Centre for Youth Mental Health - Research Publications
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ItemUltra-high risk phase: A missed opportunity for physical health care(WILEY, 2018-04)
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ItemPerceptual abnormalities in an ultra-high risk for psychosis population relationship to trauma and co-morbid disorder(WILEY, 2019-04)AIMS: The aims of this study were 3-fold. We wished to investigate whether at baseline entry to an ultra-high risk (UHR) clinic whether: (1) perceptual abnormalities are more prevalent in those young people with co-morbid psychiatric diagnoses, (2) perceptual abnormalities are more prevalent in those young people with histories of childhood adversity (childhood trauma, bullying) and (3) perceptual abnormality type is associated with co-morbid psychiatric diagnoses or histories of childhood adversity. METHODS: In a sample of 118 UHR patients we investigated the relationship between perceptual abnormalities and non-psychotic diagnoses and adverse life events at entry to a UHR clinic. RESULTS: Depressive disorder at baseline was associated with increased odds of experiencing perceptual abnormalities (OR 3.59, P = .004), particularly visual perceptual abnormalities (OR 2.36, P = .02). Borderline personality disorder at baseline was associated with increased odds of any auditory perceptual abnormalities (OR 3.44, P = .04) and specifically second person perceptual abnormalities (OR 2.69, P = .04). A history of childhood trauma and childhood bullying were both associated with increased odds of experiencing perceptual abnormalities at baseline (trauma OR 6.30, P < .001; bullying OR 5.00, P = .01). CONCLUSIONS: Our findings suggest that in the UHR population, certain types of perceptual abnormalities index risk for co-morbid non-psychotic disorder and indicate prior experience of childhood trauma. The use of detailed phenomenology of psychotic symptoms can help to shape our understanding of risk in UHR patients.
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ItemCan youth at high risk of illness progression be identified by measures of rumination and sleep-wake disturbance(WILEY, 2019-10)AIM: Clinical staging models offer a useful framework for understanding illness trajectories, where individuals are located on a continuum of illness progression from stage 0 (at-risk but asymptomatic) to stage 4 (end-stage disease). Importantly, clinical staging allows investigation of risk factors for illness progression with the potential to target trans-diagnostic mechanisms at an early stage, especially in help-seeking youth who often present with sub-threshold syndromes. While depressive symptoms, rumination and sleep-wake disturbances may worsen syndrome outcomes, the role of these related phenomena has yet to be examined as risk factors for trans-diagnostic illness progression in at-risk youth. METHODS: This study is a prospective follow-up of 248 individuals aged 12 to 25 years presenting to headspace services with sub-threshold syndromes (stage 1) classified under the clinical staging model to determine transition to threshold syndromes (stage 2). Factor analysis of depression, rumination and sleep-wake patterns was used to identify key dimensions and any associations between factors and transition to stage 2 at follow-up. RESULTS: At 1 year, 9% of cases met criteria for stage 2 (n = 22). One of three identified factors, namely the factor reflecting the commonalities shared between rumination and sleep-wake disturbance, significantly differentiated cases that transitioned to stage 2 vs those that did not demonstrate transition. Items loading onto this factor, labelled Anergia, included depression severity and aspects of rumination and sleep-wake disturbance that were characterized as introceptive. CONCLUSIONS: Common dimensions between rumination and sleep-wake disturbance present a detectable trans-diagnostic marker of illness progression in youth, and may represent a target for early intervention.
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ItemExploring functional impairment in young people at ultra-high risk for psychosis: A qualitative study(WILEY, 2019-08)AIM: Many young people at ultra-high risk (UHR) of developing psychosis exhibit marked and persistent impairments in social and occupational functioning. We aimed to explore UHR patients' subjective experiences of these difficulties and their causes. METHODS: We conducted semi-structured interviews with 20 UHR individuals recruited from Early Detection and Intervention Teams in Northwest England. Topics covered included how participants spent their time, their interpersonal relationships, academic and occupational performance, premorbid functioning and clinical treatment. Thematic analysis was used to examine the prevailing themes. RESULTS: The sample included individuals with varying degrees of functional impairment, ranging from mild to severe difficulties in functioning. Analysis of the qualitative data elicited themes around 2 topics: breadth of functional difficulties and subjective reasons for poor functioning. Participants reported a range of impairments in their social and occupational functioning which they attributed to a combination of clinical, cognitive and psychological factors. These included variables previously identified in the quantitative literature such as psychiatric symptoms, adverse life experiences and cognitive deficits. However, our findings also included other factors which have received comparably little attention such as self-stigmatizing attitudes and dysfunctional metacognitive beliefs. CONCLUSIONS: We propose a model that attempts to explain how these variables interact to drive and sustain functional impairment in the UHR population. This will assist in the development of clinical interventions aimed at promoting functional recovery among UHR individuals.
