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There is significant interest in the possible influence of chronotype on clinical states in young people with emerging mental disorders. We apply a dynamic approach (bivariate latent change score modelling) to examine the possible prospective influence of chronotype on depressive and hypo/manic symptoms in a youth cohort with predominantly depressive, bipolar, and psychotic disorders (N = 118; 14–30-years), who completed a baseline and follow-up assessment of these constructs (mean interval = 1.8-years). Our primary hypotheses were that greater baseline eveningness would predict increases in depressive but not hypo/manic symptoms. We found moderate to strong autoregressive effects for chronotype (β = -0.447 to −0.448, p < 0.001), depressive (β = -0.650, p < 0.001) and hypo/manic symptoms (β = -0.819, p < 0.001). Against our predictions, baseline chronotypes did not predict change in depressive (β = -0.016, p = 0.810) or hypo/manic symptoms (β = 0.077, p = 0.104). Similarly, the change in chronotype did not correlate with the change in depressive symptoms (β = -0.096, p = 0.295) nor did the change in chronotype and the change in hypo/manic symptoms (β = -0.166, p = 0.070). These data suggest that chronotypes may have low utility for predicting future hypo/manic and depressive symptoms in the short term, or that more frequent assessments over longer periods are needed to observe these associations. Future studies should test whether other circadian phenotypes (e.g. sleep-wake variability) are better indicators of illness course.

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.

A rate-limiting step in the prevention and early intervention of depressive disorders in young people is our insufficient understanding of causal mechanisms. One plausible pathophysiological pathway is disturbance in the 24 h sleep-wake cycle and the underlying circadian system. Abnormalities in circadian rhythms are well documented in adults with various depressive disorders and have been linked to core clinical features, including unstable mood, daytime fatigue, non-restorative sleep, reduced motor activity, somatic symptoms, and appetite and weight change. In this Review, we summarise four areas of research: basic circadian biology and animal models of circadian disturbances; developmental changes in circadian rhythms during adolescence and implications for the emergence of adolescent-onset depressive syndromes; community and clinical studies linking 24 h sleep-wake cycle disturbances and depressive disorders; and clinical trials of circadian-based treatments. We present recommendations based on a highly personalised, early intervention model for circadian-linked depression in young people.

Major mood syndromes are among the most common and disabling mental disorders. However, a lack of clear delineation of their underlying pathophysiological mechanisms is a major barrier to prevention and optimised treatments. Dysfunction of the 24-h circadian system is a candidate mechanism that has genetic, behavioural, and neurobiological links to mood syndromes. Here, we outline evidence for a new clinical phenotype, which we have called ‘circadian depression’. We propose that key clinical characteristics of circadian depression include disrupted 24-h sleep-wake cycles, reduced motor activity, low subjective energy, and weight gain. The illness course includes early age-of-onset, phenomena suggestive of bipolarity (defined by bidirectional associations between objective motor and subjective energy/mood states), poor response to conventional antidepressant medications, and concurrent cardiometabolic and inflammatory disturbances. Identifying this phenotype could be clinically valuable, as circadian-targeted strategies show promise for reducing depressive symptoms and stabilising illness course. Further investigation of underlying circadian disturbances in mood syndromes is needed to evaluate the clinical utility of this phenotype and guide the optimal use of circadian-targeted interventions.

Sleep fragmentation and reductions in sleep spindles have been observed in individuals with depression. Sleep spindles are known to play a protective role for sleep, and there are indications that melatonin agents can enhance spindles in healthy people. Whether agomelatine, a melatonin agonist indicated for the treatment of depression, may increase spindle density sufficiently to impact sleep continuity in people with depression remains unknown. This proof-of-concept study investigated changes in spindles following agomelatine intake in young adults with depression and assessed how they may relate to potential changes in sleep continuity and depressive symptoms. This study was based on an open-label design. Fifteen participants between 17 and 28 years of age (mean = 22.2; standard deviation [SD] = 3.4) with a diagnosis of a depressive disorder underwent polysomnography before and after an intervention including a 1 hr psychoeducation session centered on sleep and circadian rhythms, and an 8-week course of agomelatine (25-50 mg) with a guided sleep phase advance. Fast spindle density significantly increased from pre- to post-intervention. This increase in spindle density significantly correlated with a reduction in wake after sleep onset, and a similar trend was found with increased sleep efficiency. There was no significant correlation between spindle parameters and depressive symptoms. These findings suggest that agomelatine may contribute to enhanced sleep consolidation, possibly in part through the modulation of spindle production. This should be confirmed by larger randomized control trials.

