Search

Objective To identify trajectories of social and occupational functioning in young people during the two years after presenting for early intervention mental health care; to identify demographic and clinical factors that influence these trajectories. Design Longitudinal, observational study of young people presenting for mental health care. Setting Two primary care-based early intervention mental health services at the Brain and Mind Centre (University of Sydney), 1 June 2008 - 31 July 2018. Participants 1510 people aged 12-25 years who had presented with anxiety, mood, or psychotic disorders, for whom two years' follow-up data were available for analysis. Main outcome measures Latent class trajectories of social and occupational functioning based on growth mixture modelling of Social and Occupational Assessment Scale (SOFAS) scores. Results We identified four trajectories of functioning during the first two years of care: deteriorating and volatile (733 participants, 49%); persistent impairment (237, 16%); stable good functioning (291, 19%); and improving, but late recurrence (249, 16%). The less favourable trajectories (deteriorating and volatile; persistent impairment) were associated with physical comorbidity, not being in education, employment, or training, having substance-related disorders, having been hospitalised, and having a childhood onset mental disorder, psychosis-like experiences, or a history of self-harm or suicidality. Conclusions Two in three young people with emerging mental disorders did not experience meaningful improvement in social and occupational functioning during two years of early intervention care. Most functional trajectories were also quite volatile, indicating the need for dynamic service models that emphasise multidisciplinary interventions and measurement-based care.

Background The World Economic Forum has recently highlighted substantial problems in mental health service provision and called for the rapid deployment of smarter, digitally-enhanced health services as a means to facilitate effective care coordination and address issues of demand. In mental health, the biggest enabler of digital solutions is the implementation of an effective model of care that is facilitated by integrated health information technologies (HITs); the latter ensuring the solution is easily accessible, scalable and sustainable. The University of Sydney’s Brain and Mind Centre (BMC) has developed an innovative digital health solution – delivered through the Youth Mental Health and Technology Program – which incorporates two components: 1) a highly personalised and measurement-based (data-driven) model of youth mental health care; and 2) an industrial grade HIT registered on the Australian Register of Therapeutic Goods. This paper describes a research protocol to evaluate the impact of implementing the BMC’s digital health solution into youth mental health services (i.e. headspace - a highly accessible, youth-friendly integrated service that responds to the mental health, physical health, alcohol or other substance use, and vocational concerns of young people aged 12 to 25 years) within urban and regional areas of Australia. Methods The digital health solution will be implemented into participating headspace centres using a naturalistic research design. Quantitative and qualitative data will be collected from headspace health professionals, service managers and administrators, as well as from lead agency and local Primary Health Network (PHN) staff, via service audits, Implementation Officer logs, online surveys, and semi-structured interviews, at baseline and then three-monthly intervals over the course of 12 months. Discussion At the time of publication, six headspace centres had been recruited to this study and had commenced implementation and impact evaluation. The first results are expected to be submitted for publication in 2021. This study will focus on the impact of implementing a digital health solution at both a service and staff level, and will evaluate digital readiness of service and staff adoption; quality, usability and acceptability of the solution by staff; staff self-reported clinical competency; overall impact on headspace centres as well as their lead agencies and local PHNs; and social return on investment.

BackgroundPredictors of new-onset bipolar disorder (BD) or psychotic disorder (PD) have been proposed on the basis of retrospective or prospective studies of ‘at-risk’ cohorts. Few studies have compared concurrently or longitudinally factors associated with the onset of BD or PDs in youth presenting to early intervention services. We aimed to identify clinical predictors of the onset of full-threshold (FT) BD or PD in this population.MethodMulti-state Markov modelling was used to assess the relationships between baseline characteristics and the likelihood of the onset of FT BD or PD in youth (aged 12–30) presenting to mental health services.ResultsOf 2330 individuals assessed longitudinally, 4.3% (n = 100) met criteria for new-onset FT BD and 2.2% (n = 51) met criteria for a new-onset FT PD. The emergence of FT BD was associated with older age, lower social and occupational functioning, mania-like experiences (MLE), suicide attempts, reduced incidence of physical illness, childhood-onset depression, and childhood-onset anxiety. The emergence of a PD was associated with older age, male sex, psychosis-like experiences (PLE), suicide attempts, stimulant use, and childhood-onset depression.ConclusionsIdentifying risk factors for the onset of either BD or PDs in young people presenting to early intervention services is assisted not only by the increased focus on MLE and PLE, but also by recognising the predictive significance of poorer social function, childhood-onset anxiety and mood disorders, and suicide attempts prior to the time of entry to services. Secondary prevention may be enhanced by greater attention to those risk factors that are modifiable or shared by both illness trajectories.

