Search

Patients with depression and bipolar disorder have previously been shown to have impaired white matter (WM) integrity compared with healthy controls. This study aimed to investigate potential sex differences that may provide further insight into the pathophysiology of these highly debilitating mood disorders.Participants aged 17 to 30 years (168 with depression [60% females], 107 with bipolar disorder [74% females], and 61 controls [64% females]) completed clinical assessment, self-report measures, and a neuropsychological assessment battery. Participants also underwent magnetic resonance imaging from which diffusion tensor imaging data were collected among five fronto-limbic WM tracts: cingulum bundle (cingulate gyrus and hippocampus subsections), fornix, stria terminalis, and the uncinate fasciculus. Mean fractional anisotropy (FA) scores were compared between groups using analyses of variance with sex and diagnosis as fixed factors.Among the nine WM tracts analyzed, one revealed a significant interaction between sex and diagnosis, controlling for age. Male patients with bipolar disorder had significantly lower FA scores in the fornix compared with the other groups. Furthermore, partial correlations revealed a significant positive association between FA scores for the fornix and psychomotor speed.Our findings suggest that males with bipolar disorder may be at increased risk of disruptions in WM integrity, especially in the fornix, which is thought to be responsible for a range of cognitive functions. More broadly, our findings suggest that sex differences may exist in WM integrity and thereby alter our understanding of the pathophysiology of mood disorders.

Background: Mindfulness training has been associated with improved attention and affect regulation in preadolescent children with anxiety related attention impairments, however little is known about the underlying neurobiology. This study sought to investigate the impact of mindfulness training on functional connectivity of attention and limbic brain networks in pre-adolescents.Methods: A total of 47 children (aged 9-11 years) participated in a 10-week mindfulness intervention. Anxiety and attention measures and resting-state fMRI were completed at pre- and post-intervention. Sustained attention was measured using the Conners Continuous Performance Test, while the anxiety levels were measured using the Spence Children’s Anxiety Scale. Functional networks were estimated using independent-component analysis, and voxel-based analysis was used to determine the difference between the time-points to identify the effect of the intervention on the functional connectivity. Results: There was a significant decrease in anxiety symptoms and improvement in attention scores following the intervention. From a network perspective, the results showed increased functional connectivity post intervention in the salience and fronto-parietal networks as well as the medial-inferior temporal component of the default mode network. Positive correlations were identified in the fronto-parietal network with Hit Response Time and the Spence Children’s Anxiety Scale total and between the default mode network and Hit Response Time.Conclusions: A 10-week mindfulness intervention in children was associated with a reduction in anxiety related attention impairments, which were underpinned by concomitant changes in functional connectivity.

Social connectedness is well established as an important aspect of adolescence, with higher levels typically resulting in positive mental health and well-being. Cyberbullying is a prevalent concern during adolescence and is a significant contributor to poor mental health outcomes during this important phase of life. Research shows that social connectedness may act as a protective factor for mental health and well-being when young people experience cyberbullying. However, further research is required to elucidate associations between social connectedness, well-being, and cyberbullying over time. This article outlines preliminary findings from the Longitudinal Adolescent Brain Study (LABS). Data are reported from

Introduction COVID-19 has resulted in major life changes to the majority of the world population, particularly adolescents, with social-distancing measures such as home-based schooling likely to impact sleep quality. Increased worry is also likely considering the substantial financial, educational and health concerns accompanying COVID-19. White matter (WM) integrity has been shown to be associated with anxiety and depression symptoms, including worry, as well being closely associated with sleep quality. This study aimed to investigate the associations between pre-COVID sleep quality, WM structural integrity and levels of worry and rumination about COVID. Methods N = 30 adolescent participants from Queensland, Australia, completed diffusion tensor imaging (DTI) scanning pre-COVID, the Pittsburgh Sleep Quality Index (PSQI) pre and during COVID, and 9 items designed to measure 3 constructs, perceived impact of COVID, general worry, and COVID-specific worry and rumination. Results Sleep quality (PSQI total) was significantly poorer during COVID compared with pre-COVID. Sleep onset latency measured pre-COVID was significantly associated with COVID-specific worry and rumination. While the structural integrity of a number of WM tracts (measured pre-COVID) were found to be significantly associated with COVID-specific worry and rumination. Follow-up regression analysis using a model including pre-COVID sleep onset latency, structural integrity of the posterior limb of the internal capsule (PLIC), gender and change in PSQI explained a significant 47% of the variance in COVID-specific worry and rumination. Conclusions These findings suggest that adolescents with poor sleep quality and perturbed WM integrity may be at risk of heightened reactivity to future stressful events and interventions should focus on improving sleep onset latency.

