MDMA-assisted psychotherapy for post-traumatic stress disorder: The devil is in the detail.

Recent years have seen escalating media, public and scientific interest in psychedelic medicine. Australia and New Zealand have been late to this research; however, in the past 2 years, rapid developments suggest that this is changing. Here, we argue for the need to critically review existing evidence in this field to guide future directions. We focus on (±)3,4-methylenedioxymethamphetamine-assisted psychotherapy for post-traumatic stress disorder, currently the most advanced area of clinical psychedelic research. Food and Drug Administration approval of this approach is likely in 2023, based on a series of promising findings. We provide a detailed overview of Phase 2 and 3 studies published to date. We identify several concerns related to this body of evidence, including methodological/design limitations and broader factors - such as robust involvement of advocacy groups in research and reliance on non-government financing leading to simplistic public messaging - that compound the methodological issues identified. We propose steps for future improvement, including the need for large, high-quality, independent efficacy trials with design enhancements, effectiveness trials and for researchers to consider their own engagement with media and public messaging around these modalities. We argue that, notwithstanding promising findings to date, rigorous and dispassionate science is needed to move the field forward and safeguard the welfare of participants.

The Role of Instrumental Swallowing Assessment in Adults in Residential Aged Care Homes: A National Modified Delphi Survey Examining Beliefs and Practices.

Many adults in residential aged care homes (RACHs) live with oropharyngeal dysphagia (OD) and its physiological, psychosocial, and economic sequalae. Timely, evidence-based assessment of OD can help healthcare teams to create OD management plans that optimize consumer health and minimize healthcare costs. Instrumental swallowing assessment (ISA), specifically flexible endoscopic evaluation of swallowing (FEES) and videofluoroscopic swallowing studies (VFSS), is generally accepted to be an important component of dysphagia assessment and management in older adults. However, its role in RACHs has not been empirically examined. This study aimed to explore the role and use of ISA in adults in RACHs from the perspective of speech-language-pathologists (SLPs) experienced in a RACH setting and/or FEES and VFSS. A three-round electronic Delphi study was conducted to guide 58 SLPs in Australia towards consensus using a combination of multiple-choice questions, statements with five-point Likert scale agreement options, and open-ended questions. Participants' responses were analyzed using descriptive statistics and content analysis after each survey round. Feedback about group responses was provided before subsequent surveys. Consensus was defined as 70% or greater agreement. Participants reached consensus about obstacles and facilitators to the use of ISA in RACHs. Participants agreed that FEES was a valuable tool in RACHs and that a mobile service model may have advantages over standard off-site assessment. SLPs believed that appropriate governance processes, infrastructure and education were necessary to develop a safe, high-quality service. These views support equitable access to ISA across settings, aligning with person-centered care, re-ablement, and care-in-place.

Adjunctive Garcinia mangostana Linn. (Mangosteen) Pericarp for Schizophrenia: A 24-Week Double-blind, Randomized, Placebo Controlled Efficacy Trial: Péricarpe d'appoint Garcinia mangostana Linn (mangoustan) pour la schizophrénie : un essai d'efficacité de 24 semaines, à double insu, randomisé et contrôlé par placebo.

OBJECTIVES: Garcinia mangostana Linn. ("mangosteen") pericarp contains bioactive compounds that may target biological pathways implicated in schizophrenia. We conducted a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp, compared to placebo, in the treatment of schizophrenia. METHODS: People diagnosed with schizophrenia or schizoaffective disorder (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), recruited across 2 sites (Brisbane and Victoria, Australia), were randomized to receive 24 weeks of adjunctive mangosteen pericarp (1,000 mg/day) or matched placebo. The primary outcome measure was the Positive and Negative Symptom Scale total score. Secondary outcomes included positive and negative symptoms, general psychopathology, clinical global severity and improvement, participant reported overall improvement, depressive symptoms, functioning, quality of life, and safety data at 24 and 28 weeks (4 weeks postdiscontinuation). Data were collected from July 2016 to February 2019. RESULTS: Baseline assessments were conducted on 148 people (mangosteen = 74, placebo = 74); data analyses were conducted on 136 (92%) participants with postbaseline data. The treatment group had significantly higher symptom severity compared to placebo, and both groups significantly improved on all symptom, functioning, and quality of life measures over time. No between-group differences were found for the rate of change between baseline and 24 or 28 weeks. CONCLUSION: Despite promising preclinical and clinical work, our results do not support mangosteen pericarp extract as an adjunctive treatment for schizophrenia or schizoaffective disorder.

