Centre for Youth Mental Health - Research Publications
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ItemNo Preview AvailableNon-psychotic Outcomes in Young People at Ultra-High Risk of Developing a Psychotic Disorder: A Long-Term Follow-up Study(OXFORD UNIV PRESS, 2024-02-16)BACKGROUND: The majority of individuals at ultra-high risk (UHR) for psychosis do not transition to a full threshold psychotic disorder. It is therefore important to understand their longer-term clinical and functional outcomes, particularly given the high prevalence of comorbid mental disorders in this population at baseline. AIMS: This study investigated the prevalence of non-psychotic disorders in the UHR population at entry and long-term follow-up and their association with functional outcomes. Persistence of UHR status was also investigated. STUDY DESIGN: The sample comprised 102 UHR young people from the Personal Assessment and Crisis Evaluation (PACE) Clinic who had not transitioned to psychosis by long-term follow-up (mean = 8.8 years, range = 6.8-12.1 years since baseline). RESULTS: Eighty-eight percent of participants at baseline were diagnosed with at least one mental disorder, the majority of which were mood disorders (78%), anxiety disorders (35%), and substance use disorders (SUDs) (18%). This pattern of disorder prevalence continued at follow-up, though prevalence was reduced, with 52% not meeting criteria for current non-psychotic mental disorder. However, 35% of participants developed a new non-psychotic mental disorder by follow-up. Presence of a continuous non-psychotic mental disorder was associated with poorer functional outcomes at follow-up. 28% of participants still met UHR criteria at follow-up. CONCLUSIONS: The study adds to the evidence base that a substantial proportion of UHR individuals who do not transition to psychosis experience persistent attenuated psychotic symptoms and persistent and incident non-psychotic disorders over the long term. Long-term treatment and re-entry into services is indicated.
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ItemNo Preview AvailableEffects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial(SPRINGERNATURE, 2023-06-10)The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone/paliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted. A healthy control group was also recruited. A cognitive battery was administered at baseline and 6 months. Intention-to-treat analysis involved 76 patients (antipsychotic medication group: 37; 18.6Mage [2.9] years; 21 women; placebo group: 39; 18.3Mage [2.7]; 22 women); and 42 healthy controls (19.2Mage [3.0] years; 28 women). Cognitive performance predominantly remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. However, a significant group-by-time interaction was observed for immediate recall (p = 0.023), verbal learning (p = 0.024) and delayed recall (p = 0.005). The medication group declined whereas the placebo group improved on each measure (immediate recall: p = 0.024; ηp2 = 0.062; verbal learning: p = 0.015; ηp2 = 0.072 both medium effects; delayed recall: p = 0.001; ηp2 = 0.123 large effect). The rate of change for the placebo and healthy control groups was similar. Per protocol analysis (placebo n = 16, medication n = 11) produced similar findings. Risperidone/paliperidone may worsen verbal learning and memory in the early months of psychosis treatment. Replication of this finding and examination of various antipsychotic agents are needed in confirmatory trials. Antipsychotic effects should be considered in longitudinal studies of cognition in psychosis.Trial registration: Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au/ ; ACTRN12607000608460).
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ItemNo Preview AvailableSocial disadvantage in early psychosis and its effect on clinical presentation and service access, engagement and use(ELSEVIER IRELAND LTD, 2023-10)Incidence of psychosis varies geographically due to factors such as social disadvantage. Whether this influences the clinical presentation and/or engagement of those experiencing psychosis remains relatively understudied. This study analysed data from young people across Australia accessing ultra-high risk (UHR) or first episode psychosis (FEP) services delivered through the headspace Early Psychosis (hEP) program between June 2017 and March 2021. The cohort was categorised into low, middle, and high tertiles of social disadvantage using the Index of Relative Socioeconomic Disadvantage (IRSD). Data from 3089 participants aged 15-25 were included (1515 UHR, 1574 FEP). The low and middle tertiles for both cohorts had greater percentages of those not in education or employment (NEET), with First Nations or culturally and linguistically diverse backgrounds. Clinical presentations to services were similar across all tertiles in both cohorts, however, functioning at presentation varied significantly within the FEP cohort. Significantly lower numbers of direct services were provided in the low tertile of both cohorts, with significantly poorer engagement in the initial three-months also occurring for these young people. This variation in early psychosis service patterns associated with geographical variation in social deprivation demonstrates the need for further research and fine tuning of national early psychosis services.
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ItemNo Preview AvailableIntegrating digital interventions with clinical practice in youth mental health services(SAGE PUBLICATIONS LTD, 2023-06)OBJECTIVE: Integrating digital technologies with clinical practice promises to improve access and enhance care in the context of high service demand and constrained capacity. METHOD: We outline the emerging research in the integration of digital tools in clinical care, known as blended care, and provide case examples of mental health technology platforms currently in use, summarise findings regarding novel technologies such as virtual reality, and outline real-world implementation challenges and potential solutions. RESULTS: Recent evidence shows that blended care approaches are clinically effective and improve service efficiency. Youth-specific technologies such as moderated online social therapy (MOST) are achieving a range of positive clinical and functional outcomes, while emerging technologies like virtual reality have strong evidence in anxiety disorder, and accumulating evidence in psychotic conditions. Implementation science frameworks show promise in helping overcome the common challenges faced in real-world adoption and ongoing use. CONCLUSION: The integrated, blended use of digital mental health technologies with face-to-face clinical care has the potential to improve care quality for young people while helping overcome the growing challenges faced by youth mental health service providers.
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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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ItemThe impact of COVID-19 on youth mental health: A mixed methods survey(ELSEVIER IRELAND LTD, 2023-03)The COVID-19 pandemic has presented profound disruptions to young people at a critical period of psychosocial development. The current study aimed to explore the perceived negative and positive impacts of the COVID-19 pandemic on young people's mental health and wellbeing across a spectrum of clinical needs. A cross-sectional online survey including both quantitative and qualitative responses captured positive and negative impacts of COVID-19 across 593 young people with and without mental health care needs. Findings revealed high levels of clinical depression (48%), anxiety (51%), and loneliness in both samples. Approximately 75% of young people in primary mental health care services, and over 80% in the general population, reported a negative impact on work, non-work activities and mental health and wellbeing. Open-ended responses reflected positive impacts in the domains of greater capacity for self-care and reflection due to the decreased pressures of daily life. Negative impacts reflected worsening mental health, disruptions to key developmental milestones regarding relationships with self and others, and limited capacity for self-care. Together, these data highlight the critical need for early intervention support for the psychosocial impacts experienced by young people due to the pandemic, particularly among those with existing mental health care needs.
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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.