BACKGROUND Developmental studies have shown adolescence is a period of ongoing white matter (WM) development, reduced sleep quality and the onset of many mental disorders. Findings indicate the WM development of the uncinate fasciculus (UF), a WM tract suggested to play a key role in mental disorders, continues throughout adolescence. While these studies provide valuable information, they are limited by long intervals between scans (1 to 4 years) leaving researchers and clinicians to infer what may be occurring between time-points. To allow inferences to be made regarding the impact that sleep quality may be having on WM development, longitudinal studies with much shorter between-scan intervals are required. METHODS The current study reports longitudinal data of self-reported sleep quality (PSQI), diffusion tensor imaging (DTI) measures of WM development and psychological distress (K10) for n = 64 early adolescents spanning the first twelve months (four time-points; Baseline, 4, 8, & 12 months) of the Longitudinal Adolescent Brain Study (LABS) study currently underway at the Thompson Institute. RESULTS Generalised Estimating Equation analysis showed a significant relationship between sleep quality and psychological distress over the four time-points. Reduced radial diffusivity and increased fractional anisotropy of the UF is also reported with increasing age suggesting that ongoing myelination is occurring. Adding sleep quality to the model, however, negatively impacted this myelination process. CONCLUSION These findings represent an important step towards elucidating how sleep, psychological distress and maturation of the UF may co-develop during early adolescence.

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.

While research has examined bystander responses in a traditional sense, there is a dearth of research regarding responses of cyberbystanders in a real-time situation, such as observing a cyberbullying scenario. This article describes a novel protocol designed to develop a series of images to be used to undertake research that aims to examine cyberbystander responses. A total of 24 scenarios (12 negative (cyberbullying) and 12 neutral) were created by the researchers and designed to mimic the way such scenarios would appear on a social networking site. The negative (cyberbullying) stimuli were rated in terms of level of severity, and the scenarios were compared to a selection of images from the International Affective Picture System using the Self-Assessment Manikin. These stimuli were compiled to form the Cyberbullying Picture Series (CyPicS). Through the development of the CyPicS, this protocol will aid future researchers in examining responses to real-life scenarios, as it is the first of its kind to develop these scenarios and test and evaluate them. CyPicS will provide researchers with the means to systematically evaluate responses to validated, real-life cyberbullying scenarios. More specifically, future researchers can utilize CyPicS to investigate how cyberbystanders respond when observing cyberbullying stimuli compared to neutral stimuli, as well as to measure and understand reactions or perceptions of cyberbullying. CyPicS can be used in any form of cyberbullying research (including electroencephalography and eye-tracking studies, psychological research, and functional magnetic resonance imaging studies) that may utilize bystander reactions and behaviors. Findings from research that utilizes CyPicS will greatly increase our understanding of bystander responses, and with variations in study design, researchers can further examine past or future associations with cyber-victim/bully status and mental health outcomes. Refereed/Peer-reviewed

Each human brain has a unique functional synchronisation pattern (functional connectome) analogous to a fingerprint that underpins brain functions and related behaviours. Here we examine functional connectome (whole-brain and 13 networks) maturation by measuring its uniqueness in adolescents who underwent brain scans longitudinally from 12 years of age every four months. The uniqueness of a functional connectome is defined as its ratio of self-similarity (from the same subject at a different time point) to the maximal similarity-to-others (from a given subject and any others at a different time point). We found that the unique whole brain connectome exists in 12 years old adolescents, with 92% individuals having a whole brain uniqueness value greater than one. The cingulo-opercular network (CON; a long-acting 'brain control network' configuring information processing) demonstrated marginal uniqueness in early adolescence with 56% of individuals showing uniqueness greater than one (i.e., more similar to her/his own CON four months later than those from any other subjects) and this increased longitudinally. Notably, the low uniqueness of the CON correlates (β = -18.6, FDR-Q 0.001) with K10 levels at the subsequent time point. This association suggests that the individualisation of CON network is related to psychological distress levels. Our findings highlight the potential of longitudinal neuroimaging to capture mental health problems in young people who are undergoing profound neuroplasticity and environment sensitivity period.

Although the primary aetiology of Eating Disorders (ED) remains unknown, research suggests a complex interplay of biological, psychological, and cultural/environmental factors. This paper aims to systematically review the literature on neuroimaging studies that measure socio-cognitive factors, in the context of body dissatisfaction and EDs in young people. Specifically, our aim was to identify patterns in the findings linked to social media-type behaviours.The review was conducted in accordance with PRISMA guidelines using PubMed, Scopus, and Web of Science databases. 799 papers were identified in the database search and 38 studies were selected based on exclusion and inclusion criteria. Selected studies were assessed using the National Institute of Health study quality assessment tool.Findings point to state-related impairments in inhibitory control and salient emotional processing. Anorexia Nervosa(AN) showed impaired set-shifting abilities, working memory and decision making, while altered activation in attention networks and associated difficulties with conflict resolution were seen for Bulimia Nervosa(BN) and Other Specified Feeding and Eating Disorders(OSFED). AN and BN also demonstrated altered sensitivity to food-related stimuli in striatal regions, suggesting aberrant top-down emotional-cognitive control. ED participants also show deficits in body representation, impaired control over social behaviours and altered integration of visual and body perception.These findings support the notion that socio-cognitive dysfunctions in ED are underpinned by a distributed network of structural and functional brain changes which influence the way young people with ED interact with and respond to social media, and ultimately places at them at increased risk for body image disturbances. This Review was registered with the PROSPERO International Register of Systematic Reviews, Registration number CRD42021270696.

