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Given the rapid development of digital mental health technologies and a focus on connecting with youth, there is an urgent need to enhance the engagement of young people with lived expertise in research. Even so, youth with lived experience of accessing mental health services are particularly affected by power imbalances and may receive limited compensation in academic settings. Therefore, an emphasis on how research engagement not only improves the work but can benefit young people themselves is required. Here, 5 young people with lived expertise report on their experience of being employed as researchers at the University of Sydney's Brain and Mind Centre. As such, this team is uniquely placed to offer reflections from their work across multiple stages of research. This led to four key insights, including (1) creating accepting work cultures, (2) providing diverse opportunities for involvement, (3) giving young people agency and flexibility around sharing lived experiences, and (4) creating accommodating work environments for all researchers. We suggest that these insights can support more diverse ways of engaging young people and maximizing the value of participation for both researchers and young people themselves., (©Josephine Brogden, Zsofi de Haan, Carla Gorban, Samuel J Hockey, Alexis Hutcheon, Frank Iorfino, Yun Ju C Song, Elizabeth Scott, Ian B Hickie, Sarah McKenna. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.10.2024.)

Competing Interests: Declaration of interests PDM is a founding director, patron, and former founding board member of headspace. He is the executive director of Orygen, Australia's National Centre of Excellence in Youth Mental Health and lead agency for five headspace centres across northwest Melbourne. He is a past President of the International Association for Youth Mental Health, and a past President of the IEPA; Early Intervention in Mental Health and of the Schizophrenia International Research Society. S-JB has provided paid expert witness work for UK charities and legal organisations. She is the author of two books related to the brain, education, and learning, for which she receives royalties. She gives talks in schools in the state and private sector, at education conferences, for education organisations, and for other public, private, and third sector organisations (some talks are remunerated). She is a member of the Rethinking Assessment group, the Steering Committee of the Cambridge Centre of Science Policy, the Technical Advisory Group for the UK Government Department of Education's Education and Outcomes Panel-C Study, the Singapore Government National Research Foundation Scientific Advisory Board, and the Singapore Government Human Potential Scientific Advisory Board. She was a member of the Times Education Commission (2021–22). IBH has received honoraria for consultancy and educational activities from Janssen Cilag. He was a member of the Clinical Advisory Group for the evaluation of the Better Access to Psychiatrists, Psychologists and General Practitioners through the Medicare Benefits Schedule initiative, and is a member of Mental Health Reform Advisory Committee (Department of Health). He is the Chief Scientific Advisor to and a 3·2% equity shareholder in InnoWell, which aims to transform mental health services through the use of innovative technologies. FAEA has received honoraria for consultancy from Grand Challenges Canada and is a past member of the World Economic Forum's Global Future Council on Mental Health. AMC is a director of headspace, Australia's National Youth Mental Health Foundation, and the National Education Alliance for Borderline Personality Disorder. AD is the Academic Secretary for the Royal College of Psychiatrists’ Faculty of Child and Adolescent Psychiatry, a research advisory group member of the UK National Society for the Prevention of Cruelty to Children, a member of the UK Trauma Council, and an evidence panel member of the Early Intervention Foundation. TF's research group receives funding for consultancy to Place2Be, a third sector organisation that provides mental health training, support, and interventions to schools across the UK. JH is executive director of Youth Wellness Hubs Ontario and receives funding from Graham Boeckh Foundation and other donors through the Centre for Addiction and Mental Health Foundation. AJ is a trustee of the Samaritans and MQ. She has received fees for lecturing from the Scottish Association of Mental Health. She is an advisory board member of Our Future Health, UK. FK-L's work is the subject of publishing contracts with multiple companies in the EU, Magellan, Cobalt Therapeutics in the USA, and the National Health Service in the UK. Although she has received no remuneration to date, she might receive royalties in the future. She is a non-executive director of Orygen. CK is the founder of Wida, a digital mental health platform. He has received consulting fees from the UN Children's Fund. He has received grants from MQ: Transforming Mental Health in the UK, the Royal Academy of Engineering in the UK, the National Institutes of Health in the USA, the Medical Research Council in the UK, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul in Brazil. DR is a Chief Scientific Advisor to headspace, Australia's National Youth Mental Health Foundation. JT receives book royalties from Simon and Schuster, legal consulting fees from Bergman and Little and the Attorney General's office of the State of Tennessee, and honoraria for speaking engagements. EK is the immediate past President of the IEPA: Early Intervention in Mental Health, and during the period of the Commission was the President elect and President. All other authors declare no competing interests.

Despite increased advocacy and investments in mental health systems globally, there has been limited progress in reducing mental disorder prevalence. In this paper, we argue that meaningful advancements in population mental health necessitate addressing the fundamental sources of shared distress. Using a systems perspective, economic structures and policies are identified as the potential cause of causes of mental ill-health. Neoliberal ideologies, prioritizing economic optimization and continuous growth, contribute to the promotion of individualism, job insecurity, increasing demands on workers, parental stress, social disconnection and a broad range of manifestations well-recognized to erode mental health. We emphasize the need for mental health researchers and advocates to increasingly engage with the economic policy discourse to draw attention to mental health and well-being implications. We call for a shift towards a well-being economy to better align commercial interests with collective well-being and social prosperity. The involvement of individuals with lived mental ill-health experiences, practitioners and researchers is needed to mobilize communities for change and influence economic policies to safeguard well-being. Additionally, we call for the establishment of national mental wealth observatories to inform coordinated health, social and economic policies and realize the transition to a more sustainable well-being economy that offers promise for progress on population mental health outcomes., ((c) 2024 The authors; licensee World Health Organization.)

