Centre for Youth Mental Health - Research Publications

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    Contribution of neurocognition to 18-month employment outcomes in first-episode psychosis
    Karambelas, GJ ; Cotton, SM ; Farhall, J ; Killackey, E ; Allott, KA (WILEY, 2019-06)
    AIM: To examine whether baseline neurocognition predicts vocational outcomes over 18 months in patients with first-episode psychosis enrolled in a randomized controlled trial of Individual Placement and Support or treatment as usual. METHODS: One-hundred and thirty-four first-episode psychosis participants completed an extensive neurocognitive battery. Principal axis factor analysis using PROMAX rotation was used to determine the underlying structure of the battery. Setwise (hierarchical) multiple linear and logistic regressions were used to examine predictors of (1) total hours employed over 18 months and (2) employment status, respectively. Neurocognition factors were entered in the models after accounting for age, gender, premorbid IQ, negative symptoms, treatment group allocation and employment status at baseline. RESULTS: Five neurocognitive factors were extracted: (1) processing speed, (2) verbal learning and memory, (3) knowledge and reasoning, (4) attention and working memory and (5) visual organization and memory. Employment status over 18 months was not significantly predicted by any of the predictors in the final model. Total hours employed over 18 months were significantly predicted by gender (P = .027), negative symptoms (P = .032) and verbal learning and memory (P = .040). Every step of the regression model was a significant predictor of total hours worked overall (final model: P = .013). CONCLUSION: Verbal learning and memory, negative symptoms and gender were implicated in duration of employment in first-episode psychosis. The other neurocognitive domains did not significantly contribute to the prediction of vocational outcomes over 18 months. Interventions targeting verbal memory may improve vocational outcomes in early psychosis.
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    Social inclusion and its interrelationships with social cognition and social functioning in first-episode psychosis
    Gardner, A ; Cotton, SM ; Allott, K ; Filia, KM ; Hester, R ; Killackey, E (WILEY, 2019-06)
    AIM: People with psychosis are at risk of social exclusion. Research is needed in this area due to the lack of direct measurement of social inclusion, which becomes salient in adolescence and is relevant to first-episode psychosis (FEP; the onset of which typically occurs during or shortly after adolescence). Social inclusion may be impacted by impaired social cognition and social functioning, which are related features observed in psychosis. The aim of this study was to explore interrelationship(s) between social cognition, social functioning and social inclusion in FEP while controlling for symptomatology (positive, negative and depressive symptoms) and demographic characteristics. METHODS: A series of cross-sectional hierarchical multiple regressions were conducted to examine whether: social cognition (theory of mind, emotion recognition) predicted social functioning; social functioning predicted social inclusion, and whether social functioning mediated the relationship between social cognition and social inclusion in people aged 15 to 25 (M = 20.49, SD = 2.41) with FEP (N = 146). Age, sex, premorbid IQ, positive and negative psychotic symptoms and depression were control variables. RESULTS: Poor facial emotion recognition (β = -.22, P < .05) and negative symptoms (β = -.45, P < .001) predicted lower social functioning. Role-specific social functioning (ie, current employment) predicted greater social inclusion (β = .17, P < .05). Higher depression symptomatology predicted lower social inclusion (β = -.43, P < .001). Social functioning did not mediate the relationship between social cognition and inclusion. Psychotic symptoms were unrelated to social inclusion. CONCLUSIONS: Employment and depression may influence social inclusion somewhat independently of psychotic symptomatology in FEP. Inferences should be viewed with caution given this study did not involve longitudinal data.
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    Staged treatment and acceptability guidelines in early psychosis study (STAGES): A randomized placebo controlled trial of intensive psychosocial treatment plus or minus antipsychotic medication for first-episode psychosis with low-risk of self-harm or aggression. Study protocol and baseline characteristics of participants
    O'Donoghue, B ; Francey, SM ; Nelson, B ; Ratheesh, A ; Allott, K ; Grahann, J ; Baldwin, L ; Alvarez-Jinnenez, M ; Thonnpson, A ; Fornito, A ; Polari, A ; Berk, M ; Macneil, C ; Crisp, K ; Pantelis, C ; Yuen, HP ; Harrigan, S ; McGorry, P (WILEY, 2019-08)
    AIM: It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented. METHODS: This study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM-IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans. RESULTS: Ninety participants have been recruited and baseline characteristics are presented. CONCLUSIONS: Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines.