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

Background Impulsivity is considered a possible phenotype underlying the expression of self-harm and suicidal behaviors. Yet impulsivity is a not a unitary construct and there is evidence that different facets of impulsivity follow different neurodevelopmental trajectories and that some facets may be more strongly associated with such behaviors than others. Moreover, it is unclear whether impulsivity is a useful predictor of self-harm or suicidal behavior in young people, a population already considered to display heightened impulsive behavior. Methods A systematic review and meta-analysis of studies published in Medline, PubMed, PsychInfo or Embase between 1970 and 2017 that used a neurocognitive measure to assess the independent variable of impulsivity and the dependent variable of self-harm and/or suicidal behavior among young people (mean age Results 6183 titles were identified, 141 full texts were reviewed, and 18 studies were included, with 902 young people with a self-harm or suicidal behavior and 1591 controls without a history of these behaviors. Deficits in inhibitory control (13 studies, SMD 0.21, p-value = 0.002, 95% confidence interval (CI) (0.08–0.34), prediction interval (PI) = 0.06–0.35) and impulsive decision-making (14 studies, SMD 0.17, p-value = 0.008, 95% CI (0.045–0.3), PI = 0.03–0.31) were associated with self-harm or suicidal behavior. There were no significant differences between measures of different facets of impulsivity (ie. delay discounting, risky decision-making, cognitive or response inhibition) and self-harm or suicidal behavior. Conclusion Multiple facets of impulsivity are associated with suicidal behavior in young people. Future suicide research should be designed to capture impulsive states and investigate the impact on different subtypes of impulsivity.

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

IntroductionApproximately 75% of major mental illness occurs before the age of 25 years. Despite this, our capacity to provide effective, early and personalised interventions is limited by insufficient evidence for characterising early-stage, and less specific, presentations of major mental disorders in youth populations. This article describes the protocol for setting up a large-scale database that will collect longitudinal, prospective data that incorporate clinical, social and occupational function, neuropsychological, circadian, metabolic, family history and genetic metrics. By collecting data in a research-purposed, standardised manner, the ‘Neurobiology Youth Follow-up Study’ should improve identification, characterisation and profiling of youth attending mental healthcare, to better inform diagnosis and treatment at critical time points. The overall goal is enhanced long-term clinical and functional outcomes.Methods and analysisThis longitudinal clinical cohort study will invite participation from youth (12–30 years) who seek help for mental health-related issues at an early intervention service (headspace Camperdown) and linked services. Participants will be prospectively tracked over 3 years with a series of standardised multimodal assessments at baseline, 6, 12, 24 and 36 months. Evaluations will include: (1) clinician-administered and self-report assessments determining clinical stage, pathophysiological pathways to illness, diagnosis, symptomatology, social and occupational function; (2) neuropsychological profile; (3) sleep–wake patterns and circadian rhythms; (4) metabolic markers and (5) genetics. These data will be used to: (1) model the impact of demographic, phenomenological and treatment variables, on clinical and functional outcomes; (2) map neurobiological profiles and changes onto a transdiagnostic clinical stage and pathophysiological mechanisms framework.Ethics and disseminationThis study protocol has been approved by the Human Research Ethics Committee of the Sydney Local Health District (2020/ETH01272, protocol V.1.3, 14 October 2020). Research findings will be disseminated through peer-reviewed journals and presentations at scientific conferences and to user and advocacy groups. Participant data will be de-identified.

Background: Although numerous studies have reported an association between sleep quality and mental health, few have focused on this association exclusively in early adolescence. Targeting this age group is vital as many mental illnesses first emerge during adolescence and remain a significant burden throughout life. Method: In the current study n = 60 participants aged 12 years completed the Pittsburgh Sleep Quality Index (PSQI) and Kessler Psychological Distress Scale (K10). Results: Consistent with previous findings, bivariate correlations revealed significant positive linear relationships between K10 total score and (i) PSQI total score; (ii) sleep quality; (iii) daytime dysfunction; and (iv) sleep disturbance. However, contrary to previous findings, there was no significant correlation between K10 scores and sleep duration. Conclusion: The association between sleep quality and psychological distress in early adolescents provides some important clues about the role that sleep may play in predicting the onset of anxiety and depressive disorders. Longitudinal studies should be undertaken to investigate age-related changes in sleep and psychological distress.

