BackgroundApproximately one-third of adults with major depressive disorder (MDD) experience limited response or intolerable side effects with existing pharmacotherapies. As such, innovative treatments targeting novel biological pathways are under investigation. One promising area of research is the gut microbiome and its influence on mood through the microbiota-gut-brain axis. Clinical studies have begun evaluating microbiome-targeted interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) as potential treatments for MDD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to evaluate the evidence for microbiome-targeted interventions in adults with MDD and to provide updated clinical recommendations.MethodsA systematic review of randomized controlled trials (RCTs) and meta-analyses was conducted, assessing interventions such as probiotics, prebiotics, synbiotics, and FMT in adults with MDD. The CANMAT methodology was used to determine levels of evidence and treatment line recommendations, which were presented in a question-and-answer format.ResultsTwenty-three RCTs and eight meta-analyses were included. Probiotics have been the most extensively studied and have demonstrated modest improvements in depressive symptoms, particularly when used in an adjunctive manner. However, recent high-quality trials yielded mixed results. Evidence for prebiotics and FMT was limited and inconclusive, while synbiotics were assessed in only one small RCT. Most interventions were well tolerated, with few serious adverse events.ConclusionsProbiotics may be cautiously considered as third-line adjunctive treatments for MDD, though findings remain inconsistent. There is currently insufficient evidence to recommend prebiotics, synbiotics, or FMT in clinical practice. Further large-scale, well-controlled trials are needed to clarify efficacy, safety, and optimal patient subgroups.

ObjectiveThe effectiveness of current treatment options for depressive symptoms has been widely investigated with acknowledgment that some patients were either not adequately responding to treatment, finding the existing treatment intolerable, or otherwise prefer alternative options. There is increasing interest in microbiota modulation as an alternate form of depression treatment, with a growing number of trials and reviews on the subject published in the last five years. This systematic review aimed to analyze all completed randomized control trials (RCTs) that assessed depression symptoms in adults not using antidepressants, before and after oral methods of microbiota manipulation.MethodAll completed parallel-arm RCTs that assessed depression symptoms in adult participants before and after oral methods of microbiota manipulation were retrieved from four databases, MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials. Data on study and intervention characteristics as well as RCT conclusions were collected independently and in duplicate, and each study's findings were summarized individually. Risk of bias was completed.ResultsWe included 66 RCTs in our review, 34 of which concluded significant differences between the intervention and control group in depressive symptom using different interventions and measures. Of the 66 trials, 54 used probiotic interventions, seven used prebiotic, eight used synbiotic and two used oral fecal microbiota transplantation. Wide variation was observed in studies' design, intervention composition and consumption methods across all 66 RCTs. No statistical synthesis or meta-analyses were possible due to the wide variety of interventions, measures and outcomes.ConclusionsThe heterogeneity of the existing RCTs did not allow for concrete conclusions on whether oral microbiota manipulation interventions are viable alternative treatment options for adults experiencing depression symptoms. We encourage the development of standardized guidelines for the design and reporting of microbiota studies in depression for the possibility of future intervention efficacy testing.

This study seeks to understand the characteristics of individuals with addictions and other mental health (AMH) conditions who had a history of homelessness compared to those who did not experience homelessness.

Patients with severe and persistent mental illness (SPMI) experience significant metabolic side effects from antipsychotic medications, including antipsychotic-induced weight gain (AIWG). This contributes to a high prevalence of obesity, insulin resistance, and type 2 diabetes in this population, ultimately reducing life expectancy. Traditional weight management strategies, such as behavioural interventions, are often less feasible in this group. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for type 2 diabetes, have shown promise in addressing AIWG by reducing weight, improving metabolic parameters, and offering potential neuroprotective and psychiatric benefits. Evidence supports the efficacy of GLP-1RAs in managing AIWG, with studies demonstrating substantial reductions in weight and body mass index without exacerbating psychiatric symptoms. However, access to these medications remains limited due to high costs and restrictive healthcare policies. Expanding access to GLP-1RAs could bridge a critical gap in care for patients with SPMI, improving both physical and mental health outcomes. Future research should focus on evaluating long-term efficacy and cost-effectiveness, particularly in the Canadian healthcare context, to inform policy changes and optimize treatment strategies.

