BACKGROUND: Chronic homelessness is a problem characterised by longstanding inability to attain or maintain secure accommodation. Longitudinal research with homeless populations is challenging, and randomised controlled trials that evaluate the effectiveness of intensive, case management interventions aimed at improving housing and health-related outcomes for chronically homelessness people are scant. More research is needed to inform programmatic design and policy frameworks in this area. This study protocol details an evaluation of the Journey to Social Inclusion - Phase 2 program, an intervention designed to reduce homelessness and improve outcomes in chronically homeless adults. METHODS/DESIGN: J2SI Phase 2 is a three-year, mixed methods, multi-site, RCT that enrolled 186 participants aged 25 to 50 years between 07 January 2016 and 30 September 2016 in Melbourne. The intervention group (n = 90 recruited) receives the J2SI Phase 2 program, a trauma-informed intervention that integrates intensive case management and service coordination; transition to housing and support to sustain tenancy; and support to build social connections, obtain employment and foster independence. The comparison group (n = 96 recruited) receives standard service provision. Prior to randomisation, participants completed a baseline survey. Follow-up surveys will be completed every six months for three years (six in total). In addition to self-report data on history of homelessness and housing, physical and mental health, substance use, quality of life, social connectedness and public service utilisation, linked administrative data on participants' public services utilisation (e.g., hospitalisation, justice system) will be obtained for the three-year period pre- and post-randomisation. Semi-structured, qualitative interviews will be conducted with a randomly selected subset of participants and service providers at three time-points to explore changes in key outcome variables and to examine individual experiences with the intervention and standard service provision. An economic evaluation of the intervention and associated costs will also be undertaken. DISCUSSION: Results of this trial will provide robust evidence on the effectiveness of J2SI Phase 2 compared to standard service provision. If the intervention demonstrates effectiveness in improving housing, health, quality-of-life, and other social outcomes, it may be considered for broader national and international dissemination to improve outcomes among chronically homeless adults. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000162415 (retrospectively registered 10-February-2016).

BACKGROUND: Metabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples. RESULTS: Significant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (≥ 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p = 0.03). CONCLUSIONS: These findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects.

BACKGROUND: Depressive and anxiety disorders have shown to be associated to premature or advanced biological aging and consequently to adversely impact somatic health. Treatments with antidepressant medication or running therapy are both found to be effective for many but not all patients with mood and anxiety disorders. These interventions may, however, work through different pathophysiological mechanisms and could differ in their impact on biological aging and somatic health. This study protocol describes the design of an unique intervention study that examines whether both treatments are similarly effective in reducing or reversing biological aging (primary outcome), psychiatric status, metabolic stress and neurobiological indicators (secondary outcomes). METHODS: The MOod Treatment with Antidepressants or Running (MOTAR) study will recruit a total of 160 patients with a current major depressive and/or anxiety disorder in a mental health care setting. Patients will receive a 16-week treatment with either antidepressant medication or running therapy (3 times/week). Patients will undergo the treatment of their preference and a subsample will be randomized (1:1) to overcome preference bias. An additional no-disease-no-treatment group of 60 healthy controls without lifetime psychopathology, will be included as comparison group for primary and secondary outcomes at baseline. Assessments are done at week 0 for patients and controls, and at week 16 and week 52 for patients only, including written questionnaires, a psychiatric and medical examination, blood, urine and saliva collection and a cycle ergometer test, to gather information about biological aging (telomere length and telomerase activity), mental health (depression and anxiety disorder characteristics), general fitness, metabolic stress-related biomarkers (inflammation, metabolic syndrome, cortisol) and genetic determinants. In addition, neurobiological alterations in brain processes will be assessed using structural and functional Magnetic Resonance Imaging (MRI) in a subsample of at least 25 patients per treatment arm and in all controls. DISCUSSION: This intervention study aims to provide a better understanding of the impact of antidepressant medication and running therapy on biological aging, metabolic stress and neurobiological indicators in patients with depressive and anxiety disorders in order to guide a more personalized medicine treatment. TRIAL REGISTRATION: Trialregister.nl Number of identification: NTR3460, May 2012.

BACKGROUND: Psychosis is associated with both dysglycaemia and low-grade inflammation, but population-based studies investigating the interplay between these factors are scarce. AIMS: (1) To explore the direction of association between markers of dysglycaemia, inflammation and psychotic experiences (PEs); and (2) To explore whether dysglycaemia moderates and/or mediates the association between inflammation and PEs. METHOD: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were modeled using logistic and linear regression to examine cross-sectional and longitudinal associations between markers of dysglycaemia (ages 9 and 18), interleukin-6 (IL-6) (age 9), and PEs (ages 12 and 18). We tested for an interaction between dysglycaemia and IL-6 on risk of PEs at age 18, and tested whether dysglycaemia mediated the relationship between IL-6 and PEs. RESULTS: Based on 2627 participants, at age 18, insulin resistance (IR) was associated with PEs (adjusted OR = 2.32; 95% CI, 1.37-3.97). IR was associated with IL-6 both cross-sectionally and longitudinally. Interaction analyses under a multiplicative model showed that IR moderated the association between IL-6 at age 9 and PEs at age 18 (adjusted OR for interaction term = 2.18; 95% C.I., 1.06-4.49). Mediation analysis did not support a model of IR mediating the relationship between IL-6 and PEs. IMPLICATIONS: IR is associated with PEs in young people even before the onset of clinical psychosis. Metabolic alterations may interact with childhood inflammation to increase risk of PEs. The findings have implications for clinical practice and future research.