Improving our understanding of the causes of functional impairment in young people is a major global challenge. Here, we investigated the relationships between self-reported days out of role and the total quantity and different patterns of self-reported somatic, anxious-depressive, psychotic-like, and hypomanic symptoms in a community-based cohort of young adults. We examined self-ratings of 23 symptoms ranging across the four dimensions and days out of role in >1900 young adult twins and non-twin siblings participating in the “19Up” wave of the Brisbane Longitudinal Twin Study. Adjusted prevalence ratios (APR) and 95% confidence intervals (95% CI) quantified associations between impairment and different symptom patterns. Three individual symptoms showed significant associations with days out of role, with the largest association for impaired concentration. When impairment was assessed according to each symptom dimension, there was a clear stepwise relationship between the total number of somatic symptoms and the likelihood of impairment, while individuals reporting ≥4 anxious-depressive symptoms or five hypomanic symptoms had greater likelihood of reporting days out of role. Furthermore, there was a stepwise relationship between the total number of undifferentiated symptoms and the likelihood of reporting days out of role. There was some suggestion of differences in the magnitude and significance of associations when the cohort was stratified according to sex, but not for age or twin status. Our findings reinforce the development of early intervention mental health frameworks and, if confirmed, support the need to consider interventions for subthreshold and/or undifferentiated syndromes for reducing disability among young people.

In a series of cognitive and neuroimaging studies we investigated the relationships between adolescent sleep quality, white matter (WM) microstructural integrity and psychological distress. Collectively these studies showed that during early adolescence (12-14 years of age), sleep quality and psychological distress are significantly related. Sleep quality and the microstructure of the posterior limb of the internal capsule (PLIC), a WM tract that provides important connectivity between the cortex, thalamus and brain stem, were also shown to be significantly correlated as too were social connectedness and psychological distress. Longitudinally the uncinate fasciculus (UF), a WM tract that provides bidirectional connectivity between the amygdala and executive control centers in the Prefrontal cortex (PFC), was observed to be undergoing continued development during this period and sleep quality was shown to impact this development. Sleep latency was also shown to be a significant predictor of worry endured by early adolescents during future stressful situations. The current review places these findings within the broader literature and proposes an empirically supported model based in a theoretical framework. This model focuses on how fronto-limbic top-down control (or lack thereof) explains how poor sleep quality during early adolescence plays a crucial role in the initial development of anxiety disorders, and possibly in the reduced ability of anxiety disorder sufferers to benefit from cognitive reappraisal based therapies. While the findings outlined in these studies highlight the importance of sleep quality for WM development and in mitigating psychological distress, further research is required to further explicate the associations proposed within the model to allow causal inferences to be made.

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.

Suicidal thoughts and behaviors (STB) are a leading cause of death in adolescence. To date, most research with youth has focused on risk factors for suicide; and less attention has been paid to resilience factors. This study examined whether positive beliefs and social connectedness moderate associations between mental health symptoms and STB. A community sample of 12-year-olds (N = 60) completed self-report questionnaires on their STB, mental health symptoms, positive beliefs and social connectedness. Nearly 20% of the adolescents reported STB. STB was associated with increased mental health symptoms and lower scores on the resilience measures. A significant moderating effect of social connectedness showed that youth with a combination of poor mental health and high levels of social support exhibited lower levels of STB. There was no significant moderating effect of positive beliefs. These results indicate that social support should be screened for in primary care and incorporated into youth suicide prevention programs.

Background Neurocognitive impairment is recognised as a risk factor for suicidal behaviour in adults. The current study aims to determine whether neurocognitive deficits also predict ongoing or emergent suicidal behaviour in young people with affective disorders. Methods Participants were aged 12-30 years and presented to early intervention youth mental health clinics between 2008 and 2018. In addition to clinical assessment a standardised neurocognitive assessment was conducted at baseline. Clinical data was extracted from subsequent visits using a standardised proforma. Results Of the 635 participants who met inclusion criteria (mean age 19.6 years, 59% female, average follow up 476 days) 104 (16%) reported suicidal behaviour during care. In 5 of the 10 neurocognitive domains tested (cognitive flexibility, processing speed, working memory, verbal memory and visuospatial memory) those with suicidal behaviour during care were superior to clinical controls. Better general neurocognitive function remained a significant predictor (OR=1.94, 95% CI 1.29- 2.94) of suicidal behaviour in care after controlling for other risk factors. Limitations The neurocognitive battery used was designed for use with affective and psychotic disorders and may not have detected some deficits more specific to suicidal behaviour. Conclusion Contrary to expectations, better neurocognitive functioning predicts suicidal behaviour during care in young people with affective disorders. While other populations with suicidal behaviour, such as adults with affective disorders or young people with psychotic disorders, tend to experience neurocognitive deficits which may limit their capacity to engage in some interventions, this does not appear to be the case for young people with affective disorders.

