Proof-of-concept randomized controlled trial of single-session nitrous oxide treatment for refractory bipolar depression: Focus on cerebrovascular target engagement.

BACKGROUND: There remain few efficacious treatments for bipolar depression, which dominates the course of bipolar disorder (BD). Despite multiple studies reporting associations between depression and cerebral blood flow (CBF), little is known regarding CBF as a treatment target, or predictor and/or indicator of treatment response, in BD. Nitrous oxide, an anesthetic gas with vasoactive and putative antidepressant properties, has a long history as a neuroimaging probe. We undertook an experimental medicine paradigm, coupling in-scanner single-session nitrous oxide treatment of bipolar depression with repeated measures of CBF. METHODS: In this double-blind randomized controlled trial, 25 adults with BD I/II and current treatment-refractory depression received either: (1) nitrous oxide (20 min at 25% concentration) plus intravenous saline (n = 12), or (2) medical air plus intravenous midazolam (2 mg total; n = 13). Study outcomes included changes in depression severity (Montgomery-Asberg Depression Rating Scale scores, primary) and changes in CBF (via arterial spin labeling magnetic resonance imaging). RESULTS: There were no significant between-group differences in 24-h post-treatment MADRS change or treatment response. However, the nitrous oxide group had significantly greater same-day reductions in depression severity. Lower baseline regional CBF predicted greater 24-h post-treatment MADRS reductions with nitrous oxide but not midazolam. In region-of-interest and voxel-wise analyses, there was a pattern of regional CBF reductions following treatment with midazolam versus nitrous oxide. CONCLUSIONS: Present findings, while tentative and based on secondary endpoints, suggest differential associations of nitrous oxide versus midazolam with bipolar depression severity and cerebral hemodynamics. Larger studies integrating neuroimaging targets and repeated nitrous oxide treatment sessions are warranted.

'Just because we're younger doesn't mean our opinions should be any less valued': A qualitative study of youth perspectives on a Youth Advisory Council in a mental healthcare context.

INTRODUCTION: Recognition of the importance of youth engagement in youth mental health and/or addiction (MHA) service design and delivery is increasing. Youth Advisory Councils embedded in MHA organizations represent one strategy that allows youth to be involved in MHA at the individual, organization and systemic levels. This level of involvement can facilitate positive outcomes for both the youth and the organization. As these councils become more common, it is important that organizations are prepared to partner with the participating youth. This study uses a descriptive qualitative approach to understand the motivations and expectations of youth with lived experience with MHA concerns who were beginning to work on a Youth Advisory Council in an MHA setting in the Greater Toronto Area. METHODS: Semistructured interviews were conducted with each youth, ages 16-26, on the advisory council (N = 8) to understand their motivations, expectations and goals coming into the work. Interviews were transcribed verbatim and analysed using a reflexive thematic analysis. RESULTS: Analysis resulted in five overarching themes: providing opportunities for youth learning and growth, platforming youth, empowering youth, embracing youth leadership and promoting youth-driven change. The findings illustrate that these youth came into the Youth Advisory Council motivated to create positive change in the mental health system, take on leadership roles and had high expectations for organizational support. Our analyses provide insight for organizations planning and implementing Youth Advisory Councils in the MHA sector with the goal of best supporting youth in driving positive change across the system. CONCLUSION: Youth want to be provided authentic opportunities for their engagement to make a difference. MHA organizations must embrace youth leadership and move towards listening to youth experience and acting on youth recommendations to enhance service design and implementation to improve access and to better meet the needs of youth utilizing these services. PATIENT OR PUBLIC CONTRIBUTIONS: This study incorporated service users, including youth ages 16-26 with lived experience of MHA concerns who served on the Youth Advisory Council at the Family Navigation Project, Sunnybrook. Youth Advisory Council members contributed to two relevant research activities: (1) youth reviewed the draft interview guide before data collection, and their feedback was prioritized in the final version and (2) youth contributed to knowledge translation through contributing to academic conference presentations.

Is the narrative the message? The relationship between suicide-related narratives in media reports and subsequent suicides.