Correction to: A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo.

The original article [1] contained two minor errors.

A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo.

BACKGROUND: A phasic dysregulation of mitochondrial bioenergetics may operate in bipolar disorder, increased in mania and decreased in depression. We aimed to examine efficacy of two add-on treatments in bipolar depression: N-acetylcysteine (NAC) and NAC with a combination of nutraceutical agents that may increase mitochondrial biogenesis. METHODS: A three-arm 16-week, double-blind, randomised, placebo-controlled trial, adjunctive to usual treatment, was conducted. Participants (n = 181) with bipolar disorder and current depressive symptoms were randomised to 2000 mg/day NAC (n = 59), 2000 mg/day NAC with the combination nutraceutical treatment (CT, n = 61), or placebo (n = 61). The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 16. Young Mania Rating Scale, Clinical Global Impression (CGI)-Improvement and CGI-Severity scales, Patient Global Impression scale, Social and Occupational Functioning Assessment Scale (SOFAS), Longitudinal Interval Follow-Up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT), and Quality of Life Enjoyment, and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) were secondary outcomes. RESULTS: One hundred forty-eight participants had post-randomisation data and were analysed (NAC = 52, CT = 47, Placebo = 49). No between-group differences were found for the rate of change between baseline and 16 weeks on any of the clinical and functioning variables. Improvements in MADRS, BDRS, SOFAS, and LIFE-RIFT scores from baseline to the week 20 post-discontinuation visit were significantly greater in the CT group compared to those in the placebo. At week 20, the CGI-I was significantly lower in the CT group versus placebo. Gastrointestinal symptoms were significantly greater in the NAC than in the placebo group. CONCLUSIONS: These overall negative results, with no significant differences between groups detected at the primary outcome but some positive secondary signals, suggest either delayed benefit of the combination or an improvement of symptoms on withdrawal which warrants further exploration regarding the composition, mechanisms, and application of mitochondrial agents in illnesses characterised by mitochondrial dysfunction. TRIAL REGISTRATION: ANZCTR ( ACTRN12612000830897 ).

Individual placement and support for vocational recovery in first-episode psychosis: randomised controlled trial.

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.

Exploring the use of the Hinting Task in first-episode psychosis.

INTRODUCTION: The aim of the study was to elucidate the association between performance-related neurocognitive abilities and Theory of Mind (ToM) as measured by the Hinting Task (HT) performance and investigate the psychometric properties of the HT for use in First-Episode Psychosis (FEP). METHODS: Cross-sectional data of 132 participants with FEP, aged 15-25 years, enrolled in a randomised controlled trial of vocational intervention, were analysed. A comprehensive cognitive battery including social cognitive and neurocognitive measures, a social and occupational functioning measure and psychopathological measures, were used. Psychometric properties were measured through bivariate correlations and associations with neurocognitive domains were assessed through hierarchical regression. RESULTS: Low convergent validity of the HT with other ToM measures, moderate discriminant validity with an emotion recognition task, low predictive validity with social and occupational functioning, and high internal consistency were revealed. HT performance was significantly associated with verbal reasoning and verbal memory. CONCLUSION: Results provide preliminary evidence of low convergent validity and moderate discriminant validity of the HT in FEP, and the influence of verbal reasoning and verbal memory on HT performance, indicating that caution is warranted when employing the HT as a screening tool in isolation for detection of ToM deficits in FEP.

Mediator effects of parameters of inflammation and neurogenesis from a N-acetyl cysteine clinical-trial for bipolar depression.

