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Background: Despite reports of altered brain morphology in established bipolar disorder (BD), there is limited understanding of when these morphological abnormalities emerge. Assessment of patients during the early course of illness can help to address this gap, but few studies have examined surface-based brain morphology in patients at this illness stage., Methods: We completed a secondary analysis of baseline data from a randomised control trial of BD individuals stabilised after their first episode of mania (FEM). The magnetic resonance imaging scans of n = 35 FEM patients and n = 29 age-matched healthy controls were analysed. Group differences in cortical thickness, surface area and gyrification were assessed at each vertex of the cortical surface using general linear models. Significant results were identified at p < 0.05 using cluster-wise correction., Results: The FEM group did not differ from healthy controls with regards to cortical thickness or gyrification. However, there were two clusters of increased surface area in the left hemisphere of FEM patients, with peak coordinates falling within the lateral occipital cortex and pars triangularis., Conclusions: Cortical thickness and gyrification appear to be intact in the aftermath of a first manic episode, whilst cortical surface area in the inferior/middle prefrontal and occipitoparietal cortex is increased compared to age-matched controls. It is possible that increased surface area in the FEM group is the outcome of abnormalities in a premorbidly occurring process. In contrast, the findings raise the hypothesis that cortical thickness reductions seen in past studies of individuals with more established BD may be more attributable to post-onset factors., Competing Interests: Declaration of Competing Interest Dr. Van Rheenen has received grants unrelated to the current study from Club Melbourne, the Henry Freeman Trust, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation and the Society of Mental Health Research. Professor Berk has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Lundbeck, Merck, Pfizer, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier. Prof Yücel also received philanthropic donations from the David Winston Turner Endowment Fund, Wilson Foundation, as well as payments in relation to court-, expert witness-, and/or expert review-reports; the funding sources had no role in the design, management, data analysis, presentation, or interpretation and write-up of the data. Professor Pantelis has been on advisory boards for AstraZeneca, Janssen-Cilag, Lundbeck and Servier; and he has received honoraria for talks presented at educational meetings organized by AstraZeneca, Eli Lilly, Janssen-Cilag, Lundbeck, Pfizer and Shire. Prof Cotton, Dr. Dandash, Miss Ringin, Miss Cooper, Dr. Daglas-Georgiou, A/Prof Allott, Dr. Chye, Dr. Suo, Dr. MacNeil, Dr. Hasty, Dr. Hallam, Prof McGorry and Prof Fornito do not have any disclosures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Childhood trauma is related to an increased number of depressive episodes and more severe depressive symptoms in bipolar disorder. The evaluation of the networks of depressive symptoms-or the patterns of relationships between individual symptoms-among people with bipolar disorder with and without a history of childhood trauma may assist in further clarifying this complex relationship., Methods: Data from over 500 participants from the Heinz C. Prechter Longitudinal Study of Bipolar Disorder were used to construct a series of regularised Gaussian Graphical Models. The networks of individual depressive symptoms-self-reported (Patient Health Questionnaire-9; n = 543) and clinician-rated (Hamilton Depression Rating Scale-17; n = 529)-among participants with bipolar disorder with and without a history of childhood trauma (Childhood Trauma Questionnaire) were characterised and compared., Results: Across the sets of networks, depressed mood consistently emerged as a central symptom (as indicated by strength centrality and expected influence); regardless of participants' history of childhood trauma. Additionally, feelings of worthlessness emerged as a key symptom in the network of self-reported depressive symptoms among participants with-but not without-a history of childhood trauma., Conclusion: The present analyses-although exploratory-provide nuanced insights into the impact of childhood trauma on the presentation of depressive symptoms in bipolar disorder, which have the potential to aid detection and inform targeted intervention development., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Objective: Caregivers of individuals with severe mental illness often experience significant negative experiences of care, which can be associated with higher levels of expressed emotion. Expressed emotion is potentially a modifiable target early in the course of illness, which might improve outcomes for caregivers and patients. However, expressed emotion and caregiver experiences in the early stages of disorders might be moderated by the type of severe mental illness. The aim was to determine whether experiences of the caregiver role and expressed emotion differ in caregivers of young people with first-episode psychosis versus young people with 'first-presentation' borderline personality disorder features., Method: Secondary analysis of baseline (pre-treatment) data from three clinical trials focused on improving caregiver outcomes for young people with first-episode psychosis and young people with borderline personality disorder features was conducted (ACTRN12616000968471, ACTRN12616000304437, ACTRN12618000616279). Caregivers completed self-report measures of experiences of the caregiver role and expressed emotion. Multivariate generalised linear models and moderation analyses were used to determine group differences., Results: Data were available for 265 caregivers. Higher levels of negative experiences and expressed emotion, and stronger correlations between negative experiences and expressed emotion domains, were found in caregivers of young people with borderline personality disorder than first-episode psychosis. Caregiver group (borderline personality disorder, first-episode psychosis) moderated the relationship between expressed emotion and caregiver experiences in the domains of need to provide backup and positive personal experiences., Conclusion: Caregivers of young people with borderline personality disorder experience higher levels of negative experiences related to their role and expressed emotion compared with caregivers of young people with first-episode psychosis. The mechanisms underpinning associations between caregiver experiences and expressed emotion differ between these two caregiver groups, indicating that different supports are needed. For borderline personality disorder caregivers, emotional over-involvement is associated with both negative and positive experiences, so a more detailed understanding of the nature of emotional over-involvement for each relationship is required to guide action.

