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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ItemExtinction of a cocaine-taking context that protects against drug-primed reinstatement is dependent on the metabotropic glutamate 5 receptor(WILEY, 2015-05)We investigated the effects of extinguishing action-reward versus context-reward associations on drug-primed reinstatement, and the potential role of the metabotropic glutamate 5 receptor (mGlu5) in these different types of extinction in rats that self-administer cocaine. We observed that daily context extinction (non-reinforced exposures to the cocaine-taking context with retracted levers) was just as effective as daily lever extinction in reducing cocaine-primed reinstatement compared with passive abstinence. Additionally, systemic injections of the mGlu5 negative allosteric modulator MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine) following each extinction session significantly impaired the ability of context extinction to reduce cocaine-primed reinstatement, without affecting reinstatement after lever extinction or passive abstinence.
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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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ItemPeripheral telomere length and hippocampal volume in adolescents with major depressive disorder(SPRINGERNATURE, 2015-11-10)Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.
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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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ItemComparative efficacy and tolerability of first-generation and newer-generation antidepressant medications for depressive disorders in children and adolescents: study protocol for a systematic review and network meta-analysis.(BMJ, 2015-09-09)INTRODUCTION: Depressive disorders are among the most common psychiatric disorders in children and adolescents, and have adverse effects on their psychosocial functioning. Questions concerning the efficacy and safety of antidepressant medications in the treatment of depression in children and adolescents, led us to integrate the direct and indirect evidence using network meta-analysis to create hierarchies of these drugs. METHODS AND ANALYSIS: Seven databases with PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL, LiLACS and PsycINFO will be searched from 1966 to December 2013 (updated to May, 2015). There are no restrictions on language or type of publication. Randomised clinical trials assessing first-generation and newer-generation antidepressant medications against active comparator or placebo as acute treatment for depressive disorders in children and adolescents (under 18 years of age) will be included. The primary outcome for efficacy will be mean improvement in depressive symptoms, as measured by the mean change score of a depression rating scale from baseline to post-treatment. The tolerability of treatment will be defined as side effect discontinuation, as defined by the proportion of patients who discontinued treatment due to adverse events during the trial. We will also assess the secondary outcome for efficacy (response rate), acceptability (all-cause discontinuation) and suicide-related outcomes. We will perform the Bayesian network meta-analyses for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. DISSEMINATION: The network meta-analysis will provide useful information on antidepressant treatment for child and adolescent depression. The results will be disseminated through peer-reviewed publication or conference presentations. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015016023.
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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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ItemFusiform Gyrus Dysfunction is Associated with Perceptual Processing Efficiency to Emotional Faces in Adolescent Depression: A Model-Based Approach(FRONTIERS MEDIA SA, 2016-02-01)While the extant literature has focused on major depressive disorder (MDD) as being characterized by abnormalities in processing affective stimuli (e.g., facial expressions), little is known regarding which specific aspects of cognition influence the evaluation of affective stimuli, and what are the underlying neural correlates. To investigate these issues, we assessed 26 adolescents diagnosed with MDD and 37 well-matched healthy controls (HCL) who completed an emotion identification task of dynamically morphing faces during functional magnetic resonance imaging (fMRI). We analyzed the behavioral data using a sequential sampling model of response time (RT) commonly used to elucidate aspects of cognition in binary perceptual decision making tasks: the Linear Ballistic Accumulator (LBA) model. Using a hierarchical Bayesian estimation method, we obtained group-level and individual-level estimates of LBA parameters on the facial emotion identification task. While the MDD and HCL groups did not differ in mean RT, accuracy, or group-level estimates of perceptual processing efficiency (i.e., drift rate parameter of the LBA), the MDD group showed significantly reduced responses in left fusiform gyrus compared to the HCL group during the facial emotion identification task. Furthermore, within the MDD group, fMRI signal in the left fusiform gyrus during affective face processing was significantly associated with greater individual-level estimates of perceptual processing efficiency. Our results therefore suggest that affective processing biases in adolescents with MDD are characterized by greater perceptual processing efficiency of affective visual information in sensory brain regions responsible for the early processing of visual information. The theoretical, methodological, and clinical implications of our results are discussed.