ObjectiveIdentifying brain differences associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and generating effective approaches to early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth.MethodsFirst, we examined associations among regional brain structure and STBs, which were assessed in six samples of youth with mood disorders, using the Columbia Suicide Severity Rating Scale (C-SSRS;N=577). Second, we combined this sample with a larger sample (total 21 sites) in which STBs were assessed using various instruments. MRI metrics were compared among healthy controls without STBs (HC;N=688), clinical controls without STBs (CC;N=648), and young people with psychiatric diagnoses and current suicidal ideation (N=406). In separate analyses, MRI metrics were compared among HCs (N=335), CCs (N=768), and suicide attempters (N=254).ResultsIn the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and history of actual suicide attempts (N=163) than those without (N=394; FDR-pd=.334). When expanding to more clinically heterogeneous samples, we also found lower surface area of the frontal pole in those with a history of suicide attempts (Cohen’sd=.22).ConclusionsLower frontal pole surface area may represent a vulnerability for a suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.

Most mental disorders emerge before the age of 25 years and, if left untreated, have the potential to lead to considerable lifetime burden of disease. Many services struggle to manage high demand and have difficulty matching individuals to timely interventions due to the heterogeneity of disorders. The technological implementation of clinical staging for youth mental health may assist the early detection and treatment of mental disorders. We describe the development of a theory-based automated protocol to facilitate the initial clinical staging process, its intended use, and strategies for protocol validation and refinement. The automated clinical staging protocol leverages the clinical validation and evidence base of the staging model to improve its standardization, scalability, and utility by deploying it using Health Information Technologies (HIT). Its use has the potential to enhance clinical decision-making and transform existing care pathways, but further validation and evaluation of the tool in real-world settings is needed.

Neurocognitive impairment is commonly associated with functional disability in established depressive, bipolar and psychotic disorders. However, little is known about the longer-term functional implications of these impairments in early phase transdiagnostic cohorts. We aimed to examine associations between neurocognition and functioning at baseline and over time. We used mixed effects models to investigate associations between neurocognitive test scores and longitudinal social and occupational functioning (“Social and Occupational Functioning Assessment Scale”) at 1–7 timepoints over five-years in 767 individuals accessing youth mental health services. Analyses were adjusted for age, sex, premorbid IQ, and symptom severity. Lower baseline functioning was associated with male sex (coefficient −3.78, 95% CI −5.22 to −2.34 p

Neuropsychological assessments have provided the field of psychiatry with important information about patients. As an assessment tool, a neuropsychological battery can be useful in a clinical setting; however, implementation as standard clinical care in an inpatient unit has not been extensively evaluated. A computerized cognitive battery was administered to 103 current young adult inpatients (19.2 ± 3.1 years; 72% female) with affective disorder. Neurocognitive tasks included Verbal Recognition Memory (VRM), Attention Switching (AST), Paired Association Learning (PAL), and Rapid Visual Processing (RVP). Patients also completed a computerized self-report questionnaire evaluating subjective impressions of their cognition. Hierarchical cluster analysis determined three neurocognitive subgroups: cluster 1 (n = 17) showed a more impaired neurocognitive profile on three of the four variables compared to their peers in cluster 2 (n = 59), and cluster 3 (n = 27), who had the most impaired attentional shifting. Two of the four neurocognitive variables were significantly different between all three cluster groups (verbal learning and sustained attention). Overall group results showed an association between poorer sustained attention and increased suicidal ideation. These findings strengthen the idea that neurocognitive profiles may play an important role in better understanding the severity of illness in young inpatients with major psychiatric disorders.