Background: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia., Methods: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262)., Findings: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference -7·53 (95% CI -14·45 to 0·60; Cohen's d -0·53)., Interpretation: A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited., Funding: UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council., Competing Interests: Declaration of interests AIG reports personal fees from University of Manchester, personal fees from University of Exeter, personal fees from British Association for Behavioural and Cognitive Psychotherapies and other interests with UK National Health Service (NHS) Education for Scotland outside the submitted work. JA, SL, and SB report other interests with CareLoop Health, outside the submitted work. SB reports grants from the Medical Research Council and UK National Institute for Health Research (NIHR) during the conduct of the study. SL reports grants from the UK Medical Research Council (MRC) during the conduct of the study. JA reports grants from MRC, Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR, and the US National Institute for Health, and was a Fellow of the Alan Turing Institute during the conduct of the study. AB reports personal fees from Bayer, Merck, Janssen, Novartis, Sword Health, Amgen, and Daiichi Sankyo outside the submitted work. JF reports grants from National Health and Medical Research Council (Australia) during the conduct of the study and other interests with Melbourne Health (NorthWestern Mental Health) outside the submitted work. HMcL reports grants from NIHR Health Technology Assessment (HTA) during the conduct of the study, and grants with Academy of Medical Sciences, Glasgow Children's Hospital Charity, and Scotland's Chief Scientist's Office. CM reports grants from National Health and Medical Research Council (Australia) during the conduct of the study. JN reports grants from the University of Aberdeen and the University of Edinburgh during the conduct of the study and declares membership of the following NIHR boards: Cardio Pulmonary Resusitation decision making committee; HTA commissioning board; HTA commissioning sub-board (expression of interest); HTA funding boards policy group; HTA general board; HTA post-board funding teleconference; NIHR clinical trials unit standing advisory committee; NIHR HTA and Efficacy Mechanism Evaluation editorial board; pre-exposure prophylaxis impact review panel. PF is a member of the HTA mental health prioritisation panel. CW reports grants from NIHR during the conduct of the study and from the Royal College of Psychiatrists, and other interests with Five Areas outside the submitted work. AY reports an NIHR Senior Investigator Grant. JG reports grants from the National Health Medical Research Council. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: There is a lack of existing research regarding young people with bipolar I disorder (BD-I) and psychotic features, who are not in education, employment, and training (NEET). Thus, the aims of the study were to: (a) establish rates of NEET at service entry to a specialist early intervention service; (b) delineate premorbid and current variables associated with NEET status at service entry and (c) examine correlates of NEET status at discharge., Method: Medical file audit methodology was utilized to collect information on 118 patients with first episode psychotic mania treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. NEET status was determined using the modified vocation status index (MVCI). Bivariate and multivariable logistic variables were used to examine relationships between premorbid, service entry and treatment variables, and NEET status at service entry and discharge., Results: The NEET rate was 33.9% at service entry, and 39.2% at discharge. Variables associated with NEET status at service entry were premorbid functioning and polysubstance use. NEET status at service entry was the only significant correlate of NEET status at discharge. When service entry NEET was taken out of the model, substance use during treatment was predictive of NEET status at discharge., Conclusions: NEET status at service entry was related to a history of premorbid decline, and risk factors such as substance use and forensic issues. NEET status can decline during treatment, and utility of vocational intervention programs specifically for BD, in addition to specialist early intervention, needs to be examined., (© 2021 John Wiley & Sons Australia, Ltd.)