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., Competing Interests: Declaration of interests JO is head of systems modelling, simulation and data science at the Brain and Mind Centre at the University of Sydney and is managing director of Computer Simulation and Advanced Research Technologies. SH is a member of the Hunter New England Central Coast Primary Health Network's Community Advisory Committee. IBH is the co-director of Health and Policy at the Brain and Mind Centre at the University of Sydney, which operates early-intervention youth services at Camperdown under contract to Headspace; has previously led community-based and projects supported by the pharmaceutical industry (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca, Janssen, Cilag), focused on the identification and better management of anxiety and depression; and is the Chief Scientific Advisor to, and a 3·2% equity shareholder in, InnoWell, which aims to transform mental health services through the use of innovative technologies. PC, NH, HH, CV, AS, AN, RH, YJCS, SR, PM, EM, GYL, and DM declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Australia's Fifth National Mental Health Plan required governments to report, not only on the progress of changes to mental health service delivery, but to also plan for services that should be provided. Future population demand for treatment and care is challenging to predict and one solution involves modelling the uncertain demands on the system. Modelling can help decision-makers understand likely future changes in mental health service demand and more intelligently choose appropriate responses. It can also support greater scrutiny, accountability and transparency of these processes. Australia has an emerging national capacity for systems modelling in mental health which can enhance the next phase of mental health reform. This paper introduces concepts useful for understanding mental health modelling and identifies where modelling approaches can support health service planners to make evidence-informed decisions regarding planning and investment for the Australian population., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Competing interests: Professor Ian Hickie is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney, Australia. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. Professor Hickie has previously led community-based and pharmaceutical industry-supported (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca, Janssen Cilag) projects focused on the identification and better management ofanxiety and depression. He is the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell Pty Ltd which aims to transform mental health services through the use of innovative technologies. A/Prof Elizabeth Scott is a Research Affiliate, The University of Sydney and Consultant Psychiatrist. She has received honoraria for educational seminars related to the clinical management of depressive disorders supported by Servier and Eli-Lilly pharmaceuticals. She has participated in a national advisory board for the antidepressant compound Pristiq, manufactured by Pfizer. She was the National Coordinator of an antidepressant trial sponsored by Servier. Professor Jan Scott is a visiting professor at Diderot University, the Norwegian University of Science and Technology, Swinburne University of Technology and The University of Sydney and a ‘Science without Borders’ fellow (Brazil). She has received grant funding from the UK Medical Research Council and from the UK Research for Patient Benefit programme; she declares no financial or other conflict of interests in relation to the topics addressed in this paper., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: There is an ongoing necessity to match clinical interventions with the multidimensional needs of young people. A key step toward better service planning and the design of optimal models of care is to use multidimensional assessment to understand the clinical needs of those presenting to primary mental health care., Methods: 1284 people aged 12-25 years presenting to primary youth mental health services completed an online assessment at service entry. Latent class analysis was conducted for seven scales assessing anxiety, depression, psychosis, mania, functioning (indexed by Work and Social Adjustment Scale), and suicidality., Results: A three-class solution was identified as the optimal solution. Class 1 (n = 305, 23.75%), an early illness stage group, had low and mixed symptomatology with limited functional impairment, class 2 (n = 353, 27.49%) was made up of older persons with established depression and functional impairment, and class 3 (n = 626, 48.75%) had very high and complex needs, with functional impairment, suicidality, and at-risk mental states (psychosis or mania). Additional differentiating characteristics included psychological distress, circadian disturbances, social support, mental health history, eating disorder behaviours, and symptoms of post-traumatic stress disorder., Conclusions: A large proportion of help-seeking young people present with symptoms and functional impairment that may exceed the levels of care available from basic primary care or brief intervention services. These subgroups highlight the importance of multidimensional assessments to determine appropriate service pathways and care options., Competing Interests: Declaration of Competing Interest Tracey Davenport is now Director (Research and Evaluation) of the Design and Strategy Division, Australian Digital Health Agency. A/Prof Elizabeth Scott is Principal Research Fellow at the Brain and Mind Centre, The University of Sydney. She is Discipline Leader of Adult Mental Health, School of Medicine, University of Notre Dame, and a Consultant Psychiatrist. She was the Medical Director, Young Adult Mental Health Unit, St Vincent’s Hospital Darlinghurst until January 2021. She has received honoraria for educational seminars related to the clinical management of depressive disorders supported by Servier, Janssen and Eli-Lilly pharmaceuticals. She has participated in a national advisory board for the antidepressant compound Pristiq, manufactured by Pfizer. She was the National Coordinator of an antidepressant trial sponsored by Servier. Professor Ian B Hickie is the Co-director, Health and Policy at the Brain and Mind Centre, University of Sydney. The Brain and Mind Centre operates an early-intervention youth service at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell Pty Ltd. InnoWell was formed as a joint venture by the University of Sydney (32% equity) and PwC (Australia; 32% equity) to deliver the $30 million Australian Government–funded Project Synergy (2017–2020; a three-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. No other competing interests were reported., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: This retrospective cohort study aimed to identify the cardiometabolic characteristics, cross-sectionally and longitudinally, associated with clinical stage in youth accessing early intervention mental health services., Methods: Cardiometabolic data we collected in 511 young people (aged 12-25 years at entry) receiving mental health care at the early intervention services in Sydney, Australia., Results: The majority of young people (N = 448, 87.67%) were classified in stage 1a or 1b at entry. At entry to care, there was no cross-sectional relationship between clinical stage and age, gender, fasting insulin, fasting glucose, updated homeostatic model assessment for insulin resistance (HOMA2-IR) score, BMI or waist circumference. Of the 111 (21.7%) young people initially classified at stage 1a ('non-specific symptoms') and the 337 (65.9%) classified in stage 1b ('attenuated syndromes'), 40 individuals transitioned to stage 2+ (7.8%) ("full-threshold disorders") longitudinally. No cardiometabolic factors predicted clinical stage transitions. However, those with an increase in BMI over the course of care (n = 54) were 1.46 (OR; 95% CI: 1.02-2.17) times more likely to progress to stage 2+ at follow up., Conclusions: Whilst no relationships were found between demographic or cardiometabolic variables and clinical stage at entry to care, an increased BMI over time was associated with clinical stage transition longitudinally. Further longitudinal research is needed to understand the demographic, clinical, illness progression or treatment factors associated with changes in cardiometabolic status., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in youth. Moreover, we propose that novel approaches towards early diagnosis and interventions are required that reflect the evolution of emerging psychopathology, the importance of novel service models, and knowledge exchange between science and practitioners. Taken together, we propose a transformative early intervention paradigm for research and clinical care that could significantly enhance mental health in young people and initiate a shift towards the prevention of severe mental disorders., (© 2023. The Author(s).)

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., (© 2023 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Background: Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the first 12 months of care., Methods: Demographic and clinical information of 2901 young people who accessed mental health care at age 12-25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to define three fixed groups for analyses (stage 1a: 'non-specific anxious or depressive symptoms', 1b: 'attenuated mood or psychotic syndromes', 2+: 'full-threshold mood or psychotic syndromes'). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care., Results: Of the entire cohort, 2093 young people aged 12-25 years were followed up at least once over the first 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60-4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36-3.28), develop suicidal ideations (OR=1.92; CI 1.30-2.84) and circadian disturbances (OR=1.94, CI 1.31-2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity., Conclusions: The differential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model's assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specific intervention packages., (© 2022. The Author(s).)

Objectives: The aim of this study was to determine the prevalence of disordered eating in young people attending a headspace centre, an enhanced primary care centre providing early intervention services for mental health disorders for young people aged 12-25 years, in metropolitan Sydney., Design: Cross-sectional assessment of disordered eating symptoms and behaviours., Setting: An enhanced primary care youth mental health service in inner urban Sydney, Australia., Participants: A sequential cohort of 530 young people aged 14-26 years presenting to headspace Camperdown for support with mental health concerns., Outcome Measures: Participants completed a series of questionnaires online which included items assessing the presence of eating disorder symptoms and behaviours., Results: Over one-third of young people aged 14-26 years presenting to headspace Camperdown in a 22-month period reported symptoms of disordered eating. Of these, 32% endorsed overeating behaviours, 25% endorsed dietary restriction and 8% reported purging behaviours. In total, 44% reported engaging in one of more of these behaviours on a regular basis. Almost half reported experiencing significant shape and weight concerns. Eating disorder behaviours were particularly prevalent among female and gender-diverse participants (48% of females and 46% of gender-diverse participants compared with 35% of males) and overall scores across all of the eating disorder and body image items assessed were significantly higher for female participants compared with males., Conclusions: Disordered eating behaviours and symptoms are common among those presenting to youth mental health primary care services. Proactive screening for these behaviours presents opportunities for early detection and specific interventions., Trial Registration Number: ACTRN12618001676202; Results., Competing Interests: Competing interests: At the time of data collection, ALB was the clinical lead at headspace Camperdown. BH is the Clinical Services Manager at headspace Camperdown. ALB and BH have no other potential competing interests to declare. IBH is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 5% equity shareholder in, Innowell. Innowell is a joint venture between the University of Sydney (45% equity) and PwC (Australia; 45% equity), originally created to deliver the $30 million Australian Commonwealth Government-funded Project Synergy (2017–2020, a 3-year programme for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. EMS is Principal Research Fellow at the BMC, The University of Sydney. She is Discipline Leader of Adult Mental Health, School of Medicine, University of Notre Dame, and a Consultant Psychiatrist. She was the Medical Director, Young Adult Mental Health Unit, St Vincent’s Hospital Darlinghurst until January 2021. She has received honoraria for educational seminars related to the clinical management of depressive disorders supported by Servier and Eli-Lilly pharmaceuticals. She has participated in a national advisory board for the antidepressant compound Pristiq, manufactured by Pfizer. She was the National Coordinator of an antidepressant trial sponsored by Servier., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The ongoing COVID-19 pandemic has impacted the mental health of populations and highlighted the limitations of mental health care systems. As the trajectory of the pandemic and the economic recovery are still uncertain, decision tools are needed to help evaluate the best interventions to improve mental health outcomes. We developed a system dynamics model that captures causal relationships among population, demographics, post-secondary education, health services, COVID-19 impact, and mental health outcomes. The study was conducted in the Australian state of Victoria. The model was calibrated using historical data and was stratified by age group and by geographic remoteness. Findings demonstrate that the most effective intervention combination includes economic, social, and health sector initiatives. Assertive post-suicide attempt care is the most impactful health sector intervention, but delaying implementation reduces the potency of its impact. Some evidence-based interventions, such as population-wide community awareness campaigns, are projected to worsen mental health outcomes when implemented on their own. Systems modelling offers a powerful decision-support tool to test alternative strategies for improving mental health outcomes in the Victorian context.

