Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin's acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. METHODS: Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures. DISCUSSION: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin's antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

Implementation of caring contacts using patient feedback to reduce suicide-related outcomes following psychiatric hospitalization.

INTRODUCTION: Suicide risk is substantially elevated following discharge from a psychiatric hospitalization. Caring Contacts (CCs) are brief communications delivered post-discharge that can help to improve mental health outcomes. METHOD: This three-phase, mixed-method quality-improvement study revised an existing CC intervention using iterative patient and community feedback. Inpatients (n = 2) and community members (n = 13) participated in focus groups to improve existing CC messages (phases 1 and 2). We piloted these messages among individuals with a suicide-related concern following discharge from an inpatient psychiatric hospitalization (n = 27), sending CCs on days 2 and 7 post-discharge (phase 3). Phase 3 participants completed mental health symptom measures at baseline and day 7, and provided feedback on these messages. RESULTS: Phase 1 and 2 focus group participants indicated preferences for shorter, more visually appealing messages that featured personalized, recovery-focused content. Phase 3 participants demonstrated reductions in depressive symptoms at day-7 post-discharge (-6.4% mean score on Hopkins-Symptom-Checklist, -9.0% mean score on Entrapment-Scale). Most participants agreed that CC messages helped them feel more connected to the hospital and encouraged help-seeking behavior post-discharge. CONCLUSION: This study supports the use of an iterative process, including patient feedback, to improve CC messages and provides further pilot evidence that CC can have beneficial effects.

Sex Differences in the Global Prevalence of Nonsuicidal Self-Injury in Adolescents: A Meta-Analysis.

Importance: Nonsuicidal self-injury (NSSI) is a strong predictor of suicide attempts. The prevalence of NSSI has been increasing among female adolescents in North America and Europe, but less is known about trends in other geographical regions. Objective: To examine sex differences in the prevalence of NSSI among adolescents within and between geographical regions. Data Sources: MEDLINE and PsycINFO were searched using the keywords adolescents, self-injury, sex factors, and synonyms for articles published in English between January 1, 2000, and May 10, 2022. Study Selection: Studies were included if they presented original data (any study design), included adolescents aged 10 to 19 years, reported results stratified by sex, and explicitly defined self-injury as behaviors occurring without suicidal intent. Data Extraction and Synthesis: This meta-analysis was registered with PROSPERO and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles were assessed for quality by 2 independent coders (F.M. and J.A.). A random-effects model was used to calculate prevalence. Data were analyzed from July 2022 to April 2023. Main Outcomes and Measures: The prevalence of NSSI in male and female adolescents within and between regions was the main outcome. Odds ratios (OR) with 95% CIs were calculated for community samples. Results: Eight hundred and two studies were screened, and 38 were included (266 491 participants). Across 17 countries, the pooled prevalence of NSSI was 17.7% (female:male OR, 1.60; 95% CI, 1.29-1.98). NSSI was twice as prevalent among female adolescents compared with male adolescents in North America (OR, 2.49; 95% CI, 2.16-2.86) and Europe (OR, 2.08; 95% CI, 1.69-2.58), but not in Asia (OR, 1.00; 95% CI, 0.71-1.41). Conclusions and Relevance: In this meta-analysis of sex differences in global prevalence of NSSI, the female predominance of NSSI observed among adolescents in North America and Europe aligned with rising rates of suicide in these populations. The comparable prevalence of NSSI among male and female adolescents in Asia also aligned with the lower male-to-female suicide ratio compared with other countries. More research is needed to characterize regional (and potentially cultural) sex differences among adolescents with NSSI to prevent and treat the behavior and to understand the possible interplay with corresponding regional trends in suicide.

Suicide on the Toronto Transit Commission subway system in Canada (1998-2021): a time-series analysis.