Importance: Clinical trials have neither focused on early intervention for psychosocial impairment nor on the contribution of components of borderline personality disorder (BPD) treatment beyond individual psychotherapy., Objective: To evaluate the effectiveness of 3 early interventions for BPD of differing complexity., Design, Settings, and Participants: This single-blinded randomized clinical trial recruited young people between March 17, 2011, and September 30, 2015, into parallel groups. The study took place at 2 government-funded mental health services for young people in Melbourne, Australia. Inclusion criteria were age 15 to 25 years (inclusive), recent DSM-IV-TR BPD diagnosis, and never receiving evidence-based BPD treatment. A total of 139 participants were randomized (pool of 876; 70 declined, 667 excluded), balanced for sex, age, and depressive symptomatology. Data analysis completed May 2020., Interventions: (1) The Helping Young People Early (HYPE) dedicated BPD service model for young people, combined with weekly cognitive analytic therapy (CAT); (2) HYPE combined with a weekly befriending psychotherapy control condition; and (3) a general youth mental health service (YMHS) model, combined with befriending. Therefore, the 3 treatment arms were HYPE + CAT, HYPE + befriending, and YMHS + befriending. Participants were randomly assigned both to 1 treatment arm (in a 1:1:1 ratio) and to a clinician., Main Outcomes and Measures: Psychosocial functioning, measured with the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale Self-report., Results: One hundred twenty-eight participants (104 [81.3%] were female; mean [SD] age, 19.1 [2.8] years; HYPE + CAT: 40 [31.3%]; HYPE + befriending: 45 [35.2%]; YMHS + befriending: 43 [33.6%]) who provided postbaseline data were included in the intent-to-treat analysis. Regardless of group, from baseline to 12 months, there was a mean of 19.3% to 23.8% improvement in the primary outcomes and 40.7% to 52.7% for all secondary outcomes, except severity of substance use and client satisfaction. The latter remained high across all time points. Planned comparisons (YMHS + befriending vs HYPE; HYPE + CAT vs befriending) showed that neither the service model nor the psychotherapy intervention was associated with a superior rate of change in psychosocial functioning by the 12-month primary end point. The HYPE service model was superior to YMHS + befriending for treatment attendance (median [IQR], 22 [19] vs 3 [16] contacts; median duration, 200 [139.5] vs 94 [125] days) and treatment completion (44 of 92 [47.8%] vs 9 of 47 [19.2%]). HYPE + CAT was superior to befriending for treatment attendance (median [IQR], 12 [16.5] vs 3 [9.8] sessions) and treatment completion (24 of 46 [52.2%] vs 29 of 93 [31.2%])., Conclusions and Relevance: In this randomized clinical trial of 3 interventions for young people with BPD, effective early intervention was not reliant on availability of specialist psychotherapy but did require youth-oriented clinical case management and psychiatric care. A dedicated early intervention BPD service model (HYPE), with or without individual psychotherapy, achieved greater treatment attendance and completion, making it more likely to meet service user, family, and community expectations of care., Trial Registration: anzctr.org.au Identifier: ACTRN12610000100099.