Introduction: Worsened cardiometabolic profiles in youth with mental ill health have been associated with a number of modifiable lifestyle risk factors. It is becoming increasingly evident that clinical interventions need to be multimodal in focus to improve mental health symptoms and the physical health symptoms in this already at-risk cohort., Methods and Analysis: This 12-week pilot clinical trial examines the efficacy, feasibility and acceptability of an adjunctive online psychoeducation programme for improving cardiometabolic risk parameters and affective symptoms in a transdiagnostic sample of at least 44 young people aged 16-25 years presenting for mental healthcare for mood and/or psychotic syndromes (including anxiety, depression, bipolar disorder and psychosis). Individuals will be invited to participate in a pilot clinical trial for a structured online psychoeducation programme incorporating nutritional, physical activity, sleep-wake and healthy lifestyle information, delivered fortnightly over six online modules. Participants will undergo a series of assessments including: (1) self-report and clinician administered assessments determining mental health symptomatology; (2) fasting blood tests to assess cardiometabolic markers (fasting insulin, fasting glucose and blood lipids); (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) sleep-wake behaviours and circadian rhythm assessments. Changes in scores for all cardiometabolic and affective measures will be assessed via paired samples t-tests, and correlations between change scores will be assessed via Pearson's or Spearman's correlations. Feasibility will be assessed via completion rates, and the acceptability of the programme will be assessed via programme satisfaction measures., Ethics and Dissemination: This pilot clinical trial has been approved by the Sydney Local Health District Research Ethics and Governance Office (X20-0228 & 2020/ETH01201). The results of this pilot clinical trial 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: ACTRN12620000772943, Date 28 August 2020., Competing Interests: Competing interests: Professor Ian Hickie was an inaugural Commissioner on Australia’s National Mental Health Commission (2012-18). He is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates early-intervention youth services at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 5% equity shareholder in, InnoWell Pty LTd. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30M Australian Government-funded Project Synergy (2017-20; a three-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies.A/Prof Elizabeth Scott is Principal Research Fellow at the Brain and Mind Centre, The University of Sydney. She is Discipline Leader of Adult Mental Health, School of Medicine, University of Notre Dame, and a Consultant Psychiatrist. She was the Medical Director, Young Adult Mental Health Unit, St Vincent’s Hospital Darlinghurst until January 2021. She has received honoraria for educational seminars related to the clinical management of depressive disorders supported by Servier and Eli-Lilly pharmaceuticals. She has participated in a national advisory board for the antidepressant compound Pristiq, manufactured by Pfizer. She was the National Coordinator of an antidepressant trial sponsored by Servier., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Approximately 75% of major mental illness occurs before the age of 25 years. Despite this, our capacity to provide effective, early and personalised interventions is limited by insufficient evidence for characterising early-stage, and less specific, presentations of major mental disorders in youth populations. This article describes the protocol for setting up a large-scale database that will collect longitudinal, prospective data that incorporate clinical, social and occupational function, neuropsychological, circadian, metabolic, family history and genetic metrics. By collecting data in a research-purposed, standardised manner, the 'Neurobiology Youth Follow-up Study' should improve identification, characterisation and profiling of youth attending mental healthcare, to better inform diagnosis and treatment at critical time points. The overall goal is enhanced long-term clinical and functional outcomes., Methods and Analysis: This longitudinal clinical cohort study will invite participation from youth (12-30 years) who seek help for mental health-related issues at an early intervention service (headspace Camperdown) and linked services. Participants will be prospectively tracked over 3 years with a series of standardised multimodal assessments at baseline, 6, 12, 24 and 36 months. Evaluations will include: (1) clinician-administered and self-report assessments determining clinical stage, pathophysiological pathways to illness, diagnosis, symptomatology, social and occupational function; (2) neuropsychological profile; (3) sleep-wake patterns and circadian rhythms; (4) metabolic markers and (5) genetics. These data will be used to: (1) model the impact of demographic, phenomenological and treatment variables, on clinical and functional outcomes; (2) map neurobiological profiles and changes onto a transdiagnostic clinical stage and pathophysiological mechanisms framework., Ethics and Dissemination: This study protocol has been approved by the Human Research Ethics Committee of the Sydney Local Health District (2020/ETH01272, protocol V.1.3, 14 October 2020). Research findings will be disseminated through peer-reviewed journals and presentations at scientific conferences and to user and advocacy groups. Participant data will be de-identified., Competing Interests: Competing interests: IBH was an inaugural Commissioner on Australia’s National Mental Health Commission (2012–2018). He is the co-director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates early-intervention youth services at Camperdown under contract to headspace. He is the chief scientific advisor to, and a 5% equity shareholder in, InnoWell. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 million Australian government-funded Project Synergy (2017–2020; a 3-year programme for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the widely acknowledged potential for health information technologies to improve the accessibility, quality and clinical safety of mental health care, implementation of such technologies in services is frequently unsuccessful due to varying consumer, health professional, and service-level factors. The objective of this co-design study was to use process mapping (i.e. service mapping) to illustrate the current consumer journey through primary mental health services, identify barriers to and facilitators of quality mental health care, and highlight potential points at which to integrate the technology-enabled solution to optimise the provision of care based on key service performance indicators., Methods: Interactive, discussion-based workshops of up to six hours were conducted with representative stakeholders from each participating service, including health professionals, service managers and administrators from Open Arms - Veterans & Families Counselling Service (Sydney), a counselling service for veterans and their families, and five headspace centres in the North Coast Primary Health Network, primary youth mental health services. Service maps were drafted and refined in real time during the workshops. Through both group discussion and the use of post-it notes, participants worked together to evaluate performance indicators (e.g. safety) at each point in the consumer journey (e.g. intake) to indicate points of impact for the technology-enabled solution, reviewing and evaluating differing opinions in order to reach consensus., Results: Participants (n=84 across participating services) created service maps illustrating the current consumer journey through the respective services and highlighting barriers to and facilitators of quality mental health care. By consensus, the technology-enabled solution as facilitated by the InnoWell Platform was noted to enable the early identification of risk, reduce or eliminate lengthy intake processes, enable routine outcome monitoring to revise treatment plans in relation to consumer response, and serve as a personal data record for consumers, driving person-centred, coordinated care., Conclusions: Service mapping was shown to be an effective methodology to understand the consumer's journey through a service and served to highlight how the co-designed technology-enabled solution can optimise service pathways to improve the accessibility, quality and clinical safety of care relative to key service performance indicators, facilitating the delivery of the right care.

