Identifying pathways to early-onset metabolic dysfunction, insulin resistance and inflammation in young adult inpatients with emerging affective and major mood disorders.

AIM: Young people with common mood disorders face the prospect of shortened life expectancy largely due to premature cardiovascular disease. Metabolic dysfunction is a risk factor for premature cardiovascular disease. There is an ongoing debate whether metabolic dysfunction can be simply explained by weight gain secondary to psychotropic medications or whether shared genetic vulnerability, intrinsic immune-metabolic disturbances or other system perturbations (e.g. dysregulated sympathetic nervous system, circadian dysfunction) are more relevant determinants of premature cardiovascular disease. Thus, we aimed to investigate underlying drivers of metabolic dysfunction and premature cardiovascular disease in young people in the early phases of common mood disorders. METHODS: We evaluated the relationships between insulin resistance (assessed by HOMA2-IR) and body mass index (BMI), sex, diagnosis, medication, inflammatory markers and hormonal factors in 327 inpatients with emerging affective and major mood disorders admitted to the Young Adult Mental Health Unit, St Vincent's Private Hospital, Sydney. RESULTS: While HOMA2-IR scores were positively associated with BMI (rs  = 0.465, p < .001), they were also higher in those prescribed mood stabilizers (p = .044) but were not associated with specific diagnoses, other medication types or the number of prescribed medications. Further, high-sensitivity C-reactive protein levels (but not thyroid-stimulating hormone and ferritin levels) were positively associated with HOMA2-IR (rs  = 0. 272, p < .001) and BMI (rs  = . 409, p < .001). CONCLUSIONS: In addition to BMI, other non-specific markers of inflammation are associated with early metabolic dysfunction in young people with emerging affective and major mood disorders.

Protocol for a young adult mental health (Uspace) cohort: personalising multidimensional care in young people admitted to hospital.

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.

Youth Mental Health Tracker: protocol to establish a longitudinal cohort and research database for young people attending Australian mental health services.

INTRODUCTION: Mental 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 ANALYSIS: Recruitment 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 DISSEMINATION: The 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.

Transdiagnostic neurocognitive subgroups and functional course in young people with emerging mental disorders: a cohort study.

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.

Right care, first time: a highly personalised and measurement-based care model to manage youth mental health.

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, includingreal-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.

Developing neurocognitive standard clinical care: A study of young adult inpatients.

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 ±â€¯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.

A case study of feedback and cognitive assessment of a young adult inpatient with major depressive disorder.

OBJECTIVES: Neurocognitive assessment and feedback to a young adult inpatient. METHODS: Computerised neurocognitive assessment and feedback. RESULTS: A collaborative process of personalised intervention. CONCLUSIONS: Personalised feedback in this setting can be employed as a management tool to identify and prioritise care.

The course of neuropsychological functioning in young people with attenuated vs discrete mental disorders.

AIM: Clinical staging of mental disorders is designed to facilitate the selection of stage-appropriate interventions, early in the course of illness. Neuropsychological performance, particularly at early stages of mental disorder, is a strong predictor of medium-term functional outcomes. Despite this, the longitudinal examination of neuropsychological profiles in early stages of illness is poorly researched. Thus, we examined baseline and longitudinal neuropsychological profiles of young patients with attenuated syndromes vs those with discrete disorders. METHODS: Neuropsychological testing of 497 help-seeking young people (21.2 ± 3 years; 56% female). Clinical staging, assigned separately from testing, rated 262 individuals as "attenuated syndrome" (stage 1b) and 235 as "discrete" or "persistent" disorder (stage 2+). Follow-up testing was undertaken in 170 individuals (54% at stage 1b) after 19.8 ± 9 months (range: 3 to 51 months). RESULTS: At baseline, attenuated and discrete/persistent disorders significantly differed in 4 of the 9 neuropsychological measures (verbal learning, verbal memory, visual memory and set shifting). Despite this, both groups showed similar improvement in neuropsychological functioning at follow-up, particularly in processing speed, sustained attention and visual memory. Longitudinal improvement in cognition corresponded with increases in socio-occupational functioning. DISCUSSION: The degree of baseline neuropsychological dysfunction discriminates those with attenuated syndromes from those with a discrete/persistent disorder. Furthermore, improvement in neuropsychological functioning corresponded with improvement in clinical and functional status, despite stage of illness. This suggests that neuropsychological functioning remains relatively stable in young people with a mental illness and may be a critical window for intervention.

Neurocognitive clusters: A pilot study of young people with affective disorders in an inpatient facility.

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.