Centre for Youth Mental Health - Research Publications

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    Baseline data of a sequential multiple assignment randomized trial (STEP study)
    Hartmann, JA ; Nelson, B ; Amminger, GP ; Spark, J ; Yuen, HP ; Kerr, MJ ; Polari, A ; Wallis, N ; Blasioli, J ; Dixon, L ; Carter, C ; Loewy, R ; Niendam, TA ; Shumway, M ; McGorry, PD (WILEY, 2022-10)
    AIM: Research has shown that preventative intervention in individuals at ultra-high risk of psychosis (UHR) improves symptomatic and functional outcomes. The staged treatment in early psychosis (STEP) trial aims to determine the most effective type, timing and sequence of interventions in the UHR population by sequentially studying the effectiveness of (1) support and problem solving, (2) cognitive-behavioural case management and (3) antidepressant medication with an embedded fast-fail option of (4) omega-3 fatty acids or low-dose antipsychotic medication. This paper presents the recruitment flow and baseline clinical characteristics of the sample. METHODS: STEP is a sequential multiple assignment randomized trial. We present the baseline demographics, clinical characteristics and acceptability and feasibility of this treatment approach as indicated by the flow of participants from first contact up until enrolment into the trial. Recruitment took place between April 2016 and January 2019. RESULTS: Of 1343, help-seeking young people who were considered for participation, 402 participants were not eligible and 599 declined/disengaged, resulting in a total of 342 participants enrolled in the study. The most common reason for exclusion was an active prescription of antidepressant medication. Eighty-five percent of the enrolled sample had a non-psychotic DSM-5 diagnosis and symptomatic/functional measures showed a moderate level of clinical severity and functional impairment. DISCUSSION: The present study demonstrates the acceptability and participant's general positive appraisal of sequential treatment. It also shows, in line with other trials in UHR individuals, a significant level of psychiatric morbidity and impairment, demonstrating the clear need for care in this group and that treatment is appropriate.
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    "They may be confronting but they are good questions to be asking" young people's experiences of completing a trauma and PTSD screening tool in an early psychosis program
    Dryden-Mead, T ; Nelson, B ; Bendall, S (WILEY, 2022-12)
    BACKGROUND: There is a history of inadequate enquiry about, and assessment of, trauma in young people within Early Psychosis services and even when screening does occur there is little known about how young people experience this process. AIMS: This study aimed to explore young people's experiences of completing a trauma and PTSD screening tool when receiving a service in an Early Psychosis Program. METHOD: Semi-structured interviews were conducted with 10 young people, aged 18-24 years, to explore their subjective experience of this process. Transcripts were analysed via interpretative phenomenological analysis. RESULTS: Four super-ordinate themes were identified: (i) an emotional experience, (ii) the importance of the relationship with the clinician, (iii) an opportunity to reflect on past experiences, and (iv) the ability to be able to provide honest responses. Results from this study indicated that young people expected to be asked about their trauma experiences, acknowledged that this was challenging for them but found that this was made easier due to the relationship they had built with the clinician, the timing of the screening and also, possibly, by the written style format of the questionnaires. CONCLUSIONS: Young people in this study accepted the need for screening for traumatic histories, and expected to be asked about their traumatic experiences, despite the possibility of a short-term increase in distress. The support offered by a trusted clinician, whom the young person had built a relationship with, appeared to be an important component to the willingness and the ability of the young person to complete the questionnaires. This reinforces the fact that screening for trauma in an early psychosis service can be conducted in a way that is safe and acceptable to young people.
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    Has improved treatment contributed to the declining rate of transition to psychosis in ultra-high-risk cohorts?