OBJECTIVE: This study aimed to explore effects of adjunctive treatment with N-acetyl cysteine (NAC) on markers of inflammation and neurogenesis in bipolar depression. METHODS: This is a secondary analysis of a placebo-controlled randomised trial. Serum samples were collected at baseline, week 8, and week 32 of the open-label and maintenance phases of the clinical trial to determine changes in interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following adjunctive NAC treatment, and to explore mediation and moderator effects of the listed markers. RESULTS: Levels of brain-derived neurotrophic factor (BDNF), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukins (IL) -6, 8, or 10 were not significantly changed during the course of the trial or specifically in the open-label and maintenance phases. There were no mediation or moderation effects of the biological factors on the clinical parameters. CONCLUSION: The results suggest that these particular biological parameters may not be directly involved in the therapeutic mechanism of action of adjunctive NAC in bipolar depression.

A controlled trial of implementing a complex mental health intervention for carers of vulnerable young people living in out-of-home care: the ripple project.

BACKGROUND: Out-of-home care (OoHC) refers to young people removed from their families by the state because of abuse, neglect or other adversities. Many of the young people experience poor mental health and social function before, during and after leaving care. Rigorously evaluated interventions are urgently required. This publication describes the protocol for the Ripple project and notes early findings from a controlled trial demonstrating the feasibility of the work. The Ripple project is implementing and evaluating a complex mental health intervention that aims to strengthen the therapeutic capacities of carers and case managers of young people (12-17 years) in OoHC. METHODS: The study is conducted in partnership with mental health, substance abuse and social services in Melbourne, with young people as participants. It has three parts: 1. Needs assessment and implementation of a complex mental health intervention; 2. A 3-year controlled trial of the mental health, social and economic outcomes; and 3. Nested process evaluation of the intervention. RESULTS: Early findings characterising the young people, their carers and case managers and implementing the intervention are available. The trial Wave 1 includes interviews with 176 young people, 52% of those eligible in the study population, 104 carers and 79 case managers. CONCLUSIONS: Implementing and researching an affordable service system intervention appears feasible and likely to be applicable in other places and countries. Success of the intervention will potentially contribute to reducing mental ill-health among these young people, including suicide attempts, self-harm and substance abuse, as well as reducing homelessness, social isolation and contact with the criminal justice system. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000501549 . Retrospectively registered 19 May 2015.

Therapeutic exercises for affecting post-treatment swallowing in people treated for advanced-stage head and neck cancers.

BACKGROUND: Head and neck cancer treatment has developed over the last decade, with improved mortality and survival rates, but the treatments often result in dysphagia (a difficulty in swallowing) as a side effect. This may be acute, resolving after treatment, or remain as a long-term negative sequela of head and neck cancer (HNC) treatment. Interventions to counteract the problems associated with dysphagia include swallowing exercises or modification of diet (bolus texture, size), or both. OBJECTIVES: To determine the effects of therapeutic exercises, undertaken before, during and/or immediately after HNC treatment, on swallowing, aspiration and adverse events such as chest infections, aspiration pneumonia and profound weight loss, in people treated curatively for advanced-stage (stage III, stage IV) squamous cell carcinoma of the head and neck. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 6); MEDLINE; PubMed; Embase; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; Web of Science; ClinicalTrials.gov; ICTRP; speechBITE; Google Scholar; Google and additional sources for published and unpublished trials. The date of the search was 1 July 2016. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of adults with head and neck cancer (stage III, stage IV) who underwent therapeutic exercises for swallowing before, during and/or immediately after HNC treatment to help produce safe and efficient swallowing. The main comparison was therapeutic exercises versus treatment as usual (TAU). Other possible comparison pairs included: therapeutic exercises versus sham exercises and therapeutic exercises plus TAU versus TAU. TAU consisted of reactive management of a patient's dysphagia, when this occurred. When severe, this included insertion of either a percutaneous endoscopic gastroscopy or nasogastric tube for non-oral feeding. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: safety and efficiency of oral swallowing, as measured by reduced/no aspiration; oropharyngeal swallowing efficiency (OPSE) measures, taken from videofluoroscopy swallowing studies; and adverse events, such as chest infections, aspiration pneumonia and profound weight loss. Secondary outcomes were time to return to function (swallowing); self-reported changes to quality of life; changes to psychological well-being - depression, anxiety and stress; patient satisfaction with the intervention; patient compliance with the intervention; and cost-effectiveness of the intervention. MAIN RESULTS: We included six studies (reported as seven papers) involving 326 participants whose ages ranged from 39 to 83 years, with a gender bias towards men (73% to 95% across studies), reflecting the characteristics of patients with HNC. The risk of bias in the studies was generally high.We did not pool data from studies because of significant differences in the interventions and outcomes evaluated. We found a lack of standardisation and consistency in the outcomes measured and the endpoints at which they were evaluated.We found no evidence that therapeutic exercises were better than TAU, or any other treatment, in improving the safety and efficiency of oral swallowing (our primary outcome) or in improving any of the secondary outcomes.Using the GRADE system, we classified the overall quality of the evidence for each outcome as very low, due to the limited number of trials and their low quality. There were no adverse events reported that were directly attributable to the intervention (swallowing exercises). AUTHORS' CONCLUSIONS: We found no evidence that undertaking therapeutic exercises before, during and/or immediately after HNC treatment leads to improvement in oral swallowing. This absence of evidence may be due to the small participant numbers in trials, resulting in insufficient power to detect any difference. Data from the identified trials could not be combined due to differences in the choice of primary outcomes and in the measurement tools used to assess them, and the differing baseline and endpoints across studies.Designing and implementing studies with stronger methodological rigour is essential. There needs to be agreement about the key primary outcomes, the choice of validated assessment tools to measure them and the time points at which those measurements are made.