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    Factors associated with vocational disengagement among young people entering mental health treatment
    Caruana, E ; Allott, K ; Farhall, J ; Parrish, EM ; Davey, CG ; Chanen, AM ; Killackey, E ; Cotton, SM (WILEY, 2019-08)
    AIM: Most mental disorders have their onset by age 25, disrupting normative vocational engagement. Factors associated with vocational disengagement at first contact with specialist treatment are important for service planning. The aim of this paper was to investigate the association between theoretically important factors and vocational disengagement for youth entering mental health treatment. METHODS: A file audit was used to extract vocational data of 145 young people aged 15 to 25 years entering treatment in 2011 at a public youth mental health service in Melbourne, Australia. Comparisons were made across three specialist programs for: psychosis (n = 50), mood disorders (n = 52) and borderline personality pathology (n = 43). Individual characteristics were entered into univariate and multivariate logistic regressions to investigate their associations with vocational disengagement. RESULTS: Educational disengagement was associated with being older (OR = 4.38, P = 0.004) and not living with parents (OR = 2.87, P = 0.038). Unemployment and being NEET (Not in Education, Employment or Training) were both associated with not having commenced tertiary education (OR = 0.23, P = 0.022; OR = 0.05, P = 0.002; respectively). Being NEET was also associated with being older (OR = 6.18, P = 0.004). Primary diagnostic grouping was not associated with vocational disengagement, once accounting for other factors. CONCLUSIONS: The likelihood of vocational disengagement did not differ across disorder groups, implying that intervention should be "transdiagnostic" and might best target education first, specifically post-secondary qualifications. Other domains or variables not measured in this study are also likely to be important, and this might include young people's support systems and symptom severity. Qualitative studies may be useful for exploring further factors relevant to vocational engagement.
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    Vocational engagement among young people entering mental health treatment compared with their general population peers
    Caruana, E ; Farhall, J ; Cotton, SM ; Parrish, E ; van-der-EL, K ; Davey, CG ; Chanen, AM ; Bryce, SD ; Killackey, E ; Allott, K (WILEY, 2019-06)
    AIM: To compare rates of vocational engagement for youth entering specialist mental health treatment with the general population. METHODS: A file audit retrieved vocational data for 145 youth aged 15 to 25 entering treatment. Clinical and population data were stratified by age and sex and compared between cohorts. RESULTS: Compared to the population, young people entering mental health treatment were less likely to have completed at least Year 11 in school (77% vs 42%, P < 0.001); and demonstrated higher rates of "Not in Education, Employment or Training" (9% vs 33%, P < 0.001). Individuals aged 15 to 18 years entering treatment experienced greater rates of educational disengagement than the population (30% vs 11%, P < 0.001), whereas people aged 19 to 25 years showed higher unemployment rates (52% vs 35%, P = 0.003). CONCLUSIONS: Youth entering specialist mental health treatment have marked levels of vocational disengagement compared to demographically-matched peers. Early vocational intervention for these young people is essential.
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    Subjective experiences of neurocognitive functioning in young people with major depression
    Morey-Nase, C ; Phillips, LJ ; Bryce, S ; Hetrick, S ; Wright, AL ; Caruana, E ; Allott, K (BMC, 2019-07-04)
    BACKGROUND: Research suggests that young people with major depressive disorder (MDD) experience neurocognitive deficits and that these are associated with poorer functional and clinical outcomes. However, we are yet to understand how young people experience such difficulties. The aim of the current study was to explore the subjective experiences of neurocognitive functioning among young people with MDD. METHODS: Semi-structured qualitative interviews were conducted with 11 young people (aged 17-24 years) attending a specialist clinic for youth experiencing moderate-severe depression. Interview transcripts were analysed via Thematic Analysis to identify patterns and themes representing how young people with MDD subjectively experience neurocognitive deficits. RESULTS: Five main themes were identified: (1) experience of neurocognitive complaints; (2) relationship between neurocognitive complaints and depression; (3) impact on functioning; (4) strategies and supports; and (5) neurocognitive complaints and treatment. Overall, young people with MDD commonly experienced a range of subjective neurocognitive complaints. These appeared to have a bidirectional relationship with depressive symptomatology and significantly disrupted vocational, social and independent functioning, and aspects of psychological well-being including self-esteem. Neurocognitive difficulties represented an experiential barrier to psychological therapeutic engagement and were perceived as variably responsive to psychotropic medications, highlighting the need for targeted intervention. DISCUSSION: Neurocognitive difficulties are a common and pervasive experience for young people with MDD, with perceived impacts on depressive symptoms, attitudinal beliefs, everyday functioning and therapeutic engagement. Subjective neurocognitive complaints may therefore contribute to or exacerbate personal challenges faced by young people with MDD and thus, require early identification, consideration in psychological formulation, and treatment. Further research into the mechanisms of neurocognitive impairment in MDD is also needed.