IntroductionApproximately 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 analysisThis 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 disseminationThis 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.

Background The schizophrenia polygenic risk score (SCZ-PRS) is an emerging tool in psychiatry. Aims We aimed to evaluate the utility of SCZ-PRS in a young, transdiagnostic, clinical cohort. Method SCZ-PRSs were calculated for young people who presented to early-intervention youth mental health clinics, including 158 patients of European ancestry, 113 of whom had longitudinal outcome data. We examined associations between SCZ-PRS and diagnosis, clinical stage and functioning at initial assessment, and new-onset psychotic disorder, clinical stage transition and functional course over time in contact with services. Results Compared with a control group, patients had elevated PRSs for schizophrenia, bipolar disorder and depression, but not for any non-psychiatric phenotype (for example cardiovascular disease). Higher SCZ-PRSs were elevated in participants with psychotic, bipolar, depressive, anxiety and other disorders. At initial assessment, overall SCZ-PRSs were associated with psychotic disorder (odds ratio (OR) per s.d. increase in SCZ-PRS was 1.68, 95% CI 1.08–2.59, P = 0.020), but not assignment as clinical stage 2+ (i.e. discrete, persistent or recurrent disorder) (OR = 0.90, 95% CI 0.64–1.26, P = 0.53) or functioning (R = 0.03, P = 0.76). Longitudinally, overall SCZ-PRSs were not significantly associated with new-onset psychotic disorder (OR = 0.84, 95% CI 0.34–2.03, P = 0.69), clinical stage transition (OR = 1.02, 95% CI 0.70–1.48, P = 0.92) or persistent functional impairment (OR = 0.84, 95% CI 0.52–1.38, P = 0.50). Conclusions In this preliminary study, SCZ-PRSs were associated with psychotic disorder at initial assessment in a young, transdiagnostic, clinical cohort accessing early-intervention services. Larger clinical studies are needed to further evaluate the clinical utility of SCZ-PRSs, especially among individuals with high SCZ-PRS burden.

The demand for mental health services is projected to rapidly increase as a direct and indirect result of the COVID-19 pandemic. Given that young people are disproportionately disadvantaged by mental illness and will face further challenges related to the COVID-19 pandemic, it is crucial to deliver appropriate mental health care to young people as early as possible. Integrating digital health solutions into mental health service delivery pathways has the potential to greatly increase efficiencies, enabling the provision of “right care, first time.” We propose an innovative digital health solution for demand management intended for use by primary youth mental health services, comprised of (1) a youth mental health model of care (ie, the Brain and Mind Centre Youth Model) and (2) a health information technology specifically designed to deliver this model of care (eg, the InnoWell Platform). We also propose an operational protocol of how this solution could be applied to primary youth mental health service delivery processes. By “flipping” the conventional service delivery models of majority in-clinic and minority web-delivered care to a model where web-delivered care is the default, this digital health solution offers a scalable way of delivering quality youth mental health care both in response to public health crises (such as the COVID-19 pandemic) and on an ongoing basis in the future.

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.