    Formica, MJC ; Phillips, LJ ; Hartmann, JA ; Yung, AR ; Wood, SJ ; Lin, A ; Amminger, GP ; McGorry, PD ; Nelson, B (ELSEVIER, 2022-05)
    BACKGROUND: The factors contributing to declining psychotic disorder transition rates in ultra-high-risk populations remain unclear. We examined the contribution of longitudinal changes in standard clinical treatment ('treatment as usual') to this decline. METHOD: An audit was conducted on 105 clinical files of patients who received standard care at a specialised ultra-high-risk service. The session notes of these files were quantified, allowing examination of treatment quantity, targets, psychotherapy, and medication. Differences in these aspects across patients' year of clinic entry were assessed. Variables with significant differences across years were examined using cox regression to assess their contribution to psychosis transition rates. RESULTS: Findings were that, as a function of patients' year of clinic entry, there were increases in: patients' number of sessions, cognitive behavioural therapy (CBT), problem and solving therapy. There was a relationship between baseline year cohort and psychosis transition rate, with lower rates observed in more recent cohorts. When changes in treatment between cohorts were adjusted for, the relationship between baseline year cohort and transition rate disappeared. The relationship between baseline year and transition rate was attenuated most by increases in CBT. CONCLUSION: Changes in standard treatment, particularly increases in CBT, may have contributed to the decline in psychosis risk observed in recent ultra-high-risk cohorts, although these variables do not fully explain this trend. Implications for clinical practice, prediction and intervention research are discussed. Future ultra-high-risk research should investigate the impact of other treatment factors, such as therapeutic alliance.
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    Outcomes for first-episode psychosis after entry via an at-risk mental state clinic compared to direct entry to a first episode of psychosis service: A systematic review and meta-analysis
    Sizer, H ; Brown, E ; Geros, H ; Yung, A ; Nelson, B ; McGorry, P ; O'Donoghue, B (ELSEVIER, 2022-02)
    OBJECTIVE: Early intervention for psychosis services have been established worldwide and consist of specialist services for those with the At-Risk Mental State (ARMS) and a first episode of psychosis (FEP). This systematic review identified the literature on the outcomes of people who initially presented via an ARMS clinic and later transitioned to a psychotic disorder (UHR-T), compared to those who presented directly to an EI service with a FEP (FEP-D). The outcomes examined were (i) symptomatic (ii) functional, (iii) morbidity and mortality (including physical health) and (iv) service-usage. METHOD: A systematic search strategy was employed using three databases: MEDLINE, PsycInfo, and EMBASE. Studies published in English and that compared any of the above outcomes in a cohort of people with a first episode of psychosis who initially presented via an ARMS clinic to those who presented directly to a FEP service were included. Meta-analysis was performed for any outcome data from at least two studies. RESULTS: A total of 988 unique articles were identified and of these, three studies fulfilled the inclusion criteria and these included a total of 78 UHR-T and 253 FEP-D individuals. In the one study examining remission rates, there was no difference observed after one year in the UHR-T and FEP-D groups. In the one study that examined neurocognition, no differences were observed in any of the neurocognitive domains between groups after one year. Two studies examined psychiatric admission rates within one year and one of these found that UHR-T individuals were less likely to have any psychiatric admission (46% vs 68%) and admissions were less likely to be involuntary (30% vs 74%), while the other study found no difference in admission rates. In the meta-analysis, UHR-T individuals had lower odds for any psychiatric hospital admission within one year compared to FEP-D individuals (OR = 0.54, 95% C.I. 0.32 - 0.94, p = .03). No studies examined functional outcomes or mortality and morbidity between the groups. CONCLUSION: The limited research indicates similar or superior outcomes for people with a FEP who present initially via an ARMS clinic. The reduced psychiatric admission rate is an important potential benefit of ARMS clinics that requires replication.