One hundred and eleven youth with mental ill-health underwent systematic clinical, laboratory and actigraphy monitoring to report associations between 24-h sleep–wake patterns and cardiometabolic risk factors. Multiple linear regression analyses, controlling for medication usage and class, age and sex, found significant associations between: later sleep onset and BMI; standard variation (SV) in the sleep offset with both insulin values and the updated homeostatic model assessment of insulin resistance (HOMA2-IR) values; and the SV of the sleep midpoint with both poorer fasting insulin, and HOMA2-IR values. Further longitudinal research is required to determine the causative relationships between 24-h sleep–wake cycle patterns, and cardiometabolic outcomes.

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.

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.

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

IntroductionSleep-wake and circadian disturbance is a key feature of mood disorders with a potential causal role and particular relevance to young people. Brexpiprazole is a second-generation antipsychotic medication with demonstrated efficacy as an adjunct to antidepressant treatment for major depressive disorder (MDD) in adults, with preliminary evidence suggesting greater effectiveness in subgroups of depressed patients with sleep disturbances. This clinical trial aims to evaluate the relationships between changes in sleep-wake and circadian parameters and changes in depressive symptoms following adjunctive brexpiprazole treatment in young adults with MDD and sleep-wake disturbance.Methods and analysisThis study is designed as a 16 week (8 weeks active treatment, 8 weeks follow-up) mechanistic, open-label, single-arm, phase IV clinical trial and aims to recruit 50 young people aged 18–30 with MDD and sleep-wake cycle disturbance through an early intervention youth mental health clinic in Sydney, Australia. At baseline, participants will undergo multidimensional outcome assessment and subsequently receive 8 weeks of open-label treatment with brexpiprazole as adjunctive to their stable psychotropic medication. Following 4 weeks of treatment, clinical and self-report measures will be repeated. Ambulatory sleep-wake monitoring will be conducted continuously for the duration of treatment. After 8 weeks of treatment, all multidimensional outcome assessments will be repeated. Follow-up visits will be conducted 4 and 8 weeks after trial completion (including sleep-wake, clinical and self-report assessments). Circadian rhythm biomarkers including salivary melatonin, cortisol and core body temperature will be collected during an in-lab assessment. Additionally, metabolic, inflammatory and genetic risk markers will be collected at baseline and after 8 weeks of treatment.Ethics and disseminationThis trial protocol has been approved by the Human Research Ethics Committee of the Sydney Local Health District (X19-0417 and 2019/ETH12986, Protocol Version 1–3, dated 25 February 2021). The results of this study, in deidentified form, will be disseminated through publication in peer-reviewed journals, scholarly book chapters, presentation at conferences and publication in conference proceedings.Trial registration numberACTRN12619001456145.

IntroductionWorsened 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 analysisThis 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 disseminationThis 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 numberAustralian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12620000772943, Date 28 August 2020.

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.

Considerable sleep-wake cycle changes occur throughout adolescence and young adulthood, typically involving reductions of sleep duration and sleep-wake phase delays. The purpose of this review is to synthesize current evidence regarding sleep-wake cycle and circadian rhythm disturbance in adolescence, particularly in the context of emerging mental disorders. The clinical presentation of sleep-wake disturbances in adolescents with emerging mood or psychotic disorders is heterogeneous and multifaceted both between individuals and across studies. Whilst the available evidence suggests that sleep-wake cycle disturbances are common in adolescents with emerging psychopathologies, there are limited studies conducted on this age group. The pathophysiological mechanisms underlying these relationships are yet to be clarified. Several fundamental gaps remain in the literature concerning the role of the sleep-wake cycle in emerging adolescent psychopathology. Further research is essential to better characterize sleep-wake patterns in relation to specific mental health syndromes, and more longitudinal research is needed to elucidate causal relationships and treatment implications.

Background Major depressive disorder (MDD) is associated with poorer behavioral performance in domains of working memory and associated cognitive systems for cognitive control and attention. Functional neuroimaging studies show altered functioning in MDD in frontal executive control circuits implicated in these cognitive processes. It is not yet known whether poor cognitive performance involving these circuits is part of the familial risk for MDD, and we addressed this issue using a multi-modal imaging, behavioral and self-report approach in unaffected first-degree relatives of parent probands with MDD. Methods 72 unaffected adult first-degree relatives of probands with MDD (mean age 30.5 ± 13.4 years) with and 66 case-wise matched non-relative controls underwent functional magnetic resonance imaging during performance of ‘n-back’ working memory task, a Go/No-go task assessing cognitive control and an Auditory Oddball test of selective attention. Groups were compared on imaging data analyzed voxel wise with a focus on dorsolateral prefrontal cortex, anterior cingulate cortex and insula regions of interest, and on corresponding behavioral accuracy and reaction time data. Symptoms were assessed using self-report scales. Results Relatives were distinguished by comparatively decreased activation in the left dorsolateral prefrontal cortex (DLPFC) during updating of working memory. Behaviorally, relatives also showed more errors of omission during working memory updating. DLPFC hypo-activation was associated with greater depressive symptom severity. Conclusions Deficits in cognitive processing may be part of the profile of familial risk for depression, preceding illness onset, specifically in the domain of working memory.