OBJECTIVES: When journalists report on the details of a suicide, the way that they contextualize the meaning of the event (i.e. the 'narrative') can have significant consequences for readers. The 'Werther' and 'Papageno' narrative effects refer to increases and decreases in suicides across populations following media reports on suicidal acts or mastery of crises, respectively. The goal of this study was to investigate the impact of these different narrative constructs on subsequent suicides. METHODS: This study examined the change in suicide counts over time in Toronto, Canada. It used latent difference score analysis, examining suicide-related print media reports in the Toronto media market (2011-2014). Articles (N = 6367) were coded as having a potentially harmful narrative if they described suicide in a celebrity or described a suicide death in a non-celebrity and included the suicide method. Articles were coded as having potentially protective narratives if they included at least one element of protective content (e.g. alternatives to suicide) without including any information about suicidal behaviour (i.e. suicide attempts or death). RESULTS: Latent difference score longitudinal multigroup analyses identified a dose-response relationship in which the trajectory of suicides following harmful 'Werther' narrative reports increased over time, while protective 'Papageno' narrative reports declined. The latent difference score model demonstrated significant goodness of fit and parameter estimates, with each group demonstrating different trajectories of change in reported suicides over time: (χ2[6], N = 6367) = 13.16; χ2/df = 2.19; Akaike information criterion = 97.16, comparative fit index = 0.96, root mean square error of approximation = 0.03. CONCLUSION: Our findings support the notion that the 'narrative' matters when reporting on suicide. Specifically, 'Werther' narratives of suicides in celebrities and suicides in non-celebrities where the methods were described were associated with more subsequent suicides while 'Papageno' narratives of survival and crisis mastery without depictions of suicidal behaviours were associated with fewer subsequent suicides. These results may inform efforts to prevent imitation suicides.

Transitions in mental health and addiction care for youth and their families: a scoping review of needs, barriers, and facilitators.

INTRODUCTION: Transitional-aged youth (TAY) with mental health and/or addictions (MHA) concerns and their families experience significant challenges finding, accessing, and transitioning through needed MHA care. To develop appropriate supports that assist TAY and their families in navigating MHA care, their experiences of transitions in the MHA care system must be better understood. This scoping review identifies and explores the needs, barriers, and facilitators for TAY and their families when transitioning through MHA care. METHODS: This scoping review commenced with a search of five relevant databases. Three research team members were involved in title, abstract, and full-text scanning and data extraction. Sources focusing on TAY anywhere between the ages of 12-29 years and meeting the study objectives were included. Extractions compiled background and narrative information about the nature and extent of the data. Analysis and synthesis of findings involved numerical description of the general information extracted (e.g., numbers of sources by country) and thematic analysis of narrative information extracted (e.g., family involvement in TAY help-seeking). RESULTS: A total of 5894 sources were identified. Following title and abstract scanning, 1037 sources remained for full-text review. A total of 66 sources were extracted. Findings include background information about extracted sources, in addition to five themes that emerged pertaining to barriers and facilitators to access and transitions through care and the needs and roles of TAY and families in supporting help-seeking and care transitions: holistic supports, proactive preparation, empowering TAY and families, collaborative relationships, and systemic considerations. These five themes demonstrate approaches to care that can ensure TAY and families' needs are met, barriers are mitigated, and facilitators are enhanced. CONCLUSION: This review provides essential contextual information regarding TAY with MHA concerns and their families' needs when seeking care. Such findings lend to an enhanced understanding of how MHA programs can support this population's needs, involve family members as appropriate, reduce the barriers experienced, and work to build upon existing facilitators.

Supporting Individuals with Mental Health and/or Addictions Issues Through Patient Navigation: A Scoping Review.

Pathways through the mental health care system can be complex and laden with barriers that prevent individuals from finding the most appropriate care. Navigation has been proposed as a solution for improving access to and transition through complex health care systems. While several MHA navigation programs have emerged in the past decade, no study has explored the core themes of MHA navigation, which was the goal of the current review. A scoping review was conducted; the search yielded 11,525 unique results, of which 26 were entered into extraction and subsequent descriptive and thematic analysis. Barrier reduction, client-centered support, and integrated care emerged as the distinct themes underlying MHA services, and overall, navigation significantly improved outcomes for individuals experiencing MHA issues. These findings may support evidence-based implementation of navigation services and point to a need for increased exploration and reporting of MHA navigation outcomes in the literature.

Inflammatory markers, brain-derived neurotrophic factor, and the symptomatic course of adolescent bipolar disorder: A prospective repeated-measures study.