Aims: A disproportionate number of people with mental ill-health experience social exclusion. Appropriate measurement tools are required to progress opportunities to improve social inclusion. We have developed a novel measure, the Filia Social Inclusion Measure (F-SIM). Here we aimed to present a more concise, easy-to-use form, while retaining its measurement integrity by (i) refining the F-SIM using traditional and contemporary item-reduction techniques; and (ii) testing the psychometric properties of the reduced measure., Methods: Five hundred and six participants completed the F-SIM, younger and older groups of people with serious mental illness (including psychosis, mood, anxiety disorders) and same-aged community counterparts. The F-SIM was completed at baseline and 2-week follow-up, alongside other measures (including social inclusion, loneliness). The F-SIM was refined using multidimensional scaling network analysis, confirmatory factor analysis and item response theory. The psychometric evaluation included assessment of dimensionality, internal consistency, test-retest reliability, discriminant ability and construct validity., Results: The F-SIM was reduced from 135-items to 16; with 4-items in each domain of housing and neighbourhood, finances, employment and education and social participation and relationships. Psychometric properties were sound, including strong internal consistency within domains (all α > 0.85) and excellent overall (α = 0.92). Test-retest reliability was also high (γ = 0.90). Differences between groups were observed; clinical subgroups consistently reported lower levels of social inclusion compared to community counterparts., Conclusions: The F-SIM16 is a sound, reliable, brief self-report measure of social inclusion suitable for use in clinical and research settings. It has the potential to evaluate the effectiveness of interventions, and aid in fostering targeted and personalised needs-based care.

Background: Cognitive impairment is prevalent and often highly burdensome in people with schizophrenia. The aim of this study was to investigate if mangosteen ( Garcinia mangostana Linn.) pericarp extract may be an effective intervention to improve cognitive performance in this population. Methods: This was a secondary analysis of a larger randomized placebo-controlled trial that investigated a 24-weeks intervention of mangosteen pericarp extract supplementation in people diagnosed with schizophrenia. A subset of n = 114 participants with completed cognitive outcomes at follow up were included in this analysis. Using the Cogstate Brief Battery, the following cognitive outcomes were assessed: psychomotor function, attention, visual learning and memory (visual and working). Subgroup analyses investigated whether baseline clinical parameters (baseline cognitive functioning, illness severity and duration, depressive symptoms) moderated the relationship between mangosteen pericarp extract intervention and change in cognitive outcomes. Results: There were no significant between-group changes in any cognitive outcomes assessed. Subgroup analysis based on baseline cognition and clinical characteristics did not reveal any significant between-group difference in change. Conclusions: Mangosteen pericarp extract did not affect cognitive outcomes in people with schizophrenia. Further investigation regarding optimal dosing strategies for mangosteen interventions and the testing of additional cognitive domains may be warranted. Trial Registration: ANZCTR.org.au identifier: ACTRN12616000859482, registered 30 June 3 2016., Competing Interests: AT has received grant/research support from the National Health and Medical Research Council (NHMRC), AMP Foundation and Deakin University. OD was a R.D. Wright NHMRC Biomedical Career Development Fellow (APP1145634) and has received grant support from the Brain and Behavior Foundation, Simons Autism Foundation, Stanley Medical Research Institute, Deakin University, Lilly, NHMRC and ASBDD/Servier. She has also received in kind support from BioMedica Nutraceuticals, NutritionCare and Bioceuticals. AW has previously received grant/research support from a Trisno Family Fellowship and Deakin University. SD has received grant support from Stanley Medical Research Institute, NHMRC, Beyond Blue, ARHRF, Simons Foundation, Geelong Medical Research Foundation, Fondation FondaMental, Eli Lilly, Glaxo SmithKline, Organon, Mayne Pharma and Servier. He has received speaker's fees from Eli Lilly, advisory board fees from Eli Lilly and Novartis and conference travel support from Servier. SC was supported by a NHMRC Senior Research Fellowship (APP1136344). SC has received grant support from the NHMRC, the Stanley Medical Research Institute, BeyondBlue, Movember, The University of Melbourne, Australian Catholic University, ARHRF, and Mental Illness Research Fund (Victoria Department of Human Services). JS was supported by a National Health and Medical Research Council Practitioner Fellowship Grant (APP1105807), has been a speaker for Janssen Cilag, Lundbeck, Servier, and Shire Pharmaceuticals, and served as a consultant to Janssen Cilag, Lundbeck and Roche. BK has received grant/research support from the Australian Postgraduate Research Training Scholarship, Deakin University, Ian Scott Mental Health Ph.D. Scholarship, Australian Rotary Health, and the International Society for the Study of Personality Disorders. MA has received grant/research support from Deakin University, Australasian Society for Bipolar Depressive Disorders, Lundbeck, Australian Rotary Health, Ian Parker Bipolar Research Fund, Cooperative Research