Mental disorders and their functional impacts evolve dynamically over time. Neurocognition and clinical symptoms are commonly modelled as predictors of functioning, however, studies tend to rely on static variables and adult samples with chronic disorders, with limited research investigating change in these variables in young people with emerging mental disorders. These relationships were explored in a longitudinal clinical cohort of young people accessing early intervention mental health services in Australia, around three-quarters of whom presented with a mood disorder (N = 176, aged 12-30 at baseline). Bivariate latent change score models quantified associations between neurocognition (a latent variable of working memory, verbal memory, visuospatial memory, and cognitive flexibility), global clinical symptoms, and functioning (self- and clinician-rated) and their relative change over follow-up (median = 20 months). We found that longitudinal changes in functioning were coupled with changes in global clinical symptoms (β = -0.43, P 0.001), such that improvement in functioning was related to improvement in clinical symptoms. Changes in neurocognition were not significantly associated with changes in functioning or clinical symptoms. Main findings were upheld in three sensitivity analyses restricting the sample to: (a) adults aged 18-30; (b) participants with 12-24 months of follow-up; and (c) participants without a psychotic disorder. Our findings show that global symptom reduction and functional improvement are related in young people with emerging mental disorders. More work is needed to determine the temporal precedence of change in these variables. Future studies should apply this methodology to intervention studies to untangle the causal dynamics between neurocognition, symptoms, and functioning.

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

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.

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.

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.

The study assessed the longitudinal clinical and functional outcomes of young people receiving early intervention services for subthreshold manifestations of severe mental disorders at a youth mental health service in Sydney, Australia.The six-month, prospective, longitudinal study collected data on clinical outcomes of 243 young people treated for subsyndromal presentations of putative major mental disorders. Reliable change index scores and effect sizes were calculated to compare results at baseline, three months, and six months for measures of symptoms (Brief Psychiatric Rating Scale [BPRS]), psychological distress (Kessler 10 [K10]), and social functioning (Social and Occupational Functioning Assessment Scale [SOFAS]).There was variability in outcomes across each of the outcome measures, with 25%, 33%, and 23% of patients showing reliable improvement and 9%, 13%, and 5% showing reliable deterioration for the SOFAS, K10, and BPRS, respectively. Many individuals did not show linear improvement or deterioration, with reliable change within individuals varying significantly between the zero- to three-month and three- to six-month time points. After the analyses were controlled for covariates, baseline severity or impairment and number of sessions with a psychiatrist or psychologist contributed a small (4%-8%) but significant amount to the total variance in outcomes at six months.Most individuals did not show significant deterioration, and about one in four showed reliable improvement by six months. However, individual patterns of change were diverse, highlighting the importance of further research into factors that influence treatment outcomes among youths with subthreshold presentations of severe mental disorders.

Background Sex differences in rates of depression emerge during adolescence. However, it is unclear whether symptom patterns and trajectories differ significantly according to gender in youth. Barriers to research include the fact that most self-report tools are weighted towards psychological rather than somatic symptoms. Methods Data were collected on symptoms of depression in about 1800 individuals at ages 12, 14 and 16 years. Odds ratios and 95% confidence intervals were used to examine the trajectory of psychological and somatic phenotypes and self-reported depression caseness over time. Results At age 12, 24% of participants met criteria for self-reported depression caseness. Although there was only a small incremental increase in the prevalence over time (about 5%), 57% of participants met criteria for self-reported depression caseness at least once. Generic symptoms at age 12 were associated with depression longitudinally, although early transition to caseness was reported in females only. Categorization as a psychological phenotype at age 12 predicted depression at age 14 and/or 16 years, especially in females. The somatic phenotype was more common in males, but showed a weaker association with self-reported depression caseness over time. Limitations Depression was assessed by self-report; only 30% of participants had ratings for age 12, 14 and 16. Conclusions Although sub-threshold psychological and somatic syndromes often co-occur in cases of self-reported depression in adolescence, longitudinally they may represent independent symptom trajectories. However, it is important to remember that self-reported depression is indicative of, but not confirmation of a depressive episode that meets diagnostic criteria.

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.