Background: The Toronto Transit Commission (TTC) operates the public transit system in Toronto, Canada. From 1954 to 1980, there were 430 suicide deaths/attempts on the TTC subway system. In 2011, TTC implemented Crisis Link, a suicide helpline to connect subway passengers with counsellors. Upstream factors such as media reporting about suicide incidents may also influence suicidal behaviour. Our objectives were to investigate how Crisis Link and media reports about TTC suicide incidents influenced suicide rates. Methods: Suicide data were obtained from the TTC and Coroner, with Crisis Link data provided by Distress Centres of Greater Toronto (1998-2021). Media articles were identified through a database search of Toronto media publications. Interrupted time-series analysis investigated the association between Crisis Link calls, media articles, and quarterly suicide rates on the subway system. Findings: There were 302 suicides on TTC's subway system from 1998 to 2021. The introduction of Crisis Link was associated with a large but non-significant decrease in TTC-related suicide rate in the same quarter (IRR = 0.64, 95% CI = 0.36-1.12). Each subsequent post-Crisis-Link quarter experienced an average 2% increase in suicide rate (IRR = 1.02, 95% CI = 1.004-1.04). Furthermore, for each TTC-related media article in the previous quarter, the suicide rate on the TTC increased by 2% (IRR = 1.02, 95% CI = 1.004-1.04). Interpretation: The Crisis Link helpline was associated with a large but non-significant short-term decrease in suicide rates. However, this outcome was not sustained; this may, in part, be attributable to media reporting which was associated with increased suicides. This should inform suicide prevention policies in Canada and worldwide. Funding: No funding.

Evaluating Population-Level Interventions and Exposures for Suicide Prevention.

Evaluations of interventions targeting the population level are an essential component of the policy development cycle. Pre-post designs are widespread in suicide prevention research but have several significant limitations. To inform future evaluations, our aim is to explore the three most frequently used approaches for assessing the association between population-level interventions or exposures and suicide - the pre-post design, the difference-in-difference design, and Poisson regression approaches. The pre-post design and the difference-in-difference design will only produce unbiased estimates of an association if there are no underlying time trends in the data and there is no additional confounding from other sources. Poisson regression approaches with covariates for time can control for underlying time trends as well as the effects of other confounding factors. Our recommendation is that the default position should be to model the effects of population-level interventions or exposures using regression methods that account for time effects. The other designs should be seen as fall-back positions when insufficient data are available to use methods that control for time effects.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. METHODS: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. RESULTS: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. CONCLUSIONS: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.

A Comparison of Suicides in Public Safety Personnel With Suicides in the General Population in Ontario, 2014 to 2018.

Background: There is conflicting evidence on the suicide rates of different public safety personnel (PSP). There have been few studies that compare suicides in PSP with the general population and none that have used a detailed comparison of coroner records. Aims: The current study estimates suicide rates among different PSP and compares PSP suicides with the general population. Method: We identified coroner records of PSP suicides from January 2014 to December 2018 and compared each one to two matched general population controls. Results: We identified 36 PSP suicides and 72 general population controls. Police had a higher suicide rate than other PSP groups. PSP were more likely to die by firearm, be separated/divorced or married, die in a motor vehicle, have problems at work, and have a PTSD diagnosis. PSP were less likely to die by jumping. Limitations: The study may have not identified all PSP suicides. Apart from the cause of death, data in coroner records are not systematically collected, so information may be incomplete. Conclusion: PSP suicides appear different than the general population. Death records need to have an occupation identifier to enable monitoring of trends in occupational groups, such as PSP.

Self-harm presentations to hospital trauma centre emergency departments during the first year of the COVID-19 pandemic.