BACKGROUND: Numerous studies have found elevated pro-inflammatory markers and reduced brain-derived neurotrophic factor (BDNF) during symptomatic episodes of bipolar disorder (BD) in adults. There is a paucity of research examining these markers in youth with BD, or longitudinally in any BD age group. METHODS: 79 adolescents, ages 13-19 years, were enrolled, including 43 symptomatic adolescents with BD and 36 age-matched healthy controls (HC). Blood samples were collected from all participants at intake, and repeatedly from BD participants at pre-specified intervals over the course of two years. Serum was assayed for levels of pro-inflammatory markers (c-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor alpha [TNF-α]), BDNF and the anti-inflammatory marker, IL-10. Week-by-week severity of mood symptoms was assessed using semi-structured interviews. RESULTS: Adolescents with BD provided an average of 4.6 blood samples, on average every 5.0 months. During the most severe symptomatic interval (i.e., highest sum of mood symptom scores) among BD adolescents, levels of CRP (p = 0.01) and pro- to anti-inflammatory ratios (CRP/IL-10; p < 0.001 and IL-6/IL-10; p = 0.046) were significantly greater, and IL-10 levels (p = 0.004) were significantly lower, vs. HC. There were no differences between BD and HC in IL-6, TNF-α or BDNF. Within BD participants, higher BDNF (p = 0.01) and IL-10 levels (p = 0.001) significantly predicted greater burden of mood symptoms over the subsequent epoch. Moreover, higher CRP levels (p = 0.009) at intake predicted greater time to recovery from the index symptomatic episode. CONCLUSIONS: In the first repeated-measures study on this topic in adolescents with BD, we found evidence that CRP, an inexpensive and ubiquitous blood test, may be useful in predicting the prospective course of BD symptoms. Future larger studies are warranted.

Youth voices and experiences regarding a school-based cognitive behavioral therapy skills intervention: lessons for future engagement and adaptation.

BACKGROUND: The Cognitive Behavioral Therapy Skills Intervention (or CBTSI) aims to build mental health literacy and knowledge, allowing youth to build resilience and improve mental health broadly. In Ontario, Canada, youth voice is scant and European studies have largely reported on youth factors supporting stigma reduction, help-seeking intentions and overall satisfaction with a given intervention. Process evaluations and implementation that underpin what youth require to embrace mental health literacy interventions, particularly those that embed key learning principles in the everyday curriculum, have not been broached. The goal of this study is to understand both barriers and facilitators to engagement with the CBTSI (an intervention novel in itself because of the combined mental health plus cognitive behavior therapy (CBT) skills principles embedded in literacy) and the resources and structures that students report requiring, to fully engage with such an intervention. METHODS: Student focus groups were conducted utilizing qualitative interviews that were analyzed thematically. Analysis was informed using principles of pragmatism and analyzed inductively using thematic analysis (Braun and Clarke, Qual Res Psychol 3:77-101, 2006), first looking at the whole and then coding for themes, within an interpretivist framework. Youth were in middle school (grade 7 and 8) in Toronto, Canada who had received the CBTSI. Face to face interview guides with iterative questioning were conducted in February of 2020, and these interviews were audio-recorded and professionally transcribed. Teachers randomly chose a subset of youth whose parents consented to the research to ensure ethno-racial similarity to classroom demographics. RESULTS: There were eight groups with sixty students who participated. Students were 12 to 14 years of age. Major themes were identified: maximizing the opportunities for involvement and self-determination created an atmosphere where confidence and self-compassion could flourish, signalling to the students that they understood and were able to deploy the strategies they were taught; students expressed that the intervention needs to be adapted to enhance personal dignity, respecting both individual wishes and goals in light of the variability in student reported mental health. A model explains the structures and adaptations required to maximize learning based on youth feedback. INTERPRETATION: Mental health literacy incorporating CBT is a promising population-based health promotion intervention. Future adaptations and implementation decisions regarding the CBTSI need to address the wishes and experiences of these youth. Youth voice in this study explored factors that prevent and promote the uptake of the key lessons within the context of existing variability in student mental health that is often found within the context of a regular classroom. The results should be used to adapt the CBTSI as it is disseminated more broadly.