Center for Mental Health and PDG Geoff and Betty Betts Award from Rotary Club of Geelong. EB has received grant/research support from the University of Melbourne, the Australian Department of Health, Western Victoria PHN, and the University of the West of England, UK. MB was supported by a NHMRC Senior Principal Research Fellowship (1059660 and 1156072). MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Abbot, Astra Zeneca, Janssen and Janssen, Lundbeck and Merck and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Janssen and Janssen, Lundbeck Merck, Pfizer and Servier—all unrelated to this work. WM was currently funded by an Alfred Deakin Postdoctoral Research Fellowship and a Multiple Sclerosis Research Australia early-career fellowship. WM has previously received funding from the Cancer Council Queensland and university grants/fellowships from La Trobe University, Deakin University, University of Queensland, and Bond University, received industry funding and has attended events funded by Cobram Estate Pty. Ltd, received travel funding from Nutrition Society of Australia, received consultancy funding from Nutrition Research Australia, and has received speakers honoraria from The Cancer Council Queensland and the Princess Alexandra Research Foundation. MM has received Grant/research support from NHMRC, Deakin University School of Medicine, Deakin Biostatistics Unit, Institute for Mental and Physical Health and Clinical Translation, and Medibank Health Research Fund. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer NN declared a past co-authorship with four of the authors WM, OD, MA, and MB to the handling editor., (Copyright © 2021 Marx, Skvarc, Mohebbi, Walker, Meehan, Turner, Baker, Dodd, Cotton, Scott, Kavanagh, Ashton, Brown, McGrath, Berk and Dean.)

Background: Suicidal ideation (SI) is a common feature of depression and is closely associated with suicidal behaviour. Social support is implicated as an important determinant of suicide, but it is unclear how different social support dimensions influence SI in young people with depression. This study examines relationships between social support dimensions and SI in young people with major depressive disorder (MDD)., Methods: 283 Australians aged 15-25, diagnosed with MDD, were recruited from two clinical trials conducted in youth-specific outpatient mental health services. The Multidimensional Scale of Perceived Social Support (MSPSS) was used to evaluate perceived support from Family, Friends, and a Significant Other. Suicidal ideation was assessed using the Suicidal Ideation Questionnaire (SIQ). Hierarchical regression was used to explore associations between social support and SI, controlling for demographics and depression severity., Results: A hierarchical regression model predicted 9% of the variability in SI, with depression severity being the most significant predictor. Family Support was inversely related to SI and uniquely contributed 2% of the variance; β = -0.15 (95% CI -0.27 - -0.02) p < .05. Demographics and support from Friends or a Significant Other were not significantly associated with SI., Limitations: Findings are correlational; it cannot be determined that increasing family support would decrease SI severity., Conclusion: Perceived Family Support was negatively associated with SI in young people with MDD. This suggests that family members might play important roles in suicide prevention efforts. More work is needed exploring ways to empower families to develop adaptive family functioning and support., (Copyright © 2020. Published by Elsevier B.V.)

Background: Family and friends ('carers') of adults with borderline personality disorder (BPD) and carers of young people with other serious illnesses experience significant adversity but research on the experiences of caring for a young person with BPD features is sparse. This study aimed to: (i) describe the experiences of carers of young people with BPD features; (ii) compare them with published data assessing carers of young people with other serious illnesses and with adults from the general population., Methods: Eighty-two carers (M age = 44.74, SD = 12.86) of 54 outpatient young people (M age = 18.76, SD = 3.02) who met 3 to 9 DSM-IV BPD criteria completed self-report measures on distress, experiences of caregiving, coping, and expressed emotion. Independent-samples t-tests were employed to compare scores with those reported by convenience comparison groups of general population adults or carers of young people with eating disorders, cancer, or psychosis., Results: Carers of young people with BPD features reported significantly elevated levels of distress, negative caregiving experiences, and expressed emotion, as well as maladaptive coping strategies, compared with general population adults or carers of young people with other serious illnesses., Conclusions: Carers of young people with BPD features experience elevated levels of adversity compared with their peers in the general adult population. This adversity is similar to, or greater than, that reported by carers of young people with other severe illnesses. Research is needed to clarify factors underlying adverse caregiving experiences and to develop and evaluate interventions to support carers of young people with BPD features., Trial Registration: Prospectively registered with the Australian New Zealand Clinical Trial Registry ACTRN12616000304437 on 08 March 2016, https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369867., Competing Interests: Competing interestsThe authors declare they have no competing interests., (© The Author(s) 2020.)

