Emotion Processing and Its Relationship to Social Functioning and Symptoms in Psychotic Disorder: A Systematic Review and Meta-analysis.

BACKGROUND: Emotion processing (EP) is impaired in individuals with psychosis and associated with social functioning; however, it is unclear how symptoms fit into this relationship. The aim of this systematic review and meta-analysis was to examine interrelationships between EP, symptoms, and social functioning, test whether different symptom domains mediate the relationship between EP and social functioning, and examine the moderating effects of illness stage and EP task type. STUDY DESIGN: MEDLINE, Embase, and PsycINFO databases were searched for studies that included individuals with psychosis and reported correlations between EP, symptom domains (positive, negative, depressive, and disorganization), and social functioning. Random effects meta-analyses determined the strength of correlations, and subgroup analyses included illness stage and EP task type (lower- vs higher-level processing). Meta-analytic structural equation models tested whether symptom domains mediated the relationship between EP and social functioning. RESULTS: There was a small relationship (r = .18) between EP and social functioning. Positive, negative, and disorganization symptoms mediated this relationship, although indirect effects were small. Higher-level EP tasks were more strongly associated with negative symptoms than lower-level tasks. Relationships between EP and both social functioning and positive symptoms were smaller in the first episode of psychosis than in established illness. CONCLUSIONS: The mediating relationship suggests that EP not only influences social dysfunction directly but contributes to negative and disorganization symptoms, which in turn impair social functioning. This pathway suggests that targeting negative and disorganization symptoms may ultimately improve social outcomes for individuals with psychosis. Future research, particularly in early psychosis, is needed to determine other factors impacting these interrelationships.

Capturing the clinical complexity in young people presenting to primary mental health services: a data-driven approach.

AIMS: The specific and multifaceted service needs of young people have driven the development of youth-specific integrated primary mental healthcare models, such as the internationally pioneering headspace services in Australia. Although these services were designed for early intervention, they often need to cater for young people with severe conditions and complex needs, creating challenges in service planning and resource allocation. There is, however, a lack of understanding and consensus on the definition of complexity in such clinical settings. METHODS: This retrospective study involved analysis of headspace's clinical minimum data set from young people accessing services in Australia between 1 July 2018 and 30 June 2019. Based on consultations with experts, complexity factors were mapped from a range of demographic information, symptom severity, diagnoses, illness stage, primary presenting issues and service engagement patterns. Consensus clustering was used to identify complexity subgroups based on identified factors. Multinomial logistic regression was then used to evaluate whether these complexity subgroups were associated with other risk factors. RESULTS: A total of 81,622 episodes of care from 76,021 young people across 113 services were analysed. Around 20% of young people clustered into a 'high complexity' group, presenting with a variety of complexity factors, including severe disorders, a trauma history and psychosocial impairments. Two moderate complexity groups were identified representing 'distress complexity' and 'psychosocial complexity' (about 20% each). Compared with the 'distress complexity' group, young people in the 'psychosocial complexity' group presented with a higher proportion of education, employment and housing issues in addition to psychological distress, and had lower levels of service engagement. The distribution of complexity profiles also varied across different headspace services. CONCLUSIONS: The proposed data-driven complexity model offers valuable insights for clinical planning and resource allocation. The identified groups highlight the importance of adopting a holistic and multidisciplinary approach to address the diverse factors contributing to clinical complexity. The large number of young people presenting with moderate-to-high complexity to headspace early intervention services emphasises the need for systemic change in youth mental healthcare to ensure the availability of appropriate and timely support for all young people.

Multiscale heterogeneity of white matter morphometry in psychiatric disorders.

Background: Inter-individual variability in neurobiological and clinical characteristics in mental illness is often overlooked by classical group-mean case-control studies. Studies using normative modelling to infer person-specific deviations of grey matter volume have indicated that group means are not representative of most individuals. The extent to which this variability is present in white matter morphometry, which is integral to brain function, remains unclear. Methods: We applied Warped Bayesian Linear Regression normative models to T1-weighted magnetic resonance imaging data and mapped inter-individual variability in person-specific white matter volume deviations in 1,294 cases (58% male) diagnosed with one of six disorders (attention-deficit/hyperactivity, autism, bipolar, major depressive, obsessive-compulsive and schizophrenia) and 1,465 matched controls (54% male) recruited across 25 scan sites. We developed a framework to characterize deviation heterogeneity at multiple spatial scales, from individual voxels, through inter-regional connections, specific brain regions, and spatially extended brain networks. Results: The specific locations of white matter volume deviations were highly heterogeneous across participants, affecting the same voxel in fewer than 8% of individuals with the same diagnosis. For autism and schizophrenia, negative deviations (i.e., areas where volume is lower than normative expectations) aggregated into common tracts, regions and large-scale networks in up to 35% of individuals. Conclusions: The prevalence of white matter volume deviations was lower than previously observed in grey matter, and the specific location of these deviations was highly heterogeneous when considering voxel-wise spatial resolution. Evidence of aggregation within common pathways and networks was apparent in schizophrenia and autism but not other disorders.