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    ENACT: a protocol for a randomised placebo-controlled trial investigating the efficacy and mechanisms of action of adjunctive N-acetylcysteine for first-episode psychosis
    Cotton, SM ; Berk, M ; Watson, A ; Wood, S ; Allott, K ; Bartholomeusz, CF ; Bortolasci, CC ; Walder, K ; O'Donoghue, B ; Dean, OM ; Chanen, A ; Amminger, GP ; McGorry, PD ; Burnside, A ; Uren, J ; Ratheesh, A ; Dodd, S (BMC, 2019-11-28)
    BACKGROUND: First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness; however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N-acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2 g/day for 26 weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups. METHODS/DESIGN: ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15-25 years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration. DISCUSSION: Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ID: ACTRN12618000413224. Registered on 21 March 2018.
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    Can 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
    Weller, A ; Gleeson, J ; Alvarez-Jimenez, M ; McGorry, P ; Nelson, B ; Allott, K ; Bendall, S ; Bartholomeusz, C ; Koval, P ; Harrigan, S ; O'Donoghue, B ; Fornito, A ; Pantelis, C ; Amminger, GP ; Ratheesh, A ; Polari, A ; Wood, SJ ; van der El, K ; Ellinghaus, C ; Gates, J ; O'Connell, J ; Mueller, M ; Wunderink, L ; Killackey, E (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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    The missing voice of engagement: an exploratory study from the perspectives of case-managers at an early intervention service for first-episode psychosis
    Tindall, RM ; Allott, K ; Simmons, M ; Roberts, W ; Hamilton, BE (BMC, 2019-10-24)
    BACKGROUND: A key component of case-management in early intervention services for first-episode psychosis is engaging a person with the service and building a relationship from which therapy and treatment can be facilitated. The aim of this study was to understand how case-managers at an early intervention service experience the process of engagement and working with varying levels of attendance and participation. METHODS: Qualitative interviews were conducted with the case-managers of nine young people treated at an early intervention service for first-episode psychosis within 6 months of treatment entry. Interviews discussed the process of working with the young person and factors that influenced service engagement. Interviews were analyzed using thematic analysis. RESULTS: Case-managers described a range of influences on engagement which were grouped under the themes: young person and caregiver influences on engagement, case-manager influences on engagement, and influences of the early intervention service system on engagement. The experience of engagement was described as relational, however it occurred in the context of broader influences, some of which were unable to be changed or challenged by the case-manager (e.g., resource allocation, models of treatment, young person demographics). CONCLUSION: This study illustrates the challenges that case-managers face when working with young people with first-episode psychosis, and the direct influence this has on engagement with treatment. Understanding these challenges and addressing them in policy and service design may lead to improvements in young peoples' recovery from first-episode psychosis and increase case-manager job satisfaction.
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    Individual placement and support for vocational recovery in first-episode psychosis: randomised controlled trial
    Killackey, E ; Allott, K ; Jackson, HJ ; Scutella, R ; Tseng, Y-P ; Borland, J ; Proffitt, T-M ; Hunt, S ; Kay-Lambkin, F ; Chinnery, G ; Baksheev, G ; Alvarez-Jimenez, M ; McGorry, PD ; Cotton, SM (Cambridge University Press, 2019)
    BACKGROUND: High unemployment is a hallmark of psychotic illness. Individual placement and support (IPS) may be effective at assisting the vocational recoveries of young people with first-episode psychosis (FEP).AimsTo examine the effectiveness of IPS at assisting young people with FEP to gain employment (Australian and Clinical Trials Registry ACTRN12608000094370). METHOD: Young people with FEP (n = 146) who were interested in vocational recovery were randomised using computer-generated random permuted blocks on a 1:1 ratio to: (a) 6 months of IPS in addition to treatment as usual (TAU) or (b) TAU alone. Assessments were conducted at baseline, 6 months (end of intervention), 12 months and 18 months post-baseline by research assistants who were masked to the treatment allocations. RESULTS: At the end of the intervention the IPS group had a significantly higher rate of having been employed (71.2%) than the TAU group (48.0%), odds ratio 3.40 (95% CI 1.17-9.91, z = 2.25, P = 0.025). However, this difference was not seen at 12- and 18-month follow-up points. There was no difference at any time point on educational outcomes. CONCLUSIONS: This is the largest trial to our knowledge on the effectiveness of IPS in FEP. The IPS group achieved a very high employment rate during the 6 months of the intervention. However, the advantage of IPS was not maintained in the long term. This seems to be related more to an unusually high rate of employment being achieved in the control group rather than a gross reduction in employment among the IPS group.Declaration of interestNone.