BACKGROUND: Relapse prevention strategies based on monitoring of early warning signs (EWS) are advocated for the management of psychosis. However, there has been a lack of research exploring how staff, carers and patients make sense of the utility of EWS, or how these are implemented in context. AIMS: To develop a multiperspective theory of how EWS are understood and used, which is grounded in the experiences of mental health staff, carers and patients. METHOD: Twenty-five focus groups were held across Glasgow and Melbourne (EMPOWER Trial, ISRCTN: 99559262). Participants comprised 88 mental health staff, 21 patients and 40 carers from UK and Australia (total n = 149). Data were analysed using constructivist grounded theory. RESULTS: All participants appeared to recognise EWS and acknowledged the importance of responding to EWS to support relapse prevention. However, recognition of and acting on EWS were constructed in a context of uncertainty, which appeared linked to risk appraisals that were dependent on distinct stakeholder roles and experiences. Within current relapse management, a process of weighted decision-making (where one factor was seen as more important than others) described how stakeholders weighed up the risks and consequences of relapse alongside the risks and consequences of intervention and help-seeking. CONCLUSIONS: Mental health staff, carers and patients speak about using EWS within a weighted decision-making process, which is acted out in the context of relationships that exist in current relapse management, rather than an objective response to specific signs and symptoms.

Identifying brain alterations that contribute to suicidal thoughts and behaviors (STBs) are important to develop more targeted and effective strategies to prevent suicide. In the last decade, and especially in the last 5 years, there has been exponential growth in the number of neuroimaging studies reporting structural and functional brain circuitry correlates of STBs. Within this narrative review, we conducted a comprehensive review of neuroimaging studies of STBs published to date and summarize the progress achieved on elucidating neurobiological substrates of STBs, with a focus on converging findings across studies. We review neuroimaging evidence across differing mental disorders for structural, functional, and molecular alterations in association with STBs, which converges particularly in regions of brain systems that subserve emotion and impulse regulation including the ventral prefrontal cortex (VPFC) and dorsal PFC (DPFC), insula and their mesial temporal, striatal and posterior connection sites, as well as in the connections between these brain areas. The reviewed literature suggests that impairments in medial and lateral VPFC regions and their connections may be important in the excessive negative and blunted positive internal states that can stimulate suicidal ideation, and that impairments in a DPFC and inferior frontal gyrus (IFG) system may be important in suicide attempt behaviors. A combination of VPFC and DPFC system disturbances may lead to very high risk circumstances in which suicidal ideation is converted to lethal actions via decreased top-down inhibition of behavior and/or maladaptive, inflexible decision-making and planning. The dorsal anterior cingulate cortex and insula may play important roles in switching between these VPFC and DPFC systems, which may contribute to the transition from suicide thoughts to behaviors. Future neuroimaging research of larger sample sizes, including global efforts, longitudinal designs, and careful consideration of developmental stages, and sex and gender, will facilitate more effectively targeted preventions and interventions to reduce loss of life to suicide.

BACKGROUND: First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness; however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N-acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2 g/day for 26 weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups. METHODS/DESIGN: ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15-25 years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration. DISCUSSION: Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ID: ACTRN12618000413224. Registered on 21 March 2018.

Despite the prevalence of methamphetamine (meth) use disorder, research on meth is disproportionately scarce compared to research on other illicit drugs. Existing evidence highlights cognitive deficits as an impediment against daily function and treatment of chronic meth use. Similar deficits are also observed in schizophrenia, and this review therefore draws on schizophrenia research by examining similarities and differences between the two disorders on cognition and related neural findings. While meth use disorder and schizophrenia are two distinct disorders, they are highly co-morbid and share impairments in similar cognitive domains and altered brain structure/function. This narrative review specifically identifies overlapping features such as deficits in learning and memory, social cognition, working memory and inhibitory/impulse control. We report that while working memory deficits are a core feature of schizophrenia, such deficits are inconsistently observed following chronic meth use. Similar structural and functional abnormalities are also observed in cortical and limbic regions between the two disorders, except for cingulate activity where differences are observed. There is growing evidence that targeting cognitive symptoms may improve functional outcome in schizophrenia, with evidence of normalized abnormal brain activity in regions associated with cognition. Considering the overlap between meth use disorder and schizophrenia, targeting cognitive symptoms in people with meth use disorder may also improve treatment outcome and daily function.