Inequitable access to mental healthcare for socially excluded adolescents.

BACKGROUND: Adolescence is a critical period for mental health and social exclusion, a key social determinant of mental health. Early intervention approaches are key to mitigating the impact of mental ill-health during adolescence, however social exclusion can create additional barriers to accessing care. AIM: We aimed to better understand help-seeking experiences of adolescents facing co-occurring social exclusion and mental ill-health, including sources of support, barriers and preferences for service provision. METHOD: Cross-sectional data were analysed, from the 2022 Mission Australia Youth Survey (N = 18,800). Adolescents aged 15 to 19 years were recruited from around Australia, through schools, community organisations and digital platforms. Indices of four domains of social exclusion (housing, finances, relational and education/employment) were created using existing Youth Survey variables, and supplemented with demographic characteristics, psychological distress and help-seeking behaviours (perceived need, mental health supports, barriers to access and preferences). Relationships between social exclusion domains, mental health concerns and help-seeking behaviours were explored using logistic regression models. RESULTS: A total of 9,743 young people reported having needed mental health support, yet only 58.1% reportedly sought support (n = 5,565). Social exclusion domains were associated with different help-seeking behaviours: housing challenges with higher help-seeking (OR = 1.28; 95% CI [1.15, 1.42]); relational difficulties and edu-employment issues with lower (OR = 0.75; 95% CI [0.68, 0.83] and OR = 0.82; 95% CI [0.75, 0.89]). Stigma, confidentiality concerns, cost and not knowing where to seek help were common barriers to help-seeking; those experiencing social exclusion more likely to report these. Participants reported a strong preference for face-to-face support. CONCLUSIONS: This study highlights the additional needs and challenges faced by adolescents dealing with both social exclusion and mental ill-health. With greater barriers to help-seeking, concerted efforts are needed to reduce stigma, improve mental health literacy and increase access to trusted information sources. Further initiatives should focus on structural factors that socially exclude young people and exacerbate inequitable access to mental healthcare.

Early Maladaptive Schemas and Depression in Caregivers of Individuals With Schizophrenia Spectrum and Bipolar Disorders.

OBJECTIVES: Early maladaptive schemas represent unhelpful frameworks of cognitions, emotions and subsequent behavioural responses and can be associated with depressive symptoms. Caregivers of individuals with serious mental illness (SMI) frequently report experiencing depressive symptoms. It is unclear whether depressive symptoms in caregivers are influenced by schemas. We aimed to compare activated schemas in caregivers of people with schizophrenia spectrum (SSD) and bipolar disorder (BD) diagnoses and to determine whether they were differentially related to depressive symptoms. DESIGN AND METHODS: Caregivers completed validated measures of depression and schemas. Independent samples t-tests and multivariate generalised linear models were used to assess differences in schemas and depressive symptoms between caregiver groups. Interrelationships between schema domains and caregiver depressive symptoms were delineated using correlational analyses and forward stepwise regressions. RESULTS: One hundred eight caregivers participated in the study (SSD n = 68, BD n = 40). No differences in depressive symptom severity or activated schemas were observed between caregiver groups. All schemas were significantly associated with depressive symptoms, and the Disconnection-Rejection schema domain explained the most variance in depressive symptoms in both caregiver groups. CONCLUSIONS: Schemas contribute to the severity of caregiver depression regardless of whether the person receiving care is diagnosed with SSD or BD. Schema therapeutic frameworks may be beneficial for use with caregivers to address schemas within the Disconnection-Rejection domain and alleviate depressive symptoms by reducing experiences of social isolation and alienation.

A Prototype Software Framework for Transferable Computational Health Economic Models and Its Early Application in Youth Mental Health.