Introduction: Currently, the literature on personalised and measurement-based mental healthcare is inadequate with major gaps in the development and evaluation of 21st century service models. Clinical presentations of mental ill health in young people are heterogeneous, and clinical and functional outcomes are often suboptimal. Thus, treatments provided in a person-centred and responsive fashion are critical to meet the unique needs of young people and improve individual outcomes. Personalised care also requires concurrent assessment of factors relating to outcomes and underlying neurobiology. This study builds on a completed feasibility study and will be the first to incorporate clinical, cognitive, circadian, metabolic and hormonal profiling with personalised and measurement-based care in a cohort of young people admitted to hospital., Methods and Analysis: This prospective, transdiagnostic, observational study will be offered to all young people between the ages of 16 and 30 years admitted to the inpatient unit of the participating centre. In total, 400 participants will be recruited. On admission to hospital, young people will undergo clinical and diagnostic assessment, cognitive testing, self-report questionnaires, metabolic and hormonal data collection, and anthropomorphic measurements. Participants will wear an actigraphy watch for at least 1 week during admission to measure circadian patterns and sleep-wake cycles. A feedback session between clinician and participant will occur after clinical and other laboratory assessments to tailor individual treatment plans, explain the ongoing process of measurement-based care, and provide participant and family education. Associations between cognitive impairments, disturbed sleep-wake behaviours, circadian rhythms, clinical symptoms and functional impairments will be evaluated to improve the understanding of parameters affecting clinical outcomes., Ethics and Dissemination: This study protocol was approved by the Human Research Ethics Committees of the University of Sydney (HREC USYD 2015/867) and St Vincent's Hospital (HREC SVH 17/045). This study will be published on completion in a peer-reviewed journal., Competing Interests: Competing interests: IBH was an inaugural Commissioner on Australia’s National Mental Health Commission (2012–2018). He is the codirector, health and policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. IBH has previously led communitybased and pharmaceutical industry-supported (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca) projects focused on the identification and better management of anxiety and depression. He was a member of the Medical Advisory Panel for Medibank Private until October 2017, a Board Member of Psychosis Australia Trust and a member of Veterans Mental Health Clinical Reference group. He is the chief scientific advisor to, and a 5% equity shareholder in, InnoWell. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $A30 M Australian Government-funded Project Synergy (2017–2020; a 3-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. ES is the Medical Director, Young Adult Mental Health Unit, St Vincent’s Hospital Darlinghurst, Discipline Leader of Adult Mental Health, School of Medicine, University of Notre Dame, Research Affiliate, The University of Sydney and Consultant Psychiatrist. She has received honoraria for educational seminars related to the clinical management of depressive disorders supported by Servier and Eli-Lilly pharmaceuticals. She has participated in a national advisory board for the antidepressant compound Pristiq, manufactured by Pfizer. She was the National Coordinator of an antidepressant trial sponsored by Servier, (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The '16Up' study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16-18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.

Importance: The large contribution of psychiatric disorders to premature death and persistent disability among young people means that earlier identification and enhanced long-term care for those who are most at risk of developing life-threatening or chronic disorders is critical. Clinical staging as an adjunct to diagnosis to address emerging psychiatric disorders has been proposed for young people presenting for care; however, the longer-term utility of this system has not been established., Objectives: To determine the rates of transition from earlier to later stages of anxiety, mood, psychotic, or comorbid disorders and to identify the demographic and clinical characteristics that are associated with the time course of these transitions., Design, Setting, and Participants: A longitudinal, observational study of 2254 persons aged 12 to 25 years who obtained mental health care at 2 early intervention mental health services in Sydney, Australia, and were recruited to a research register between June 18, 2008, and July 24, 2018 (the Brain and Mind Centre Optymise Cohort)., Main Outcomes and Measures: The primary outcome of this study was transition from earlier to later clinical stages. A multistate Markov model was used to examine demographic (ie, age, sex, engagement in education, employment, or both) and clinical (ie, social and occupational function, clinical presentation, personal history of mental illness, physical health comorbidities, treatment use, self-harm, suicidal thoughts and behaviors) factors associated with these transitions., Results: Of the 2254 individuals included in the study, mean (SD) age at baseline was 18.18 (3.33) years and 1330 (59.0%) were female. Data on race/ethnicity were not available. Median (interquartile range) follow-up was 14 (5-33) months. Of 685 participants at stage 1a (nonspecific symptoms), 253 (36.9%) transitioned to stage 1b (attenuated syndromes). Transition was associated with lower social functioning (hazard ratio [HR], 0.77; 95% CI, 0.66-0.90), engagement with education, employment, or both (HR, 0.47; 95% CI, 0.25-0.91), manic-like experiences (HR, 2.12; 95% CI, 1.19-3.78), psychotic-like experiences (HR, 2.13; 95% CI, 1.38-3.28), self-harm (HR, 1.42; 95% CI, 1.01-1.99), and older age (HR, 1.27; 95% CI, 1.11-1.45). Of 1370 stage 1b participants, 176 (12.8%) transitioned to stage 2 (full-threshold) disorders. Transition was associated with psychotic-like experiences (HR, 2.31; 95% CI, 1.65-3.23), circadian disturbance (HR, 1.66; 95% CI, 1.17-2.35), psychiatric medication (HR, 1.43; 95% CI, 1.03-1.99), childhood psychiatric disorder (HR, 1.62; 95% CI, 1.03-2.54), and older age (HR, 1.24; 95% CI, 1.05-1.45)., Conclusions and Relevance: Differential rates of progression from earlier to later stages of anxiety, mood, psychotic, or comorbid disorders were observed in young persons who presented for care at various stages. Understanding the rate and factors associated with transition assists planning of stage-specific clinical interventions and secondary prevention trials.

