Centre for Youth Mental Health - Research Publications

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    Brain Aging in Major Depressive Disorder: Results From the ENIGMA MDD Consortium
    Schmaal, L ; Han, L ; Dinga, R ; Thompson, P ; Veltman, D ; Penninx, B (ELSEVIER SCIENCE INC, 2018-05-01)
    Background: Major Depressive Disorder has been associated with accelerated biological aging. From a brain perspective, normal aging is associated with significant loss of grey matter and depression may have an accelerating effect on age-related brain atrophy. Here, data on brain aging in MDD from the ENIGMA MDD Working Group will be presented. Methods: A normative model of brain-based age was devel- oped in 4708 healthy controls by applying a Gaussian Process Regression analysis with 10-fold cross-validation to estimate chronological age from structural MRI scans, separately for males and females. This model was then applied to 2924 MDD individuals to predict their brain-based age. Accelerated brain aging was measured as the difference between predicted brain-based age and actual chronological age (brain age gap). Results: The brain age model explained 92% and 93% of the age variance in female and male healthy controls, respectively. The mean absolute error (MAE) was 6.79 years in females and 6.60 in males. Application of the model to MDD patients showed a mean brain age gap of 0.75 years in females (MAE¼6.82) and 0.64 in males (MAE¼6.68), which were significantly lower than brain age gap estimates in healthy controls in both females (F(1,4379)¼6.10,P¼0.01) and males (F(1,3166)¼4.07,P¼0.04). Our preliminary analysis also showed greater brain age gap associations with various clinical characteristics. Conclusions: We found preliminary evidence for accelerated brain aging in MDD, however, the brains of patients were estimated to be only <1 years older than healthy controls. The impact of different methods, feature selection and potential confounding effects will also be discussed.
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    High levels of mitochondrial DNA are associated with adolescent brain structural hypoconnectivity and increased anxiety but not depression
    Tymofiyeva, O ; Blom, EH ; Ho, TC ; Connolly, CG ; Lindqvist, D ; Wolkowitz, OM ; Lin, J ; LeWinn, KZ ; Sacchet, MD ; Han, LKM ; Yuan, JP ; Bhandari, SP ; Xu, D ; Yang, TT (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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    Epigenetic Aging in Major Depressive Disorder
    Han, LKM ; Aghajani, M ; Clark, SL ; Chan, RF ; Hattab, MW ; Shabalin, AA ; Zhao, M ; Kumar, G ; Xie, LY ; Jansen, R ; Milaneschi, Y ; Dean, B ; Aberg, KA ; van den Oord, EJCG ; Penninx, BWJH (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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    Trends in opioid utilisation in Australia, 2006-2015: Insights from multiple metrics
    Karanges, EA ; Buckley, NA ; Brett, J ; Blanch, B ; Litchfield, M ; Degenhardt, L ; Pearson, S-A (WILEY, 2018-05)
    PURPOSE: Population-based observational studies have documented global increases in opioid analgesic use. Many studies have used a single population-adjusted metric (number of dispensings, defined daily doses [DDDs], or oral morphine equivalents [OMEs]). We combine these volume-based metrics with a measure of the number of persons dispensed opioids to gain insights into Australian trends in prescribed opioid use. METHODS: We obtained records of prescribed opioid dispensings (2006-2015) subsidised under Australia's Pharmaceutical Benefits Scheme. We used dispensing claims to quantify annual changes in use according to 3 volume-based metrics: DDD/1000 pop/day, OME/1000 pop/day, and dispensings/1000 pop. We estimated the number of persons dispensed at least one opioid in a given year (persons)/1000 pop using data from a 10% random sample of Pharmaceutical Benefits Scheme-eligible Australians. RESULTS: Total opioid use increased according to all metrics, especially OME/1000 pop/day (51% increase) and dispensings/1000 pop (44%). Weaker opioid use remained stable or declined; strong opioid use increased. The rate of persons accessing weaker opioids only decreased 31%, and there was a 238% increase in persons dispensed only strong opioids. Strong opioid use also increased according to dispensings/1000 pop (140%), OME/1000 pop/day (80%), and DDD/1000 pop/day (71% increase). CONCLUSIONS: Our results suggest that the increases in total opioid use between 2006 and 2015 were predominantly driven by a growing number of people treated with strong opioids at lower medicine strengths/doses. This method can be used with or without person-level data to provide insights into factors driving changes in medicine use over time.
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    The CHOICE pilot project: Challenges of implementing a combined peer work and shared decision-making programme in an early intervention service
    Simmons, MB ; Coates, D ; Batchelor, S ; Dimopoulos-Bick, T ; Howe, D (WILEY, 2018-10)
    AIM: Youth participation is central to early intervention policy and quality frameworks. There is good evidence for peer support (individuals with lived experience helping other consumers) and shared decision making (involving consumers in making decisions about their own care) in adult settings. However, youth programs are rarely tested or described in detail. This report aims to fill this gap by describing a consumer focused intervention in an early intervention service. METHODS: This paper describes the development process, intervention content and implementation challenges of the Choices about Healthcare Options Informed by Client Experiences and Expectations (CHOICE) Pilot Project. This highly novel and innovative project combined both youth peer work and youth shared decision making. RESULTS: Eight peer workers were employed to deliver an online shared decision-making tool at a youth mental health service in New South Wales, Australia. The intervention development involved best practice principles, including international standards and elements of co-design. The implementation of the peer workforce in the service involved a number of targeted strategies designed to support this new service model. However, several implementation challenges were experienced which resulted in critical learning about how best to deliver these types of interventions. CONCLUSIONS: Delivering peer work and shared decision making within an early intervention service is feasible, but not without challenges. Providing adequate detail about interventions and implementation strategies fills a critical gap in the literature. Understanding optimal youth involvement strategies assists others to deliver acceptable and effective services to young people who experience mental ill health.