A signal detection analysis of executive control performance among adolescent inhalant and cannabis users.

BACKGROUND: Inhalant users have multiple comorbid issues (e.g., polydrug use) that complicate identifying inhalant-specific cognitive deficits. OBJECTIVES: The aim of the present study was to use signal detection theory to identify inhalant-specific differences in executive control. METHODS: We examined three well-matched groups: 19 inhalant users, 19 cannabis users, and 19 controls using Stroop and Go/No-Go tasks. RESULTS: Inhalant users demonstrated significantly lower d-prime scores relative to controls, but not cannabis users, on both tasks, suggesting possible executive deficits relative to controls. CONCLUSIONS/IMPORTANCE: The results of this study raise questions regarding inhalant toxicity and the vulnerability of the adolescent brain to drugs of abuse.

The Quik Fix study: a randomised controlled trial of brief interventions for young people with alcohol-related injuries and illnesses accessing emergency department and crisis support care.

BACKGROUND: Alcohol is a major preventable cause of injury, disability and death in young people. Large numbers of young people with alcohol-related injuries and medical conditions present to hospital emergency departments (EDs). Access to brief, efficacious, accessible and cost effective treatment is an international health priority within this age group. While there is growing evidence for the efficacy of brief motivational interviewing (MI) for reducing alcohol use in young people, there is significant scope to increase its impact, and determine if it is the most efficacious and cost effective type of brief intervention available. The efficacy of personality-targeted interventions (PIs) for alcohol misuse delivered individually to young people is yet to be determined or compared to MI, despite growing evidence for school-based PIs. This study protocol describes a randomized controlled trial comparing the efficacy and cost-effectiveness of telephone-delivered MI, PI and an Assessment Feedback/Information (AF/I) only control for reducing alcohol use and related harm in young people. METHODS/DESIGN: Participants will be 390 young people aged 16 to 25 years presenting to a crisis support service or ED with alcohol-related injuries and illnesses (including severe alcohol intoxication). This single blinded superiority trial randomized young people to (i) 2 sessions of MI; (ii) 2 sessions of a new PI or (iii) a 1 session AF/I only control. Participants are reassessed at 1, 3, 6 and 12 months on the primary outcomes of alcohol use and related problems and secondary outcomes of mental health symptoms, functioning, severity of problematic alcohol use, alcohol injuries, alcohol-related knowledge, coping self-efficacy to resist using alcohol, and cost effectiveness. DISCUSSION: This study will identify the most efficacious and cost-effective telephone-delivered brief intervention for reducing alcohol misuse and related problems in young people presenting to crisis support services or EDs. We expect efficacy will be greatest for PI, followed by MI, and then AF/I at 1, 3, 6 and 12 months on the primary and secondary outcome variables. Telephone-delivered brief interventions could provide a youth-friendly, accessible, efficacious, cost-effective and easily disseminated treatment for addressing the significant public health issue of alcohol misuse and related harm in young people. TRIAL REGISTRATION: This trial is registered with the Australian and New Zealand Clinical Trials Registry ACTRN12613000108718.