Background: Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of EWS interventions., Objective: This study was designed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) against treatment as usual (TAU). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, safety, and outcome signals of a digital health intervention as an adjunct to usual care that is deliverable in the UK National Health Service and Australian community mental health service (CMHS) settings. We will assess the feasibility of candidate primary outcomes, candidate secondary outcomes, and candidate mechanisms for a definitive trial., Methods: We will randomize CMHSs to EMPOWER or TAU. We aim to recruit up to 120 service user participants from 8 CMHSs and follow them for 12 months. Eligible service users will (1) be aged 16 years and above, (2) be in contact with local CMHSs, (3) have either been admitted to a psychiatric inpatient service or received crisis intervention at least once in the previous 2 years for a relapse, and (4) have an International Classification of Diseases-10 diagnosis of a schizophrenia-related disorder. Service users will also be invited to nominate a carer to participate. We will identify the feasibility of the main trial in terms of recruitment and retention to the study and the acceptability, usability, safety, and outcome signals of the EMPOWER intervention. EMPOWER is a mobile phone app that enables the monitoring of well-being and possible EWSs of relapse on a daily basis. An algorithm calculates changes in well-being based on participants' own baseline to enable tailoring of well-being messaging and clinical triage of possible EWSs. Use of the app is blended with ongoing peer support., Results: Recruitment to the trial began September 2018, and follow-up of participants was completed in July 2019. Data collection is continuing. The database was locked in July 2019, followed by analysis and disclosing of group allocation., Conclusions: The knowledge gained from the study will inform the design of a definitive trial including finalizing the delivery of our digital health intervention, sample size estimation, methods to ensure successful identification, consent, randomization, and follow-up of participants, and the primary and secondary outcomes. The trial will also inform the final health economic model to be applied in the main trial., Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 99559262; http://isrctn.com/ISRCTN99559262., International Registered Report Identifier (irrid): DERR1-10.2196/15058., (©Andrew Gumley, Simon Bradstreet, John Ainsworth, Stephanie Allan, Mario Alvarez-Jimenez, Louise Beattie, Imogen Bell, Max Birchwood, Andrew Briggs, Sandra Bucci, Emily Castagnini, Andrea Clark, Sue M Cotton, Lidia Engel, Paul French, Reeva Lederman, Shon Lewis, Matthew Machin, Graeme MacLennan, Claire Matrunola, Hamish McLeod, Nicola McMeekin, Cathrine Mihalopoulos, Emma Morton, John Norrie, Frank Reilly, Matthias Schwannauer, Swaran P Singh, Lesley Smith, Suresh Sundram, David Thomson, Andrew Thompson, Helen Whitehill, Alison Wilson-Kay, Christopher Williams, Alison Yung, John Farhall, John Gleeson. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.01.2020.)

Background: Medication is commonly used to treat youth depression, but whether medication should be added to cognitive behavioural therapy (CBT) as first-line treatment is unclear. We aimed to examine whether combined treatment with CBT and fluoxetine was more effective than CBT and placebo in youth with moderate-to-severe major depressive disorder., Methods: The Youth Depression Alleviation-Combined Treatment (YoDA-C) trial was a randomised, double-blind, placebo-controlled, multicentre clinical trial. Participants were aged 15-25 years with moderate-to-severe MDD and had sought care at one of four clinical centres in metropolitan Melbourne, Australia. Patients were randomly assigned (1:1) to receive CBT for 12 weeks, plus either fluoxetine or placebo. Participants began on one 20 mg capsule of fluoxetine or one placebo pill per day. All participants received CBT, delivered by therapists in weekly 50-minute sessions and attended interviews at baseline, and at weeks 4, 8, and 12, during which they completed assessments with research assistants. Participants saw a psychiatrist or psychiatry trainee to complete medical assessments at the same timepoints. The primary outcome was change in the interviewer-rated Montgomery-Åsberg Depression Rating Scale (MADRS) score at 12 weeks. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001281886)., Findings: 153 participants (mean age 19·6 years [SD 2·7]) were enrolled from Feb 20, 2013, to Dec 13, 2016. 77 (50%) patients were allocated to CBT and placebo and 76 (50%) to CBT and fluoxetine. Participants had severe depression at baseline (mean MADRS score 33·6 [SD 5·1] in the CBT and placebo group and 32·2 [5·6] in the CBT and fluoxetine group), with high proportions of participants with anxiety disorder comorbidity (47 [61%] in the CBT and placebo group and 49 [64%] in the CBT and fluoxetine group) and past-month suicidal ideation (55 [71%] in the CBT and placebo group and 59 [78%] in the CBT and fluoxetine group). 