BackgroundA priority for health services is to reduce self-harm in young people. Predicting self-harm is challenging due to their rarity and complexity, however this does not preclude the utility of prediction models to improve decision-making regarding a service response in terms of more detailed assessments and/or intervention. The aim of this study was to predict self-harm within six-months after initial presentation.MethodThe study included 1962 young people (12–30 years) presenting to youth mental health services in Australia. Six machine learning algorithms were trained and tested with ten repeats of ten-fold cross-validation. The net benefit of these models were evaluated using decision curve analysis.ResultsOut of 1962 young people, 320 (16%) engaged in self-harm in the six months after first assessment and 1642 (84%) did not. The top 25% of young people as ranked by mean predicted probability accounted for 51.6% - 56.2% of all who engaged in self-harm. By the top 50%, this increased to 82.1%-84.4%. Models demonstrated fair overall prediction (AUROCs; 0.744–0.755) and calibration which indicates that predicted probabilities were close to the true probabilities (brier scores; 0.185–0.196). The net benefit of these models were positive and superior to the ‘treat everyone’ strategy. The strongest predictors were (in ranked order); a history of self-harm, age, social and occupational functioning, sex, bipolar disorder, psychosis-like experiences, treatment with antipsychotics, and a history of suicide ideation.ConclusionPrediction models for self-harm may have utility to identify a large sub population who would benefit from further assessment and targeted (low intensity) interventions. Such models could enhance health service approaches to identify and reduce self-harm, a considerable source of distress, morbidity, ongoing health care utilisation and mortality.

Background Evidence from family and twin studies suggests that mood and anxiety disorders, and related temperamental factors may share common etiologic factors. We examine the familial aggregation and coaggregation of anxiety disorder subtypes and anxiety-related temperamental traits, and their association with mood disorders. Methods A total of 477 probands and 549 first-degree adult relatives from a large community based family study of affective spectrum disorders completed semi-structured diagnostic interviews and self-reported assessments of temperamental traits including: negative affectivity on the ‘Positive and Negative Affect Schedule’ (PANAS), neuroticism anxiety on the ‘Zuckerman-Kuhlman Personality Questionnaire’ (ZKPQ), and anxiety sensitivity on the ‘Anxiety Sensitivity Index’ (ASI). Results The anxiety-related temperamental traits of negative affectivity, neuroticism anxiety and anxiety sensitivity had significant familial specificity, even after controlling for comorbid mood and anxiety disorders in probands and relatives. Yet, these traits in probands did not predict anxiety disorders in relatives. Although some anxiety subtypes were familial, there were no longer familial links between anxiety disorder subtypes (generalized anxiety disorder, social anxiety or panic disorder) after controlling for mood disorder subtypes in probands and relatives. Limitations Cross-sectional interviews were used to estimate disorders, and self-report measures were used for temperamental traits. Conclusions These results confirm previous research regarding familial overlap between anxiety subtypes and mood disorders, however their shared liability cannot be fully explained by anxiety-related temperamental traits. These findings suggest that anxiety-related temperamental traits may indicate a vulnerability for mood and anxiety disorders or a potential consequence of these conditions.

Background: There is growing evidence to support the need for personalised intervention in the early stages of a major psychiatric illness, as well as the clear delineation of subgroups in psychiatric disorders based on cognitive impairment. Affective disorders are often accompanied by neurocognitive deficits; however a lack of research among young adult inpatients highlights the need to assess the utility of cognitive testing in this population. Methods: A computerised cognitive battery was administered to 50 current inpatient young adults (16–30 years; 75% female) with an affective disorder. Patients also completed a computerised self-report questionnaire (to measure demographics and clinical features) that included items evaluating subjective impressions of their cognition. Results: Hierarchical cluster analysis determined two neurocognitive subgroups: cluster 1 (n = 16) showed more severe impairments in sustained attention and memory as well as higher anxiety levels, compared to their peers in cluster 2 (n = 30) who showed the most impaired attentional switching. Across the sample, poor sustained attention was significantly correlated with higher levels of current anxiety and depressive symptoms, whereas poor verbal memory was significantly associated with increased psychological distress. Limitations: This study has a relatively small sample size (due to it being a pilot/feasibility study). Furthermore, future studies should aim to assess inpatient samples compared to community care samples, as well as healthy controls, on a larger scale. Conclusions: The findings suggest neurocognitive profiles are important in understanding phenotypes within young people with severe affective disorders. With clear subgroups based on cognitive impairment being demonstrated, the clinical utility and use of new and emerging technologies is warranted in such inpatients facilities. This pilot/feasibility study has strengthened the utility of cognitive screening as standard clinical care in an inpatient unit.

