Centre for Youth Mental Health - Research Publications
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ItemInduction of sodium iodide symporter gene and molecular characterisation of HNF3β/FoxA2, TTF-1 and C/EBPβ in thyroid carcinoma cells(NATURE PUBLISHING GROUP, 2008-08)Thyroid carcinoma cells often do not express thyroid-specific genes including sodium iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (TG), and thyrotropin-stimulating hormone receptor (TSHR). Treatment of thyroid carcinoma cells (four papillary and two anaplastic cell lines) with histone deacetylase inhibitors (SAHA or VPA) modestly induced the expression of the NIS gene. The promoter regions of the thyroid-specific genes contained binding sites for hepatocyte nuclear factor 3 beta (HNF3 beta)/forkhead box A2 (FoxA2), thyroid transcription factor 1 (TTF-1), and CCAAT/enhancer binding protein (C/EBP beta). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed decreased expression of HNF3 beta/FoxA2 and TTF-1 mRNA in papillary thyroid carcinoma cell lines, when compared with normal thyroid cells. Forced expression of these genes in papillary thyroid carcinoma cells inhibited their growth. Furthermore, the CpG island in the promoter region of HNF3 beta/FoxA2 was aberrantly methylated; and treatment with 5-aza-2-deoxycytidine (5-Az) induced its expression. Immunohistochemical staining showed that C/EBP beta was localised in the nucleus in normal thyroid cells but was detected in the cytoplasm in papillary thyroid carcinoma cells. Subcellular fractionation of papillary thyroid carcinoma cell lines also demonstrated high levels of expression of C/EBP beta in the cytoplasm, suggesting that a large proportion of C/EBP beta protein is inappropriately localised in the cytoplasm. In summary, these findings reveal novel abnormalities in thyroid carcinoma cells.
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ItemEffects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis(NATURE PUBLISHING GROUP, 2013-04)Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis. In a prospective cohort (follow-up=2.4-14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis. Two NRG1 htSNPs (rs12155594 and rs4281084) predicted transition to psychosis. Carriers of the rs12155594 T/T or T/C genotype had a 2.34 (95% confidence interval (CI)=1.37-4.00) times greater risk of transition compared with C/C carriers. For every rs4281084 A-allele the risk of transition increased by 1.55 (95% CI=1.05-2.27). For every additional rs4281084-A and/or rs12155594-T allele carried the risk increased ∼1.5-fold, with 71.4% of those carrying a combination of 3 of these alleles transitioning to psychosis. None of the assessed DAOA htSNPs were associated with transition. Our findings suggest NRG1 genetic variation may improve our ability to identify UHR individuals at risk for transition to psychosis.
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ItemStudy protocol: The development of a pilot study employing a randomised controlled design to investigate the feasibility and effects of a peer support program following discharge from a specialist first-episode psychosis treatment centre(BMC, 2010-05-25)BACKGROUND: Young people with first-episode psychosis (FEP) are at risk of a range of negative outcomes. Specialist FEP services have been developed to provide comprehensive, multi-disciplinary treatment. However, these services are often available for a restricted period and the services that young people may be transferred to are less comprehensive. This represents a risk of drop out from treatment services in a group already considered to be at risk of disengagement. Peer support groups have been shown to improve social relationships among people with psychosis however individual peer support programs have not been tested on young people with first-episode psychosis; nor have they been tested at the point of discharge from services. METHODS/DESIGN: The study is an 18-month randomised controlled trial being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. The aim of the study is to test the feasibility and effects of a 6-month peer support intervention delivered to young people with FEP over the period of discharge. Participants are young people aged 15-24 who are being discharged from a specialist first-episode psychosis treatment centre. There is a 6-month recruitment period. The intervention comprises two hours of contact per fortnight during which peer support workers can assist participants to engage with their new services, or other social and community activities. Participants will be assessed at baseline and post intervention (6 months). DISCUSSION: This paper describes the development of a randomised-controlled trial which aims to pilot a peer support program among young people who are being discharged from a specialist FEP treatment centre. If effective, the intervention could lead to benefits not only for participants over the discharge period, but for peer support workers as well.
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ItemStudy protocol: the development of a randomised controlled trial testing a postcard intervention designed to reduce suicide risk among young help-seekers(BMC, 2009-09-23)BACKGROUND: Suicidal behaviour and deliberate self harm are common among adolescents. Limited evidence exists regarding interventions that can reduce risk; however research indicates that maintaining contact either via letter or postcard with at-risk adults following discharge from services can reduce risk. The aim of the study is to test a postcard intervention among people aged 15-24 who presented to mental health services but are not accepted, yet are at risk of suicide. METHODS/DESIGN: The study is a 3-year randomised controlled trial conducted at Orygen Youth Health Research Centre in Melbourne Australia. Participants are young help-seekers aged 15-24 who are at risk of suicide. Participants will be recruited over a 12 month period. The intervention comprises a regular postcard to be sent monthly for 12 months. The postcard enquires after their well being and includes information regarding individual sources of help and evidence-based self help strategies. Participants are assessed at baseline, 12 and 18 months. DISCUSSION: This paper describes the development of a study which aims to reduce suicide risk in a sample of young help-seekers. If effective, this intervention could have significant clinical and research implications for a population who can be hard to treat and difficult to research. TRIAL REGISTRATION: The study was registered with the Australian Clinical Trials Registry; number: ACTRN012606000274572.