Changes in Perception of Caregiving Experience Following Caregiver Peer Support Within a Mental Health and Addictions Navigation Service.

Interest in navigation services in the mental health and/or addiction (MHA) sphere has grown over the past decade. However, little is known about the value of caregiver peer support in enhancing the navigation process. The Parent Advocate with Lived experience (PAL) service at the Family Navigation Project (FNP) provides peer support to caregivers supporting youth with MHA concerns. Caregivers (n = 26) were asked to rate their perceptions of their caregiver experience retrospectively and then 7 weeks following contact with FNP. A repeated-measures MANOVA comparing participants who had and had not accessed PAL services demonstrated a significant main effect of time, (F(15, 8) = 5.82, p = .008, [Formula: see text] = .916), and a significant time-by-group interaction, (F(15, 8) = 3.69, p = .034, [Formula: see text] = .874), signifying participants who accessed PAL services had more positive perceptions about their caregiving experience compared to participants who had not accessed PAL service. These findings support the future development of caregiver peer support roles within MHA services.

Magnetic resonance-guided focused ultrasound capsulotomy for refractory obsessive compulsive disorder and major depressive disorder: clinical and imaging results from two phase I trials.

Obsessive compulsive disorder (OCD) and major depressive disorder (MDD) are common, often refractory, neuropsychiatric conditions for which new treatment approaches are urgently needed. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel surgical technique permitting incisionless ablative neurosurgery. We examined the safety profile, clinical response, and imaging correlates of MRgFUS bilateral anterior capsulotomy in patients with refractory obsessive compulsive disorder (OCD, N = 6) and major depressive disorder (MDD, n = 6). There were no serious adverse events. Nonserious adverse events included headaches and pin-site swelling in 7/12 patients. The response rate was 4/6 and 2/6 in the OCD and MDD cohorts respectively. To delineate the white-matter tracts impacted by capsulotomy, a normative diffusion MRI-based structural connectome was used, revealing tracts terminating primarily in the frontal pole, medial thalamus, striatum, and medial-temporal lobe. Positron emission tomography (PET) analysis (nine subjects) revealed widespread decreases in metabolism bilaterally in the cerebral hemispheres at 6 months post treatment, as well as in the right hippocampus, amygdala, and putamen. A pretreatment seed-to-voxel resting-state functional magnetic resonance imaging (rs-fMRI) analysis (12 subjects) revealed three voxel clusters significantly associated with eventual clinical response. MRgFUS capsulotomy appears to be safe, well tolerated, and according to these initial results, may be an important treatment option for patients with refractory OCD and MDD. MRgFUS capsulotomy results in both targeted and widespread changes in neural activity, and neuroimaging may hold potential for the prediction of outcome.

Quality of Life Impacts of Bright Light Treatment, Fluoxetine, and the Combination in Patients with Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial.

OBJECTIVE: Bright light therapy is increasingly recommended (alone or in combination with antidepressant medication) to treat symptoms of nonseasonal major depressive disorder (MDD). However, little is known about its impacts on quality of life (QoL), a holistic, patient-valued outcome. METHODS: This study utilizes secondary outcome data from an 8-week randomized, controlled, double blind trial comparing light monotherapy (n = 32), fluoxetine monotherapy (n = 30), and the combination of these (n = 27) to placebo (n = 30). QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Treatment-related differences in QoL improvements were assessed using a repeated measures analysis of variance. The influence of potential predictors of QoL (demographic variables and change in depressive symptoms) were investigated via hierarchical linear regression. RESULTS: Q-LES-Q-SF scores significantly improved across all treatment conditions; however, no significant differences were observed between treatment arms. QoL remained poor relative to community norms by the end of the trial period: Across conditions, 70.6% of participants had significantly impaired QoL at the 8-week assessment. Reduction in depressive scores was a significant predictor of improved QoL, with the final model accounting for 54% of variance in QoL change scores. CONCLUSION: The findings of this study emphasize that improvement in QoL and reduction in depressive symptoms in MDD, while related, cannot be taken to be synonymous. Adjunctive therapies may be required to address unmet QoL needs in patients with MDD receiving antidepressant or light therapies. Further research is required to explore additional predictors of QoL in order to better refine treatments for MDD.

The needs and service preferences of caregivers of youth with mental health and/or addictions concerns.

