Centre for Youth Mental Health - Research Publications

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    Genetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks
    Fornito, A ; Zalesky, A ; Bassett, DS ; Meunier, D ; Ellison-Wright, I ; Yuecel, M ; Wood, SJ ; Shaw, K ; O'Connor, J ; Nertney, D ; Mowry, BJ ; Pantelis, C ; Bullmore, ET (SOC NEUROSCIENCE, 2011-03-02)
    The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09-0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization.
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    Psychosocial Well-Being and Functional Outcomes in Youth With Type 1 Diabetes 12 years After Disease Onset
    Northam, EA ; Lin, A ; Finch, S ; Weather, GA ; Cameron, FJ (AMER DIABETES ASSOC, 2010-07)
    OBJECTIVE: Type 1 diabetes in youth and community controls were compared on functional outcomes. Relationships were examined between psychosocial variables at diagnosis and functional outcome 12 years later. RESEARCH DESIGN AND METHODS: Participants were subjects with type 1 diabetes (n = 110, mean age 20.7 years, SD 4.3) and control subjects (n = 76, mean age 20.8 years, SD 4.0). The measures used included the Youth Self-Report and Young Adult Self-Report and a semi-structured interview of functional outcomes. Type 1 diabetes participants also provided information about current diabetes care and metabolic control from diagnosis. RESULTS: Type 1 diabetes participants and control subjects reported similar levels of current well-being but for the youth with type 1 diabetes, the mental health referral rates over the previous 12 years were higher by 19% and school completion rates were lower by 17%. Over one-third of clinical participants were not currently receiving specialist care and this group had higher mental health service usage in the past (61 vs. 33%) and lower current psychosocial well- being. Within the type 1 diabetes group, behavior problems, high activity, and low family cohesion at diagnosis predicted lower current well-being, but were not associated with metabolic control history. Poorer metabolic control was associated with higher mental health service usage. CONCLUSIONS: Type 1 diabetes participants report similar levels of current psychosocial well-being compared with control subjects, but higher levels of psychiatric morbidity since diagnosis and lower school completion rates. Psychiatric morbidity was associated with poor metabolic control and failure to transition to tertiary adult diabetes care.
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    Increased Extent of and Risk Factors for Pandemic (H1N1) 2009 and Seasonal Influenza among Children, Israel
    Engelhard, D ; Bromberg, M ; Averbuch, D ; Tenenbaum, A ; Goldmann, D ; Kunin, M ; Shmueli, E ; Yatsiv, I ; Weintraub, M ; Mandelboim, M ; Strauss-Liviatan, N ; Anis, E ; Mendelson, E ; Shohat, T ; Wolf, DG ; Shapiro, M ; Grotto, I (CENTERS DISEASE CONTROL, 2011-09)
    During the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. Children hospitalized for pandemic (H1N1) 2009 were older and had more underlying chronic diseases than those hospitalized for seasonal influenza.
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    Addition of aripiprazole to the clozapine may be useful in reducing anxiety in treatment-resistant schizophrenia.
    Chanachev, A ; Ansermot, N ; Crettol Wavre, S ; Nowotka, U ; Stamatopoulou, M-E ; Conus, P ; Eap, CB (Hindawi Limited, 2011)
    There exist many case reports and studies on the antipsychotic augmentation by aripirazole in partial responders to clozapine, the most seem to be finding a slight difference in the PANSS and CGI scores after the aripirazole addition. The results of our report are compatible with those of other studies but, we have found a considerable antianxiety action in both of the cases. The 5HT1A agonism of aripirazole could be hypothesized as mechanism contributing to this effect.
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    Cognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: the POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial.
    Klingberg, S ; Wittorf, A ; Meisner, C ; Wölwer, W ; Wiedemann, G ; Herrlich, J ; Bechdolf, A ; Müller, BW ; Sartory, G ; Wagner, M ; Kircher, T ; König, H-H ; Engel, C ; Buchkremer, G (Springer Science and Business Media LLC, 2010-12-29)
    BACKGROUND: It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention. METHODS/DESIGN: The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency. DISCUSSION: This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion on psychotherapy in psychotic disorders, and to help implement psychotherapy in routine care. Furthermore, the study will allow drawing conclusions about the mediators of treatment effects of CBT of psychotic disorders.