The utility of key phenotypes of depression in predicting response to repetitive transcranial magnetic stimulation (rTMS), namely sleep-wake behaviour, cognition and illness chronicity, has been understudied and not been extended to young samples. This study aimed to determine whether sleep-wake disturbance, cognition or depression chronicity are associated with rTMS outcome in young depressed adults. Sixteen depressed young adults diagnosed with mood disorders (aged 18–29 years) completed this open-label study. Neuronavigationally targeted high-frequency rTMS was administered at 110% of motor threshold on the left dorsolateral prefrontal cortex for 20 sessions over 4 weeks. Clinical, sleep-wake and cognitive assessments were undertaken pre- and post-treatment. Repeated-measures and correlational analyses determined pre- and post-treatment changes and predictors of treatment outcome. rTMS significantly reduced depression and anxiety. Better cognitive flexibility, verbal learning, later age of onset and greater number of depressive episodes were associated with better treatment outcome. There were no other significant/trend-level associations. rTMS had no effect on sleep-wake or cognitive measures. We provide the first evidence for the utility of cognitive flexibility and verbal learning in predicting rTMS outcome in depressed young adults. This research provides preliminary support for rTMS as an early intervention for depression and supports the need for sham-controlled trials.

Study Objectives To investigate the influence of genetic and environmental factors on sleep-wake behaviors across adolescence. Methods Four hundred and ninety-five participants (aged 9–17; 55% females), including 93 monozygotic and 117 dizygotic twin pairs, and 75 unmatched twins, wore an accelerometry device and completed a sleep diary for 2 weeks. Results Individual differences in sleep onset, wake time, and sleep midpoint were influenced by both additive genetic (44%–50% of total variance) and shared environmental (31%–42%) factors, with a predominant genetic influence for sleep duration (62%) and restorative sleep (43%). When stratified into younger (aged 9–14) and older (aged 16–17) subsamples, genetic sources were more prominent in older adolescents. The moderate correlation between sleep duration and midpoint (rP = −.43, rG = .54) was attributable to a common genetic source. Sleep-wake behaviors on school and nonschool nights were correlated (rP = .44–.72) and influenced by the same genetic and unique environmental factors. Genetic sources specific to night-type were also identified, for all behaviors except restorative sleep. Conclusions There were strong genetic influences on sleep-wake phenotypes, particularly on sleep timing, in adolescence. Moreover, there may be common genetic influences underlying both sleep and circadian rhythms. The differences in sleep-wake behaviors on school and nonschool nights could be attributable to genetic factors involved in reactivity to environmental context.

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.

OBJECTIVES: Network analysis is increasingly applied to psychopathology research. We used it to examine the core phenomenology of emerging bipolar disorder (BD I and II) and ‘at risk’ presentations (major depression with a family history of BD). METHODOLOGY: The study sample comprised a community cohort of 1867 twin and non-twin siblings (57% female; mean age ~26) who had completed self-report ratings of (i) depression-like, hypomanic-like and psychotic-like experiences; (ii) family history of BD; and (iii) were assessed for mood and psychotic syndromes using the Composite International Diagnostic Interview (CIDI). Symptom networks were compared for recent onset BD versus other cohort members and then for individuals at risk of BD (depression with/without a family history of BD). RESULTS: The four key symptoms that differentiated recent onset BD from other cohort members were: anergia, psychomotor speed, hypersomnia and (less) loss of confidence. The four key symptoms that differentiated individuals at high risk of BD from unipolar depression were: anergia, psychomotor speed, impaired concentration, and hopelessness. However, the latter network was less stable and more error prone. CONCLUSIONS: We are encouraged by the overlaps between our findings and those from two recent publications reporting network analyses of BD psychopathology, especially as the studies recruited from different populations and employed different network models. However, the advantages of applying network analysis to youth mental health cohorts (which include many individuals with multi-morbidity) must be weighed against the disadvantages including basic issues such as judgements regarding the selection of items for inclusion in network models.

