Centre for Youth Mental Health - Research Publications
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ItemPathways to care for first-generation migrants with first episode psychosis in northwestern metropolitan Melbourne(SAGE PUBLICATIONS LTD, 2022-12)OBJECTIVE: Understanding the pathways to care for migrants experiencing a first episode of psychosis is important, as they are more likely to experience longer delays to treatment and negative experiences, such as involuntary treatment. Despite the increased risk of developing a psychotic illness and barriers associated with pathways to care, there are limited studies exploring pathways to care in migrants in Australia. This study seeks to examine pathways to care for young people with a first episode of psychosis to a publicly funded youth mental health service. METHODS: This study included all young people aged 15-24 years who presented with a first episode of psychosis to the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1 February 2011 and 31 December 2016. Referral sources and place of birth were recorded at the time of presentation. The severity of psychotic symptoms was rated at baseline. RESULTS: A total of 1220 young people presented with a first episode of psychosis during the study period, including 293 (24.5%) first-generation migrants. First-generation migrants with a first episode of psychosis were more likely to be admitted to hospital than Australian-born youth (odds ratio = 1.67, 95% confidence interval = [1.27, 2.18], p < 0.001) and this remained significant when controlled for demographic (adjusted odds ratio = 1.41, 95% confidence interval = [1.07, 1.88], p = 0.016) and clinical factors (adjusted odds ratio = 1.38,95% confidence interval = [1.01, 1.89], p = 0.044). First-generation migrants were also more likely to have an involuntary admission (odds ratio = 1.67, 95% confidence interval = [1.26, 2.21], p < 0.001) and this remained significant when controlled for demographic (adjusted odds ratio = 1.42, 95% confidence interval = [1.05, 1.91], p = 0.022) and clinical factors (adjusted odds ratio = 1.50, 95% confidence interval = [1.08, 2.09], p = 0.017). Migrants had more severe delusions (p = 0.005), bizarre behavior (p < 0.001) and positive formal thought disorder (p = 0.003) at the time of presentation. Migrants were also more likely to attend the emergency department during their presentation with first episode of psychosis (odds ratio = 1.76, 95% confidence interval = [1.31, 2.36], p < 0.001). CONCLUSION: First-generation migrants who develop a psychotic disorder are at greater risk of experiencing negative pathways to care than the Australian-born population. Further research is needed to identify the factors that lead to migrants being involuntarily admitted to hospital for first episode of psychosis.
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ItemNo Preview AvailableIntelligence trajectories in individuals at ultra-high risk for psychosis: An 8-year longitudinal analysis(ELSEVIER, 2022-10)Cognitive impairment is a well-documented predictor of transition to a full-threshold psychotic disorder amongst individuals at ultra-high risk (UHR) for psychosis. However, less is known about whether change in cognitive functioning differs between those who do and do not transition. Studies to date have not examined trajectories in intelligence constructs (e.g., acquired knowledge and fluid intelligence), which have demonstrated marked impairments in individuals with schizophrenia. This study aimed to examine intelligence trajectories using longitudinal data spanning an average of eight years, where some participants completed assessments over three time-points. Participants (N = 139) at UHR for psychosis completed the Wechsler Abbreviated Scale of Intelligence (WASI) at each follow-up. Linear mixed-effects models mapped changes in WASI Full-Scale IQ (FSIQ) and T-scores on Vocabulary, Similarities, Block Design, and Matrix Reasoning subtests. The sample showed stable and improving trajectories for FSIQ and all subtests. There were no significant differences in trajectories between those who did and did not transition to psychosis and between individuals with good and poor functional outcomes. However, although not significant, the trajectories of the acquired knowledge subtests diverged between transitioned and non-transitioned individuals (β = -0.12, 95 % CI [-0.29, 0.05] for Vocabulary and β = -0.14, 95 % CI [-0.33, 0.05] for Similarities). Overall, there was no evidence for long-term deterioration in intelligence trajectories in this UHR sample. Future studies with a larger sample of transitioned participants may be needed to explore potential differences in intelligence trajectories between UHR transition groups and other non-psychosis outcomes.