59 (77%) participants in the CBT and placebo group and 64 (84%) in the CBT and fluoxetine group completed follow-up at week 12. After 12 weeks of treatment both groups showed a reduction in MADRS scores (-13·7, 95% CI -16·0 to -11·4, in the CBT and placebo group and -15·1, -17·4 to -12·9, in the CBT and fluoxetine group). There was no significant between-group difference in MADRS scores (-1·4, -4·7 to 1·8; p=0·39). There were five suicide attempts in the CBT and placebo group and one suicide attempt in the CBT and fluoxetine group (odds ratio 0·2, 0·0-1·8; p=0·21), and no significant between-group differences for other suicidal behaviours., Interpretation: We did not find evidence that the addition of fluoxetine (rather than placebo) to CBT further reduced depressive symptoms in young people with moderate-to-severe MDD. Exploratory analyses showed that the addition of medication might be helpful for patients with comorbid anxiety symptoms and for older youth., Funding: Australian National Health and Medical Research Council., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Both major depressive disorder (MDD) and first episode schizophrenia spectrum (FES) are associated with significant neurocognitive deficits. However, it remains unclear whether the neurocognitive deficits in individuals with FES are more severe if there is comorbid depressive disorder. The aim of this study was to compare the neurocognitive profiles between those with and without full-threshold depressive disorder in FES., Method: This study involved secondary analysis of baseline data from a randomized controlled trial of vocational intervention for young people with first-episode psychosis (N = 82; age range: 15-25 years)., Results: Those with full-threshold depressive disorder (n = 24) had significantly better information processing speed than those without full-threshold depressive disorder. Severity of depressive symptoms was also associated with better information processing speed., Limitations: In additional to the cross-sectional design, limitations of this study include the absence of assessing insight as a potential mediator., Conclusions: After the first psychotic episode, it could be speculated that those with better information processing speed may be more likely to develop full-threshold depressive disorder, as their ability to efficiently process information may allow them to be more aware of their situations and environments, and consequently to have greater insight into the devastating consequences of FES. Such novel findings support the examination of full-threshold depressive disorder in relation to neurocognitive performance across illness phases in future work., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Anhedonia is prevalent among substance-dependent populations. The hedonic allostasis model suggests this is due to the effects of addictive substances on neural substrates of reward processing. However, previous research may have been confounded by other factors likely to influence anhedonia, including tobacco use, psychopathology, and history of trauma and other stressors. Thus it remains unclear whether elevated anhedonia in substance-dependent populations is caused by substance use itself, or is due to other correlates of substance dependence., Methods: Multivariate analysis of covariance was conducted to test whether opioid-dependent participants' anhedonia scores were elevated, relative to a non-dependent control group, after controlling for psychosocial factors likely to influence anhedonia. Correlational analyses within opioid-dependent participants were also conducted to examine whether anhedonia was associated with recent illicit opioid use or duration of abstinence., Results: There was a modest, but significant, elevation in anhedonia in opioid-dependent participants, relative to controls (Partial η 2 =0.034, p=0.041) after controlling for psychosocial variables that were associated with anhedonia. Depressive symptoms and history of post-traumatic stress disorder also remained significantly associated with anhedonia in the adjusted model. Among participants on opioid pharmacotherapy, there were significant associations between frequency of recent illicit opioid use and scores on anhedonia measures (all r s >0.25, p<0.013), but among abstinent opioid-dependent participants, relationships between duration of abstinence and anhedonia were not significant (all r s <0.24, p>0.22)., Conclusion: These findings support the hypothesis that use of opioids can cause anhedonia, although other psychosocial factors may also contribute to the high prevalence of anhedonia among opioid-dependent populations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Data from the literature suggests that some first episode psychosis (FEP) patients may recover without antipsychotic medication. There is however no reliable way to identify them. In a previous paper we found, in a cohort of 584 FEP patients, that those consistently refusing medication had poorer pre-morbid functioning, less insight, higher rate of substance use and poorer outcome. However, some medication refusers, had a favourable outcome. The study aim was to identify predictors of good short term outcome despite non-exposure to medication., Methods: The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 FEP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. Data on medication adherence was available in 584 patients. Among the 17.9% of patients who consistently refused medication over the