Centre for Youth Mental Health - Research Publications
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ItemBroad clinical high-risk mental state (CHARMS): Methodology of a cohort study validating criteria for pluripotent risk(WILEY, 2019-06)AIM: The development of the ultra-high risk (UHR) criteria for psychosis created a new paradigm for the prevention research in psychiatry. Since (1) prevention research faces the challenge of achieving adequate statistical power when focusing on single low-incidence syndromes and (2) early clinical phenotypes are overlapping and non-specific, this study broadens the UHR state beyond psychosis as an outcome. The CHARMS (clinical high at-risk mental state) study aims to prospectively validate a set of trans-diagnostic criteria to identify help-seeking young people at risk of developing a range of serious mental illnesses. METHODS: This paper describes the methodology of the CHARMS study, which involves applying the CHARMS criteria to a cohort of help-seeking young people aged 12 to 25 attending youth mental health services in Melbourne. New referrals meeting the CHARMS criteria are allocated to the CHARMS+ group; referrals not meeting CHARMS threshold are allocated to CHARMS- group (control group); referrals meeting criteria for a full-threshold disorder are excluded. Transition status and clinical and functional outcomes are re-assessed at 6 and 12 months. CONCLUSIONS: This study will be the first to introduce and validate clinical criteria to identify a broader at-risk patient population, which may facilitate young people's access to clinical services and early treatment by reducing the reliance on "caseness" defined according to current diagnostic categories being required for service entry. These criteria may introduce a new, trans-diagnostic approach for understanding risk factors and pathogenic mechanisms that drive the onset of severe mental illness and the next generation of preventive intervention trials.
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ItemStaged Treatment in Early Psychosis: A sequential multiple assignment randomised trial of interventions for ultra high risk of psychosis patients(WILEY, 2018-06)AIM: Previous research indicates that preventive intervention is likely to benefit patients "at risk" of psychosis, in terms of functional improvement, symptom reduction and delay or prevention of onset of threshold psychotic disorder. The primary aim of the current study is to test outcomes of ultra high risk (UHR) patients, primarily functional outcome, in response to a sequential intervention strategy consisting of support and problem solving (SPS), cognitive-behavioural case management and antidepressant medication. A secondary aim is to test biological and psychological variables that moderate and mediate response to this sequential treatment strategy. METHODS: This is a sequential multiple assignment randomised trial (SMART) consisting of three steps: Step 1: SPS (1.5 months); Step 2: SPS vs Cognitive Behavioural Case Management (4.5 months); Step 3: Cognitive Behavioural Case Management + Antidepressant Medication vs Cognitive Behavioural Case Management + Placebo (6 months). The intervention is of 12 months duration in total and participants will be followed up at 18 months and 24 months post baseline. CONCLUSION: This paper reports on the rationale and protocol of the Staged Treatment in Early Psychosis (STEP) study. With a large sample of 500 UHR participants this study will investigate the most effective type and sequence of treatments for improving functioning and reducing the risk of developing psychotic disorder in this clinical population.
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ItemRelationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial(FRONTIERS MEDIA SA, 2019-06-06)Background: Deficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we investigated associations of membrane PUFA with clinical symptoms and functioning in a large sample of individuals at ultra-high risk (UHR) for psychosis. Methods: A total of 285 participants of the NEURAPRO clinical trial were investigated for erythrocyte PUFA levels, including the n-3 index, n-6/n-3 PUFA ratio, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Severity of general psychopathology [Brief Psychiatric Rating Scale (BPRS)], psychotic symptoms (BPRS psychosis subscale), negative symptoms [Scale for the Assessment of Negative Symptoms (SANS)], manic symptoms [Young Mania Rating Scale (YMRS)], depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS)], and functioning [Social and Occupational Functioning Scale (SOFAS), Global Functioning Social (GF-S) and Role (GF-R) scales] were assessed concurrently. Partial correlation taking into account the effects of gender, age, and smoking was used to examine the relationship between PUFAs and symptoms severity. Results: The n-3 index negatively correlated with the severity of general psychopathology, psychotic symptoms, depressive symptoms, and manic symptoms. The n-6/n-3 PUFA ratio positively correlated with severity of psychotic and depressive symptoms. The n-3 PUFA DHA negatively correlated with the severity of general psychopathology, positive, manic, and depressive symptoms. EPA negatively correlated with manic symptoms. Nervonic acid, an n-9 monounsaturated fatty acid, positively correlated with general psychopathology, positive and negative symptoms, depressive symptoms, and manic symptoms. The long-chain saturated fatty acid tetracosanoic acid positively correlated with general psychopathology, positive, manic, and depressive symptoms. Conclusions: Partially consistent with a previous study, psychotic symptoms, depressive symptoms, and symptoms of mania were associated with several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in the UHR for psychosis group. Clinical Trial Registration: ANZCTR, identifier: 12608000475347.
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ItemNo Preview AvailableCan antipsychotic dose reduction lead to better functional recovery in first-episode psychosis? A randomized controlled-trial of antipsychotic dose reduction. The reduce trial: Study protocol(WILEY, 2019-12)UNLABELLED: Antipsychotic medication has been the mainstay of treatment for psychotic illnesses for over 60 years. This has been associated with improvements in positive psychotic symptoms and a reduction in relapse rates. However, there has been little improvement in functional outcomes for people with psychosis. At the same time there is increasing evidence that medications contribute to life shortening metabolic and cardiovascular illnesses. There is also uncertainty as to the role played by antipsychotic medication in brain volume changes. AIM: The primary aim of the study is, in a population of young people with first-episode psychosis, to compare functional outcomes between an antipsychotic dose reduction strategy with evidence-based intensive recovery treatment (EBIRT) group (DRS+) and an antipsychotic maintenance treatment with EBIRT group (AMTx+) at 24-months follow-up. METHODS: Our single-blind randomized controlled trial, within a specialist early psychosis treatment setting, will test the whether the DRS+ group leads to better vocational and social recovery than, the AMTx+ group over a 2-year period in 180 remitted first-episode psychosis patients. Additionally, we will examine the effect of DRS+ vs AMTx+ on physical health, brain volume and cognitive functioning. This study will also determine whether the group receiving DRS+ will be no worse off in terms of psychotic relapses over 2 years follow-up. RESULTS: This paper presents the protocol, rationale and hypotheses for this study which commenced recruitment in July 2017. CONCLUSION: This study will provide evidence as to whether an antipsychotic dose-reduction recovery treatment leads to improved functioning and safer outcomes in first-episode psychosis patients. In addition, it will be the first-controlled experiment of the effect of exposure to antipsychotic maintenance treatment on brain volume changes in this population.
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ItemNEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders-medium-term follow-up and clinical course.(Springer Science and Business Media LLC, 2018-06-25)This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6-12. Mean time to follow-up was 3.4 (median = 3.3; SD = 0.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11-13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.