Centre for Youth Mental Health - Research Publications
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ItemEarly specific cognitive-behavioural psychotherapy in subjects at high risk for bipolar disorders: study protocol for a randomised controlled trial.(Springer Science and Business Media LLC, 2014-05-08)BACKGROUND: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their social relationships. We aimed to identify subjects at risk of developing BD and investigate the efficacy and safety of early specific cognitive-behavioural psychotherapy (CBT) in this subpopulation. METHODS/DESIGN: EarlyCBT is a randomised controlled multi-centre clinical trial to evaluate the efficacy and safety of early specific CBT, including stress management and problem solving strategies, with elements of mindfulness-based therapy (MBT) versus unstructured group meetings for 14 weeks each and follow-up until week 78. Participants are recruited at seven university hospitals throughout Germany, which provide in- and outpatient care (including early recognition centres) for psychiatric patients. Subjects at high risk must be 15 to 30 years old and meet the combination of specified affective symptomatology, reduction of psychosocial functioning, and family history for (schizo)affective disorders. Primary efficacy endpoints are differences in psychosocial functioning and defined affective symptomatology at 14 weeks between groups. Secondary endpoints include the above mentioned endpoints at 7, 24, 52 and 78 weeks and the change within groups compared to baseline; perception of, reaction to and coping with stress; and conversion to full BD. DISCUSSION: To our knowledge, this is the first study to evaluate early specific CBT in subjects at high risk for BD. Structured diagnostic interviews are used to map the risk status and development of disease. With our study, the level of evidence for the treatment of those young patients will be significantly raised. TRIAL REGISTRATION: WHO International Clinical Trials Platform (ICTRP), identifier: DRKS00000444, date of registration: 16 June 2010.
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ItemNESSTI: Norms for Environmental Sound Stimuli(PUBLIC LIBRARY SCIENCE, 2013-09-04)In this paper we provide normative data along multiple cognitive and affective variable dimensions for a set of 110 sounds, including living and manmade stimuli. Environmental sounds are being increasingly utilized as stimuli in the cognitive, neuropsychological and neuroimaging fields, yet there is no comprehensive set of normative information for these type of stimuli available for use across these experimental domains. Experiment 1 collected data from 162 participants in an on-line questionnaire, which included measures of identification and categorization as well as cognitive and affective variables. A subsequent experiment collected response times to these sounds. Sounds were normalized to the same length (1 second) in order to maximize usage across multiple paradigms and experimental fields. These sounds can be freely downloaded for use, and all response data have also been made available in order that researchers can choose one or many of the cognitive and affective dimensions along which they would like to control their stimuli. Our hope is that the availability of such information will assist researchers in the fields of cognitive and clinical psychology and the neuroimaging community in choosing well-controlled environmental sound stimuli, and allow comparison across multiple studies.
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ItemSocial judgement in borderline personality disorder.(Public Library of Science (PLoS), 2013)BACKGROUND: Borderline personality disorder (BPD) is a common and serious mental illness, associated with a high risk of suicide and self harm. Those with a diagnosis of BPD often display difficulties with social interaction and struggle to form and maintain interpersonal relationships. Here we investigated the ability of participants with BPD to make social inferences from faces. METHOD: 20 participants with BPD and 21 healthy controls were shown a series of faces and asked to judge these according to one of six characteristics (age, distinctiveness, attractiveness, intelligence, approachability, trustworthiness). The number and direction of errors made (compared to population norms) were recorded for analysis. RESULTS: Participants with a diagnosis of BPD displayed significant impairments in making judgements from faces. In particular, the BPD Group judged faces as less approachable and less trustworthy than controls. Furthermore, within the BPD Group there was a correlation between scores on the Childhood Trauma Questionnaire (CTQ) and bias towards judging faces as unapproachable. CONCLUSION: Individuals with a diagnosis of BPD have difficulty making appropriate social judgements about others from their faces. Judging more faces as unapproachable and untrustworthy indicates that this group may have a heightened sensitivity to perceiving potential threat, and this should be considered in clinical management and treatment.