entire treatment phase we compared patients who had a favourable symptomatic and functional outcome with those who did not., Results: Among patients who consistently refused medication, 41% achieved symptomatic remission and 33% reached functional recovery. Predictors of symptomatic remission were a better premorbid functioning level, higher education and employment status at baseline. Predictors of functional recovery were a shorter duration of the prodrome phase, less severe psychopathology at baseline and lower cannabis use., Conclusions: Despite limitations mainly linked to the fact that non-exposure to antipsychotic medication was based on patient's treatment refusal, this study identified some characteristics which may contribute to the identification of a sub-group of FEP patients who may have good short term outcome without antipsychotic treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background Lithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other. Aims To investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania. Method Maintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.) Results In total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine. Conclusions In people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution., Competing Interests: Declaration of interestThis study was supported by an unrestricted grant from AstraZeneca. R.D., M.H. and K.H. worked on a study that has received research support by AstraZeneca. M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier and Woolworths, has been a speaker for AstraZeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen-Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth, and served as a consultant to AstraZeneca, Bioadvantex, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen-Cilag, Lundbeck Merck and Servier. C.M. has received a grant/research support from Eli Lilly and AstraZeneca, Janssen Cilag and Sanofi Aventis, and served as a consultant to AstraZeneca and Eli Lilly. P.D.M. has received investigator initiated research grants from AstraZeneca, Janssen-Cilag, Eli Lilly and BMS. He has received honoraria for educational events from Janssen-Cilag, Eli Lilly, BMS, AstraZeneca, Pfizer and Lundbeck. C.P. has participated on Advisory Boards for Janssen-Cilag, AstraZeneca, Lundbeck and Servier, has received honoraria for talks presented at educational meetings organised by AstraZeneca, Janssen-Cilag, Eli-Lilly, Pfizer, Lundbeck and Shire., (© The Royal College of Psychiatrists 2017.)

Background: Individuals with substance dependence commonly experience anhedonia. Theories of anhedonia distinguish between anticipatory and consummatory reward deficits, with the Temporal Experience of Pleasure Scale (TEPS) the first self-report scale to separately measure these two constructs. Several psychometric studies have analysed the trait version of the TEPS, but the state version of the TEPS has not been previously validated., Methods: We examined the psychometric properties of the state version of the TEPS in 121 individuals with opiate dependence (81% Australian-born), to confirm its 2-factor structure and examine the internal consistency, convergent and divergent validity, test-retest reliability, and performance as a state measure., Results: Confirmation of the 2-factor solution required removal of two items and allowing correlation between residuals of three pairs of highly-similar items. The resulting consummatory and anticipatory scales correlated strongly with each other (r=.76), suggesting poor divergent validity between them. Nevertheless, the scale showed good internal consistency (Chronbach's α: anticipatory=.90; consummatory=.84; total=.92), convergent (TEPS total and Snaith-Hamilton Pleasure Scale r=-.76) and divergent validity (-.38

Context: The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Long-chain omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that omega-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation., Objective: To determine whether omega-3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis., Design: Randomized, double-blind, placebo-controlled trial conducted between 2004 and 2007., Setting: Psychosis detection unit of a large public hospital in Vienna, Austria., Participants: Eighty-one individuals at ultra-high risk of psychotic disorder., Interventions: A 12-week intervention period of 1.2-g/d omega-3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months., Main Outcome Measures: The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of omega-6 to omega-3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition., Results: Seventy-six of 81 participants (93.8%) completed the intervention. By study's end (12 months), 2 of 41 individuals (4.9%) in the omega-3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P = .007). The difference between the groups in the cumulative risk of progression to full-threshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). omega-3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P = .01), negative symptoms (P = .02), and general symptoms (P = .01) and improved functioning (P = .002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups., Conclusions: Long-chain omega-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states. Trial Registration clinicaltrials.gov Identifier: NCT00396643.