We are developing an economic model to explore multiple topics in Australian youth mental health policy. To help make that model more readily transferable to other jurisdictions, we developed a software framework for authoring modular computational health economic models (CHEMs) (the software files that implement health economic models). We specified framework user requirements for: a simple programming syntax; a template CHEM module; tools for authoring new CHEM modules; search tools for finding existing CHEM modules; tools for supplying CHEM modules with data; reproducible analysis and reporting tools; and tools to help maintain a CHEM project website. We implemented the framework as six development version code libraries in the programming language R that integrate with online services for software development and research data archiving. We used the framework to author five development version R libraries of CHEM modules focussed on utility mapping in youth mental health. These modules provide tools for variable validation, dataset description, multi-attribute instrument scoring, construction of mapping models, reporting of mapping studies and making out of sample predictions. We assessed these CHEM module libraries as mostly meeting transparency, reusability and updatability criteria that we have previously developed, but requiring more detailed documentation and unit testing of individual modules. Our software framework has potential value as a prototype for future tools to support the development of transferable CHEMs.Code: Visit https://www.ready4-dev.com for more information about how to find, install and apply the prototype software framework.

Guidance on Minimum Standards for Canine-Assisted Psychotherapy in Adolescent Mental Health: Delphi Expert Consensus on Health, Safety, and Canine Welfare.

As interest in animal-assisted therapy (AAT) and canine-assisted psychotherapy (CAP) grows, there are increasing calls for the management of related health, safety, and welfare concerns for canines, providers, and clients. Existing health and safety guidelines lack empirical support and are, at times, contradictory. Welfare is increasingly prioritized; however, tools to monitor and manage welfare are underutilized and under-reported. The aim of this study was to provide expert consensus on the minimum health, safety, and welfare standards required to develop and deliver a CAP group program to adolescents experiencing common mental health disorders. Diverse AAT experts were recruited globally. Using Delphi methodology, over two rounds, 40 panelists reached a consensus agreement to include 32 items from a possible 49 into the minimum standards. Health and safety measures included risk assessment, veterinary screening, preventative medicine, training in infection control, and first aid. Welfare measures included training in welfare assessment, documentation of welfare, and flexible, individualized responses to promote wellbeing. Intestinal screening for parasites and the prohibition of raw food were not supported. Flexible and individualized assessment and management of canine welfare were supported over fixed and time-limited work schedules. Clinical practice implications are discussed, and recommendations are made.

Systematic Review and Meta-analysis: Rates of Violence During First-Episode Psychosis (FEP).

BACKGROUND: Most people with psychotic disorders will never commit an act of violence. However, the risk of violence committed by people with schizophrenia is higher than the general population. Violence risk is also known to be highest during the first episode of psychosis compared to later stages of illness. Despite this, there have been no comprehensive reviews conducted in the past 10 years examining rates of violence during FEP. We aimed to provide an updated review of the rate of violence in people with FEP. STUDY DESIGN: Meta-analytical techniques were used to identify pooled proportions of violence according to severity (less serious, serious, severe) and timing of violence (before presentation, at first presentation, after presentation to services). STUDY RESULTS: Twenty-two studies were included. The pooled prevalence was 13.4% (95% CI [9.0%-19.5%]) for any violence, 16.3% (95% CI [9.1%-27.4%]) for less serious violence, 9.7% (95% CI [5.4%-17.0%]) for serious violence and 2.7% for severe violence, regardless of time point. The pooled prevalence of any violence was 11.6% (95% CI [6.8%-18.9%]) before presentation, 20.8% (95% CI [9.8%-38.7%]) at first presentation and 13.3% (95% CI [7.3%-23.0%]) after presentation to services. CONCLUSION: Overall, rates of violence appear to be lower in more recent years. However, due to the high between-study heterogeneity related to study design, the findings must be interpreted with consideration of sample characteristics and other contextual factors. The prevalence of violence remained high at all-time points, suggesting that more targeted, holistic, and early interventions are needed for clinical FEP groups.

The Influence of Personality Disorder Symptoms on Treatment Outcomes in Bipolar Disorder: A Secondary Analysis of a Randomised Controlled Trial: L'influence des symptômes du trouble de la personnalité sur les résultats du traitement dans le trouble bipolaire : Une analyse secondaire d'un essai randomisé contrôlé.