Childhood maltreatment (CM) is associated with enhanced risk of psychiatric illness and reduced subcortical grey matter in adulthood. The hippocampus and amygdala, due to their involvement in stress and emotion circuitries, have been subject to extensive investigations regarding the effect of CM. However, the complex relationship between CM, subcortical grey matter and mental illness remains poorly understood partially due to a lack of longitudinal studies. Here we used segmentation and linear mixed effect modelling to examine the impact of CM on hippocampal and amygdala development in young people with emerging mental illness. A total of 215 structural magnetic resonance imaging (MRI) scans were acquired from 123 individuals (age: 14-28 years, 79 female), 52 of whom were scanned twice or more. Hippocampal and amygdala volumes increased linearly with age, and their developmental trajectories were not moderated by symptom severity. However, exposure to CM was associated with significantly stunted right hippocampal growth. This finding bridges the gap between child and adult research in the field and provides novel evidence that CM is associated with disrupted hippocampal development in youth. Although CM was associated with worse symptom severity, we did not find evidence that CM-induced structural abnormalities directly underpin psychopathology. This study has important implications for the psychiatric treatment of individuals with CM since they are clinically and neurobiologically distinct from their peers who were not maltreated.

Research shows that adolescents with mental illnesses have a bias for processing negative facial emotions, and this may play a role in impaired social functioning that often co-exists with a mental health diagnosis. This study examined associations between psychological and somatic problems and facial emotion recognition in early adolescence, as any processing biases in this age-group may be an early indicator of later mental illnesses. A community sample of 40 12-year-olds self-rated their symptoms of anxiety, depression, and somatization via two mental health screeners. They also completed a computerized emotion recognition task in which they identified photographs of 40 faces showing expressions of anger, fear, sadness, happiness, or neutral expression. Results showed that increased symptoms of anxiety, depression, and somatization were significantly associated with fewer correct responses to angry expressions. These symptoms were also associated with faster and more accurate recognition of fearful expressions. However, there was no association between mental health and recognition of sad affect. Finally, increased psychological and/or somatic symptomology was also associated with better identification of neutral expressions. In conclusion, youth with increased psychological and/or somatic problems exhibited a processing bias for negative anger and fear expressions, but not sadness. They showed better processing of neutral faces than youth with fewer psychological and/or somatic problems. Findings are discussed in relation to indicators of mental illnesses in early adolescence and the potential underpinning neural mechanisms associated with mental health and emotional facial recognition.

Introduction Poor sleep quality has been linked to reduced neural connectivity through decreased white matter (WM) structural integrity. WM tract development has been shown to continue throughout adolescence with studies reporting positive correlations between diffusion-derived estimates of structural integrity and reduced sleep quality in adult samples. Few studies have investigated this relationship exclusively within a sample of young adolescents. Methods N = 51 participants aged 12 years (M = 151.5 months, SD = 4 months) completed a self-report questionnaire which included the Pittsburgh Sleep Quality Index (PSQI) and underwent Diffusion Tensor Imaging (DTI) as part of their baseline assessment in the Longitudinal Adolescent Brain Study (LABS) being undertaken in Queensland, Australia. Fractional anisotropy (FA) were extracted using Tract-Based Spatial Statistics (TBSS) to investigate associations between sleep quality and WM integrity across the brain. Results Significant correlations were found between the posterior limb of the internal capsule and the PSQI total sleep quality and sleep latency scores. There was also a significant difference in sleep duration between male and female participants. Conclusion These findings provide an important insight of the impact that sleep may have on early adolescent WM development. Ongoing longitudinal assessment of sleep on WM development across adolescence is likely to provide further important information about how WM maturation relates to variations in sleep quality as circadian rhythm changes occur during middle and late adolescence.

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.

There is a dearth of research that has investigated the neural correlates of cyberbullying, using task-based functional magnetic resonance imaging (fMRI) and, specifically, in a real-time context such as observing cyberbullying scenarios. This article presents pilot data from a novel protocol designed to undertake such research with the overall aim being to elucidate the neurobiological underpinnings of cyberbullying via task-based fMRI (tb-fMRI)) in passive cyberbystanders. Young adults (N = 32, 18 to 25 years old) viewed six negative (cyberbullying) and six neutral stimuli from the Cyberbullying Picture Series (CyPicS) while undergoing tb-fMRI. Our results revealed 12 clusters of significantly greater blood-oxygenation-level-dependent (BOLD) responses (family wise error corrected p FWE

The hippocampus and amygdala have justifiably been the focus of much mental health research due to their putative roles in top-down processing control of emotion, fear, and anxiety. However, understanding the causal relationship between these regions and mental illness has been limited as current literature is lacking in the observation of neuro-structural changes preceding first episodes. Here, we report whole and sub-structural hippocampal and amygdala volume correlates of psychological distress in early adolescence. Automated hippocampal subfield and amygdala nuclei segmentation was carried out in 32 participants (12–13 years old) recruited for the Longitudinal Adolescent Brain Study (LABS) who had psychological distress scores measured by the Kessler-10. Partial correlation analyses revealed significant negative association between left whole amygdala volume and psychological distress. Sub-structure analysis revealed that smaller left hippocampal CA1 volume and left basal and accessory basal amygdala nuclei volumes were all significantly associated with higher levels of psychological distress. Four-month follow-up analysis also revealed an association between change in K10 and CA1 volume suggesting a continued relationship between this hippocampal substructure and psychological distress. Grey matter volume of subcortical sub-structures involved within the hippocampal-basolateral amygdala-prefrontal cortex loop are highly correlated and are significantly reduced in adolescents with higher levels of psychological distress, indicating these nuclei and subfields play an important role in the emergence of mental illness.