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ItemNo Preview AvailableMachine learning based prediction and the influence of complement - Coagulation pathway proteins on clinical outcome: Results from the NEURAPRO trial(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022-07)BACKGROUND: Functional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could predict future functional outcome in CHR individuals. The complement and coagulation pathways have previously been identified as being of relevance to the pathophysiology of psychosis and have been found to contribute to the prediction of clinical outcome in CHR participants. Hence, in the second part we extended the analysis to evaluate specifically the relationship of complement and coagulation proteins with psychotic symptoms and functional outcome in CHR. MATERIALS AND METHODS: We carried out plasma proteomics and measured plasma cytokine levels, and erythrocyte membrane fatty acid levels in a sub-sample (n = 158) from the NEURAPRO clinical trial at baseline and 6 months follow up. Functional outcome was measured using Social and Occupational Functional assessment Score (SOFAS) scale. Firstly, we used support vector machine learning techniques to develop predictive models for functional outcome at 12 months. Secondly, we developed linear regression models to understand the association between 6-month follow-up levels of complement and coagulation proteins with 6-month follow-up measures of positive symptoms summary (PSS) scores and functional outcome. RESULTS AND CONCLUSION: A prediction model based on clinical and biological data including the plasma proteome, erythrocyte fatty acids and cytokines, poorly predicted functional outcome at 12 months follow-up in CHR participants. In linear regression models, four complement and coagulation proteins (coagulation protein X, Complement C1r subcomponent like protein, Complement C4A & Complement C5) indicated a significant association with functional outcome; and two proteins (coagulation factor IX and complement C5) positively associated with the PSS score. Our study does not provide support for the utility of cytokines, proteomic or fatty acid data for prediction of functional outcomes in individuals at high-risk for psychosis. However, the association of complement protein levels with clinical outcome suggests a role for the complement system and the activity of its related pathway in the functional impairment and positive symptom severity of CHR patients.
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ItemEvidence that complement and coagulation proteins are mediating the clinical response to omega-3 fatty acids: A mass spectrometry-based investigation in subjects at clinical high-risk for psychosis(SPRINGERNATURE, 2022-10-28)Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins.
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ItemA single-blind, randomised controlled trial of a physical health nurse intervention to prevent weight gain and metabolic complications in first-episode psychosis: the Physical Health Assistance in Early Psychosis (PHAstER) study(CAMBRIDGE UNIV PRESS, 2022-10-18)BACKGROUND: Factors that contribute to the early mortality observed in psychotic disorders, specifically obesity, smoking and sedentary behaviour, occur early in the disorder. AIMS: We aimed to determine whether the integration of a physical health nurse in the care of young people with first-episode psychosis could prevent clinically significant weight gain (≥7% body weight). Secondary outcomes included rates of smoking, metabolic syndrome and sedentary behaviour. METHOD: In this single-blind, randomised controlled trial, participants who had received under 4 weeks of antipsychotic medication were randomly allocated to either the intervention (addition of a physical health nurse to their care) or treatment as usual (TAU) for 12 weeks. RESULTS: Of the 77 participants, there were follow-up data for 86.8% (n = 33) of the intervention group and 82.1% (n = 32) of the TAU group. After 12 weeks, 27.3% of the intervention group experienced clinically significant weight gain compared with 34.4% of the TAU group (odds ratio 0.72, 95% CI 0.25-2.06, P = 0.54). After 6 months, 40.7% of the intervention group gained clinically significant weight compared with 44.1% of the TAU group (P = 0.79). There was no difference in mean change in weight between groups after 12 weeks (2.6 kg v. 2.9 kg, P = 0.87) or 6 months (3.6 kg v. 4.3 kg, P = 0.64). There were no differences in the rates of tobacco smoking cessation, prevalence of metabolic syndrome or physical activity levels. CONCLUSIONS: This intervention failed to prevent the metabolic complications that are highly prevalent in psychotic disorders in the short to medium term, indicating that more intensive interventions are required.