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ItemMonitoring of physical health in services for young people at ultra-high risk of psychosis(WILEY, 2018-04)AIM: People with schizophrenia have poor physical health and high rates of premature mortality. Risk factors for later cardiovascular disease are present from an early stage, and recording of these factors is recommended in first-episode services. However, it is unclear whether cardiometabolic risk factors are monitored prior to first-episode psychosis. METHODS: A retrospective analysis was conducted on case notes of individuals accepted into a specialized early detection service for young people at ultra-high risk for psychosis. Notes were assessed to determine whether the following physical health measures were recorded: height, weight, body mass index, blood pressure, blood glucose and lipids, physical activity levels, smoking status, substance use and alcohol intake. RESULTS: Forty individuals were deemed at ultra-high risk for psychosis and accepted into the service. The two measures reported most frequently were whether a person used substances (82.5%) or alcohol (72.5%), but more specific details were not commonly reported. A minority of case files contained information on height (2.5%), weight (7.5%), body mass index (5%), blood glucose (2.5%), smoking status (15%) and physical activity (7.5%). Six case files had no measure of physical health. CONCLUSIONS: Physical health and unhealthy lifestyle factors were not assessed routinely in the specialized service. Clear monitoring guidelines should be developed to establish routine assessment of common metabolic risk factors present in this population.
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ItemStudy protocol for a randomised controlled trial of CBT vs antipsychotics vs both in 14-18-year-olds: Managing Adolescent first episode Psychosis: a feasibility study (MAPS)(BMC, 2019-07-04)BACKGROUND: Adolescent-onset psychosis is associated with more severe symptoms and poorer outcomes than adult-onset psychosis. The National Institute for Clinical Excellence (NICE) recommend that adolescents with first episode psychosis (FEP) should be offered a combination of antipsychotic medication (APs), cognitive behavioural therapy (CBT) and family intervention (FI). The evidence for APs in treating psychosis is limited in adolescents compared to adults. Nevertheless, it indicates that APs can reduce overall symptoms in adolescents but may cause more severe side effects, including cardiovascular and metabolic effects, than in adults. CBT and FI can improve outcomes in adults, but there are no studies of psychological interventions (PI) in patients under 18 years old. Given this limited evidence base, NICE made a specific research recommendation for determining the clinical and cost effectiveness of APs versus PI versus both treatments for adolescent FEP. METHODS/DESIGN: The current study aimed to establish the feasibility and acceptability of conducting such a trial by recruiting 14-18-year-olds with a first episode of psychosis into a feasibility prospective randomised open blinded evaluation (PROBE) design, three-arm, randomised controlled trial of APs alone versus PI alone versus a combination of both treatments. We aimed to recruit 90 participants from Early Intervention and Child and Adolescent Mental Health Teams in seven UK sites. APs were prescribed by participants' usual psychiatrists. PI comprised standardised cognitive behavioural therapy and family intervention sessions. DISCUSSION: This is the first study to compare APs to PI in an adolescent population with FEP. Recruitment finished on 31 October 2018. The study faced difficulties with recruitment across most sites due to factors including clinician and service-user treatment preferences. TRIAL REGISTRATION: Current controlled trial with ISRCTN, ISRCTN80567433 . Registered on 27 February 2017.