An analysis of real-time suicidal ideation and its relationship with retrospective reports among young people with borderline personality disorder.

INTRODUCTION: This study aimed to analyze the real-time variability of suicidal ideation intensity and the relationship between real-time and retrospective reports of suicidal ideation made on the Beck Scale for Suicidal Ideation (BSS), among young people with borderline personality disorder (BPD). METHODS: Young people (15-25-year olds) with BPD (N = 46), recruited from two government-funded mental health services, rated the intensity of their suicidal ideation six times per day for 7 days before completing the BSS. RESULTS: For 70% of participants, suicidal ideation changed in intensity approximately five times across the week, both within and between days. BSS ratings were most highly correlated with the highest real-time ratings of suicidal ideation. However, this was not significantly different from the relationship between the BSS and both the average and most recent ratings. Median ratings of suicidal ideation intensity were higher on the BSS compared with an equivalent question asked in real time. CONCLUSION: Findings suggest that young people with BPD experience high levels of fluctuation in their intensity of suicidal ideation across a week and that retrospective reports of suicidal ideation might be more reflective of the most intense experience of suicidal ideation across the week.

Alternating and sequential motion rates in older adults.

BACKGROUND: Alternating motion rate (AMR) and sequential motion rate (SMR) are tests of articulatory diadochokinesis that are widely used in the evaluation of motor speech. However, there are no quality normative data available for adults aged 65 years and older. AIMS: There were two aims: (1) to obtain a representative, normative dataset of diadochokinetic rates from adults aged 65 years and older; and (2) to examine the effects of age and gender on those rates. METHODS & PROCEDURES: Seventy-six healthy adults (65-86 years) were recruited; 45 females and 31 males. Participants were divided across two age groups (65-74 and 75-86 years) and audio-recorded while undertaking AMR (/pa/, /ta/ and /ka/) and SMR (/pataka/). The rate of the first nine syllables for each task was measured using acoustic analysis software, and age and gender effects were examined using a series of generalized linear models. The effect of age on rate variability between groups was also assessed. OUTCOMES & RESULTS: Normative data were obtained for both age groups and across gender. Age was not a significant factor for any task. Males had significantly higher AMR than females (/pa/ p = 0.001, /ta/ p = 0.001, /ka/ p = 0.010). No such gender difference was found for SMR. There was no significant difference in rate variability between the age groups. CONCLUSIONS & IMPLICATIONS: Normative values for AMR and SMR in both genders and across two older age groups were acquired. Diadochokinetic rates outside such values cannot be attributed to normal ageing, so will merit further clinical investigation.

Instrumental swallowing assessment in adults in residential aged care homes: Practice patterns and opportunities.

OBJECTIVE: To describe practice patterns in the use of instrumental swallowing assessment (ISA) for older adults in residential aged care homes (RACHs). METHODS: A retrospective audit of medical records of residents living in RACHs in Melbourne, Australia to extract data on speech-language pathologist (SLP) involvement, indications for ISA and ISA practice patterns. RESULTS: Medical files of 323 residents across four Melbourne facilities were reviewed. 36% (n = 115) of residents were referred to SLP for swallowing assessment. Referral to SLP was related to length of stay (U = 7393.00, p < 0.001), dementia status (χ2 [1] = 7.06, p = 0.008), texture modification (χ2 [1] = 93.34, p < 0.001) and an existing dysphagia diagnosis (χ2 [1] = 112.89, p < 0.001). There were no referrals for ISA and no instances of ISA being used. Among 115 residents who were referred to SLP for swallowing assessment, there were 33 instances where ISA might be clinically relevant according to ISA indicators. CONCLUSIONS: Instrumental swallowing assessment is not being used for the management of swallowing in RACHs in Australia despite a clinical need for ISA and a potential role for ISA to improve swallowing care quality. Lack of timely ISA may fail to meet the complex health-care needs of older adults living with dysphagia in RACHs, increasing their vulnerability to complications of dysphagia and its management.