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ItemNo Preview AvailableInsights into Aurora-A Kinase Activation Using Unnatural Amino Acids Incorporated by Chemical Modification(AMER CHEMICAL SOC, 2013-10)Most protein kinases are regulated through activation loop phosphorylation, but the contributions of individual sites are largely unresolved due to insufficient control over sample phosphorylation. Aurora-A is a mitotic Ser/Thr protein kinase that has two regulatory phosphorylation sites on its activation loop, T287 and T288. While phosphorylation of T288 is known to activate the kinase, the function of T287 phosphorylation is unclear. We applied site-directed mutagenesis and selective chemical modification to specifically introduce bioisosteres for phospho-threonine and other unnatural amino acids at these positions. Modified Aurora-A proteins were characterized using a biochemical assay measuring substrate phosphorylation. Replacement of T288 with glutamate and aspartate weakly stimulated activity. Phospho-cysteine, installed by chemical synthesis from a corresponding cysteine residue introduced at position 288, showed catalytic activity approaching that of the comparable phospho-serine protein. Unnatural amino acid residues, with longer side chains, inserted at position 288 were autophosphorylated and supported substrate phosphorylation. Aurora-A activity is enhanced by phosphorylation at position 287 alone but is suppressed when position 288 is also phosphorylated. This is rationalized by competition between phosphorylated T287 and T288 for a binding site composed of arginines, based on a structure of Aurora-A in which phospho-T287 occupies this site. This is, to our knowledge, the first example of a Ser/Thr kinase whose activity is controlled by the phosphorylation state of adjacent residues in its activation loop. Overall we demonstrate an approach that combines mutagenesis and selective chemical modification of selected cysteine residues to investigate otherwise impenetrable aspects of kinase regulation.
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ItemThe ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data(SPRINGER, 2014-06)The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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ItemContribution of Brain Size to IQ and Educational Underperformance in Extremely Preterm Adolescents(PUBLIC LIBRARY SCIENCE, 2013-10-09)OBJECTIVES: Extremely preterm (EP) survivors have smaller brains, lower IQ, and worse educational achievement than their term-born peers. The contribution of smaller brain size to the IQ and educational disadvantages of EP is unknown. This study aimed (i) to compare brain volumes from multiple brain tissues and structures between EP-born (< 28 weeks) and term-born (≥ 37 weeks) control adolescents, (ii) to explore the relationships of brain tissue volumes with IQ and basic educational skills and whether this differed by group, and (iii) to explore how much total brain tissue volume explains the underperformance of EP adolescents compared with controls. METHODS: Longitudinal cohort study of 148 EP and 132 term controls born in Victoria, Australia in 1991-92. At age 18, magnetic resonance imaging-determined brain volumes of multiple tissues and structures were calculated. IQ and educational skills were measured using the Wechsler Abbreviated Scale of Intelligence (WASI) and the Wide Range Achievement Test(WRAT-4), respectively. RESULTS: Brain volumes were smaller in EP adolescents compared with controls (mean difference [95% confidence interval] of -5.9% [-8.0, -3.7%] for total brain tissue volume). The largest relative differences were noted in the thalamus and hippocampus. The EP group had lower IQs(-11.9 [-15.4, -8.5]), spelling(-8.0 [-11.5, -4.6]), math computation(-10.3 [-13.7, -6.9]) and word reading(-5.6 [-8.8, -2.4]) scores than controls; all p-values<0.001. Volumes of total brain tissue and other brain tissues and structures correlated positively with IQ and educational skills, a relationship that was similar for both the EP and controls. Total brain tissue volume explained between 20-40% of the IQ and educational outcome differences between EP and controls. CONCLUSIONS: EP adolescents had smaller brain volumes, lower IQs and poorer educational performance than controls. Brain volumes of multiple tissues and structures are related to IQ and educational outcomes. Smaller total brain tissue volume is an important contributor to the cognitive and educational underperformance of adolescents born EP.
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ItemA Review of Programs That Targeted Environmental Determinants of Aboriginal and Torres Strait Islander Health(MDPI AG, 2013-08)OBJECTIVE: Effective interventions to improve population and individual health require environmental change as well as strategies that target individual behaviours and clinical factors. This is the basis of implementing an ecological approach to health programs and health promotion. For Aboriginal People and Torres Strait Islanders, colonisation has made the physical and social environment particularly detrimental for health. METHODS AND RESULTS: We conducted a literature review to identify Aboriginal health interventions that targeted environmental determinants of health, identifying 21 different health programs. Program activities that targeted environmental determinants of health included: Caring for Country; changes to food supply and/or policy; infrastructure for physical activity; housing construction and maintenance; anti-smoking policies; increased workforce capacity; continuous quality improvement of clinical systems; petrol substitution; and income management. Targets were categorised according to Miller's Living Systems Theory. Researchers using an Indigenous community based perspective more often identified interpersonal and community-level targets than were identified using a Western academic perspective. CONCLUSIONS: Although there are relatively few papers describing interventions that target environmental determinants of health, many of these addressed such determinants at multiple levels, consistent to some degree with an ecological approach. Interpretation of program targets sometimes differed between academic and community-based perspectives, and was limited by the type of data reported in the journal articles, highlighting the need for local Indigenous knowledge for accurate program evaluation. IMPLICATIONS: While an ecological approach to Indigenous health is increasingly evident in the health research literature, the design and evaluation of such programs requires a wide breadth of expertise, including local Indigenous knowledge.