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ItemA factor analytic investigation of the Tripartite model of affect in a clinical sample of young Australians(BMC, 2008-09-18)BACKGROUND: The Mood and Anxiety Symptom Questionnaire (MASQ) was designed to specifically measure the Tripartite model of affect and is proposed to offer a delineation between the core components of anxiety and depression. Factor analytic data from adult clinical samples has shown mixed results; however no studies employing confirmatory factor analysis (CFA) have supported the predicted structure of distinct Depression, Anxiety and General Distress factors. The Tripartite model has not been validated in a clinical sample of older adolescents and young adults. The aim of the present study was to examine the validity of the Tripartite model using scale-level data from the MASQ and correlational and confirmatory factor analysis techniques. METHODS: 137 young people (M = 17.78, SD = 2.63) referred to a specialist mental health service for adolescents and young adults completed the MASQ and diagnostic interview. RESULTS: All MASQ scales were highly inter-correlated, with the lowest correlation between the depression- and anxiety-specific scales (r = .59). This pattern of correlations was observed for all participants rating for an Axis-I disorder but not for participants without a current disorder (r = .18). Confirmatory factor analyses were conducted to evaluate the model fit of a number of solutions. The predicted Tripartite structure was not supported. A 2-factor model demonstrated superior model fit and parsimony compared to 1- or 3-factor models. These broad factors represented Depression and Anxiety and were highly correlated (r = .88). CONCLUSION: The present data lend support to the notion that the Tripartite model does not adequately explain the relationship between anxiety and depression in all clinical populations. Indeed, in the present study this model was found to be inappropriate for a help-seeking community sample of older adolescents and young adults.
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ItemManaging deliberate self-harm in young people: An evaluation of a training program developed for school welfare staff using a longitudinal research design(BMC, 2008-09-15)BACKGROUND: Although deliberate self-harm is prevalent among young people, many who engage in deliberate self-harm receive sub-optimal care. Although schools are a well placed setting to support young people who engage in self-harm there are no specific training packages designed to assist school welfare staff to support these young people.The current study aimed to design, deliver and evaluate a training course specifically for school staff. METHODS: The study employed a longitudinal design. Two hundred and thirteen people participated in the training and evaluation. A questionnaire was administered at baseline, immediately after the training and at 6-month follow-up in order to determine if the training led to improvements in confidence when working with young people who self-harm, perceived skill, knowledge of, and attitudes towards people who self harm. RESULTS: Prior to the course, the majority of participants demonstrated relatively high levels of confidence, perceived skill and knowledge of self-harm and endorsed relatively positive attitudes towards people who engage in self-harm. Despite this, significant improvements were observed in terms of increased confidence, increased perceptions of skill along with increased knowledge of deliberate self-harm. These improvements were sustained over the follow-up period. CONCLUSION: The results demonstrated that the provision of specifically designed training can help school welfare staff to feel better equipped to support young people who are engaging in deliberate self-harm.
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ItemClinical utility of the Mood and Anxiety Symptom Questionnaire (MASQ) in a sample of young help-seekers(BMC, 2007-09-17)BACKGROUND: The overlap between Depression and Anxiety has led some researchers to conclude that they are manifestations of a broad, non-specific neurotic disorder. However, others believe that they can be distinguished despite sharing symptoms of general distress. The Tripartite Model of Affect proposes an anxiety-specific, a depression-specific and a shared symptoms factor. Watson and Clark developed the Mood and Anxiety Symptom Questionnaire (MASQ) to specifically measure these Tripartite constructs. Early research showed that the MASQ distinguished between dimensions of Depression and Anxiety in non-clinical samples. However, two recent studies have cautioned that the MASQ may show limited validity in clinical populations. The present study investigated the clinical utility of the MASQ in a clinical sample of adolescents and young adults. METHODS: A total of 204 Young people consecutively referred to a specialist public mental health service in Melbourne, Australia were approached and 150 consented to participate. From this, 136 participants completed both a diagnostic interview and the MASQ. RESULTS: The majority of the sample rated for an Axis-I disorder, with Mood and Anxiety disorders most prevalent. The disorder-specific scales of the MASQ significantly discriminated Anxiety (61.0%) and Mood Disorders (72.8%), however, the predictive accuracy for presence of Anxiety Disorders was very low (29.8%). From ROC analyses, a proposed cut-off of 76 was proposed for the depression scale to indicate 'caseness' for Mood Disorders. The resulting sensitivity/specificity was superior to that of the CES-D. CONCLUSION: It was concluded that the depression-specific scale of the MASQ showed good clinical utility, but that the anxiety-specific scale showed poor discriminant validity.