BACKGROUND: Caregivers experience significant strains as a result of navigating the complex mental health and/or addiction (MHA) system for their youth with MHA issues. We examined the characteristics of Ontario families with youth with MHA issues and their service needs. METHODS: A cross-sectional survey study investigated the characteristics and service needs of families with youth with MHA issues across the province of Ontario, Canada. A total of 840 caregivers were recruited. RESULTS: 259 participants (Mage = 45.94, SD = 7.11) identified as caregiving for at least one youth with MHA issues. The majority of the participants were female (70.7%), married (73.4%), and completed at least some college/Bachelor degree (59.1%). The mean age of youth was 16.72 years (SD = 5.33) and the most frequently reported diagnoses were Depression (30.1%), ADHD (27.8%) and Generalized Anxiety Disorder (21.2%). Regression results demonstrated that presently accessing services, presently seeking services, and higher levels of barriers MHA services were significantly predictive of identifying navigation as helpful for finding appropriate MHA services (χ2(7) = 28.69, p < .001, Nagelkerke R2 = .16). Furthermore, presently accessing services was significantly predictive of identifying case management as helpful (χ2(7) = 29.59, p < .001, Nagelkerke R2 = .156), and of identifying a primary healthcare provider as helpful (χ2(7) = 38.75, p < .001, Nagelkerke R2 = .197) for finding appropriate MHA services. CONCLUSION: Identifying the nature and extent of youth MHA issues, service needs, and family preferences can inform the development of services that address families' needs and lend vital support for accessing services within a complex system.

Identifying the key features and outcomes of family navigation services for mental health and/or addictions concerns: a Delphi study.

BACKGROUND: Family navigation in mental health and addictions is a mode of support aimed at helping families through the complex mental health and addictions system, making well-informed service matches, and engaging with families throughout their care journeys. As family navigation services emerge and grow, understanding their unique features and impacts is essential to defining evaluation measures and driving good outcomes for families. METHODS: This Delphi study investigated the defining features of family mental health and addictions navigation, factors involved in a successful service match, and important outcomes of the process through perspectives of clients and team members of a family navigation program, as well as those of local mental health and/or addictions service providers. In the first phase, participants (n = 41), were asked to respond to a series of prompts pertaining to 1) the key features of a successful family navigation process, 2) the features of good matches between youth or families and the services to which they are navigated, and 3) the outcomes of importance in family navigation. In Phase 2, findings from Phase 1 were presented to participants (n = 32) to select and rank their top ten responses to each prompt. Responses which passed a cut-point were carried into Phase 3, in which participants (n = 20), rated the importance of the remaining items. Items rated as "very" or "extremely" important by 80% or more of participants in Phase 3 had achieved consensus. Intra-class correlation coefficients were calculated to confirm participant agreement on all items having achieved consensus. RESULTS: Sample items with 100% consensus were as follows: navigator determines the best fit by understanding and considering the youth and families' needs, by collaborating with team members and service providers, and by providing individualized suggestions; navigation involves knowledge and understanding of mental health and addictions system and existing services; referred service providers are knowledgeable and up-to-date on evidence-based practice and have multidisciplinary perspectives in service. Overall ICC across all finalized statements following Phase 3 was .84. CONCLUSIONS: Exploring the key features of successful navigation, outcomes of importance to stakeholders, and elements of successful matches can inform the development of navigation services that address families' needs, can support service providers in ensuring well-matched services, and lend vital support to families seeking services within a complex system.

The association between suicide deaths and putatively harmful and protective factors in media reports.