Mood and psychotic syndromes most often emerge during adolescence and young adulthood, a period characterised by major physical and social change. Consequently, the effects of adolescent-onset mood and psychotic syndromes can have long term consequences. A key clinical challenge for youth mental health is to develop and test new systems that align with current evidence for comorbid presentations and underlying neurobiology, and are useful for predicting outcomes and guiding decisions regarding the provision of appropriate and effective care. Our highly personalised and measurement-based care model includes three core concepts: ▶ A multidimensional assessment and outcomes framework that includes: social and occupational function; self-harm, suicidal thoughts and behaviour; alcohol or other substance misuse; physical health; and illness trajectory. ▶ Clinical stage. ▶ Three common illness subtypes (psychosis, anxious depression, bipolar spectrum) based on proposed pathophysiological mechanisms (neurodevelopmental, hyperarousal, circadian). The model explicitly aims to prevent progression to more complex and severe forms of illness and is better aligned to contemporary models of the patterns of emergence of psychopathology. Inherent within this highly personalised approach is the incorporation of other evidence-based processes, including real-time measurement-based care as well as utilisation of multidisciplinary teams of health professionals. Data-driven local system modelling and personalised health information technologies provide crucial infrastructure support to these processes for better access to, and higher quality, mental health care for young people. CHAPTER 1: MULTIDIMENSIONAL OUTCOMES IN YOUTH MENTAL HEALTH CARE: WHAT MATTERS AND WHY?: Mood and psychotic syndromes present one of the most serious public health challenges that we face in the 21st century. Factors including prevalence, age of onset, and chronicity contribute to substantial burden and secondary risks such as alcohol or other substance misuse. Mood and psychotic syndromes most often emerge during adolescence and young adulthood, a period characterised by major physical and social change; thus, effects can have long term consequences. We propose five key domains which make up a multidimensional outcomes framework that aims to address the specific needs of young people presenting to health services with emerging mental illness. These include social and occupational function; self-harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness type, stage and trajectory. Impairment and concurrent morbidity are well established in young people by the time they present for mental health care. Despite this, services and health professionals tend to focus on only one aspect of the presentation - illness type, stage and trajectory - and are often at odds with the preferences of young people and their families. There is a need to address the disconnect between mental health, physical health and social services and interventions, to ensure that youth mental health care focuses on the outcomes that matter to young people. CHAPTER 2: COMBINING CLINICAL STAGE AND PATHOPHYSIOLOGICAL MECHANISMS TO UNDERSTAND ILLNESS TRAJECTORIES IN YOUNG PEOPLE WITH EMERGING MOOD AND PSYCHOTIC SYNDROMES: Traditional diagnostic classification systems for mental disorders map poorly onto the early stages of illness experienced by young people, and purport categorical distinctions that are not readily supported by research into genetic, environmental and neurobiological risk factors. Consequently, a key clinical challenge in youth mental health is to develop and test new classification systems that align with current evidence on comorbid presentations, are consistent with current understanding of underlying neurobiology, and provide utility for predicting outcomes and guiding decisions regarding the provision of appropriate and effective care. This chapter outlines a transdiagnostic framework for classifying common adolescent-onset mood and psychotic syndromes, combining two independent but complementary dimensions: clinical staging, and three proposed pathophysiological mechanisms. Clinical staging reflects the progression of mental disorders and is in line with the concept used in general medicine, where more advanced stages are associated with a poorer prognosis and a need for more intensive interventions with a higher risk-to-benefit ratio. The three proposed pathophysiological mechanisms are neurodevelopmental abnormalities, hyperarousal and circadian dysfunction, which, over time, have illness trajectories (or pathways) to psychosis, anxious depression and bipolar spectrum disorders, respectively. The transdiagnostic framework has been evaluated in young people presenting to youth mental health clinics of the University of Sydney's Brain and Mind Centre, alongside a range of clinical and objective measures. Our research to date provides support for this framework, and we are now exploring its application to the development of more personalised models of care. CHAPTER 3: A COMPREHENSIVE ASSESSMENT FRAMEWORK FOR YOUTH MENTAL HEALTH: GUIDING HIGHLY PERSONALISED AND MEASUREMENT-BASED CARE USING MULTIDIMENSIONAL AND OBJECTIVE MEASURES: There is an urgent need for improved care for young people with mental health problems, in particular those with subthreshold mental disorders that are not sufficiently severe to meet traditional diagnostic criteria. New comprehensive assessment frameworks are needed to capture the biopsychosocial profile of a young person to drive highly personalised and measurement-based mental health care. We present a range of multidimensional measures involving five key domains: social and occupational function; self-harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness type, stage and trajectory. Objective measures include: neuropsychological function; sleep-wake behaviours and circadian rhythms; metabolic and immune markers; and brain structure and function. The recommended multidimensional measures facilitate the development of a comprehensive clinical picture. The objective measures help to further develop informative and novel insights into underlying pathophysiological mechanisms and illness trajectories to guide personalised care plans. A panel of specific multidimensional and objective measures are recommended as standard clinical practice, while others are recommended secondarily to provide deeper insights with the aim of revealing alternative clinical paths for targeted interventions and treatments matched to the clinical stage and proposed pathophysiological mechanisms of the young person. CHAPTER 4: PERSONALISING CARE OPTIONS IN YOUTH MENTAL HEALTH: USING MULTIDIMENSIONAL ASSESSMENT, CLINICAL STAGE, PATHOPHYSIOLOGICAL MECHANISMS, AND INDIVIDUAL ILLNESS TRAJECTORIES TO GUIDE TREATMENT SELECTION: New models of mental health care for young people require that interventions be matched to illness type, clinical stage, underlying pathophysiological mechanisms and individual illness trajectories. Narrow syndrome-focused classifications often direct clinical attention away from other key factors such as functional impairment, self-harm and suicidality, alcohol or other substance misuse, and poor physical health. By contrast, we outline a treatment selection guide for early intervention for adolescent-onset mood and psychotic syndromes (ie, active treatments and indicated and more specific secondary prevention strategies). This guide is based on experiences with the Brain and Mind Centre's highly personalised and measurement-based care model to manage youth mental health. The model incorporates three complementary core concepts: ▶A multidimensional assessment and outcomes framework including: social and occupational function; self-harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness trajectory. ▶Clinical stage. ▶Three common illness subtypes (psychosis, anxious depression, bipolar spectrum) based on three underlying pathophysiological mechanisms (neurodevelopmental, hyperarousal, circadian). These core concepts are not mutually exclusive and together may facilitate improved outcomes through a clinical stage-appropriate and transdiagnostic framework that helps guide decisions regarding the provision of appropriate and effective care options. Given its emphasis on adolescent-onset mood and psychotic syndromes, the Brain and Mind Centre's model of care also respects a fundamental developmental perspective - categorising childhood problems (eg, anxiety and neurodevelopmental difficulties) as risk factors and respecting the fact that young people are in a period of major biological and social transition. Based on these factors, a range of social, psychological and pharmacological interventions are recommended, with an emphasis on balancing the personal benefit-to-cost ratio. CHAPTER 5: A SERVICE DELIVERY MODEL TO SUPPORT HIGHLY PERSONALISED AND MEASUREMENT-BASED CARE IN YOUTH MENTAL HEALTH: Over the past decade, we have seen a growing focus on creating mental health service delivery models that better meet the unique needs of young Australians. Recent policy directives from the Australian Government recommend the adoption of stepped-care services to improve the appropriateness of care, determined by severity of need. Here, we propose that a highly personalised approach enhances stepped-care models by incorporating clinical staging and a young person's current and multidimensional needs. It explicitly aims to prevent progression to more complex and severe forms of illness and is better aligned to contemporary models of the patterns of emergence of psychopathology. Inherent within a highly personalised approach is the incorporation of other evidence-based processes, including real-time measurement-based care and use of multidisciplinary teams of health professionals. Data-driven local system modelling and personalised health information technologies provide crucial infrastructure support to these processes for better access to, and higher quality of, mental health care for young people., (© 2019 AMPCo Pty Ltd.)

