Centre for Youth Mental Health - Research Publications
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ItemRemote Control in Formation of 3D Multicellular Assemblies Using Magnetic Forces(AMER CHEMICAL SOC, 2019-05)Cell constructs have been utilized as building blocks in tissue engineering to closely mimic the natural tissue and also overcome some of the limitations caused by two-dimensional cultures or using scaffolds. External forces can be used to enhance the cells' adhesion and interaction and thus provide better control over production of these structures compared to methods like cell seeding and migration. In this paper, we demonstrate an efficient method to generate uniform, three-dimensional cell constructs using magnetic forces. This method produced spheroids with higher densities and more symmetrical structures than the commonly used centrifugation method for production of cell spheroids. It was also shown that shape of the cell constructs could be changed readily by using different patterns of magnetic field. The application of magnetic fields to impart forces on the cells enhanced the fusion of these spheroids, which could be used to produce larger and more complicated structures for future tissue engineering applications.
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ItemThe operational environment and rotational acceleration of asteroid (101955) Bennu from OSIRIS-REx observations(NATURE PUBLISHING GROUP, 2019-03-19)During its approach to asteroid (101955) Bennu, NASA's Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) spacecraft surveyed Bennu's immediate environment, photometric properties, and rotation state. Discovery of a dusty environment, a natural satellite, or unexpected asteroid characteristics would have had consequences for the mission's safety and observation strategy. Here we show that spacecraft observations during this period were highly sensitive to satellites (sub-meter scale) but reveal none, although later navigational images indicate that further investigation is needed. We constrain average dust production in September 2018 from Bennu's surface to an upper limit of 150 g s-1 averaged over 34 min. Bennu's disk-integrated photometric phase function validates measurements from the pre-encounter astronomical campaign. We demonstrate that Bennu's rotation rate is accelerating continuously at 3.63 ± 0.52 × 10-6 degrees day-2, likely due to the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect, with evolutionary implications.
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ItemAn investigation into the association of pre- and post-migration experiences on the self-rated health status among new resettled adult humanitarian refugees to Australia: a protocol for a mixed methods study.(Springer Science and Business Media LLC, 2019-04-30)BACKGROUND: Refugees are one of the most vulnerable groups in our society. They are at risk of poor physical and mental health outcomes, much of this attributed to traumatic events prior to migration and the additional risk factors refugees face in the host nations. However, how migration factors shape the health of resettling refugees is not well understood. This study uses a mixed methods approach to examine how pre- and post-migration factors shape the self-rated health of resettling adult refugees in an effort to address the current knowledge gap. METHODS: This study will use a sequential explanatory mixed method study design. We begin by analyzing resettlement and health data from the 'Building a New Life In Australia' longitudinal study of humanitarian refugees resettled in Australia to identify significant associations between migration factors and refugee health. Then, a series of semi-structured interviews with resettled refugees will further explore the lived experiences of refugees with respect to the relationship between migration and refugee health. Finally, we will integrate both sets of findings to develop a detailed understanding of how and why migratory factors contribute to refugee health during resettlement. DISCUSSION: There is a paucity of studies that examine the multidimensional nature of refugee health during resettlement and as a result, little is understood about their resettlement health needs. This information is required to inform existing or new resettlement interventions to help promote or improve refugee health. To overcome these limitations in the research knowledge, this study will use a mixture of study methods to illustrate the complex and multifaceted determinants of refugee health during resettlement in Australia.
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ItemImproving access to primary healthcare for vulnerable populations in Australia and Canada: protocol for a mixed-method evaluation of six complex interventions.(BMJ, 2019-07-27)INTRODUCTION: Access to primary healthcare (PHC) has a fundamental influence on health outcomes, particularly for members of vulnerable populations. Innovative Models Promoting Access-to-Care Transformation (IMPACT) is a 5-year research programme built on community-academic partnerships. IMPACT aims to design, implement and evaluate organisational innovations to improve access to appropriate PHC for vulnerable populations. Six Local Innovation Partnerships (LIPs) in three Australian states (New South Wales, Victoria and South Australia) and three Canadian provinces (Ontario, Quebec and Alberta) used a common approach to implement six different interventions. This paper describes the protocol to evaluate the processes, outcomes and scalability of these organisational innovations. METHODS AND ANALYSIS: The evaluation will use a convergent mixed-methods design involving longitudinal (pre and post) analysis of the six interventions. Study participants include vulnerable populations, PHC practices, their clinicians and administrative staff, service providers in other health or social service organisations, intervention staff and members of the LIP teams. Data were collected prior to and 3-6 months after the interventions and included interviews with members of the LIPs, organisational process data, document analysis and tools collecting the cost of components of the intervention. Assessment of impacts on individuals and organisations will rely on surveys and semistructured interviews (and, in some settings, direct observation) of participating patients, providers and PHC practices. ETHICS AND DISSEMINATION: The IMPACT research programme received initial ethics approval from St Mary's Hospital (Montreal) SMHC #13-30. The interventions received a range of other ethics approvals across the six jurisdictions. Dissemination of the findings should generate a deeper understanding of the ways in which system-level organisational innovations can improve access to PHC for vulnerable populations and new knowledge concerning improvements in PHC delivery in health service utilisation.