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    Young migrants to Australia identified as being at ultra-high risk for psychosis: Pathways to care and clinical characteristics
    O'Donoghue, B ; Polari, A ; McGorry, P ; Nelson, B (ELSEVIER, 2022-03)
    INTRODUCTION: Despite the established finding that migrants are at higher risk of developing a first-episode psychosis, they are under-represented in cohorts of young people identified as being at ultra-high risk for psychosis (UHR). Therefore, in order to determine the reasons for these conflicting findings, this study examined the pathways to care and clinical presentation of migrants attending an At-Risk Mental State clinic. METHODOLOGY: This study included consecutive UHR cases identified over five years attending the PACE clinic in Melbourne, Australia. The CAARMS was used to assess the severity of attenuated psychotic symptoms. Depressive symptoms and functioning were measured using the PHQ9 and GAF, respectively. RESULTS: Over the five-year study period, 461 UHR young people attended the PACE clinic and 13.7% were first-generation migrants. A higher proportion of migrants were referred by community health services, such as general practitioners, than other referral sources. Australian born UHR patients were more likely to be referred via another mental health service. There was no difference in the type or severity of attenuated psychotic symptoms based on migrant status, except that there was a trend for young African migrants to have more severe unusual thought content. Depressive symptoms and poor functioning were highly prevalent across the total cohort and did not differ according to migrant status. CONCLUSIONS: It is not yet understood why migrants are under-represented in UHR cohorts. Qualitative interviews of migrants, who are not typically identified in the UHR stage, could provide insights into the barriers to accessing care.
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    Intelligence trajectories in individuals at ultra-high risk for psychosis: An 8-year longitudinal analysis
    Cheng, N ; Lin, A ; Bowden, S ; Gao, C ; Yung, AR ; Nelson, B ; Thompson, A ; Yuen, HP ; Brewer, WJ ; Cagliarini, D ; Bruxner, A ; Simmons, M ; Broussard, C ; Pantelis, C ; McGorry, PD ; Allott, K ; Wood, SJ (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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    Pineal morphology of the clinical high-risk state for psychosis and different psychotic disorders
    Takahashi, T ; Wood, SJ ; Yung, AR ; Nelson, B ; Lin, A ; Yuen, HP ; Phillips, LJ ; Suzuki, M ; McGorry, PD ; Velakoulis, D ; Pantelis, C (ELSEVIER, 2022-06)
    BACKGROUND: Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders. METHODS: This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups. RESULTS: Pineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups. CONCLUSION: These results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis.
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    Machine learning based prediction and the influence of complement - Coagulation pathway proteins on clinical outcome: Results from the NEURAPRO trial
    Susai, SR ; Mongan, D ; Healy, C ; Cannon, M ; Cagney, G ; Wynne, K ; Byrne, JF ; Markulev, C ; Schafer, MR ; Berger, M ; Mossaheb, N ; Schlogelhofer, M ; Smesny, S ; Hickie, IB ; Berger, GE ; Chen, EYH ; de Haan, L ; Nieman, DH ; Nordentoft, M ; Riecher-Rossler, A ; Verma, S ; Street, R ; Thompson, A ; Yung, AR ; Nelson, B ; McGorry, PD ; Focking, M ; Amminger, GP ; Cotter, D (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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    Evidence 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
    Susai, SR ; Healy, C ; Mongan, D ; Heurich, M ; Byrne, JF ; Cannon, M ; Cagney, G ; Wynne, K ; Markulev, C ; Schafer, MR ; Berger, M ; Mossaheb, N ; Schlogelhofer, M ; Smesny, S ; Hickie, IB ; Berger, GE ; Chen, EYH ; de Haan, L ; Nieman, DH ; Nordentoft, M ; Riecher-Rossler, A ; Verma, S ; Street, R ; Thompson, A ; Yung, AR ; Nelson, B ; McGorry, PD ; Focking, M ; Amminger, GP ; Cotter, D (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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    Effects 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
    Cheng, N ; McLaverty, A ; Nelson, B ; Markulev, C ; Schafer, MR ; Berger, M ; Mossaheb, N ; Schlogelhofer, M ; Smesny, S ; Hicikie, IB ; Berger, GE ; Chen, EYH ; de Haan, L ; Nieman, DH ; Nordentoft, M ; Riecher-Rossler, A ; Verma, S ; Street, R ; Thompson, A ; Yuen, HP ; Hester, R ; Yung, AR ; McGorry, PD ; Allott, K ; Amminger, GP (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.