IntroductionCurrently, 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 analysisThis 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 disseminationThis 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.

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.

Purpose The Brain and Mind Centre (BMC) Optymise cohort 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 of Optymise have completed detailed neuropsychological and neurobiological assessments, permitting investigation of associations between these measures and longitudinal course. Participants Young 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 in Optymise based on the availability of at least one detailed clinical assessment. Measures Trained 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 date There 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 plans Future 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.

Introduction Young people with mental disorders present with diverse social, vocational, physical, and developmental needs. However, multifaceted interventions are rare. We examine the effectiveness of a clinical trial targeting social participation and physical well-being in young people accessing clinical services. Methods The ‘Youth Early-intervention Study’ (‘YES’) was an unblinded, two-phase, pilot randomized controlled trial offered as an adjunct to standard clinical care, consisting of group activities. Mixed effects models were used to examine functional outcomes over time measured by the ‘Social and Occupational Functioning Assessment Scale’, ‘Functioning Assessment Short Test’, and ‘Brief Disability Questionnaire’ (items 7 and 8). Results 133 participants aged 14-25 were recruited. 87 participants completed both arms and 83 participants completed a 12-month post-trial assessment. Functioning improved across all outcomes. While diagnoses differed in functioning at baseline (lower functioning in psychotic and bipolar disorders compared to depression), they did not differ in the rate of improvement across any measure. Randomization groups did not differ in baseline functioning or the rate of improvement, suggesting a non-specific impact of the intervention. Engagement with education increased from 11% at baseline to 51% at 12-months post-trial and full-time employment increased from 8% at baseline to 20% at 12-months post-trial. Limitations Small sample, no control group, and unmeasured potential moderators (e.g. neurocognitive impairment). Conclusions ‘YES’ was effective and preliminary positive outcomes were observed across all functional outcomes. Future studies should compare the ‘YES’ intervention to a treatment-as-usual control condition and conduct a multi-centre trial across early intervention service sites.

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.

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.

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.

Background Major depressive disorder (MDD) is characterized by maladaptions in affective brain circuitry and in emotion regulation. It remains unknown whether these maladaptions characterize first-degree relatives of probands who are unaffected yet have a higher risk of developing MDD. Methods Participants were 72 unaffected first-degree relatives of probands with MDD and 66 matched non-relative controls. We investigated brain circuit function and self-reported emotion regulation strategies for reappraisal and suppression. During functional magnetic resonance imaging, we probed circuitry relevant to both negative and positive valence systems using facial expressions signaling potential threat, sadness and happiness, presented under both conscious and subliminal viewing conditions. We compared groups using a statistically controlled region of interest (ROI) approach including the amygdala, insula, anterior cingulate cortex (ACC), ventromedial prefrontal cortex and dorsolateral prefrontal cortex. We also used a data-driven cluster analytic approach for characterizing the relatives by their brain function profiles. Results As a group, relatives were distinguished by hyper-reactivity of the pregenual ACC during subliminal viewing of threat-related expressions but hypo-activation of the amygdala, insula and dorsal ACC during explicit viewing of the same threat-related expressions and sadness. When considered individually, this brain function profile characterized two-thirds of relatives, and these relatives were also less likely to use reappraisal to regulate negative emotion. Limitations The design was cross-sectional and therefore does not provide direct evidence as to the trait- (versus state-) like profile observed in relatives. Conclusions Familial risk for MDD may involve a disruption to the normal recruitment of neural circuits for appraising salient emotions, both implicit and explicit. Interventions targeting reappraisal strategies for regulating negative emotion may serve to buffer this risk.

While disturbances of the sleep-wake cycle are common in people with affective disorders, the characteristics of these disturbances differ greatly between individuals. This heterogeneity is likely to reflect multiple underlying pathophysiologies, with different perturbations in circadian systems contributing to the variation in sleep-wake cycle disturbances. Such disturbances may be particularly relevant in adolescents and young adults with affective disorders as circadian rhythms undergo considerable change during this key developmental period. This study aimed to identify profiles of sleep-wake disturbance in young people with affective disorders and investigate associations with biological circadian rhythms. Fifty young people with affective disorders and 19 control participants (aged 16-31 years) underwent actigraphy monitoring for approximately two weeks to derive sleep-wake cycle parameters, and completed an in-laboratory assessment including evening dim-light saliva collection for melatonin assay and overnight continuous core body temperature measurement. Cluster analysis based on sleep-wake cycle parameters identified three distinct patient groups, characterised by 'delayed sleep-wake', 'disrupted sleep', and 'long sleep' respectively. The 'delayed sleep-wake' group had both delayed melatonin onset and core temperature nadir; whereas the other two cluster groups did not differ from controls on these circadian markers. The three groups did not differ on clinical characteristics. These results provide evidence that only some types of sleep-wake disturbance in young people with affective disorders are associated with fundamental circadian perturbations. Consequently, interventions targeting endogenous circadian rhythms to promote a phase shift may be particularly relevant in youth with affective disorders presenting with delayed sleep-wake cycles.