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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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ItemImproving Mood with Physical ACTivity (IMPACT) trial: a cluster randomised controlled trial to determine the effectiveness of a brief physical activity behaviour change intervention on depressive symptoms in young people, compared with psychoeducation, in addition to routine clinical care within youth mental health services - a protocol study(BMJ PUBLISHING GROUP, 2019-10)INTRODUCTION: Depression is highly prevalent and the leading contributor to the burden of disease in young people worldwide, making it an ongoing priority for early intervention. As the current evidence-based interventions of medication and psychological therapy are only modestly effective, there is an urgent need for additional treatment strategies. This paper describes the rationale of the Improving Mood with Physical ACTivity (IMPACT) trial. The primary aim of the IMPACT trial is to determine the effectiveness of a physical activity intervention compared with psychoeducation, in addition to routine clinical care, on depressive symptoms in young people. Additional aims are to evaluate the intervention effects on anxiety and functional outcomes and examine whether changes in physical activity mediate improvements in depressive symptoms. METHODS AND ANALYSIS: The study is being conducted in six youth mental health services across Australia and is using a parallel-group, two-arm, cluster randomised controlled trial design, with randomisation occurring at the clinician level. Participants aged between 12 years and 25 years with moderate to severe levels of depression are randomised to receive, in addition to routine clinical care, either: (1) a physical activity behaviour change intervention or (2) psychoeducation about physical activity. The primary outcome will be change in the Quick Inventory of Depressive Symptomatology, with assessments occurring at baseline, postintervention (end-point) and 6-month follow-up from end-point. Secondary outcome measures will address additional clinical outcomes, functioning and quality of life. IMPACT is to be conducted between May 2014 and December 2019. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Melbourne Human Research Ethics Committee on 8 June 2014 (HREC 1442228). Trial findings will be published in peer-reviewed journals and presented at conferences. Key messages will also be disseminated by the youth mental health services organisation (headspace National Youth Mental Health Foundation). TRIAL REGISTRATION NUMBER: ACTRN12614000772640.
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ItemIndividualized Prediction of Transition to Psychosis in 1,676 Individuals at Clinical High Risk: Development and Validation of a Multivariable Prediction Model Based on Individual Patient Data Meta-Analysis(FRONTIERS MEDIA SA, 2019-05-21)Background: The Clinical High Risk state for Psychosis (CHR-P) has become the cornerstone of modern preventive psychiatry. The next stage of clinical advancements rests on the ability to formulate a more accurate prognostic estimate at the individual subject level. Individual Participant Data Meta-Analyses (IPD-MA) are robust evidence synthesis methods that can also offer powerful approaches to the development and validation of personalized prognostic models. The aim of the study was to develop and validate an individualized, clinically based prognostic model for forecasting transition to psychosis from a CHR-P stage. Methods: A literature search was performed between January 30, 2016, and February 6, 2016, consulting PubMed, Psychinfo, Picarta, Embase, and ISI Web of Science, using search terms ("ultra high risk" OR "clinical high risk" OR "at risk mental state") AND [(conver* OR transition* OR onset OR emerg* OR develop*) AND psychosis] for both longitudinal and intervention CHR-P studies. Clinical knowledge was used to a priori select predictors: age, gender, CHR-P subgroup, the severity of attenuated positive psychotic symptoms, the severity of attenuated negative psychotic symptoms, and level of functioning at baseline. The model, thus, developed was validated with an extended form of internal validation. Results: Fifteen of the 43 studies identified agreed to share IPD, for a total sample size of 1,676. There was a high level of heterogeneity between the CHR-P studies with regard to inclusion criteria, type of assessment instruments, transition criteria, preventive treatment offered. The internally validated prognostic performance of the model was higher than chance but only moderate [Harrell's C-statistic 0.655, 95% confidence interval (CIs), 0.627-0.682]. Conclusion: This is the first IPD-MA conducted in the largest samples of CHR-P ever collected to date. An individualized prognostic model based on clinical predictors available in clinical routine was developed and internally validated, reaching only moderate prognostic performance. Although personalized risk prediction is of great value in the clinical practice, future developments are essential, including the refinement of the prognostic model and its external validation. However, because of the current high diagnostic, prognostic, and therapeutic heterogeneity of CHR-P studies, IPD-MAs in this population may have an limited intrinsic power to deliver robust prognostic models.