Bipolar At-Risk Criteria and Risk of Bipolar Disorder Over 10 or More Years.

Importance: Predicting the onset of bipolar disorder (BD) could facilitate preventive treatments. Among risk measures, bipolar at-risk (BAR) criteria have shown promise in predicting onset of bipolar disorder in the first year in clinical cohorts; however, it is not known whether BAR criteria are associated with the onset of BD in the longer term. Objective: To assess the association of BAR criteria with onset of BD over 10 to 13 years follow-up. Design, Setting, and Participants: This prospective cohort study, completed between May 1, 2020, and November 7, 2022, included consenting people seeking help for nonpsychotic major mental health difficulties, including mood, personality, and substance use disorders, who were originally recruited at ages 15 to 25 years from a tertiary youth mental health setting in metropolitan Melbourne, Victoria, Australia, from May 1, 2008, to September 30, 2010. Exposure: Meeting BAR criteria at baseline. Criteria included subthreshold mania, cyclothymic features, subthreshold depression, and family history of BD. A matched clinical comparison group was recruited from the same help-seeking population. Main Outcomes and Measures: The primary outcome was expert consensus diagnosis of BD I or II based on the Mini International Neuropsychiatric Interview, self-reported information collected through online assessments, and linked data on mental health service utilization in Victoria over 10 to 13 years of follow-up. Results: Among 69 eligible participants, follow-up data were available for 60 (88.2%). The mean (SD) age at the end of follow-up was 32.9 (2.8) years, and 49 (81.7%) were women. A total of 28 participants met BAR criteria, and 32 were in the comparison group. In the BAR group, 8 patients (28.6%) developed BD over a mean (SD) of 11.1 (0.7) years of follow-up, and no patients in the comparison group developed BD. The risk of developing BD was higher in the BAR group than in the non-BAR group (χ21 = 70.0; P < .001). The proportions of transitions to BD were equal in the first and second halves of the follow-up period. Conclusions and relevance: In this cohort study of participants seeking care for mental health difficulties, patients meeting the BAR criteria were significantly more likely to transition to BD over a decade after ascertainment compared with patients not meeting the BAR criteria. The findings suggest that those meeting BAR criteria may benefit from longer-term monitoring and support. Evaluation of predictive properties in longer-term studies using a risk measure will help with implementation of BAR criteria in clinical settings.

The specific phenotype of depression in recent onset schizophrenia spectrum disorders: A symptom profile and network comparison to recent onset major depressive disorder without psychotic features.

The specific phenotype of depression in recent-onset schizophrenia spectrum disorders (SSD) and its relation to non-psychotic depression is unknown. Symptom profile and network analysis are complementary statistical techniques that may provide important insights into the presentation and relative importance of individual symptoms that give rise to depression. The aim of the current study was to characterise the profile and network of depressive symptoms in SSD and compare it to individuals with major depressive disorder (MDD) without psychotic features. This study involved analysis of baseline data pertaining to 109 individuals with comorbid SSD and depression and 283 with MDD without psychotic features. Study cohorts were the Psychosis Recent Onset GRoningen Survey (PROGR-S) and Youth Depression Alleviation (YoDA) trials, respectively. Profile and network analyses revealed that SSD and MDD differed in the profile and relative importance of individual depressive symptoms. While reported sadness was the primary hallmark of depression in both SSD and MDD, individuals with depression in SSD were more likely to sleep more, and have lower lassitude and pessimism. While sadness had great importance in MDD and SSD, in SSD but not MDD lassitude, sleep, appetite, concentration difficulties, and inability to feel were important in the network of depressive symptoms. The specific phenotype of depression might be different in SSD compared to MDD. Symptom inequivalence or underlying functional mechanisms in SSD might result in depression in SSD that is similar to MDD with atypical features.

Severe and complex youth depression: Clinical and historical features of young people attending a tertiary mood disorders clinic.