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.

Objectives Converging evidence identifies that the offspring of parents with bipolar disorder (BD), individuals at clinical high risk of BD, and young people with recent onset BD may differ from other clinical cases or healthy controls in terms of sleep–wake profiles. However, it is possible that these differences may reflect current mental state, subtype of mood disorder, or familial traits. This study aimed to determine objective and subjective sleep–wake profiles in individuals aged 15–25 years with a current major depressive episode, in relation to familial traits. Methods Frequency matching was employed to ensure that each individual with a confirmed family history of BD (FH+) could be compared to four controls who did not have a familial mood disorder (FH–). Pre-selected objective actigraphy and subjective Pittsburgh Sleep Quality Index (PSQI) ratings were compared using one-way analysis of variance (ANOVA) and applying the Benjamini–Hochberg (BH) correction for false discoveries. Results The sample comprised 60 individuals with a mean age of 19 years. The FH+ (n=12) and FH– groups (n=48) differed on three key sleep parameters: mean sleep duration on week nights (P=.049), variability in waking after sleep onset (P=.038), and daily disturbances (PSQI dimension of sleep disturbance and daytime dysfunction; P=.01). Conclusions The sleep profiles we identified in this study, especially the daily disturbances phenotype, provide support for research into endophenotypes for BD. Also, the findings may offer the opportunity for more tailored, personalized interventions that target specific components of the sleep–wake cycle in individuals with a family history of BD.

Affective disorders in young people have been associated with disruptions in circadian rhythms, including abnormalities in secretion of the pineal hormone melatonin. Previous research reports relationships between pineal gland volumes, melatonin secretion, and sleep-wake cycles, but the relationship between these factors has not been explored in affective disorders. This study aimed to characterize these factors and explore associations with mood symptoms and functioning in a sample of young people with affective disorders. Pineal volume from magnetic resonance imaging and melatonin assay from evening dim-light saliva collection were evaluated in 50 individuals (15-30 years old; 72 % female) with bipolar, depressive, or anxiety disorders. Actigraphy monitoring was also conducted for approximately two weeks to derive sleep-wake measures. Pineal volume was associated with melatonin secretion across the evening, replicating previous findings in psychiatrically healthy individuals. Pineal volume was smaller in participants in which melatonin onset was not detected. Timing of melatonin secretion was related to sleep timing, but amount of melatonin and pineal volume were not related to any sleep-wake measures. A shorter phase angle between onset of melatonin secretion and sleep onset was associated with longer total sleep time. Lower melatonin levels were associated with poorer social and occupational functioning. Although pineal volume is not directly related to sleep disturbances or symptoms, melatonin may influence both sleep-wake cycles and functioning in the early stages of affective disorder. Causal links remain to be established, however, treatments that target circadian rhythms may be useful in improving functioning in young people with affective disorders.

Mood disorders are characterized by disabling symptoms and cognitive difficulties which may vary in intensity throughout the course of the illness. Sleep–wake cycles and circadian rhythms influence emotional regulation and cognitive functions. However, the relationships between the sleep–wake disturbances experienced commonly by people with mood disorders and the longitudinal changes in their clinical and cognitive profile are not well characterized. This study investigated associations between initial sleep–wake patterns and longitudinal changes in mood symptoms and cognitive functions in 50 young people (aged 13–33 years) with depression or bipolar disorder. Data were based on actigraphy monitoring conducted over approximately 2 weeks and clinical and neuropsychological assessment. As part of a longitudinal cohort study, these assessments were repeated after a mean follow-up interval of 18.9 months. No significant differences in longitudinal clinical changes were found between the participants with depression and those with bipolar disorder. Lower sleep efficiency was predictive of longitudinal worsening in manic symptoms (P = 0.007). Shorter total sleep time (P = 0.043) and poorer circadian rhythmicity (P = 0.045) were predictive of worsening in verbal memory. These findings suggest that some sleep–wake and circadian disturbances in young people with mood disorders may be associated with less favourable longitudinal outcomes, notably for subsequent manic symptoms and memory difficulties. © 2016 European Sleep Research Society

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.