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    Surface Feature-Guided Mapping of Cerebral Metabolic Changes in Cognitively Normal and Mildly Impaired Elderly
    Apostolova, LG ; Thompson, PM ; Rogers, SA ; Dinov, ID ; Zoumalan, C ; Steiner, CA ; Siu, E ; Green, AE ; Small, GW ; Toga, AW ; Cummings, JL ; Phelps, ME ; Silverman, DH (SPRINGER, 2010-04)
    PURPOSE: The aim of this study was to investigate the longitudinal positron emission tomography (PET) metabolic changes in the elderly. PROCEDURES: Nineteen nondemented subjects (mean Mini-Mental Status Examination 29.4 +/- 0.7 SD) underwent two detailed neuropsychological evaluations and resting 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG)-PET scan (interval 21.7 +/- 3.7 months), baseline structural 3T magnetic resonance (MR) imaging, and apolipoprotein E4 genotyping. Cortical PET metabolic changes were analyzed in 3-D using the cortical pattern matching technique. RESULTS: Baseline vs. follow-up whole-group comparison revealed significant metabolic decline bilaterally in the posterior temporal, parietal, and occipital lobes and the left lateral frontal cortex. The declining group demonstrated 10-15% decline in bilateral posterior cingulate/precuneus, posterior temporal, parietal, and occipital cortices. The cognitively stable group showed 2.5-5% similarly distributed decline. ApoE4-positive individuals underwent 5-15% metabolic decline in the posterior association cortices. CONCLUSIONS: Using 3-D surface-based MR-guided FDG-PET mapping, significant metabolic changes were seen in five posterior and the left lateral frontal regions. The changes were more pronounced for the declining relative to the cognitively stable group.
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    Induction of sodium iodide symporter gene and molecular characterisation of HNF3β/FoxA2, TTF-1 and C/EBPβ in thyroid carcinoma cells
    Akagi, T ; Luong, QT ; Gui, D ; Said, J ; Selektar, J ; Yung, A ; Bunce, CM ; Braunstein, GD ; Koeffler, HP (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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    Mental health first aid training for the public: evaluation of effects on knowledge, attitudes and helping behavior
    Kitchener, BA ; Jorm, AF (BIOMED CENTRAL LTD, 2002)
    BACKGROUND: Many members of the public have poor mental health literacy. A Mental Health First Aid training course was developed in order to improve this. This paper describes the training course and reports an evaluation study looking at changes in knowledge, stigmatizing attitudes and help provided to others. METHODS: Data are reported on the first 210 participants in public courses. Evaluation questionnaires were given at the beginning of courses, at the end and at 6 months follow-up. Data were analyzed using an intention-to-treat approach. RESULTS: The course improved participants' ability to recognize a mental disorder in a vignette, changed beliefs about treatment to be more like those of health professionals, decreased social distance from people with mental disorders, increased confidence in providing help to someone with a mental disorder, and increased the amount of help provided to others. CONCLUSIONS: Mental Health First Aid training appears to be an effective method of improving mental health literacy which can be widely applied.
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    Development of guidelines to assist organisations to support employees returning to work after an episode of anxiety, depression or a related disorder: a Delphi consensus study with Australian professionals and consumers
    Reavley, NJ ; Ross, A ; Killackey, EJ ; Jorm, AF (BMC, 2012-09-03)
    BACKGROUND: Mental disorders are a significant cause of disability and loss of workplace productivity. The scientific evidence for how organisations should best support those returning to work after common mental disorders is relatively limited. Therefore a Delphi expert consensus study was carried out with professional and consumer experts. METHODS: A systematic review of websites, books and journal articles was conducted to develop a 387 item survey containing strategies that organisations might use to support those returning to work after common mental disorders. Three panels of Australian experts (66 health professionals, 30 employers and 80 consumers) were recruited and independently rated the items over three rounds, with strategies reaching consensus on importance written into the guidelines. RESULTS: The participation rate across all three rounds was 60.2% (57.6% health professionals, 76.7% employers, 56.3% consumers). 308 strategies were endorsed as essential or important by at least 80% of all three panels. The endorsed strategies provided information on policy and procedures, the roles of supervisors, employees and colleagues in managing absence and return to work, and provision of mental health information and training. CONCLUSIONS: The guidelines outline strategies for organisations supporting those returning to work after common mental disorders. It is hoped that they may be used to inform policy and practice in a variety of workplaces.
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    Very low-dose risperidone in first-episode psychosis: a safe and effective way to initiate treatment.
    McGorry, PD ; Cocks, J ; Power, P ; Burnett, P ; Harrigan, S ; Lambert, T (Hindawi Limited, 2011)
    Patients experiencing a first psychotic episode have high rates of extrapyramidal symptoms (EPSs) when treated with the doses of neuroleptics used in multiepisode or chronic schizophrenia. There is some evidence that lower doses may be equally, if not more, effective but less toxic in this population. Here, we report the results of a biphasic open label trial designed to assess the efficacy, safety, and tolerability of low-dose (2-4 mg/day) risperidone treatment in a group of 96 first-episode nonaffective psychosis patients. At the end of the trial, 62% of patients met the response criteria although approximately 80% had achieved a response at some time during the study. Reports of EPS remained low, and there were no dystonic reactions. We conclude that even at a dose of 2 mg/day, risperidone was highly effective in reducing acute symptomatology in a real world sample of young first-episode psychosis patients.