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ItemEffects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial(CAMBRIDGE UNIV PRESS, 2022-09-08)BACKGROUND: Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. AIMS: To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis. METHOD: Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n-3 PUFA levels predicted change in cognitive performance. RESULTS: The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months. CONCLUSIONS: We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n-3 PUFAs.
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ItemNo Preview AvailableThe association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022-01)There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample. In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 FAs and clinical outcomes were mediated via plasma immune markers. Clinical outcomes for CHR participants in the NEURAPRO clinical trial were measured using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) scales. The erythrocyte omega-3 index [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] and plasma concentrations of inflammatory markers were quantified at baseline (n = 268) and 6 month follow-up (n = 146) by gas chromatography and multiplex immunoassay, respectively. In linear regression models, the baseline plasma concentrations of Interleukin (IL)-15, Intercellular adhesion molecule (ICAM)-1 and Vascular cell adhesion molecule (VCAM)-1 were negatively associated with baseline omega-3 index. In addition, 6-month change in IL-12p40 and TNF-α showed a negative association with change in omega-3 index. In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with VCAM-1 and TNF-α respectively at follow-up. Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 FAs and clinical outcomes (psychotic symptoms and functioning) in CHR participants. Our results indicate a predominantly anti-inflammatory relationship of omega-3 FAs on plasma inflammatory status in CHR individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up. Both immune and non-immune biological effects of omega-3 FAs would be resourceful in understanding the clinical benefits of omega-3 FAs in CHR papulation.
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ItemNo Preview AvailableThe association between migrant status and transition in an ultra-high risk for psychosis population(SPRINGER HEIDELBERG, 2021-06)PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.
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ItemTwelve-Month Cognitive Trajectories in Individuals at Ultra-High Risk for Psychosis: A Latent Class Analysis(Oxford University Press (OUP), 2022-01-01)Abstract Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, 6- and 12-months (N = 288). Using Growth Mixture Modeling, a single unimpaired improving trajectory class was observed for motor function, speed of processing, verbal fluency, and BACS composite. A two-class solution was observed for executive function and working memory, showing one unimpaired and a second impaired class. A three-class solution was found for verbal learning and memory: unimpaired, mildly impaired, and initially extremely impaired, but improved (“caught up”) to the level of the mildly impaired. IQ, omega-3 index, and premorbid adjustment were associated with class membership, whereas clinical variables (symptoms, substance use), including transition to psychosis, were not. Working memory and verbal learning and memory trajectory class membership was associated with functioning outcomes. These findings suggest there is no short-term progressive cognitive decline in help-seeking UHR individuals, including those who transition to psychosis. Screening of cognitive performance may be useful for identifying UHR individuals who may benefit from targeted cognitive interventions.
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ItemThe utility of a fidelity measure to monitor implementation of new early psychosis services across Australia(WILEY, 2021-10)AIM: Early psychosis delivery models have proliferated worldwide, but there is limited research into establishing model fidelity. In this context, this article aims to describe the development and implementation of a fidelity tool in a national network of early psychosis services across Australia-the headspace Early Psychosis program. METHODS: Following a detailed consultation process, and based on the Australian Early Psychosis model, an 80-item Early Psychosis Prevention and Intervention Centre Model Integrity Tool (EMIT) was developed along with predefined thresholds for fidelity. The tool was used to assess adherence to the model in six clusters of service sites across Australia. Ratings on the EMIT were informed by interviews with site staff and young people receiving the service, routinely collected data and site policies and procedures. RESULTS: All six clusters of headspace Early Psychosis programs participated in five fidelity assessments across a period of two and a half years. In the initial two visits, the average fidelity score was in the 'low' fidelity range (i.e., <75%). By the fifth fidelity visit, the network average improved to 92.35%, reflecting 'superior' fidelity. CONCLUSIONS: Results of the longitudinal fidelity assessments indicate the successful implementation of the Australian Early Psychosis model across the headspace Early Psychosis program. Utilisation of ongoing fidelity assessments has proved an effective method to improve and maintain adherence to the model.