BACKGROUND: Exposure to media reporting on suicide can lead to suicide contagion and, in some circumstances, may also lead to help-seeking behaviour. There is limited evidence for which specific characteristics of media reports mediate these phenomena. METHODS: This observational study examined associations between putatively harmful and protective elements of media reports about suicide in 13 major publications in the Toronto media market and subsequent suicide deaths in Toronto (2011-2014). We used multivariable logistic regression to determine whether specific article characteristics were associated with increases or decreases in suicide deaths in the 7 days after publication, compared with a control window. RESULTS: From 2011 to 2014, there were 6367 articles with suicide as the major focus and 947 suicide deaths. Elements most strongly and independently associated with increased suicides were a statement about the inevitability of suicide (odds ratio [OR] 1.97, confidence interval [CI] 1.07-3.62), about asphyxia by a method other than car exhaust (OR 1.72, CI 1.36-2.18), about suicide by jumping from a building (OR 1.70, CI 1.28-2.26) or about suicide pacts (OR 1.63, CI 1.14-2.35), or a headline that included the suicide method (OR 1.41, CI 1.07-1.86). Elements most strongly and independently associated with decreased suicides were unfavourable characteristics (negative judgments about the deceased; OR 1.85, CI 1.20-2.84), or mentions of railway (OR 1.61, CI 1.10-2.36) and cutting or stabbing (OR 1.59, CI 1.19-2.13) deaths, and individual murder-suicide (OR 1.50, CI 1.23-1.84). INTERPRETATION: This large study identified significant associations between several specific elements of media reports and suicide deaths. It suggests that reporting on suicide can have a meaningful impact on suicide deaths and that journalists and media outlets and organizations should carefully consider the specific content of reports before publication.

Satisfaction with Mental Health Navigation Services: Piloting an Evaluation with a New Scale.

As mental health navigation services continue to be implemented, the need for valid and reliable tools to assess the quality of these services increases. While case managers target individuals with severe mental illness and aim to reduce burden and cost, and increase independence, navigation services target all individuals with a range of mental health and/or substance use issues, with the aim of reducing barriers to treatment and coordinating individualized care. The current study evaluated satisfaction with a navigation service using a new 22-item questionnaire, the Navigation Satisfaction Tool (NAVSAT). Forty clients completed a web-based version of the NAVSAT to evaluate satisfaction with a family mental health navigation service in Toronto, Canada. Descriptive statistics on the sample and range of treatments/services are provided. The NAVSAT has excellent reliability (Cronbach's alpha = 0.96) and face validity. Satisfaction with the following navigation-level factors were the best predictors of overall satisfaction with navigation; the navigator's ability to recommend the appropriate treatment (ß = 0.116, p = .05), intake procedures (ß = 0.364, p = .005), and the principal contact's satisfaction with his/her frequency of contact with the navigator (ß = 0.602, p = .001). Satisfaction with the following provider-level factors were the best predictors of overall satisfaction with the referred service; the referred service's ability to improve the youth's well being (ß = 0.684, p < .001), and the referred service's ability to listen and understand the family's concerns (ß = 0.356, p = .001). The NAVSAT appears to be a reliable tool for measuring satisfaction in the current sample. If these findings are replicated in a larger population serving youth and young adults in transition, the NAVSAT may prove to be a helpful guide for program evaluation and development for navigation and treatment services for this population.

Perinatal suicide in Ontario, Canada: a 15-year population-based study.

BACKGROUND: Death by suicide during the perinatal period has been understudied in Canada. We examined the epidemiology of and health service use related to suicides during pregnancy and the first postpartum year. METHODS: In this retrospective, population-based cohort study, we linked health administrative databases with coroner death records (1994-2008) for Ontario, Canada. We compared sociodemographic characteristics, clinical features and health service use in the 30 days and 1 year before death between women who died by suicide perinatally, women who died by suicide outside of the perinatal period and living perinatal women. RESULTS: The perinatal suicide rate was 2.58 per 100 000 live births, with suicide accounting for 51 (5.3%) of 966 perinatal deaths. Most suicides occurred during the final quarter of the first postpartum year, with highest rates in rural and remote regions. Perinatal women were more likely to die from hanging (33.3% [17/51]) or jumping or falling (19.6% [10/51]) than women who died by suicide non-perinatally (p = 0.04). Only 39.2% (20/51) had mental health contact within the 30 days before death, similar to the rate among those who died by suicide non-perinatally (47.7% [762/1597]; odds ratio [OR] 0.71, 95% confidence interval [CI] 0.40-1.25). Compared with living perinatal women matched by pregnancy or postpartum status at date of suicide, perinatal women who died by suicide had similar likelihood of non-mental health primary care and obstetric care before the index date but had a lower likelihood of pediatric contact (64.5% [20/31] v. 88.4% [137/155] at 30 days; OR 0.24, 95% CI 0.10-0.58). INTERPRETATION: The perinatal suicide rate for Ontario during the period 1994-2008 was comparable to international estimates and represents a substantial component of Canadian perinatal mortality. Given that deaths by suicide occur throughout the perinatal period, all health care providers must be collectively vigilant in assessing risk.