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    Comment on Hopwood et al., "the time has come for dimensional personality disorder diagnosis"
    Huprich, SK ; Herpertz, SC ; Bohus, M ; Chanen, A ; Goodman, M ; Mehlum, L ; Moran, P ; Newton-Howe, G ; Scott, L ; Sharp, C (WILEY, 2018-02)
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    Evaluating effectiveness in adolescent mental health inpatient units: A systematic review
    Hayes, C ; Simmons, M ; Simons, C ; Hopwood, M (WILEY, 2018-04)
    Adolescent mental health research is a developing area. Inpatient units are the most widely used acute element of adolescent mental health services internationally. Little is known about inpatient units, particularly when it comes to measuring improvement for adolescents. Clinical outcome measurement in the broad context has gathered momentum in recent years, driven by the need to assess services. The measurement of outcomes for adolescents who access inpatient care is critical, as they are particularly vulnerable and are often considered the most difficult to treat. Following the PRISMA guidelines, the aim of this review was to assess whether adolescent inpatient units are effective and understand how outcomes are measured. CINAHL, MEDLINE with Full Text, ERIC, PsycINFO, and Cochrane databases were systematically searched. Studies were included if the inpatient units were generic and adolescents were between the mean age of 12-25 years. Furthermore, studies published in English within the last ten years were included. Exclusions were outpatient and disorder-specific inpatient settings. A total of 16 studies were identified. Each study demonstrated effectiveness on at least one outcome measure in terms of symptom stabilization. However, several outcome measures were used and therefore inpatient units lack consistency in how they measure improvement. Inpatient units are effective for the majority of young people as they result in symptom stabilization. Whilst symptom stabilization can be achieved, future research examining the mechanism of change is needed.
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    Who benefits from adolescent sleep interventions? Moderators of treatment efficacy in a randomized controlled trial of a cognitive-behavioral and mindfulness-based group sleep intervention for at-risk adolescents
    Blake, MJ ; Blake, LM ; Schwartz, O ; Raniti, M ; Waloszek, JM ; Murray, G ; Simmons, JG ; Landau, E ; Dahl, RE ; McMakin, DL ; Dudgeon, P ; Trinder, J ; Allen, NB (WILEY, 2018-06)
    BACKGROUND: The aim of this study was to test moderators of therapeutic improvement in an adolescent cognitive-behavioral and mindfulness-based group sleep intervention. Specifically, we examined whether the effects of the program on postintervention sleep outcomes were dependent on participant gender and/or measures of sleep duration, anxiety, depression, and self-efficacy prior to the interventions. METHOD: Secondary analysis of a randomized controlled trial conducted with 123 adolescent participants (female = 59.34%; mean age = 14.48 years, range 12.04-16.31 years) who had elevated levels of sleep problems and anxiety symptoms. Participants were randomized into either a group sleep improvement intervention (n = 63) or group active control 'study skills' intervention (n = 60). The sleep intervention ('Sleep SENSE') was cognitive behavioral in approach, incorporating sleep education, sleep hygiene, stimulus control, and cognitive restructuring, but also had added anxiety-reducing, mindfulness, and motivational interviewing elements. Components of the active control intervention ('Study SENSE') included personal organization, persuasive writing, critical reading, referencing, memorization, and note taking. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Spence Children's Anxiety Scale (SCAS), Center for Epidemiologic Studies Depression Scale (CES-D), and General Self-Efficacy Scale (GSE) and wore an actigraph and completed a sleep diary for five school nights prior to the interventions. Sleep assessments were repeated at postintervention. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001177842; http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12612001177842&isBasic=True). RESULTS: The results showed that compared with the active control intervention, the effect of the sleep intervention on self-reported sleep quality (PSQI global score) at postintervention was statistically significant among adolescents with relatively moderate to high SCAS, CES-D, and GSE prior to the intervention, but not among adolescents with relatively low SCAS, CES-D, and GSE prior to the intervention. The results were consistent across genders. However, the effects of the sleep intervention on actigraphy-measured sleep onset latency and sleep diary-measured sleep efficiency at postintervention were not dependent on actigraphy-measured total sleep time, SCAS, CES-D, or GSE prior to the intervention. CONCLUSIONS: This study provides evidence that some sleep benefits of adolescent cognitive-behavioral sleep interventions are greatest among those with higher levels of anxiety and depressive symptoms, suggesting that this may be an especially propitious group to whom intervention efforts could be targeted. Furthermore, adolescents with lower levels of self-efficacy may need further targeted support (e.g. additional motivational interviewing) to help them reach treatment goals.
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    Ultra-high risk phase: A missed opportunity for physical health care
    Carney, R ; Bradshaw, T ; Yung, AR (WILEY, 2018-04)