ObjectiveOlder adults with severe mental illness (SMI) represent a complex population with various healthcare needs, even more so when they subsequently develop dementia. While home care (HC) services are advocated for both patients with SMI and dementia, little is known regarding real-life practices, especially for individuals having both conditions. Therefore, we aimed to describe healthcare use and transitions in older adults with SMI across HC user profiles, before and after an incident dementia diagnosis.MethodWe used a retrospective cohort study drawn from Quebec health administrative data on individuals with SMI living in the community, aged 65 and older, and who received a first dementia diagnosis between 2013 and 2015. We described healthcare use 8 months prior and 2 years after the diagnosis, including hospital admissions, visits to the emergency department (ED), and long-term care (LTC) placement.ResultsA total of 3,713 individuals were included, 53% of whom were already receiving HC services before the diagnosis (Group 1), 28% received HC services only after the diagnosis (Group 2), and 19% did not receive any HC (Group 3). While Group 1 showed the highest overall healthcare use before the diagnosis, the most striking increase after the diagnosis was observed for Group 2, catching up with Group 1's levels for many indicators, and even surpassing them in some cases. HC was mainly introduced in the four months following the diagnosis in Group 2. Group 3, while showing the lowest healthcare use throughout the study period, had the second highest mortality rate after Group 1. Groups 2 and 3 were transferred to LTC and died at younger ages than Group 1, in average.ConclusionsThis study highlights potential missed opportunities for intervention, such as an earlier HC introduction which could contribute to prevent an increase in hospitalizations and ED visits, or any HC in Group 3 to mitigate mortality risk and postpone LTC placement.

ObjectiveSmoking has been associated with psychiatric and somatic comorbidities in bipolar disorder (BD) populations. However, studies in older age BD (OABD) populations are sparse. We hypothesized that among individuals with OABD, current and former smokers would have worse psychiatric and somatic comorbidities parameters compared to never smokers.MethodOur study used baseline cross-sectional data from 27 international studies reporting data on adults 50 years old and older ( = 984). Smoking status was categorized into current smokers, former smokers, and never smokers. The distribution of demographic and clinical variables was assessed. The associations between smoking status and the clinical variables were examined using multivariable models that adjusted for age, sex, and study. Multivariable models were repeated, restricting to individuals with and without cardiovascular or respiratory (cardiorespiratory) comorbidity.ResultsOur study sample was 52.8% female with a mean age of 62 years and included 347 (35.3%) never smokers, 222 (22.6%) former smokers, and 415 (42.2%) current smokers. After controlling for age, sex, and study, current depression was more prevalent in former versus never smokers and current versus never smokers. Cardiovascular comorbidity was more prevalent among former than never smokers. More current versus never smokers were taking antipsychotic medications and more current versus never smokers having lifetime substance use disorders. When stratifying by the presence of cardiorespiratory comorbidity, the only statistically significant association was higher functioning in never versus current smokers in participants without cardiorespiratory comorbidity, though non-statistically significant relationships were present between lifetime smoking and depression across strata.ConclusionsThe relationship of smoking with depression and substance use disorders is largely independent of age, sex, and, for the depression relationship, cardiorespiratory comorbidity. More smokers taking antipsychotic medications suggests that smoking is associated with a more severe BD course. Cardiovascular comorbidity may serve as a motivating factor for smoking cessation.

BackgroundDeep brain stimulation targeting the subcallosal cingulate (SCC-DBS) is a promising therapy for treatment-resistant depression. However, the lack of a consistent, rapid behavioural response to SCC-DBS complicates the selection of optimal stimulation settings following implantation, requiring a prolonged and burdensome trial-and-error process. Immediate biomarkers of effective stimulation could overcome this problem.MethodsIn this proof-of-concept study, three patients with SCC-DBS implants were scanned at 3 T using a block-design paradigm in which stimulation alternated between "ON" and "OFF" states in 30-s cycles during a single 6.5-min acquisition. Scans were performed using participants' clinically optimized parameters. Blood-oxygen-level-dependent (BOLD) response maps were generated by contrasting DBS-ON and DBS-OFF conditions, and exploratory correlations with clinical outcome-indexed by percentage reduction in Hamilton Depression Rating Scale scores at 12 months-were also assessed.ResultsContrasting stimulation settings enabled the identification of regional BOLD signal changes associated with DBS, revealing consistent hemodynamic changes in several brain regions during active stimulation. Specifically, the precuneus, posterior cingulate cortex, middle frontal gyrus, and frontal pole exhibited decreased BOLD responses during active DBS, while the occipital cortex, middle temporal gyrus, inferior parietal lobule, and superior frontal gyrus showed increased BOLD responses. Exploratory analysis further suggested a potential correlation between precuneus BOLD signal change and clinical improvement ( = -0.98, p = 0.09).ConclusionThese findings speak to the utility of block-design fMRI with cycling DBS stimulation as a tool to identify objective, brain-based biomarkers of effective SCC-DBS, potentially expediting stimulation parameter selection and therapeutic optimization.

