increased relative to population. Prior health service use and method of self-harm are useful predictors of future mortality. Enhanced care pathways following emergency department presentations should not be limited to those reporting suicidal ideation or intent.

Patterns of emergency department presentations for a youth mental health cohort: data-linkage cohort study.

BACKGROUND: Primary youth mental health services in Australia have increased access to care for young people, yet the longer-term outcomes and utilisation of other health services among these populations is unclear. AIMS: To describe the emergency department presentation patterns of a help-seeking youth mental health cohort. METHOD: Data linkage was performed to extract Emergency Department Data Collection registry data (i.e. emergency department presentations, pattern of re-presentations) for a transdiagnostic cohort of 7024 youths (aged 12-30 years) who presented to mental health services. Outcome measures were pattern of presentations and reason for presentations (i.e. mental illness; suicidal behaviours and self-harm; alcohol and substance use; accident and injury; physical illness; and other). RESULTS: During the follow-up period, 5372 (76.5%) had at least one emergency department presentation. The presentation rate was lower for males (IRR = 0.87, 95% CI 0.86-0.89) and highest among those aged 18 to 24 (IRR = 1.117, 95% CI 1.086-1.148). Almost one-third (31.12%) had an emergency department presentation that was directly associated with mental illness or substance use, and the most common reasons for presentation were for physical illness and accident or injury. Index visits for mental illness or substance use were associated with a higher rate of re-presentation. CONCLUSIONS: Most young people presenting to primary mental health services also utilised emergency services. The preventable and repeated nature of many presentations suggests that reducing the ongoing secondary risks of mental disorders (i.e. substance misuse, suicidality, physical illness) could substantially improve the mental and physical health outcomes of young people.

Double-blind, randomised placebo-controlled clinical trial of metformin as an adjunct to a sleep-wake, activity and metabolically focused behavioural intervention to improve cardiometabolic outcomes and mood symptoms in youth with major mood syndromes: study protocol.

INTRODUCTION: Metformin is a medication likely to improve measures of cardiometabolic disturbance in young people with mental illness. Evidence also suggests metformin may improve depressive symptoms. This 52-week double-blind randomised control trial (RCT) aims to investigate the efficacy of metformin pharmacotherapy as an adjunct to a healthy lifestyle behavioural intervention in improving cardiometabolic outcomes, and depressive, anxiety and psychotic symptoms in youth with clinically diagnosed major mood syndromes. METHODS AND ANALYSIS: At least 266 young people aged 16-25 presenting for mental healthcare for major mood syndromes who are also at risk for poor cardiometabolic outcomes will be invited to participate in this study. All participants will engage in a 12-week sleep-wake, activity and metabolically focused behavioural intervention programme. As an adjunctive intervention, participants will receive either metformin (500-1000 mg) or placebo pharmacotherapy for 52 weeks.Participants will undergo a series of assessments including: (1) self-report and clinician-administered assessments; (2) blood tests; (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) actigraphy. Univariate and multivariate tests (generalised mixed-effects models) will be used to examine changes in primary and secondary outcomes (and associations with predetermined predictor variables). ETHICS AND DISSEMINATION: This study has been approved by the Sydney Local Health District Research Ethics and Governance Office (X22-0017). The results of this double-blind RCT will be disseminated into the scientific and broader community through peer-reviewed journals, conference presentations, social media and university websites. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12619001559101p, 12 November 2019.

Designing an App for Parents and Caregivers to Promote Cognitive and Socioemotional Development and Well-being Among Children Aged 0 to 5 Years in Diverse Cultural Settings: Scientific Framework.

Recent years have seen remarkable progress in our scientific understanding of early childhood social, emotional, and cognitive development, as well as our capacity to widely disseminate health information by using digital technologies. Together, these scientific and technological advances offer exciting opportunities to deliver high-quality information about early childhood development (ECD) to parents and families globally, which may ultimately lead to greater knowledge and confidence among parents and better outcomes among children (particularly in lower- and middle-income countries). With these potential benefits in mind, we set out to design, develop, implement, and evaluate a new parenting app-Thrive by Five-that will be available in 30 countries. The app will provide caregivers and families with evidence-based and culturally appropriate information about ECD, accompanied by sets of collective actions that go beyond mere tips for parenting practices. Herein, we describe this ongoing global project and discuss the components of our scientific framework for developing and prototyping the app's content. Specifically, we describe (1) 5 domains that are used to organize the content and goals of the app's information and associated practices; (2) 5 neurobiological systems that are relevant to ECD and can be behaviorally targeted to potentially influence social, emotional, and cognitive development; (3) our anthropological and cultural framework for learning about local contexts and appreciating decolonization perspectives; and (4) our approach to tailoring the app's content to local contexts, which involves collaboration with in-country partner organizations and local and international subject matter experts in ECD, education, medicine, psychology, and anthropology, among others. Finally, we provide examples of the content that was incorporated in Thrive by Five when it launched globally.

EMPOWERED trial: protocol for a randomised control trial of digitally supported, highly personalised and measurement-based care to improve functional outcomes in young people with mood disorders.

OBJECTIVES: Many adolescents and young adults with emerging mood disorders do not achieve substantial improvements in education, employment, or social function after receiving standard youth mental health care. We have developed a new model of care referred to as 'highly personalised and measurement-based care' (HP&MBC). HP&MBC involves repeated assessment of multidimensional domains of morbidity to enable continuous and personalised clinical decision-making. Although measurement-based care is common in medical disease management, it is not a standard practice in mental health. This clinical effectiveness trial tests whether HP&MBC, supported by continuous digital feedback, delivers better functional improvements than standard care and digital support. METHOD AND ANALYSIS: This controlled implementation trial is a PROBE study (Prospective, Randomised, Open, Blinded End-point) that comprises a multisite 24-month, assessor-blinded, follow-up study of 1500 individuals aged 15-25 years who present for mental health treatment. Eligible participants will be individually randomised (1:1) to 12 months of HP&MBC or standardised clinical care. The primary outcome measure is social and occupational functioning 12 months after trial entry, assessed by the Social and Occupational Functioning Assessment Scale. Clinical and social outcomes for all participants will be monitored for a further 12 months after cessation of active care. ETHICS AND DISSEMINATION: This clinical trial has been reviewed and approved by the Human Research Ethics Committee of the Sydney Local Health District (HREC Approval Number: X22-0042 & 2022/ETH00725, Protocol ID: BMC-YMH-003-2018, protocol version: V.3, 03/08/2022). Research findings will be disseminated through peer-reviewed journals, presentations at scientific conferences, and to user and advocacy groups. Participant data will be deidentified. TRIAL REGISTRATION NUMBER: ACTRN12622000882729.