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ItemPrimary care and youth mental health in Ireland: qualitative study in deprived urban areas(BMC, 2013-12-17)BACKGROUND: Mental disorders account for six of the 20 leading causes of disability worldwide with a very high prevalence of psychiatric morbidity in youth aged 15-24 years. However, healthcare professionals are faced with many challenges in the identification and treatment of mental and substance use disorders in young people (e.g. young people's unwillingness to seek help from healthcare professionals, lack of training, limited resources etc.) The challenge of youth mental health for primary care is especially evident in urban deprived areas, where rates of and risk factors for mental health problems are especially common. There is an emerging consensus that primary care is well placed to address mental and substance use disorders in young people especially in deprived urban areas. This study aims to describe healthcare professionals' experience and attitudes towards screening and early intervention for mental and substance use disorders among young people (16-25 years) in primary care in deprived urban settings in Ireland. METHODS: The chosen method for this qualitative study was inductive thematic analysis which involved semi-structured interviews with 37 healthcare professionals from primary care, secondary care and community agencies at two deprived urban centres. RESULTS: We identified three themes in respect of interventions to increase screening and treatment: (1) Identification is optimised by a range of strategies, including raising awareness, training, more systematic and formalised assessment, and youth-friendly practices (e.g. communication skills, ensuring confidentiality); (2) Treatment is enhanced by closer inter-agency collaboration and training for all healthcare professionals working in primary care; (3) Ongoing engagement is enhanced by motivational work with young people, setting achievable treatment goals, supporting transition between child and adult mental health services and recognising primary care's longitudinal nature as a key asset in promoting treatment engagement. CONCLUSIONS: Especially in deprived areas, primary care is central to early intervention for youth mental health. Identification, treatment and continuing engagement are likely to be enhanced by a range of strategies with young people, healthcare professionals and systems. Further research on youth mental health and primary care, including qualitative accounts of young people's experience and developing complex interventions that promote early intervention are priorities.
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ItemA randomized controlled trial investigating the effects of PCSO-524®, a patented oil extract of the New Zealand green lipped mussel (Perna canaliculus), on the behaviour, mood, cognition and neurophysiology of children and adolescents (aged 6-14 years) experiencing clinical and subclinical levels of hyperactivity and inattention: study protocol ACTRN12610000978066(BMC, 2013-07-16)BACKGROUND: The prevalence rate of attention-deficit/hyperactivity disorder (ADHD) within Western cultures is between 5% and 12%, and is the most common psychiatric illness among school-aged children, with an estimated 50% of these children retaining ADHD symptoms for the rest of their lives. Children with ADHD have lower blood levels of long-chain Poly Unsaturated Fatty Acids (LC PUFAs) compared with children without ADHD, and following PUFA supplementation, have shown improvements in ADHD-related symptoms. One highly promising marine based LC PUFA preparation is the Omega-3-rich Lyprinol/Omega XL which is a natural formulation containing standardised lipid extract of the New Zealand green lipped mussel (Perna canaliculus) known as PCSO-524® which contains a unique combination of free fatty acids, sterol esters, polar lipids and carotenoids. It is this unique combination of marine lipids that may assist in correcting the decreased levels of LC PUFA levels in children with symptoms of ADHD. The compound is a mixture belonging to a lipid group called sterol esters (SE). The fatty acids in the SE fraction are mainly myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Lyprinol/Omega XL has previously been shown to contain a potent group of Omega-3 lipids that block the 5 - lipoxygenase metabolic pathway responsible for inflammation in the body. METHODS: A randomized double blind placebo controlled trial will be utilized to assess the effects of 14 weeks administration of Lyprinol/Omega XL versus placebo in 150 children aged 6 to 14 years with high levels of hyperactivity and inattention. Additionally, a range of cognitive, mood and central electrophysiological measures will be undertaken during the 14 week supplementation trial. The primary outcome measure, the Conners' Parent Rating Scales will be completed initially at baseline, then in weeks 4, 8, 10, 14 and then again at 4 weeks post-administration (week 18). The results will contribute to our understanding of the efficacy of marine based Omega-3 s with high anti-inflammatory actions on inattention and hyperactivity in children aged 6 to 14 years.
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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.