AIM: The concept of severe and complex youth depression has evolved from clinical experience. Here we conducted a file audit study to evaluate supporting data for the construct. METHODS: A retrospective file audit was undertaken with 84 consecutively discharged patients over 6-months from Orygen's Youth Mood Clinic (YMC; 50% female). RESULTS: Over a third (36.9%) were disengaged from vocation and education, with exposure to traumatic events common (84.5%). Almost all patients (91.7%) reported past 2-week suicidal ideation at clinic entry. Hospital emergency departments were the most frequent referral source (31.0%). Most (72.6%) had received previous mental health treatment. Multimorbidity was frequently observed. The presence of a substance use disorder, or ≥ 3 comorbidities were both associated with a greater likelihood of prior suicide attempt. CONCLUSIONS: These data highlight the clinical needs associated with severe and complex depression. Findings have implications for youth experiencing mood disorders attending tertiary and community mental health settings.

Mixed Methods Thematic Analysis of a Randomised Controlled Trial of Adjunctive Mitochondrial Agents for Bipolar Depression.

Objective: There is often a shortfall in recovery following treatment for an episode of bipolar disorder (BD). Exploration of participant's experience provides vital information to enhance statistical outcomes for novel therapy trials. This study used mixed-methods to explore participants' experience of a trial testing N -acetyl cysteine (NAC) and mitochondrially active nutraceuticals for BD depression. Case: report forms from a randomised controlled trial (RCT) of BD depression (n = 148) were analysed using a pragmatic adaption of grounded theory and thematic analysis. Results: Thematic analysis of 148 study participants indicated numerous changes in participant experience over time. For example, perceived environmental stressors reported by participants decreased over the trial in both treatment groups. Quantitative analysis of the themes revealed more positive theme reports in the combination treatment arm compared to the placebo arm and there were more negative themes identified in the placebo arm, compared to the NAC arm. Conclusion: This approach revealed additional results not elucidated in the primary quantitative analysis. This emphasises the value of mixed-methods research in capturing participants' experiences in RCTs and detecting possible latent benefits and risks. Such methods can detect latent target signals in novel therapy trials conducted in BD and generate novel hypotheses.

From rehabilitation to recovery: protocol for a randomised controlled trial evaluating a goal-based intervention to reduce depression and facilitate participation post-stroke.

BACKGROUND: There is much discourse in healthcare about the importance of client-centred rehabilitation, however in the realm of community-based therapy post-stroke there has been little investigation into the efficacy of goal-directed practice that reflects patients' valued activities. In addition, the effect of active involvement of carers in such a rehabilitation process and their subsequent contribution to functional and emotional recovery post-stroke is unclear. In community based rehabilitation, interventions based on patients' perceived needs may be more likely to alter such outcomes. In this paper, we describe the methodology of a randomised controlled trial of an integrated approach to facilitating patient goal achievement in the first year post-stroke. The effectiveness of this intervention in reducing the severity of post-stroke depression, improving participation status and health-related quality of life is examined. The impact on carers is also examined. METHODS/DESIGN: Patients (and their primary carers, if available) are randomly allocated to an intervention or control arm of the study. The intervention is multimodal and aims to screen for adverse stroke sequelae and address ways to enhance participation in patient-valued activities. Intervention methods include: telephone contacts, written information provision, home visitation, and contact with treating health professionals, with further relevant health service referrals as required. The control involves treatment as usual, as determined by inpatient and community rehabilitation treating teams. Formal blinded assessments are conducted at discharge from inpatient rehabilitation, and at six and twelve months post-stroke. The primary outcome is depression. Secondary outcome measures include participation and activity status, health-related quality of life, and self-efficacy. DISCUSSION: The results of this trial will assist with the development of a model for community-based rehabilitation management for stroke patients and their carers, with emphasis on goal-directed practice to enhance home and community participation status. Facilitation of participation in valued activities may be effective in reducing the incidence or severity of post-stroke depression, as well as enhancing the individual's perception of their health-related quality of life. The engagement of carers in the rehabilitation process will enable review of the influence of the broader social context on recovery. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000042347.