The Schizophrenia International Research Society (SIRS) recently held its first North American congress, which took place in Orlando, Florida from 10-14 April 2019. The overall theme of this year's congress was United in Progress - with the aim of cultivating a collaborative effort towards advancing the field of schizophrenia research. Student travel awardees provided reports of the oral sessions and concurrent symposia that took place during the congress. A collection of these reports is summarized and presented below and highlights the main themes and topics that emerged during the congress. In summary, the congress covered a broad range of topics relevant to the field of psychiatry today.

OBJECTIVES: Current research suggests significant disruptions in functional brain networks in individuals with mood disorder, and in those at familial risk. Studies of structural brain networks provide important insights into synchronized maturational change but have received less attention. We aimed to investigate developmental relationships of large-scale brain networks in mood disorder using structural covariance (SC) analyses. METHODS: We conducted SC analysis of baseline structural imaging data from 121 at the time of scanning unaffected high risk (HR) individuals (29 later developed mood disorder after a median time of 4.95 years), and 89 healthy controls (C-well) with no familial risk from the Scottish Bipolar Family Study (age 15-27, 64% female). Voxel-wise analyses of covariance were conducted to compare the associations between each seed region in visual, auditory, motor, speech, semantic, executive-control, salience and default-mode networks and the whole brain signal. SC maps were compared for (a) HR(all) versus C-well individuals, and (b) between those who remained well (HR-well), versus those who subsequently developed mood disorder (HR-MD), and C-well. RESULTS: There were no significant differences between HR(all) and C-well individuals. On splitting the HR group based on subsequent clinical outcome, the HR-MD group however displayed greater baseline SC in the salience and executive-control network, and HR-well individuals showed less SC in the salience network, compared to C-well, respectively (P < .001). CONCLUSIONS: These findings indicate differences in network-level inter-regional relationships, especially within the salience network, which precede onset of mood disorder in those at familial risk.

INTRODUCTION: Depression is highly prevalent and the leading contributor to the burden of disease in young people worldwide, making it an ongoing priority for early intervention. As the current evidence-based interventions of medication and psychological therapy are only modestly effective, there is an urgent need for additional treatment strategies. This paper describes the rationale of the Improving Mood with Physical ACTivity (IMPACT) trial. The primary aim of the IMPACT trial is to determine the effectiveness of a physical activity intervention compared with psychoeducation, in addition to routine clinical care, on depressive symptoms in young people. Additional aims are to evaluate the intervention effects on anxiety and functional outcomes and examine whether changes in physical activity mediate improvements in depressive symptoms. METHODS AND ANALYSIS: The study is being conducted in six youth mental health services across Australia and is using a parallel-group, two-arm, cluster randomised controlled trial design, with randomisation occurring at the clinician level. Participants aged between 12 years and 25 years with moderate to severe levels of depression are randomised to receive, in addition to routine clinical care, either: (1) a physical activity behaviour change intervention or (2) psychoeducation about physical activity. The primary outcome will be change in the Quick Inventory of Depressive Symptomatology, with assessments occurring at baseline, postintervention (end-point) and 6-month follow-up from end-point. Secondary outcome measures will address additional clinical outcomes, functioning and quality of life. IMPACT is to be conducted between May 2014 and December 2019. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Melbourne Human Research Ethics Committee on 8 June 2014 (HREC 1442228). Trial findings will be published in peer-reviewed journals and presented at conferences. Key messages will also be disseminated by the youth mental health services organisation (headspace National Youth Mental Health Foundation). TRIAL REGISTRATION NUMBER: ACTRN12614000772640.

Background: Loneliness is an emerging issue for young people, but yet many interventions to address loneliness in this group focus on providing social opportunities. While these sorts of interventions may appear to increase social connections, loneliness is more related to quality rather than quantity of social relationships. Thus, interventions addressing loneliness should focus on maximizing the quality of current relationships. Together with youth consumers both with mental ill health and those without, we developed a digital smartphone application (app) called +Connect. The 6-week program delivers positive psychology content designed to improve relationship quality. We tested the acceptability, feasibility, and safety of the program in lonely young people with or without a mental health diagnosis of social anxiety disorder. We used a mixed method study design to triangulate pilot quantitative and qualitative data in young people with and without social anxiety disorder (SAD). Method: Nine participants with a diagnosis of social anxiety disorder (Mage = 21.00; SD = 1.41) and 11 participants with no mental health conditions (Mage = 20.36; SD = 2.16) completed the +Connect digital intervention. Results: Those with social anxiety disorder reported less acceptable ratings on outcomes. Feasibility ratings, measured by uptake and app completion, met a priori threshold criteria in both groups. Those with social anxiety disorder yielded more attrition, with almost double the attrition rate compared with those without the disorder. There were no safety issues elicited during the pilot study. In terms of outcomes, exploratory analyses indicated that the app itself is likely to be beneficial rather than cause harm. Our qualitative data indicated both groups reported no negative outcomes and noted that positive outcomes were driven by three processes: reflection, learning, and real-life application. Further exploratory data on usability indicated room for improvement in terms of giving more support for different components of the app (i.e., challenges). Conclusion: The pilot findings of this proof-of-concept app indicates some promise in terms of a second iterative version of +Connect.