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.

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.

This study investigated the relative contribution of psychiatric symptoms and psychotropic medications on the sleep-wake cycle. Actigraphy and clinical assessments (Brief Psychiatric Rating Scale) were conducted in 146 youths with anxiety, depression or bipolar disorders. Independently of medications, mania symptoms were predictive of lower circadian amplitude and rhythmicity. Independently of diagnosis and symptoms severity: i) antipsychotics were related to longer sleep period and duration, ii) serotonin-norepinephrine reuptake inhibitors to longer sleep period, and iii) agomelatine to earlier sleep onset. Manic symptoms and different subclasses of medications may have independent influences on the sleep-wake cycle of young people with mental disorders.

To examine the associations between depression course, functional disability, and Not in Education or Training (NEET) status in a clinical sample of young adults with mental health problems. Young adults aged 15–25 years seeking help from four primary mental health services were invited to participate in a prospective cohort study evaluating the course of psychiatric disorders in youth. Demographic and clinical characteristics, including depressive symptomatology and functioning, were evaluated through clinical interview and self-report at baseline and 12 month follow-up. A total of 448 young adults participated (70 % female; M: 20.05 years, SD = 2.85). A significant interaction effect for time and depression course was found, such that those who became depressed reported an increase in functional disability and those whose depression remitted reported a significant reduction in functional disability. Developing depression was not a significant predictor of becoming NEET and vice versa: remitted depression did not make a person more likely to reengage in employment or education. This is the first study to examine the course of depression, functional disability, and NEET rates among help-seeking young adults. This study confirms the importance of symptom reduction for improved functioning; however, functional disability remained greater than that seen in young people in the community and there was no association between a change in depression and a change in NEET status. These results argue that services need to address functional outcomes and reengagement with education and employment in addition to symptom reduction.

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

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.

The importance of sleep for mental health has been known for some time. Although it was initially suggested that mental health conditions negatively impact sleep, it is now widely understood that this association is bidirectional. Adolescence is a period where people are at an increased risk of being sleep deprived largely due to a late shift in the circadian rhythm around puberty combined with early school start times. This combination may lead to adolescents being at an increased risk of mental health problems. Adolescence is also a period of continued brain development with white matter maturation continuing in the frontal brain regions throughout adolescence and into early adulthood. White matter development involves myelination of axons that link areas of grey matter and is integral for communication speed and efficiency. Studies have demonstrated that sufficient sleep is required for myelination to occur. The uncinate fasciculus (UF) is one of the last white matter tracts to be myelinated with this process occurring throughout adolescence and running between the amygdala in the limbic system and the orbitofrontal (OFC) and medial prefrontal cortices (mPFC). Recent studies have shown that connectivity between the amygdala and OFC is important for an individual's ability to exert top-down executive control over amygdala based automatic emotional responses to experiences perceived as threatening. The current literature review provides an overview of these mechanisms and concludes by proposing a model of adolescent sleep deprivation leading to potential life-long mental health issues through the moderating impact of reduced UF development.

Introduction: Evidence suggests that patients with psychosis who have a history of cannabis use, but currently abstain, demonstrate superior cognitive performance than patients who have never used cannabis. The present study aimed to determine the neurocognitive profiles of patients who are in adolescence or early adulthood, when both illness- and drug-onset typically occur. Methods: Subjects were 24 cannabis-using and 79 cannabis-naïve psychosis patients between 16 and 25 years of age. Patients and controls were administered a neurocognitive battery, indexing estimated pre-morbid intelligence, psychomotor speed, mental flexibility, verbal learning and memory, verbal fluency, sustained attention, motor and mental response, and visuospatial learning and memory. Results: While healthy controls outperformed both patient groups across most cognitive measures, no significant differences between cannabis-using and cannabis-abstinent patients were evident. Conclusion: Evidently although there may be a group of patients who are diagnosed with a non-affective psychosis disorder regardless of external factors (i.e. cannabis use), some may instead have their illness precipitated through cannabis use at a young age, presenting with unique cognitive and symptomatic repercussions later in life. These results demonstrate no cognitive differences between cannabis-using patients and abstinent patients at the time of illness-onset, providing partial support for an alternative pathway to schizophrenia through early cannabis use.