PurposeThe Brain and Mind Centre (BMC)Optymisecohort assesses multiple clinical and functional domains longitudinally in young people presenting for mental health care and treatment. Longitudinal tracking of this cohort will allow investigation of the relationships between multiple outcome domains across the course of care. Subsets ofOptymisehave completed detailed neuropsychological and neurobiological assessments, permitting investigation of associations between these measures and longitudinal course.ParticipantsYoung people (aged 12–30) presenting to clinics coordinated by the BMC were recruited to a research register (n=6743) progressively between June 2008 and July 2018. To date, 2767 individuals have been included inOptymisebased on the availability of at least one detailed clinical assessment.MeasuresTrained researchers use a clinical research proforma to extract key data from clinical files to detail social and occupational functioning, clinical presentation, self-harm and suicidal thoughts and behaviours, alcohol and other substance use, physical health comorbidities, personal and family history of mental illness, and treatment utilisation at the following time points: baseline, 3, 6, 12, 24, 36, 48, and 60 months, and time last seen.Findings to dateThere is moderate to substantial agreement between raters for data collected via the proforma. While wide variations in individual illness course are clear, social and occupational outcomes suggest that the majority of cohort members show no improvement in functioning over time. Differential rates of longitudinal transition are reported between early and late stages of illness, with a number of baseline factors associated with these transitions. Furthermore, there are longitudinal associations between prior suicide attempts and inferior clinical and functional outcomes.Future plansFuture reports will detail the longitudinal course of each outcome domain and examine multidirectional relationships between these domains both cross-sectionally and longitudinally, and explore in subsets the associations between detailed neurobiological measures and clinical, social and functional outcomes.

Background Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries. Aims To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course. Method Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder. Results Cluster analysis of neurocognitive test scores derived three subgroups described as ‘normal range’ (n = 243, 38.6%), ‘intermediate impairment’ (n = 252, 40.1%), and ‘global impairment’ (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI −0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI −0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time. Conclusions Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.

A key population-health priority is to reduce the rates of premature death and illness burden due to the common anxiety and mood disorders that typically have their onset during adolescence and early-adult years. From an individual clinical and health services planning perspective, evidence relating to the potential impacts of early identification, secondary prevention, and enhanced long-term care strategies is required. Over the past decade, we have accumulated substantial cross-sectional and longitudinal evidence from a cohort of more than 7000 individuals detailing how these types of services can be developed, structured, and evaluated for young people with emerging mood disorders. A clear conclusion is that impairment and concurrent morbidity is well-established in these young people (mean age 18 years) by the time they present for mental health-focused care. A clear caveat, however, is that early identification, followed by standard care, does not automatically result in improved outcomes. While much work is yet to be done in the development of individual-level and service-level care packages to reduce morbidity and mortality, our key findings support the utility of clinical staging as an adjunct to traditional diagnostic frameworks, the recognition of at least three pathophysiological underlying paths (resulting in different age-dependent phenotypes in childhood and adolescence), and a strong focus on implementing a genuinely multidimensional assessment and longitudinal outcomes framework.

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.

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.

ObjectivesTo report the distribution and predictors of insulin resistance (IR) in young people presenting to primary care-based mental health services.DesignCross-sectional.SettingHeadspace-linked clinics operated by the Brain and Mind Centre of the University of Sydney.Participants768 young people (66% female, mean age 19.7±3.5, range 12–30 years).Main outcome measuresIR was estimated using the updated homeostatic model assessment (HOMA2-IR). Height and weight were collected from direct measurement or self-report for body mass index (BMI).ResultsFor BMI, 20.6% of the cohort were overweight and 10.2% were obese. However, 6.9 mmol/L). By contrast, 9.9% had a HOMA2-IR score >2.0 (suggesting development of IR) and 11.7% (n=90) had a score between 1.5 and 2. Further, there was a positive correlation between BMI and HOMA2-IR (r=0.44, p(2,361)=52.1, pConclusionsEmerging IR is evident in a significant subgroup of young people presenting to primary care-based mental health services. While the major modifiable risk factor is BMI, a large proportion of the variance is not accounted for by other demographic, clinical or treatment factors. Given the early emergence of IR, secondary prevention interventions may need to commence prior to the development of full-threshold or major mood or psychotic disorders.