The COVID-19 pandemic raised concerns regarding increased suicide-related behaviours. We compared characteristics and counts of Emergency Department (ED) presentations for self-harm, an important suicide-related outcome, during versus prior to the pandemic's first year. We included patients presenting with self-harm to the ED of two trauma centres in Toronto, Canada. Time series models compared intra-pandemic (March 2020-February 2021) presentation counts to predictions from pre-pandemic data. The self-harm proportion of ED presentations was compared between the intra-pandemic period and preceding three years. A retrospective chart review of eligible patients seen from March 2019-February 2021 compared pre- vs. intra-pandemic patient and injury characteristics. While monthly intra-pandemic self-harm counts were largely within expected ranges, the self-harm proportion of total presentations increased. Being widowed (OR=9.46; 95 %CI=1.10-81.08), employment/financial stressors (OR=1.65, 95 %CI=1.06-2.58), job loss (OR=3.83; 95 %CI=1.36-10.76), and chest-stabbing self-harm (OR=2.50; 95 %CI=1.16-5.39) were associated with intra-pandemic presentations. Intra-pandemic self-harm was also associated with Intensive Care Unit (ICU) admission (OR=2.18, 95 %CI=1.41-3.38). In summary, while the number of self-harm presentations to these trauma centres did not increase during the early pandemic, their proportion was increased. The association of intra-pandemic self-harm with variables indicating medically severe injury, economic stressors, and being widowed may inform future suicide and self-harm prevention strategies.

The Development, Progress, and Impact of National Suicide Prevention Strategies Worldwide.

National suicide prevention strategies have been identified as evidence-informed interventions that require multisectoral efforts by governments. This article reviews the rationale for national strategies, the need for a whole-of-government approach, and current progress on national strategies worldwide, including successes and challenges regarding implementation. We highlight the limitations of existing evidence and describe how future research may help to address knowledge gaps. We conclude that national strategies are an important tool for suicide prevention worldwide. However, a more robust evidence base evaluating the impact of strategies on suicide-related outcomes is needed.

Recommendations for supporting healthcare workers' psychological well-being: Lessons learned during the COVID-19 pandemic.

Healthcare workers are at risk of adverse mental health outcomes due to occupational stress. Many organizations introduced initiatives to proactively support staff's psychological well-being in the face of the COVID-19 pandemic. One example is the STEADY wellness program, which was implemented in a large trauma centre in Toronto, Canada. Program implementors engaged teams in peer support sessions, psychoeducation workshops, critical incident stress debriefing, and community-building initiatives. As part of a project designed to illuminate the experiences of STEADY program implementors, this article describes recommendations for future hospital wellness programs. Participants described the importance of having the hospital and its leaders engage in supporting staff's psychological well-being. They recommended ways of doing so (e.g., incorporating conversations about wellness in staff onboarding and routine meetings), along with ways to increase program uptake and sustainability (e.g., using technology to increase accessibility). Results may be useful in future efforts to bolster hospital wellness programming.

Changes in Media Reporting Quality and Suicides Following National Media Engagement on Responsible Reporting of Suicide in Canada: Changements de la Qualité des reportages dans les médias sur les suicides suite à l'engagement des médias nationaux à la déclaration responsable du suicide au Canada.

OBJECTIVE: Responsible media reporting is an accepted strategy for preventing suicide. In 2015, suicide prevention experts launched a media engagement initiative aimed at improving suicide-related reporting in Canada; its impact on media reporting quality and suicide deaths is unknown. METHOD: This pre-post observational study examined changes in reporting characteristics in a random sample of suicide-related articles from major publications in the Greater Toronto Area (GTA) media market. Articles (n = 900) included 450 from the 6-year periods prior to and after the initiative began. We also examined changes in suicide counts in the GTA between these epochs. We used chi-square tests to analyse changes in reporting characteristics and time-series analyses to identify changes in suicide counts. Secondary outcomes focused on guidelines developed by media professionals in Canada and how they may have influenced media reporting quality as well as on the overarching narrative of media articles during the most recent years of available data. RESULTS: Across-the-board improvement was observed in suicide-related reporting with substantial reductions in many elements of putatively harmful content and substantial increases in all aspects of putatively protective content. However, overarching article narratives remained potentially harmful with 55.2% of articles telling the story of someone's death and 20.8% presenting an other negative message. Only 3.6% of articles told a story of survival. After controlling for potential confounders, a nonsignificant numeric decrease in suicide counts was identified after initiative implementation (ω = -5.41, SE = 3.43, t = 1.58, p = 0.12). CONCLUSIONS: We found evidence that a strategy to engage media in Canada changed the content of reporting, but there was only a nonsignificant trend towards fewer suicides. A more fundamental change in media narratives to focus on survival rather than death appears warranted.