OBJECTIVES: Many people who are diagnosed with bipolar disorder also have comorbid personality disorder. Few studies have explored how personality disorder may influence pharmacological treatment outcomes. The aim of this study was to conduct a secondary analysis of data from a clinical trial of adjunctive nutraceutical treatments for bipolar depression, to determine whether maladaptive personality traits influence treatment outcomes. METHODS: Scores on the Standardised Assessment of Personality - Abbreviated Scale screener were used to classify participants as having bipolar disorder with (n = 119) and without (n = 29) above threshold personality disorder symptoms (personality disorder). Outcome measures included: The Montgomery Åsberg Depression Rating Scale, Clinical Global Impressions and Improvement Severity Scales, Patient Global Impressions-Improvement scale, Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, Social and Occupational Functioning Assessment Scale and Quality of Life and Enjoyment Scale (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form). Generalised estimated equations examined the two-way interactions of personality disorder by time or treatment and investigated personality disorder as a non-specified predictor of outcomes. RESULTS: Over time, the Patient Global Impressions-Improvement scores were significantly higher in those in the personality disorder group. No other significant differences in the two-way interactions of personality disorder by treatment group or personality disorder by time were found. Personality disorder was a significant but non-specific predictor of poorer outcomes on the Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, regardless of time or treatment group. CONCLUSIONS: This study highlights the potential impact of maladaptive personality traits on treatment outcomes and suggests that the presence of comorbid personality disorder may confer additional burden and compromise treatment outcomes. This warrants further investigation as does the corroboration of these exploratory findings. This is important because understanding the impact of comorbid personality disorder on bipolar disorder may enable the development of effective psychological and pharmacotherapeutic options for personalised treatments.

The Cost-Effectiveness of a Novel Online Social Therapy to Maintain Treatment Effects From First-Episode Psychosis Services: Results From the Horyzons Randomized Controlled Trial.

BACKGROUND: Digital interventions have potential applications in promoting long-term recovery and improving outcomes in first-episode psychosis (FEP). This study aimed to evaluate the cost-effectiveness of Horyzons, a novel online social therapy to support young people aged 16-27 years following discharge from FEP services, compared with treatment as usual (TAU) from a healthcare sector and a societal perspective. STUDY DESIGN: A cost-effectiveness analysis (CEA), based on the change in social functioning, and a cost-utility analysis (CUA) using quality-adjusted life years were undertaken alongside a randomized controlled trial. Intervention costs were determined from study records; resources used by patients were collected from a resource-use questionnaire and administrative data. Mean costs and outcomes were compared at 18 months and incremental cost-effectiveness ratios were calculated. Uncertainty analysis using bootstrapping and sensitivity analyses was conducted. STUDY RESULTS: The sample included 170 participants: Horyzons intervention group (n = 86) and TAU (n = 84). Total costs were significantly lower in the Horyzons group compared with TAU from both the healthcare sector (-AU$4789.59; P < .001) and the societal perspective (-AU$5131.14; P < .001). In the CEA, Horyzons was dominant, meaning it was less costly and resulted in better social functioning. In the CUA, the Horyzons intervention resulted in fewer costs but also yielded fewer QALYs. However, group differences in outcomes were not statistically significant. When young people engaged more with the platform, costs were shown to decrease and outcomes improved. CONCLUSIONS: The Horyzons intervention offers a cost-effective approach for improving social functioning in young people with FEP after discharge from early intervention services.

The Study of Ketamine for Youth Depression (SKY-D): study protocol for a randomised controlled trial of low-dose ketamine for young people with major depressive disorder.

BACKGROUND: Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD). METHODS: SKY-D is a double-masked, randomised controlled trial funded by the Australian Government's National Health and Medical Research Council (NHMRC). Participants aged between 16 and 25 years (inclusive) with moderate-to-severe MDD will be randomised to receive either low-dose ketamine (intervention) or midazolam (active control) via subcutaneous injection once per week for 4 weeks. The primary outcome is change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment. Further follow-up assessment will occur at 8 and 26 weeks from treatment commencement to determine whether treatment effects are sustained and to investigate safety outcomes. DISCUSSION: Results from this trial will be important in determining whether low-dose subcutaneous ketamine is an effective treatment for young people with moderate-to-severe MDD. This will be the largest randomised trial to investigate the effects of ketamine to treat depression in young people. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ID: ACTRN12619000683134. Registered on May 7, 2019. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377513 .