The present study investigated differences in white matter (WM) integrity between 96 young people with affective and/or psychotic symptoms classified at an early stage of mental disorder (i.e. 'attenuated syndrome'; stage 1b), 85 young people classified at a more advanced stage of mental disorder (i.e. 'discrete disorder'; stage 2), and 81 demographically matched healthy controls using diffusion tensor imaging. The relationship between WM integrity (indexed by fractional anisotropy; FA) across the tracts and neuropsychological functioning was also investigated. A significant reduction in FA was identified in those with more advanced disorder in the body of the corpus callosum. Clinical stage groups were associated with significant neuropsychological impairment, which was significantly greater in those with discrete disorders. Compared to those in the earlier stage of disorder, participants at the later clinical stage showed decreased FA in the body of the corpus callosum that was associated with worse performance in attentional set formation maintenance, shifting and flexibility. These results provide further support for clinical staging of mental disorder and highlight the potential for utilising neuroanatomical biomarkers to support the classification of stages of mental disorder in the future.

Background Although numerous studies have demonstrated sex differences in the prevalence of suicidal thoughts and behaviors (STB), there is a clear lack of research examining the similarities and differences between men and women in terms of the relationship between STB, transitional life events, and the coping strategies employed after experiencing such events when they are perceived as stressful. Objective This study aims to examine the differences between men’s and women’s experiences of STB, sociodemographic predictors of STB, and how coping responses after experiencing a stressful transitional life event predict STB. Methods A web-based self-report survey was used to assess the health and well-being of a voluntary community-based sample of men and women aged 16 years and older, living in Australia, Canada, New Zealand, the United Kingdom, and the United States, who were recruited using web-based social media promotion and snowballing. Results In total, 10,765 eligible web-based respondents participated. Compared with men, a significantly greater proportion of women reported STB (P Conclusions This research highlights multiple risk factors for STB, one of which includes experiencing at least one stressful transitional life event in the past 12 months. When individuals are experiencing such events, support from services and the community alike should consider using sex-specific or targeted strategies, as this research indicates that compared with women, more men do nothing when experiencing stress after a transitional life event and may be waiting until they experience STB to engage with their social networks for support.

IntroductionMental disorders are a leading cause of long-term disability worldwide. Much of the burden of mental ill-health is mediated by early onset, comorbidities with physical health conditions and chronicity of the illnesses. This study aims to track the early period of mental disorders among young people presenting to Australian mental health services to facilitate more streamlined transdiagnostic processes, highly personalised and measurement-based care, secondary prevention and enhanced long-term outcomes.Methods and analysisRecruitment to this large-scale, multisite, prospective, transdiagnostic, longitudinal clinical cohort study (‘Youth Mental Health Tracker’) will be offered to all young people between the ages of 12 and 30 years presenting to participating services with proficiency in English and no history of intellectual disability. Young people will be tracked over 3 years with standardised assessments at baseline and 3, 6, 12, 24 and 36 months. Assessments will include self-report and clinician-administered measures, covering five key domains including: (1) social and occupational function; (2) self-harm, suicidal thoughts and behaviour; (3) alcohol or other substance misuse; (4) physical health; and (5) illness type, clinical stage and trajectory. Data collection will be facilitated by the use of health information technology. The data will be used to: (1) determine prospectively the course of multidimensional functional outcomes, based on the differential impact of demographics, medication, psychological interventions and other key potentially modifiable moderator variables and (2) map pathophysiological mechanisms and clinical illness trajectories to determine transition rates of young people to more severe illness forms.Ethics and disseminationThe study has been reviewed and approved by the Human Research Ethics Committee of the Sydney Local Health District (2019/ETH00469). All data will be non-identifiable, and research findings will be disseminated through peer-reviewed journals and scientific conference presentations.