Background: The Mental Health eClinic (MHeC) aims to deliver best-practice clinical services to young people experiencing mental health problems by making clinical care accessible, affordable, and available to young people whenever and wherever they need it most. The original MHeC consists of home page with a visible triage system for those requiring urgent help; a online physical and mental health self-report assessment; a results dashboard; a booking and videoconferencing system; and the generation of a personalized well-being plan. Populations who do not speak English and reside in English-speaking countries are less likely to receive mental health care. In Australia, international students have been identified as disadvantaged compared with their peers; have weaker social support networks; and have higher rates of psychological distress. This scenario is acquiring significant relevance as Spanish-speaking migration is rapidly growing in Australia, and the mental health services for culturally and linguistically diverse populations are limited. Having a Spanish version (MHeC-S) of the Mental Health eClinic would greatly benefit these students., Objective: We used participatory design methodologies with users (young people aged 16-30 years, supportive others, and health professionals) to (1) conduct workshops with users to co-design and culturally adapt the MHeC; (2) inform the development of the MHeC-S alpha prototype; (3) test the usability of the MHeC-S alpha prototype; (4) translate, culturally adapt, and face-validate the MHeC-S self-report assessment; and (5) collect information to inform its beta prototype., Methods: A research and development cycle included several participatory design phases: co-design workshops; knowledge translation; language translation and cultural adaptation; and rapid prototyping and user testing of the MHeC-S alpha prototype., Results: We held 2 co-design workshops with 17 users (10 young people, 7 health professionals). A total of 15 participated in the one-on-one user testing sessions (7 young people, 5 health professionals, 3 supportive others). We collected 225 source documents, and thematic analysis resulted in 5 main themes (help-seeking barriers, technology platform, functionality, content, and user interface). A random sample of 106 source documents analyzed by 2 independent raters revealed almost perfect agreement for functionality (kappa=.86; P<.001) and content (kappa=.92; P<.001) and substantial agreement for the user interface (kappa=.785; P<.001). In this random sample, no annotations were coded for help-seeking barriers or the technology platform. Language was identified as the main barrier to getting medical or psychological services, and smartphones were the most-used device to access the internet. Acceptability was adequate for the prototype's 5 main elements: home page and triage system, self-report assessment, dashboard of results, booking and video visit system, and personalized well-being plan. The data also revealed gaps in the alpha prototype, such as the need for tailored assessment tools and a greater integration with Spanish-speaking services and communities. Spanish-language apps and e-tools, as well as online mental health information, were lacking., Conclusions: Through a research and development process, we co-designed and culturally adapted, developed and user tested, and evaluated the MHeC-S. By translating and culturally adapting the MHeC to Spanish, we aimed to increase accessibility and availability of e-mental health care in the developing world, and assist vulnerable populations that have migrated to English-speaking countries., (©Laura Ospina-Pinillos, Tracey Davenport, Antonio Mendoza Diaz, Alvaro Navarro-Mancilla, Elizabeth M Scott, Ian B Hickie. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 02.08.2019.)

Background: Each year, many young Australians aged between 16 and 25 years experience a mental health disorder, yet only a small proportion access services and even fewer receive timely and evidence-based treatments. Today, with ever-increasing access to the Internet and use of technology, the potential to provide all young people with access (24 hours a day, 7 days a week) to the support they require to improve their mental health and well-being is promising., Objective: The aim of this study was to use participatory design (PD) as research methodologies with end users (young people aged between 16 and 25 years and youth health professionals) and our research team to develop the Mental Health eClinic (a Web-based mental health clinic) to improve timely access to, and better quality, mental health care for young people across Australia., Methods: A research and development (R&D) cycle for the codesign and build of the Mental Health eClinic included several iterative PD phases: PD workshops; translation of knowledge and ideas generated during workshops to produce mockups of webpages either as hand-drawn sketches or as wireframes (simple layout of a webpage before visual design and content is added); rapid prototyping; and one-on-one consultations with end users to assess the usability of the alpha build of the Mental Health eClinic., Results: Four PD workshops were held with 28 end users (young people n=18, youth health professionals n=10) and our research team (n=8). Each PD workshop was followed by a knowledge translation session. At the conclusion of this cycle, the alpha prototype was built, and one round of one-on-one end user consultation sessions was conducted (n=6; all new participants, young people n=4, youth health professionals n=2). The R&D cycle revealed the importance of five key components for the Mental Health eClinic: a home page with a visible triage system for those requiring urgent help; a comprehensive online physical and mental health assessment; a detailed dashboard of results; a booking and videoconferencing system to enable video visits; and the generation of a personalized well-being plan that includes links to evidence-based, and health professional-recommended, apps and etools., Conclusions: The Mental Health eClinic provides health promotion, triage protocols, screening, assessment, a video visit system, the development of personalized well-being plans, and self-directed mental health support for young people. It presents a technologically advanced and clinically efficient system that can be adapted to suit a variety of settings in which there is an opportunity to connect with young people. This will enable all young people, and especially those currently not able or willing to connect with face-to-face services, to receive best practice clinical services by breaking down traditional barriers to care and making health care more personalized, accessible, affordable, and available., (©Laura Ospina-Pinillos, Tracey A Davenport, Cristina S Ricci, Alyssa C Milton, Elizabeth M Scott, Ian B Hickie. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 28.05.2018.)

Objectives: Mental disorders typically emerge during adolescence and young adulthood and put young people at risk for prolonged socioeconomic difficulties. This study describes the longitudinal course of social and occupational functioning of young people attending primary care-based, early intervention services., Design: A longitudinal study of young people receiving mental healthcare., Setting: Data were collected between January 2005 and August 2017 from a designated primary care-based mental health service., Participants: 554 young people (54% women) aged 12-32 years., Measures: A systematic medical file audit collected clinical and functional information at predetermined time intervals (ie, 3 months to 5+ years) using a clinical pro forma. Group-based trajectory modelling (GBTM) was used to identify distinct trajectories of social and occupational functioning over time (median number of observations per person=4; median follow-up time=23 months)., Results: Between first clinical contact and time last seen, 15% of young people had reliably deteriorated, 23% improved and 62% did not demonstrate substantive change in function. Of the whole cohort, 69% had functional scores less than 70 at time last seen, indicative of ongoing and substantive impairment. GBTM identified six distinct functional trajectories whereby over 60% had moderate-to-serious functional impairment at entry and remained chronically impaired over time; 7% entered with serious impairment and deteriorated further; a quarter were mildly impaired at entry and functionally recovered and only a small minority (4%) presented with serious impairments and functionally improved over time. Not being in education, employment or training, previous hospitalisation and a younger age at baseline emerged as significant predictors of these functional trajectories., Conclusion: Young people with emerging mental disorders have significant functional impairment at presentation for care, and for the majority, it persists over the course of clinical care. In addition to providing clinical care earlier in the course of illness, these data suggest that more sophisticated and more intensive individual-level and organisational strategies may be required to achieve significant and sustained functional improvements., Competing Interests: Competing interests: IH has been a Commissioner in Australia’s National Mental Health Commission since 2012. He is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early intervention youth services at Camperdown under contract to headspace. IH has previously led community-based and pharmaceutical industry-supported (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca) projects focused on the identification and better management of anxiety and depression. He is a Board Member of Psychosis Australia Trust and a member of Veterans Mental Health Clinical Reference group. He was a member of the Medical Advisory Panel for Medibank Private until October 2017. He is the Chief Scientific Advisor to, and an equity shareholder in, Innowell. InnoWell has been formed by the University of Sydney and PwC to administer the $A30 million Australian Government Funded Project Synergy. Project Synergy is a 3-year programme for the transformation of mental health services through the use of innovative technologies. EMS is the Medical Director, Young Adult Mental Health Unit, St Vincent’s Hospital Darlinghurst, Discipline Leader of Adult Mental Health, School of Medicine, University of Notre Dame, Research Affiliate, The University of Sydney and Consultant Psychiatrist. She has received honoraria for educational seminars related to the clinical management of depressive disorders supported by Servier and Eli-Lilly pharmaceuticals. She has participated in a national advisory board for the antidepressant compound Pristiq, manufactured by Pfizer. She was the National Coordinator of an antidepressant trial sponsored by Servier., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To investigate systematically the associations of sleep patterns with a range of mental disorders and other outcomes among a nationally representative sample of US adolescents., Study Design: Using the National Comorbidity Survey Adolescent Supplement, a nationally representative cross-sectional survey of 10 123 US adolescents 13-18 years of age, we assessed associations between adolescent-reported sleep patterns (tertiles of weeknight bedtime, weeknight sleep duration, weekend bedtime delay, and weekend oversleep) and past-year mental disorders based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, smoking, injury, suicidality, and perceived mental and physical health, assessed via direct diagnostic interview., Results: The average weeknight bedtime was at 22:37 and sleep duration was 7.72 hours. Average weekend bedtime delay was 1.81 hours and average weekend oversleep was 1.17 hours. Later weeknight bedtime, shorter weeknight sleep duration, greater weekend bedtime delay, and both short and long periods of weekend oversleep were associated with increased odds of mood, anxiety, substance use, and behavioral disorders, as well as suicidality, tobacco smoking, and poor perceived mental and physical health. ORs ranged from 1.27 to 2.15. The only outcomes not associated with any sleep patterns were past-year injury and eating disorder., Conclusions: Suboptimal sleep patterns were associated with an array of mental disorders and other health-related outcomes among adolescents. Abnormal sleep patterns may serve as markers of prodromal or untreated mental disorders among adolescents, and may provide opportunities for prevention and intervention in mental disorders., (Copyright © 2016. Published by Elsevier Inc.)