Abnormalities in circadian rhythms have been reported in people with mood disorders, but these abnormalities are marked by considerable inter-individual variability. This study aimed to identify pathophysiological subgroups on the basis of circadian markers and evaluate how these subgroups relate to psychiatric profiles. Thirty-five young adults (18–31 years old) receiving clinical care for unipolar depressive disorders and 15 healthy controls took part to this study. The Hamilton Rating Scale for Depression and the Young Mania rating scale were used to evaluate the severity of mood symptoms in participants with depressive disorders. All participant underwent ambulatory sleep monitoring with actigraphy for about 12 days before attending a laboratory-based chronobiological assessment which included repeated salivary samples to determine dim light melatonin onset (DLMO) and continuous core body temperature (CBT) monitoring using an ingestible temperature sensor. Cluster analyses were conducted across all participants to identify subgroups with consistent circadian timing profiles based on DLMO and the nocturnal minima of CBT. Two clusters were identified: ‘delayed’ and ‘conventional timing’ circadian phase. Descriptive analyses showed that the delayed cluster was characterised by abnormal time relationships between circadian phase markers and the sleep–wake cycle. Importantly, individuals from the delayed cluster had worse depression severity (t(28) = −2.7, p = 0.011) and hypomanic symptoms (Z = −2.2, p = 0.041) than their peers with conventional circadian timing. These findings suggest that delayed and disorganised circadian rhythms may be linked to worse psychiatric profiles in young people with depressive disorders.

Although the non-stimulant medication atomoxetine is effective for attention-deficit hyperactivity disorder (ADHD) in children and adolescents, there are still significant gaps in our knowledge about whether atomoxetine improves anxiety symptoms or cognition in children. Furthermore, while cognition has been proposed as an intermediate phenotype for ADHD dysfunction, the relationships between clinical and cognitive outcomes are not yet understood. We addressed these knowledge gaps in a controlled trial using objective assessments of both general and emotional cognitive functions implicated in ADHD and in anxiety, which commonly co-occurs with ADHD. A total of 136 children and adolescents with ADHD (ages 6-17years; 80% male; 31.6% with a comorbid anxiety disorder) were enrolled in a randomized double-blind, placebo-controlled, cross-over trial of 6-weeks treatment with atomoxetine. Of these, 109 completed the second cross-over phase. Selected cognitive domains associated with ADHD and anxiety disorders (Sustained attention, response inhibition and fearful face identification) were assessed using a normed, computerized test battery. Symptom outcomes were assessed by parent reports on the ADHD Rating Scale-IV and Conners' Anxious-Shy subscale. For completers, atomoxetine caused a greater improvement in the primary cognitive outcomes of response inhibition and fear identification compared to placebo, but not in sustained attention. Atomoxetine also improved ADHD and anxiety symptoms. Anxiety symptoms improved most for ADHD and anxiety disorder combined, but presence of an anxiety disorder did not moderate any other outcomes. Changes in cognitive and clinical outcomes were not correlated. These findings contribute to the foundations of measurement-based treatment planning and offer targets for probing the mechanisms of atomoxetine action.

PurposeThe Nineteen and Up study (19Up) assessed a range of mental health and behavioural problems and associated risk factors in a genetically informative Australian cohort of young adult twins and their non-twin siblings. As such, 19Up enables detailed investigation of genetic and environmental pathways to mental illness and substance misuse within the Brisbane Longitudinal Twin Sample (BLTS).ParticipantsTwins and their non-twin siblings from Queensland, Australia; mostly from European ancestry. Data were collected between 2009 and 2016 on 2773 participants (age range 18–38, 57.8% female, 372 complete monozygotic pairs, 493 dizygotic pairs, 640 non-twin siblings, 403 singleton twins).Findings to dateA structured clinical assessment (Composite International Diagnostic Interview) was used to collect lifetime prevalence of diagnostic statistical manual (4th edition) (DSM-IV) diagnoses of major depressive disorder, (hypo)mania, social anxiety, cannabis use disorder, alcohol use disorder, panic disorder and psychotic symptoms. Here, we further describe the comorbidities and ages of onset for these mental disorders. Notably, two-thirds of the sample reported one or more lifetime mental disorder.In addition, the 19Up study assessed general health, drug use, work activity, education level, personality, migraine/headaches, suicidal thoughts, attention deficit hyperactivity disorder (ADHD) symptomatology, sleep–wake patterns, romantic preferences, friendships, familial environment, stress, anorexia and bulimia as well as baldness, acne, asthma, endometriosis, joint flexibility and internet use.The overlap with previous waves of the BLTS means that 84% of the 19Up participants are genotyped, 36% imaged using multimodal MRI and most have been assessed for psychological symptoms at up to four time points. Furthermore, IQ is available for 57%, parental report of ADHD symptomatology for 100% and electroencephalography for 30%.Future plansThe 19Up study complements a phenotypically rich, longitudinal collection of environmental and psychological risk factors. Future publications will explore hypotheses related to disease onset and development across the waves of the cohort. A follow-up study at 25+years is ongoing.