Risk-Sensitive Decision-Making and Self-Harm in Youth Bipolar Disorder.

Background: Youth with bipolar disorder (BD) are at high risk for suicide and have high rates of self-harm, which includes both suicide attempts and non-suicidal self-injury. Greater risk-taking has been associated with suicide attempts in youth with major depression, although there are no studies examining the relationship between risk-related decision-making and self-harm in youth with BD. We aimed to examine the association of suicide risk with risk-sensitive decision-making in a controlled sample of youth with BD.Methods: Eighty-one youth with BD (based on DSM-IV criteria; 52 youth with a history of self-harm [BDSH+]; 29 without a history of self-harm [BDSH-]) and 82 age- and sex-matched control youth aged 13-20 years were recruited between 2012 and 2020. Decision-making and risk-taking performance were assessed via the Cambridge Gambling Task within the Cambridge Neuropsychological Test Automated Battery (CANTAB). General linear models were used to examine differences between groups with control for age, sex, and IQ.Results: There was a significant difference in the overall proportion of points bet (F2,157 = 3.87, P = .02, η2 = 0.23) such that BDSH- youth performed better than both BDSH+ (P = .02) and control youth (P = .04). Mean latency was significant (F3,156 = 4.12, P = .017, η2 = 0.03), with BDSH- youth deliberating longer than controls (P = .03). Risk-taking significantly differed between groups (F2,157 = 3.83, P = .02, η2 = 0.23), with BDSH- youth showing greater self-control compared to BDSH+ (P = .01) and control youth (P = .01).Conclusions: BDSH- youth had greater self-control and lower risk-taking. We speculate this finding may be reflective of a compensatory process among BDSH- youth serving a protective role in suicide risk. Future longitudinal studies are needed to examine the temporal association of neurocognition and self-harm among youth with BD.

A narrative review of recent tools and innovations toward automating living systematic reviews and evidence syntheses.

Living reviews are an increasingly popular research paradigm. The purpose of a 'living' approach is to allow rapid collation, appraisal and synthesis of evolving evidence on an important research topic, enabling timely influence on patient care and public health policy. However, living reviews are time- and resource-intensive. The accumulation of new evidence and the possibility of developments within the review's research topic can introduce unique challenges into the living review workflow. To investigate the potential of software tools to support living systematic or rapid reviews, we present a narrative review informed by an examination of tools contained on the Systematic Review Toolbox website. We identified 11 tools with relevant functionalities and discuss the important features of these tools with respect to different steps of the living review workflow. Four tools (NestedKnowledge, SWIFT-ActiveScreener, DistillerSR, EPPI-Reviewer) covered multiple, successive steps of the review process, and the remaining tools addressed specific components of the workflow, including scoping and protocol formulation, reference retrieval, automated data extraction, write-up and dissemination of data. We identify several ways in which living reviews can be made more efficient and practical. Most of these focus on general workflow management, or automation through artificial intelligence and machine-learning, in the screening process. More sophisticated uses of automation mostly target living rapid reviews to increase the speed of production or evidence maps to broaden the scope of the map. We use a case study to highlight some of the barriers and challenges to incorporating tools into the living review workflow and processes. These include increased workload, the need for organisation, ensuring timely dissemination and challenges related to the development of bespoke automation tools to facilitate the review process. We describe how current end-user tools address these challenges, and which knowledge gaps remain that could be addressed by future tool development. Dedicated web presences for automatic dissemination of in-progress evidence updates, rather than solely relying on peer-reviewed journal publications, help to make the effort of a living evidence synthesis worthwhile. Despite offering basic living review functionalities, existing end-user tools could be further developed to be interoperable with other tools to support multiple workflow steps seamlessly, to address broader automatic evidence retrieval from a larger variety of sources, and to improve dissemination of evidence between review updates.