This paper describes the extent and nature of Internet use by young people, with specific reference to psychological distress and help-seeking behaviour. It draws on data from an Australian cross-sectional study of 1400 young people aged 16 to 25 years. Nearly all of these young people used the Internet, both as a source of trusted information and as a means of connecting with their peers and discussing problems. A new model of e-mental health care is introduced that is directly informed by these findings. The model creates a system of mental health service delivery spanning the spectrum from general health and wellbeing (including mental health) promotion and prevention to recovery. It is designed to promote health and wellbeing and to complement face-to-face services to enhance clinical care. The model has the potential to improve reach and access to quality mental health care for young people, so that they can receive the right care, at the right time, in the right way.

Objective: Youth with mental health problems often have difficulties engaging in education and employment. In Australia, youth mental health services have been widely established with a key aim of improving role functioning; however, there is little knowledge of those who are not engaged in employment, education or training (NEET) and the factors which may influence this. This study aimed to examine NEET status and its correlates in a sample of such youth., Design: Cross-sectional data from a longitudinal cohort study., Setting: Between January 2011 and August 2012, young people presenting to one of the four primary mental health centres in Sydney or Melbourne were invited to participate., Participants: Young adults (N=696) aged between 15 and 25 years (M=19.0, SD=2.8), 68% female, 58% (n=404) attended headspace in Sydney., Measures: Individuals 'Not in any type of Education, Employment or Training' in the past month were categorised as NEET. Demographic, psychological and clinical factors alongside disability and functioning were assessed using clinical interview and self-report., Results: A total of 19% (n=130/696) were NEET. NEETs were more likely to be male, older, have a history of criminal charges, risky cannabis use, higher level of depression, poorer social functioning, greater disability and economic hardship, and a more advanced stage of mental illness than those engaged in education, training or work. Demographics such as postsecondary education, immigrant background and indigenous background, were not significantly associated with NEET status in this sample., Conclusions: One in five young people seeking help for mental health problems were not in any form of education, employment and training. The commonly observed risk factors did not appear to influence this association, instead, behavioural factors such as criminal offending and cannabis use appeared to require targeted intervention., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: With a rapidly ageing population and increasing life expectancy, programs directed at improving the mental health and quality of life (QOL) of older persons are extremely important. This issue may be particularly relevant in the aged-care residential sector, where very high rates of depression and poor QOL are evident. This study aims to investigate the fixed and modifiable risk factors of psychological distress and QOL in a cohort of Australians aged 60 and over living in residential and community settings., Methods: The study examined the relationship between demographic, health and lifestyle factors and the outcome variables of self-reported QOL and psychological distress (K10 scores) based on data from 626 Australians aged 60 and over from the 45 and Up Study dataset. Univariate and multivariate regression analyses (performed on a subset of 496) examined risk factors related to psychological distress and QOL adjusting for age and residential status., Results: Significant psychological distress was experienced by 15% of the residential sample and 7% of the community sample and in multivariate analyses was predicted by older age, more functional limitations, more time spent sleeping and lower levels of social support (accounting for 18% of the variance). Poorer QOL was predicted by more functional limitations and greater levels of psychological distress. Together these variables accounted for 35% of the variance in QOL ratings., Conclusions: While psychological distress was more common in residential settings, programs targeting modifiable risk factors have the potential to improve QOL and reduce psychological distress in older persons living in both residential and community settings. In particular, promoting health and mobility, optimising sleep-wake cycles and increasing social support may reduce levels of psychological distress and improve QOL.

Background: After 30 years of consensus-derived diagnostic categories in mental health, it is time to head in new directions. Those categories placed great emphasis on enhanced reliability and the capacity to identify them via standardized checklists. Although this enhanced epidemiology and health services planning, it failed to link broad diagnostic groupings to underlying pathophysiology or specific treatment response., Discussion: It is time to adopt new goals that prioritize the validation of clinical entities and foster alternative strategies to support those goals. The value of new dimensions (notably clinical staging), that are both clinically relevant and directly related to emerging developmental and neurobiological research, is proposed. A strong emphasis on 'reverse translation' (that is, working back from the clinic to the laboratory) underpins these novel approaches. However, it relies on using diagnostic groupings that already have strong evidence of links to specific risk factors or patterns of treatment response., Summary: The strategies described abandon the historical divides between clinical neurology, psychiatry and psychology and adopt the promotion of pathways to illness models.

Background: This mixed-methods study was designed to explore young Australian men's attitudes and behaviour in relation to mental health and technology use to inform the development of online mental health services for young men., Methods: National online survey of 486 males (aged 16 to 24) and 17 focus groups involving 118 males (aged 16 to 24)., Results: Young men are heavy users of technology, particularly when it comes to entertainment and connecting with friends, but they are also using technology for finding information and support. The focus group data suggested that young men would be less likely to seek professional help for themselves, citing a preference for self-help and action-oriented strategies instead. Most survey participants reported that they have sought help for a problem online and were satisfied with the help they received. Focus group participants identified potential strategies for how technology could be used to overcome the barriers to help-seeking for young men., Conclusions: The key challenge for online mental health services is to design interventions specifically for young men that are action-based, focus on shifting behaviour and stigma, and are not simply about increasing mental health knowledge. Furthermore, such interventions should be user-driven, informed by young men's views and everyday technology practices, and leverage the influence of peers.

Background: Young men are particularly vulnerable to suicide, drug, and alcohol problems and yet fail to seek appropriate help. An alternative or adjunct to face-to-face services has emerged with widespread uptake of the Internet and related communication technologies, yet very little evidence exists that examines the capacity of the Internet to engage young men and promote help seeking., Objective: To explore young people's attitudes and behaviors in relation to mental health and technology use. The aim was to identify key gender differences to inform the development of online mental health interventions for young men., Methods: A cross-sectional online survey of 1038 young people (aged 16 to 24 years) was used., Results: Young men are more likely than young women to play computer games, access online video/music content, and visit online forums. More than half of young men and women reported that they sought help for a problem online, and the majority were satisfied with the help they received. Significant gender differences were identified in relation to how young people would respond to a friend in need, with young men being less likely than young women to confront the issue directly., Conclusions: Online interventions for young men need to be action-oriented, informed by young men's views and everyday technology practices, and leverage the important role that peers play in the help-seeking process.