Moderated Online Social Therapy for Carers of Early Psychosis Clients in Real-World Settings: Cluster Randomized Controlled Trial.

BACKGROUND: Family carers of youth recovering from early psychosis experience significant stress; however, access to effective family interventions is poor. Digital interventions provide a promising solution. OBJECTIVE: Our objective was to evaluate across multiple Australian early psychosis services the effectiveness of a novel, web-based early psychosis intervention for carers. METHODS: In this cluster randomized controlled trial conducted across multiple Australian early psychosis services, our digital moderated online social therapy for carers (Altitudes) plus enhanced family treatment as usual (TAU) was compared with TAU alone on the primary outcome of perceived stress and secondary outcomes including mental health symptoms and family variables at the 6-month follow-up. RESULTS: Eighty-six caregivers were randomized and data were available for 74 young people in their care. Our primary hypothesis that carers randomized to Altitudes+TAU would report greater improvements in perceived stress at follow-up compared with carers randomized to TAU alone was not supported, with the TAU alone group showing more improvement. For secondary outcomes, the TAU alone group showed improved mindfulness over time. Regardless of group assignment, we observed improvements in satisfaction with life, quality of life, emotional overinvolvement, and burden of care. In contrast, hair cortisol concentration increased. Post hoc analyses revealed more contact with early psychosis services in the intervention group compared to TAU alone and that improvements in perceived stress and social support were associated with use of the intervention in the Altitudes+TAU group. In this study, 80% (12/15) reported a positive experience with Altitudes and 93% (14/15) would recommend it to others. CONCLUSIONS: Our trial did not show a treatment effect for Altitudes in perceived stress. However, our post hoc analysis indicated that the amount of use of Altitudes related to improvements in stress and social support. Additional design work is indicated to continue users' engagement and to significantly improve outcomes in problem-solving, communication, and self-care. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12617000942358; https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12617000942358.

Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders.

The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.

Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?

Objective: Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. Methods: Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (＋4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. Results: There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. Conclusion: There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.

Distress, burden, and wellbeing in siblings of people with mental illness: a mixed studies systematic review and meta-analysis.

BACKGROUND: Family members of people with mental illness (MI) may experience a host of psychological adversities such as increased stress, burden, and reduced wellbeing. However, relatively little is known about siblings. This study aimed to characterise the experience of distress (viz. depressive and anxiety symptoms), burden, and wellbeing in siblings of people with MI. METHODS: Studies reporting on quantitative measures of depression, anxiety, burden, or wellbeing in siblings; and/or qualitative findings on siblings' experience were eligible. The literature search was conducted up until 20th October 2022. RESULTS: Sixty-two studies comprising data from 3744 siblings were included. The pooled mean percentage of depressive symptoms fell in the mild range at 15.71 (k = 28, N = 2187, 95% CI 12.99-18.43) and anxiety symptoms fell in the minimal range at 22.45 (k = 16, N = 1122, 95% CI 17.09-27.80). Moderator analyses indicate that siblings of people with a schizophrenia spectrum disorder experience greater depressive symptoms than siblings of people with other types of MI (ß = -16.38, p < 0.001). Qualitative findings suggest that individuals may be particularly vulnerable during their siblings' illness onset and times of relapse. Limited communication, confusion about MI, and the need to compensate may contribute to siblings' distress and/or burden. Siblings' experience of wellbeing and caregiving were closely related. CONCLUSION: This review highlights the complex psychological experience of siblings and the need for greater research and clinical support for this important yet often overlooked cohort.

An overview of clustering methods with guidelines for application in mental health research.

Cluster analyzes have been widely used in mental health research to decompose inter-individual heterogeneity by identifying more homogeneous subgroups of individuals. However, despite advances in new algorithms and increasing popularity, there is little guidance on model choice, analytical framework and reporting requirements. In this paper, we aimed to address this gap by introducing the philosophy, design, advantages/disadvantages and implementation of major algorithms that are particularly relevant in mental health research. Extensions of basic models, such as kernel methods, deep learning, semi-supervised clustering, and clustering ensembles are subsequently introduced. How to choose algorithms to address common issues as well as methods for pre-clustering data processing, clustering evaluation and validation are then discussed. Importantly, we also provide general guidance on clustering workflow and reporting requirements. To facilitate the implementation of different algorithms, we provide information on R functions and libraries.

A randomised controlled trial of a psychoeducational group intervention for family and friends of young people with borderline personality disorder features.