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ItemThe effectiveness of simple psychological and exercise interventions for high prevalence mental health problems in young people: a factorial randomised controlled trial(BMC, 2011-03-13)BACKGROUND: The prevalence of mental illness in young people is the highest of any age group, with the onset of depression, anxiety and substance use peaking between 18 and 24 years. Effective treatments that target sub-threshold or mild to moderate levels of disorder in young people are required to reduce the risk of persistence and recurrence. The aims of this study are to evaluate whether treatments that are less intensive than cognitive-behaviour therapy, such as problem solving therapy and exercise treatments, are acceptable and effective in managing depression and anxiety symptoms in young people and to identify possible attributes in those who are likely to respond to these treatments. METHODS/DESIGN: This is a factorial randomised controlled trial conducted at a large, metropolitan youth mental health service. Participants are young help-seekers aged 15-25 years with sub-threshold or mild to moderate levels of depression and anxiety (with or without comorbid substance use). The interventions comprise 4 treatment combinations delivered by psychologists over 6 sessions on a weekly basis: a psychological intervention (problem solving therapy versus supportive counselling) and an exercise intervention (behavioural exercise versus psychoeducation). Structured assessments occur at baseline, mid-point, end-point (6 weeks) and at a 6- and 12-month follow-up. The primary outcomes are depression and anxiety symptoms as measured by the Beck Depression and Anxiety Inventories. Secondary outcomes include remission (defined as no longer meeting the diagnostic criteria for a disorder if threshold level was reached at baseline, or no longer scoring in the clinical range on scale scores if sub-threshold at baseline), substance use, and functioning. DISCUSSION: The effectiveness of less complex psychological and exercise interventions in young help-seekers with sub-threshold or mild to moderate presentations of high prevalence disorders is yet to be explored. This study has been designed to examine the effectiveness of these interventions delivered alone, or in combination, in a youth-specific service. If effective, the interventions have the potential to prevent the progression of early symptoms and distress to later and potentially more serious stages of mental disorder and reduce the likelihood of ongoing problems associated with the risk of persistence and recurrence. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12608000550303.
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ItemNeurocognitive predictors of transition to psychosis: medium- to long-term findings from a sample at ultra-high risk for psychosis(CAMBRIDGE UNIV PRESS, 2013-11)BACKGROUND: Individuals at ultra-high risk (UHR) for psychosis show reduced neurocognitive performance across domains but it is unclear which reductions are associated with transition to frank psychosis. The aim of this study was to investigate differences in baseline neurocognitive performance between UHR participants with (UHR-P) and without transition to psychosis (UHR-NP) and a healthy control (HC) group and examine neurocognitive predictors of transition over the medium to long term. METHOD: A sample of 325 UHR participants recruited consecutively from the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne and 66 HCs completed a neurocognitive assessment at baseline. The UHR group was followed up between 2.39 and 14.86 (median = 6.45) years later. Cox regression was used to investigate candidate neurocognitive predictors of psychosis onset. RESULTS: The UHR group performed more poorly than the HC group across a range of neurocognitive domains but only performance on digit symbol coding and picture completion differed between the groups. The risk of transition was only significantly associated with poorer performance on visual reproduction [hazard ratio (HR) 0.919, 95% confidence interval (CI) 0.876-0.965, p = 0.001] and matrix reasoning (HR 0.938, 95% CI 0.883-0.996, p = 0.037). These remained significant even after controlling for psychopathology at baseline. CONCLUSIONS: This study is the longest follow-up of an UHR sample to date. UHR status was associated with poorer neurocognitive performance compared to HCs on some tasks. Cognition at identification as UHR was not a strong predictor of risk for transition to psychosis. The results suggests the need to include more experimental paradigms that isolate discrete cognitive processes to better understand neurocognition at this early stage of illness.
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ItemNo Preview AvailablePhenylthiocarbamide (PTC) perception in ultra-high risk for psychosis participants who develop schizophrenia: Testing the evidence for an endophenotypic marker(ELSEVIER IRELAND LTD, 2012-08-30)Reports suggesting that schizophrenia participants are more likely to be phenylthiocarbamide (PTC) non-tasters when compared to controls have recently been controversial. If supported, a genetic-based phenotypic variation in PTC taster status is implicated, suggesting a greater illness risk for those participants with recessive alleles for the TAS2R38 receptor. Should PTC insensitivity be a schizophrenia endophenotype, then it would be expected in follow-up of ultra high-risk for psychosis participants who later develop schizophrenia (UHR-S). UHR-S was hypothesised to show reduced PTC sensitivity compared to those who were previously at risk, but did not transition (UHR-NP). PTC perception was assessed in 219 UHR participants at long-term follow-up, of whom 53 had transitioned to psychosis (UHR-P) during the follow-up period. Fifteen of the 219 participants were diagnosed with schizophrenia. Seventy-eight had a family history of psychotic disorder. No differences in PTC taster status were found in UHR participants based upon transition to psychosis status, schizophrenia diagnosis, or family history of schizophrenia. This report indicates that schizophrenia development among UHR participants is not associated with PTC tasting deficits and fails to support previous findings that inability to detect the bitter taste of PTC is a schizophrenia endophenotype.