Centre for Youth Mental Health - Research Publications
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ItemGenetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks(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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ItemPsychosocial Well-Being and Functional Outcomes in Youth With Type 1 Diabetes 12 years After Disease Onset(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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ItemIncreased Extent of and Risk Factors for Pandemic (H1N1) 2009 and Seasonal Influenza among Children, Israel(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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ItemAddition of aripiprazole to the clozapine may be useful in reducing anxiety in treatment-resistant schizophrenia.(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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ItemCognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: the POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial.(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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ItemSurface Feature-Guided Mapping of Cerebral Metabolic Changes in Cognitively Normal and Mildly Impaired Elderly(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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ItemVery low-dose risperidone in first-episode psychosis: a safe and effective way to initiate treatment.(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.
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ItemChildhood sexual abuse and abnormal personality: a population-based study(CAMBRIDGE UNIV PRESS, 2011-06)BACKGROUND: Childhood sexual abuse (CSA) has been shown to be a risk factor for personality disorder (PD). However, no previous studies have examined whether associations exist between sexual abuse and abnormal personality as measured both categorically and dimensionally. Such enquiry would more fully illuminate the impact of CSA on adult personality. METHOD: Using a large nationally representative sample, we set out to examine associations between CSA and categorically defined PD. We also examined associations between CSA and the five dimensions of personality (openness to experience, conscientiousness, extraversion, agreeableness and neuroticism). A total of 1520 young adults were interviewed to determine the prevalence of sexual abuse occurring before age 16 years. A dimensional measure of personality was completed by 1469 participants, and 1145 had an informant-based PD assessment. RESULTS: PD was independently associated with repeated CSA [fully adjusted odds ratio (OR) 1.9, 95% confidence interval (CI) 1.1-3.4]. Repeated sexual abuse was also associated with higher neuroticism and lower agreeableness (p values for both <0.001). Adjusting for the effects of potential confounders and mediators, including earlier symptoms of anxiety and depression, had little impact on the strength of associations. CONCLUSIONS: We conclude that repeated CSA is independently associated with categorically defined PD, and also with higher neuroticism and lower agreeableness. Our findings suggest that if a dimensional classification of PDs is adopted in future classification systems, there might be meaningful continuity with previous aetiological research conducted using the current categorical system.
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ItemAltered Glycogen Metabolism in Cultured Astrocytes from Mice with Chronic Glutathione Deficit; Relevance for Neuroenergetics in Schizophrenia(PUBLIC LIBRARY SCIENCE, 2011-07-28)Neurodegenerative and psychiatric disorders including Alzheimer's, Parkinson's or Huntington's diseases and schizophrenia have been associated with a deficit in glutathione (GSH). In particular, a polymorphism in the gene of glutamate cysteine ligase modulatory subunit (GCLM) is associated with schizophrenia. GSH is the most important intracellular antioxidant and is necessary for the removal of reactive by-products generated by the utilization of glucose for energy supply. Furthermore, glucose metabolism through the pentose phosphate pathway is a major source of NADPH, the cofactor necessary for the regeneration of reduced glutathione. This study aims at investigating glucose metabolism in cultured astrocytes from GCLM knockout mice, which show decreased GSH levels. No difference in the basal metabolism of glucose was observed between wild-type and knockout cells. In contrast, glycogen levels were lower and its turnover was higher in knockout astrocytes. These changes were accompanied by a decrease in the expression of the genes involved in its synthesis and degradation, including the protein targeting to glycogen. During an oxidative challenge induced by tert-Butylhydroperoxide, wild-type cells increased their glycogen mobilization and glucose uptake. However, knockout astrocytes were unable to mobilize glycogen following the same stress and they could increase their glucose utilization only following a major oxidative insult. Altogether, these results show that glucose metabolism and glycogen utilization are dysregulated in astrocytes showing a chronic deficit in GSH, suggesting that alterations of a fundamental aspect of brain energy metabolism is caused by GSH deficit and may therefore be relevant to metabolic dysfunctions observed in schizophrenia.
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ItemParenting strategies for reducing adolescent alcohol use: a Delphi consensus study(BMC, 2011-01-06)BACKGROUND: International concern regarding the increase in preventable harms attributed to adolescent alcohol consumption has led to growing political and medical consensus that adolescents should avoid drinking for as long as possible. For this recommendation to be adopted, parents and guardians of adolescents require information about strategies that they can employ to prevent or reduce their adolescent's alcohol use that are supported by evidence. METHODS: The Delphi method was used to obtain expert consensus on parenting strategies effective in preventing and reducing adolescent alcohol consumption. A literature search identified 457 recommendations for parents to reduce their adolescent child's alcohol use. These recommendations were presented to a panel of 38 Australian experts who were asked to rate their importance over three survey rounds. RESULTS: There were 289 parenting strategies that were endorsed as important or essential in reducing adolescent alcohol use by ≥90% of the panel. These strategies were categorised into 11 sub-headings: things parents should know about adolescent alcohol use, delaying adolescent's introduction to alcohol, modelling responsible drinking and attitudes towards alcohol, talking to adolescents about alcohol, establishing family rules, monitoring adolescents when unsupervised, preparing adolescents for peer pressure, unsupervised adolescent drinking, what to do when an adolescent has been drinking without parental permission, hosting adolescent parties, and establishing and maintaining a good parent-child relationship. The endorsed strategies were written into a document suitable for parents. CONCLUSIONS: A comprehensive set of parenting strategies for preventing or reducing adolescent alcohol consumption were identified. These strategies can be promoted to parents to help them implement national recommendations for use of alcohol by young people.