Abstract. The vagus nerve is a major constituent in the bidirectional relationship between the heart and the prefrontal cortex. This study investigated the role of the vagus in social cognition using the cold face test (facial cooling) to stimulate the vagus nerve and increase prefrontal inhibitory control. Heart Rate Variability (HRV) was measured to index parasympathetic outflow while social cognition ability was tested using the Reading the Mind in the Eyes Test (RMET). Healthy males (n = 25) completed the RMET under two conditions: with and without facial cooling. Results indicated that although facial cooling increased HRV at rest, there was no improvement in the RMET during the facial cooling condition. Interestingly, completing the RMET with facial cooling abolished this increase in HRV, suggesting interference along the vagal reflex arc. These results are consistent with the involvement of a common cortico-subcortical circuit in autonomic and cognitive processes, important for emotion recognition.

Background: Globally there is increasing recognition that new strategies are required to reduce disability due to common mental health problems. As 75% of mental health and substance use disorders emerge during the teenage or early adulthood years, these strategies need to be readily accessible to young people. When considering how to provide such services at scale, new and innovative technologies show promise in augmenting traditional clinic-based services. Objective: The aim of this study was to test new and innovative technologies to assess clinical stage in early intervention youth mental health services using a prototypic online system known as the Mental Health eClinic (MHeC). Methods: The online assessment within the MHeC was compared directly against traditional clinician assessment within 2 Sydney-based youth-specific mental health services (headspace Camperdown and headspace Campbelltown). A total of 204 young people were recruited to the study. Eligible participants completed both face-to-face and online assessments, which were randomly allocated and counterbalanced at a 1-to-3 ratio. These assessments were (1) a traditional 45- to 60-minute headspace face-to-face assessment performed by a Youth Access Clinician and (2) an approximate 60-minute online assessment (including a self-report Web-based survey, immediate dashboard of results, and a video visit with a clinician). All assessments were completed within a 2-week timeframe from initial presentation. Results: Of the 72 participants who completed the study, 71% (51/72) were female and the mean age was 20.4 years (aged 16 to 25 years); 68% (49/72) of participants were recruited from headspace Camperdown and the remaining 32% (23/72) from headspace Campbelltown. Interrater agreement of participants’ stage, as determined after face-to-face assessment or online assessment, demonstrated fair agreement (kappa=.39, P

ObjectivesMental 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.DesignA longitudinal study of young people receiving mental healthcare.SettingData were collected between January 2005 and August 2017 from a designated primary care-based mental health service.Participants554 young people (54% women) aged 12–32 years.MeasuresA 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).ResultsBetween 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.ConclusionYoung 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.

Background Mood and anxiety disorders are leading causes of disability and mortality, due largely to their onset during adolescence and young adulthood and broader impact on functioning. Key factors that are associated with disability and these disorders in young people are social and economic participation (e.g. education, employment), physical health, suicide and self-harm behaviours, and alcohol and substance use. A better understanding of the objective markers (i.e. neurobiological parameters) associated with these factors is important for the development of effective early interventions that reduce the impact of disability and illness persistence. Methods We systematically reviewed the literature for neurobiological parameters (i.e. neuropsychology, neuroimaging, sleep-wake and circadian biology, neurophysiology and metabolic measures) associated with functional domains in young people (12 to 30 years) with mood and/or anxiety disorders. Results Of the one hundred and thirty-four studies selected, 7.6 % investigated social and economic participation, 2.1 % physical health, 15.3 % suicide and self-harm behaviours, 6.9 % alcohol and substance use, whereas the majority (68.1 %) focussed on clinical syndrome. Conclusions Despite the predominance of studies that solely examine the clinical syndrome of young people the literature also provides evidence of distinct associations among objective measures (indexing various aspects of brain circuitry) and other functional domains. We suggest that a shift in focus towards characterising the mechanisms that underlie and/or mediate multiple functional domains will optimise personalised interventions and improve illness trajectories.