The History and Future of Ablative Neurosurgery for Major Depressive Disorder.

BACKGROUND: There is an urgent need to develop safe and effective treatments for patients with treatment-resistant depression (TRD). Several neurosurgical procedures have been developed to treat the dysfunctional brain circuits implicated in major depression. OBJECTIVES: This review describes the most common ablative procedures used to treat major depressive disorder: anterior cingulotomy, subcaudate tractotomy, limbic leucotomy, and anterior capsulotomy. The efficacy and safety of each are discussed and compared with other current and emerging modalities, including deep brain stimulation (DBS) and MR-guided focused ultrasound (MRgFUS). METHODS: The PubMed and MEDLINE electronic databases were used in this study, through July 2016. Keywords, including "treatment resistant depression," and "ablative neurosurgery," etc. were used to generate reference hits. RESULTS: Approximately a third to half of patients who underwent ablative procedures achieved a treatment response and/or remission. The efficacy and safety profiles corresponding to both ablative procedures and DBS were very similar. CONCLUSIONS: The longitudinal experience with ablative procedures shows that there remains an important role for accurate, discrete lesions in disrupting affective circuitry in the treatment of TRD. New modalities, such as MRgFUS, have the potential to further improve the accuracy of ablative procedures, while enhancing safety by obviating the need for open brain surgery.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. METHODS: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Pharmacological Treatments" is the third of six sections of the 2016 guidelines. With little new information on older medications, treatment recommendations focus on second-generation antidepressants. RESULTS: Evidence-informed responses are given for 21 questions under 4 broad categories: 1) principles of pharmacological management, including individualized assessment of patient and medication factors for antidepressant selection, regular and frequent monitoring, and assessing clinical and functional outcomes with measurement-based care; 2) comparative aspects of antidepressant medications based on efficacy, tolerability, and safety, including summaries of newly approved drugs since 2009; 3) practical approaches to pharmacological management, including drug-drug interactions and maintenance recommendations; and 4) managing inadequate response and treatment resistance, with a focus on switching antidepressants, applying adjunctive treatments, and new and emerging agents. CONCLUSIONS: Evidence-based pharmacological treatments are available for first-line treatment of MDD and for management of inadequate response. However, given the limitations of the evidence base, pharmacological management of MDD still depends on tailoring treatments to the patient.

International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder.

OBJECTIVES: Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder. METHODS: Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which ≥ 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies. RESULTS: Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide. CONCLUSIONS: This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder.

A review of factors associated with greater likelihood of suicide attempts and suicide deaths in bipolar disorder: Part II of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder.

OBJECTIVES: Many factors influence the likelihood of suicide attempts or deaths in persons with bipolar disorder. One key aim of the International Society for Bipolar Disorders Task Force on Suicide was to summarize the available literature on the presence and magnitude of effect of these factors. METHODS: A systematic review of studies published from 1 January 1980 to 30 May 2014 identified using keywords 'bipolar disorder' and 'suicide attempts or suicide'. This specific paper examined all reports on factors putatively associated with suicide attempts or suicide deaths in bipolar disorder samples. Factors were subcategorized into: (1) sociodemographics, (2) clinical characteristics of bipolar disorder, (3) comorbidities, and (4) other clinical variables. RESULTS: We identified 141 studies that examined how 20 specific factors influenced the likelihood of suicide attempts or deaths. While the level of evidence and degree of confluence varied across factors, there was at least one study that found an effect for each of the following factors: sex, age, race, marital status, religious affiliation, age of illness onset, duration of illness, bipolar disorder subtype, polarity of first episode, polarity of current/recent episode, predominant polarity, mood episode characteristics, psychosis, psychiatric comorbidity, personality characteristics, sexual dysfunction, first-degree family history of suicide or mood disorders, past suicide attempts, early life trauma, and psychosocial precipitants. CONCLUSION: There is a wealth of data on factors that influence the likelihood of suicide attempts and suicide deaths in people with bipolar disorder. Given the heterogeneity of study samples and designs, further research is needed to replicate and determine the magnitude of effect of most of these factors. This approach can ultimately lead to enhanced risk stratification for patients with bipolar disorder.