Does knowledge have a half-life? An observational study analyzing the use of older citations in medical and scientific publications.

OBJECTIVES: In the process of scientific progress, prior evidence is both relied on and supplanted by new discoveries. We use the term 'knowledge half-life' to refer to the phenomenon in which older knowledge is discounted in favour of newer research. By quantifying the knowledge half-life, we sought to determine whether research published in more recent years is preferentially cited over older research in medical and scientific articles. DESIGN: An observational study employing a directed, systematic search of current literature. DATA SOURCES: BMJ, PNAS, JAMA, NEJM, The Annals of Internal Medicine, The Lancet, Science and Nature were searched. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eight high-impact medical and scientific journals were sampled examining original research articles from the first issue of every year over a 25-year span (1996-2020). The outcome of interest was the difference between the publication year of the article and references cited, termed 'citation lag'. DATA EXTRACTION AND SYNTHESIS: Analysis of variance was used to identify significant differences in citation lag. RESULTS: A total of 726 articles and 17 895 references were included with a mean citation lag of 7.5±8.4 years. Across all journals, >70% of references had been published within 10 years of the citing article. Approximately 15%-20% of referenced articles were 10-19 years old, and articles more than 20 years old were cited infrequently. Medical journals articles had references with significantly shorter citation lags compared with general science journals (p≤0.01). Articles published before 2009 had references with significantly shorter citation lags compared with those published in 2010-2020 (p<0.001). CONCLUSIONS: This study found evidence of a small increase in the citation of older research in medical and scientific literature over the past decade. This phenomenon deserves further characterisation and scrutiny to ensure that 'old knowledge' is not being lost.

Suicide and Self-Harm Among Immigrant Youth to Ontario, Canada From Muslim Majority Countries: A Population-Based Study.

OBJECTIVE: To examine the association between Muslim religious affiliation and suicide and self-harm presentations among first- and second-generation immigrant youth. METHODS: We performed a population-based cohort study involving individuals aged 12 to 24 years, living in Ontario, who immigrated to Canada between 1 January 2003 and 31 May 2017 (first generation) and those born to immigrant mothers (second generation). Health administrative and demographic data were used to analyze suicide and self-harm presentations. Sex-stratified logistic regression models generated odds ratios (OR) for suicide and negative binomial regression models generated rate ratios (aRR) for self-harm presentations, adjusting for refugee status and time since migration. RESULTS: Of 1,070,248 immigrant youth (50.1% female), there were 129,919 (23.8%) females and 129,446 (24.2%) males from Muslim-majority countries. Males from Muslim-majority countries had lower suicide rates (3.8/100,000 person years [PY]) compared to males from Muslim-minority countries (5.9/100,000 PY) (OR: 0.62, 95% CI, 0.42-0.92). Rates of suicide between female Muslim-majority and Muslim-minority groups were not different (Muslim-majority 1.8/100,000 PY; Muslim-minority 2.2/100,000 PY) (OR: 0.82, 95% CI, 0.46-1.47). Males from Muslim-majority countries had lower rates of self-harm presentations than males from Muslim-minority (<10%) countries (Muslim majority: 12.2/10,000 PY, Muslim-minority: 14.1/10,000 PY) (aRR: 0.82, 95% CI, 0.75, 0.90). Among female immigrants, rates of self-harm presentations were not different among Muslim-majority (30.1/10,000 PY) compared to Muslim-minority (<10%) (32.9/10,000 PY) (aRR: 0.93, 95% CI, 0.87-1.00) countries. For females, older age at immigration conferred a lower risk of self-harm presentations. CONCLUSION: Being a male from a Muslim-majority country may confer protection from suicide and self-harm presentations but the same was not observed for females. Approaches to understanding the observed sex-based differences are warranted.