Objectives: To examine the levels and growth rates of absolute funding to mental health research from 2001 to 2010, compared with other National Health Priority Areas (NHPAs), and the relative rate of mental health funding compared with other NHPAs, by taking disease burden into account. The quality of Australian research in mental health was also examined using objective indicators of research strength., Design and Setting: Retrospective analysis of levels of funding overall and as a function of mental health domains using data from the National Health and Medical Research Council, with and without adjustment for burden of disease. A keyword analysis was used to assess the success rate of mental health project grant applications. Objective indicators of the quality of Australian mental health research were sought from citation indicators., Main Outcome Measures: Funding for mental health research relative to disease burden; funding according to disease category; project grant success rates., Results: Using actual and adjusted figures, mental health research received a lower proportion of health funding than other NHPAs, including cancer, diabetes and cardiovascular disease. Research projects into substance misuse and autism were proportionately better funded than those in anxiety, depression or schizophrenia. A significant proportion of mental health research funding was awarded to research into ageing. Citation data indicated that mental health research in Australia performed better than research in neuroscience, clinical medicine, microbiology, and pharmacology and toxicology, and at a comparable level to immunology research, despite poor levels of funding., Conclusions: Low levels of funding for mental health research appear to be largely attributable to low capacity. Mental health research in Australia is of high quality, and efforts are needed to build capacity.

Reach Out Central (ROC) is a serious game drawing on the principles of cognitive behaviour theory that has been designed to improve the mental health and wellbeing of young people, particularly men. ROC was developed over a 3-year period from 2003 to 2006, in consultation with young people aged 16-25 years who use the Reach Out mental health website http://www.reachout.com). ROC was launched online in September 2007. A traditional and viral awareness campaign was designed to engage young men, particularly "gamers". In the first month after launch, ROC had 76 045 unique website visits, with 10 542 new members (52% male) joining Reach Out. An independent online evaluation involving 266 young people aged 18-25 years was conducted between August 2007 and February 2008 to examine psychological wellbeing, stigma and help seeking in ROC players. Overall results indicated that ROC was successful in attracting, engaging and educating young people. Young women reported reduced psychological distress and improved life satisfaction, problem solving and help seeking; however, no significant changes were observed for young men. Although ROC was successful in attracting young men, demonstrating that the concept resonates with them, the service failed to keep them engaged. Further research is needed to explore how (or what changes need to be made) to sustain young men's engagement in the game.

The Council of Australian Governments revitalised national mental health reform in 2006. Unfortunately, evidence-based models of collaborative care have not yet been supported. Previous attempts at national reform have lacked a strategic vision. We continue to rely on arrangements that are fragmented between different levels of government, poorly resourced community services, and an embattled public hospital sector. Our persisting unwillingness to record or publicly report key measures of health, social or economic outcomes undermines community confidence in the mental health system. Six priority areas for urgent national action are proposed and linked to key measures of improved health system performance. In Australia, we recognise special groups (such as war veterans) and organise and fund services to meet their specific health needs. Such systems could be readily adapted to meet the needs of people with psychosis.

Autistic adults report concerns with social skills and unemployment. Despite anxiety and difficulty with executive cognitive skills being associated with autism, no studies to date have investigated relationships between anxiety or executive cognition with social and work functioning. This study aimed to investigate the associations between perceived social anxiety, perceived and objective executive function, and perceived social and work functioning in a sample of autistic people. A total of 62 participants completed self-report questionnaires of social anxiety (via the Liebowitz Social Anxiety Scale), mental health (via the Depression Anxiety Stress Scale), executive cognition (via the Behaviour Rating Inventory of Executive Function) and perceived social and work functioning (the Work and Social Adjustment Scale), and a smaller subset (n = 36-40) completed performance-based executive function tasks (Trail Making Task and Rapid Visual Processing Task). Participants who reported having more social anxiety and more difficulty with executive cognition also perceived themselves as having poorer social and work functioning. Performance-based executive function was not related to social or work functioning. Our results suggest that perceived social anxiety and executive cognition are both areas that have potential to be targeted to investigate whether they improve social and vocational outcomes for autistic people.

In this study, we consecutively recruited treatment-seeking young autistic adults without intellectual impairment aged 16-30 years who presented to a mental health service and evaluated general health (distress, quality of life, and disability), functioning (work loss days and social functioning), and mood symptoms (depression, anxiety, and stress) in those diagnosed with autism spectrum disorder (n = 96). This group was compared to young adults presenting to the same service with primary mental health disorders (depression, n = 343; bipolar, n = 132; psychosis, n = 166; and anxiety, n = 303). This study also investigated the influence of mood symptoms on general health and functioning in the autism spectrum disorder group. Young autistic adults reported significant general health and functioning impairments that were of similar degree to those presenting with primary mental health disorders. Interestingly, the autistic group also reported similarly high levels of mood symptoms to those with primary depressive and anxiety disorders. In the autistic group, depressive symptoms were strongly associated with distress, quality of life, and work loss days, while stress symptoms were strongly associated with disability. This study highlights further research, and mental health services are required specifically targeting young autistic adults to address their significant unmet needs.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Purpose: This paper aims to describe the development of WorkOut, an Internet-based program designed to help young men overcome the barriers towards help-seeking and to build the skills they need to understand and manage their own mental health. Information and communication technologies (ICT) hold great potential to significantly improve mental health outcomes for hard-to-reach and traditionally underserved groups. Internet-based programs and mobile phone applications may be particularly appealing to young men due to their convenience, accessibility and privacy and they also address the strong desire for independence and autonomy held by most men. Design/Methodology/Approach: In this paper, we describe the design process itself, and the strategies used for multi-disciplinary collaboration. The initial evaluation process and results are also described which consisted of three distinct phases: website statistics; one-on-one user testing; and pilot interviews. Findings: The results suggest that WorkOut has the potential to attract young men. However, further work is needed to ensure that users remain engaged with the program. Originality/Value: The difficulties encountered and lessons learned provide an insight into the factors that should be considered in the design and evaluation of future ICT-based strategies within the mental health domain, as well as their potential applicability to clinical and educational settings.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

BackgroundVariation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder.MethodsTo conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations.FindingsWe identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10-9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86-0·93, p=6·46 × 10-9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10-21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia.InterpretationThese findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder.FundingNational Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

BackgroundChildhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.MethodsWithin the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.ResultsCM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.ConclusionsSeverity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Background and aimsCannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants.MethodsA twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals.ResultsThe twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P  0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant.ConclusionAge at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

Background and aimsDisentangling the putative impact of cannabis on brain morphology from other comorbid substance use is critical. After controlling for the effects of nicotine, alcohol and multi-substance use, this study aimed to determine whether frequent cannabis use is associated with significantly smaller subcortical grey matter volumes.DesignExploratory analyses using mixed linear models, one per region of interest (ROI), were performed whereby individual differences in volume (outcome) at seven subcortical ROIs were regressed onto cannabis and comorbid substance use (predictors).SettingTwo large population-based twin samples from the United States and Australia.ParticipantsA total of 622 young Australian adults [66% female; μage  = 25.9, standard deviation SD) = 3.6] and 474 middle-aged US males (μage  = 56.1SD = 2.6 ) of predominately Anglo-Saxon ancestry with complete substance use and imaging data. Subjects with a history of stroke or traumatic brain injury were excluded.MeasurementsMagnetic resonance imaging (MRI) and volumetric segmentation methods were used to estimate volume in seven subcortical ROIs: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens. Substance use measurements included maximum nicotine and alcohol use, total life-time multi-substance use, maximum cannabis use in the young adults and regular cannabis use in the middle-aged males.FindingsAfter correcting for multiple testing (P = 0.007), cannabis use was unrelated to any subcortical ROI. However, maximum nicotine use was associated with significantly smaller thalamus volumes in middle-aged males.ConclusionsIn exploratory analyses based on young adult and middle-aged samples, normal variation in cannabis use is unrelated statistically to individual differences in brain morphology as measured by subcortical volume.