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ItemThe association of migration experiences on the self-rated health status among adult humanitarian refugees to Australia: an analysis of a longitudinal cohort study.(Springer Science and Business Media LLC, 2019-08-22)BACKGROUND: Refugees are potentially at an increased risk for health problems due to their past and current migration experiences. How migration factors shape refugee health is not well understood. We examined the association between migration factors and the self-rated general health of adult humanitarian refugees living in Australia. METHODS: We analyzed the first three waves of data from the 'Building A New Life In Australia' longitudinal survey of 2399 humanitarian refugees resettled in Australia. The study outcome was self-rated health measured by the 36-Item Short Form Health Survey. Predictors were migration process and resettlement factors. We used generalized linear mixed models to investigate the relationship between predictor and outcome variables. RESULTS: Poor general health persisted among this refugee population at high levels throughout the three-year follow-up. At baseline, 35.7% (95% CI: 33.8-37.7%) of the study population reported poorer general health. Female gender, increasing age and post-migration financial stressors were positively associated with poorer general health. Having a university degree and absence of chronic health conditions were seemingly protective against declining general health (OR: 0.50; 95% CI: 0.65-1.81 and OR: 0.15, 95% CI: 0.09-1.04, respectively). CONCLUSION: Our results show that there is persisting high prevalence of poorer general health among adult refugees across the initial years of resettlement in Australia. This finding suggests unmet health needs which may be compounded by the challenges of resettlement in a new society, highlighting the need for increased clinical awareness of this sustained health burden to help inform and prepare refugee health care and settlement service providers.
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ItemNeurocognitive and neuroanatomical maturation in the clinical high-risk states for psychosis: A pattern recognition study(ELSEVIER SCI LTD, 2019)BACKGROUND: Findings from neurodevelopmental studies indicate that adolescents with psychosis spectrum disorders have delayed neurocognitive performance relative to the maturational state of their healthy peers. Using machine learning, we generated a model of neurocognitive age in healthy adults and investigated whether individuals in clinical high risk (CHR) for psychosis showed systematic neurocognitive age deviations that were accompanied by specific structural brain alterations. METHODS: First, a Support Vector Regression-based age prediction model was trained and cross-validated on the neurocognitive data of 36 healthy controls (HC). This produced Cognitive Age Gap Estimates (CogAGE) that measured each participant's deviation from the normal cognitive maturation as the difference between estimated neurocognitive and chronological age. Second, we employed voxel-based morphometry to explore the neuroanatomical gray and white matter correlates of CogAGE in HC, in CHR individuals with early (CHR-E) and late (CHR-L) high risk states. RESULTS: The age prediction model estimated age in HC subjects with a mean absolute error of ±2.2 years (SD = 3.3; R2 = 0.33, P < .001). Mean (SD) CogAGE measured +4.3 (8.1) years in CHR individuals compared to HC (-0.1 (5.5) years, P = .006). CHR-L individuals differed significantly from HC subjects while this was not the case for the CHR-E group. CogAGE was associated with a distributed bilateral pattern of increased GM volume in the temporal and frontal areas and diffuse pattern of WM reductions. CONCLUSION: Although the generalizability of our findings might be limited due to the relatively small number of participants, CHR individuals exhibit a disturbed neurocognitive development as compared to healthy peers, which may be independent of conversion to psychosis and paralleled by an altered structural maturation process.
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ItemNo Preview AvailableEpigenetic aging in major depressive disorder(ELSEVIER, 2019-01-01)Major depressive disorder (MDD) is associated with increased risk of mortality and aging-related diseases [1–3]. The authors examined whether MDD is associated with higher epigenetic aging (EA) [4] in blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of MDD have a further impact on these patterns, and whether findings replicate in brain tissue. DNAm age was estimated using all methylation sites in blood of 811 depressed patients and 319 control subjects from the Netherlands Study of Depression and Anxiety. The residuals of the DNAm age estimates regressed on chronological age were calculated to indicate EA. MDD diagnosis and clinical characteristics were assessed with questionnaires and psychiatric interviews. Analyses were adjusted for sociodemographic characteristics, lifestyle, and health status. Postmortem brain samples of 74 depressed patients and 64 control subjects were used for replication. Pathway enrichment analysis was conducted using ConsensusPathDB to gain insight into the biological processes underlying EA in blood and brain. Significantly higher EA was observed in MDD patients compared with control subjects, with a significant dose effect with increasing symptom severity in the overall sample. In the depression group, EA was positively and significantly associated with childhood trauma score. The case-control difference was replicated in an independent dataset of postmortem brain samples. The top significantly enriched Gene Ontology terms included neuronal processes. As compared with control subjects, MDD patients exhibited higher EA in blood and brain tissue, suggesting that they are biologically older than their corresponding chronological age. This effect was even more profound in the presence of childhood trauma.