OBJECTIVE: Preliminary evidence indicates that interventions designed to support family and friends ('carers') of young people with early-stage borderline personality disorder effectively improve carer outcomes. None of these interventions have been tested in a randomised controlled trial. METHOD: This clustered, partially nested, randomised controlled trial was conducted at Orygen, Melbourne, Australia. Carers of young people (aged 15-25 years) with borderline personality disorder features were randomly assigned as a unit in a 1:1 ratio, balanced for young person's sex and age, to receive a 15-day intervention comprising: (1) the three-session, in-person, Making Sense of BPD (MS-BPD) multi-family group programme, plus two self-directed online psychoeducational modules (MS-BPD + Online, n = 38), or (2) the two self-directed online psychoeducational modules alone (Online, n = 41). The primary outcome was 'negative experiences of care', measured with the Experience of Caregiving Inventory, at the 7-week endpoint. RESULTS: A total of 79 carers were randomised (pool of 281, 197 excluded, 94 declined) and 73 carers (51 females [69.9%], Mage = 43.8 years [standard deviation, SD = 12.9], MS-BPD + Online n = 35 [47.9%], Online n = 38 [52.1%]) provided follow-up data and were included in the intent-to-treat analysis. The intent-to-treat (and per protocol) analyses did not find any significant differences between the groups on the primary (d = -0.32; 95% confidence interval = [-17.05, 3.97]) or secondary outcomes. Regardless of treatment group, caregivers improved significantly in their personality disorder knowledge. CONCLUSION: Delivering MS-BPD in conjunction with an online psychoeducational intervention was not found to provide additional benefit over and above access to an online intervention alone. In accordance with national guidelines, carer interventions should be routinely offered by youth mental health services as part of early intervention programmes for borderline personality disorder. Further research is warranted into which interventions work for whom, carers' preferences for support and barriers to care.

The Australian Early Psychosis Collaborative Consortium (AEPCC): Improving Clinical Care in Early Psychosis.

OBJECTIVES: The field of early psychosis has undergone considerable expansion over the last few decades and has a strong evidence base of effectiveness. Like all areas of healthcare, however, early psychosis services need to more consistently deliver higher quality care to achieve better outcomes for patients and families. A national clinical research infrastructure is urgently required to enable the sector to deliver the highest quality care and expand and translate evidence more quickly and efficiently. This paper describes the establishment of the Australian Early Psychosis Collaborative Consortium (AEPCC) that aims to achieve this. CONCLUSION: AEPCC is the first of its kind in Australia (and internationally). It will deliver the required clinical research infrastructure through the implementation of a clinical quality registry, clinical trials and translation network, and lived experience network. AEPCC will provide a critical resource to better understand the state of early psychosis care, and trial new interventions on a scale that has not previously been possible in Australia.

The Impact of N-acetylcysteine on Major Depression: Qualitative Observation and Mixed Methods Analysis of Participant Change during a 12-week Randomised Controlled Trial.

Objective: N-acetylcysteine (NAC) is a novel therapeutic agent with multiple mechanisms of action in the central nervous system and a favourable side effect profile. Clinical evidence indicates that adjunctive NAC may reduce the severity of depressive symptoms in individuals with major depressive disorder (MDD). Methods: A 12-week randomised controlled trial of 2,000 mg/day adjunctive NAC for MDD found no significant improvement at the primary endpoint (week 12) but did see improvements at the post-discontinuation interview (week 16). Within the context of patient-centered treatment, mixed-methods qualitative analysis was also included to explore factors that may determine individual responses to adjunctive NAC treatment. These data were drawn, under blinded conditions, from clinician notes recorded in the case report form. Using the DSM-5 symptom profile for MDD as the initial framework, themes were developed and explored. Frequencies were compared between placebo and NAC groups. Results: Per protocol analysis of individual themes across the six interviews revealed group differences in favour of NAC for overall depressive affect, optimism, relationships and reduced functional impairment. Conclusion: This study provides further evidence for the utility of the mixed methods approach complimenting the primary findings using traditional quantitative analyses, as well as being able to capture additional, often more subtle, evidence of individual symptom-level change that reflects improvement in functional abilities in response to NAC supplementation. The use of mixed methods to explore outcomes from psychiatric studies should be considered in future to work towards improved patient-centred care and both confirm quantitative findings and generate novel hypotheses.