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ItemNo Preview AvailableHigh levels of mitochondrial DNA are associated with adolescent brain structural hypoconnectivity and increased anxiety but not depression(ELSEVIER SCIENCE BV, 2018-05)BACKGROUND: Adolescent anxiety and depression are highly prevalent psychiatric disorders that are associated with altered molecular and neurocircuit profiles. Recently, increased mitochondrial DNA copy number (mtDNA-cn) has been found to be associated with several psychopathologies in adults, especially anxiety and depression. The associations between mtDNA-cn and anxiety and depression have not, however, been investigated in adolescents. Moreover, to date there have been no studies examining associations between mtDNA-cn and brain network alterations in mood disorders in any age group. METHODS: The first aim of this study was to compare salivary mtDNA-cn between 49 depressed and/or anxious adolescents and 35 well-matched healthy controls. The second aim of this study was to identify neural correlates of mtDNA-cn derived from diffusion tensor imaging (DTI) and tractography, in the full sample of adolescents. RESULTS: There were no diagnosis-specific alterations in mtDNA-cn. However, there was a positive correlation between mtDNA-cn and levels of anxiety, but not depression, in the full sample of adolescents. A subnetwork of connections largely corresponding to the left fronto-occipital fasciculus had significantly lower fractional anisotropy (FA) values in adolescents with higher than median mtDNA-cn. LIMITATIONS: Undifferentiated analysis of free and intracellular mtDNA and use of DTI-based tractography represent this study's limitations. CONCLUSIONS: The results of this study help elucidate the relationships between clinical symptoms, molecular changes, and neurocircuitry alterations in adolescents with and without anxiety and depression, and they suggest that increased mtDNA-cn is associated both with increased anxiety symptoms and with decreased fronto-occipital structural connectivity in this population.
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ItemNo Preview AvailableEpigenetic Aging in Major Depressive Disorder(AMER PSYCHIATRIC PUBLISHING, INC, 2018-08)OBJECTIVE: Major depressive disorder is associated with an increased risk of mortality and aging-related diseases. The authors examined whether major depression is associated with higher epigenetic aging in blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of major depression have a further impact on these patterns, and whether the findings replicate in brain tissue. METHOD: DNAm age was estimated using all methylation sites in blood of 811 depressed patients and 319 control subjects with no lifetime psychiatric disorders and low depressive symptoms from the Netherlands Study of Depression and Anxiety. The residuals of the DNAm age estimates regressed on chronological age were calculated to indicate epigenetic aging. Major depression diagnosis and clinical characteristics were assessed with questionnaires and psychiatric interviews. Analyses were adjusted for sociodemographic characteristics, lifestyle, and health status. Postmortem brain samples of 74 depressed patients and 64 control subjects were used for replication. Pathway enrichment analysis was conducted using ConsensusPathDB to gain insight into the biological processes underlying epigenetic aging in blood and brain. RESULTS: Significantly higher epigenetic aging was observed in patients with major depression compared with control subjects (Cohen's d=0.18), with a significant dose effect with increasing symptom severity in the overall sample. In the depression group, epigenetic aging was positively and significantly associated with childhood trauma score. The case-control difference was replicated in an independent data set of postmortem brain samples. The top significantly enriched Gene Ontology terms included neuronal processes. CONCLUSIONS: As compared with control subjects, patients with major depression exhibited higher epigenetic aging in blood and brain tissue, suggesting that they are biologically older than their corresponding chronological age. This effect was even more profound in the presence of childhood trauma.
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ItemNo Preview AvailableAccelerating research on biological aging and mental health: Current challenges and future directions(PERGAMON-ELSEVIER SCIENCE LTD, 2019-08)Aging is associated with complex biological changes that can be accelerated, slowed, or even temporarily reversed by biological and non-biological factors. This article focuses on the link between biological aging, psychological stressors, and mental illness. Rather than comprehensively reviewing this rapidly expanding field, we highlight challenges in this area of research and propose potential strategies to accelerate progress in this field. This effort requires the interaction of scientists across disciplines - including biology, psychiatry, psychology, and epidemiology; and across levels of analysis that emphasize different outcome measures - functional capacity, physiological, cellular, and molecular. Dialogues across disciplines and levels of analysis naturally lead to new opportunities for discovery but also to stimulating challenges. Some important challenges consist of 1) establishing the best objective and predictive biological age indicators or combinations of indicators, 2) identifying the basis for inter-individual differences in the rate of biological aging, and 3) examining to what extent interventions can delay, halt or temporarily reverse aging trajectories. Discovering how psychological states influence biological aging, and vice versa, has the potential to create novel and exciting opportunities for healthcare and possibly yield insights into the fundamental mechanisms that drive human aging.