ObjectivesThe objectives of this study were to quantify the associations between preterm birth and adolescent-to-adult psychiatric disorders in the Quebec (Canada) population and to determine whether sex and socioeconomic status (SES) modified this relationship.MethodsThis was an observational cohort study using administrative data from the province of Quebec, Canada. All eligible children born preterm between 1976 and 1995 were identified ( = 100,040) and matched 1:2 with term-born children. Individuals were followed from age 11 years until either incident diagnosis of a psychiatric disorder (attention-deficit/hyperactivity disorder [ADHD], psychosis, bipolar disorder, anxiety, or depression), death, or December 2019. Preterm birth was considered as a binary (<37 weeks gestational age) and categorical exposure (extreme, <28; very, 28-31; moderate-to-late, 32-36 weeks gestational age), in addition to continuous gestational age in weeks. Cox proportional hazard models were applied. Effect-modifying roles of sex and SES were investigated in interaction analyses.ResultsCompared to term-born children, those born preterm had a higher risk of all outcomes, with magnitudes ranging from HR 1.16 for ADHD (95% confidence interval 1.13, 1.19) to 1.05 for anxiety (1.04, 1.07). A dose-response relationship was observed, with increasing risks of ADHD, psychosis, and anxiety as the degree of preterm birth increased. Despite some statistically significant associations, there was no clinically significant evidence of effect modification by sex or SES.ConclusionsChildren born preterm had an increased risk of psychiatric disorders in adolescence-to-adulthood, with similar risks across sexes and socioeconomic strata of the population. Policies for early and continued mental health surveillance in this susceptible group are important to initiate appropriate interventions.

There has been a renewed interest in the use of various psychedelic agents as potential therapies for multiple psychiatric conditions, including post-traumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), to name a few. This follows the recent accumulation of evidence for ketamine pharmacotherapy and a rapid proliferation of clinics/programs offering a variety of ketamine based treatments. A quick glance at the existing evidence, however, reveals a confusing scenario for patients, healthcare providers, and regulators. Overall, there are no standard definitions of what constitutes a psychotherapeutic intervention within a psychedelic-based or a ketamine-based treatment. More specifically, studies have not always distinguished between using a well-known, manualized psychotherapy, providing psychoeducation and psychological support, or providing a therapy specifically to integrate the drug experience in psychedelic trials. Also, it is difficult to determine the role of the psychedelic agent as a stand-alone treatment, and the relative importance (if any) of the psychedelic experience for the desired therapeutic effect. In this perspective, we discuss the evolving landscape of psychedelic-based and ketamine-based treatments, highlighting different therapeutic models, their methodologies, and the need for clearer definitions and rigorous clinical trials. The document proposes three new definitions to improve clarity in evaluating the effects of these agents and the role of psychotherapies. We suggest language that will distinguish: (1) when the drug is used for its pharmacologic effects as a stand-alone treatment, without requiring the psychedelic experience or combined psychotherapy; (2) when the treatment requires the acute psychological effects of the drug to assist psychotherapy and (3) When ketamine or a psychedelic agent is used in combination with a structured, manualized psychotherapy that could be implemented even in the absence of these agents. We hope that this new terminology and definitions will help distinguish the various therapeutic roles of these agents (as stand-alone treatments or in combination with psychotherapies), and facilitate study designs, regulatory pathways, and more informed patient care.

BackgroundTrials of deep brain stimulation (DBS) to the subcallosal cingulate gyrus (SCG) for treatment-resistant depression (TRD) have yielded mixed results. While open-label studies suggest effectiveness, randomized controlled trials (RCTs) have not consistently supported these findings. The study compared the efficacy of active versus sham SCG stimulation for TRD.MethodsParticipants ( = 35) in a major depressive episode and treatment resistance completed a 6-month double blind, crossover RCT, with an 18-month open-label phase. A Balaam design was applied with participants randomized to 1 of 4 stimulation groups over two 3-month phases. The primary outcome was a change in Hamilton Depression Rating Scale (HDRS) score at 6 months, with response defined as ≥50% reduction in HDRS-17 scores.ResultsWhile all groups showed improvement at 3 and 6 months, no significant differences were found among them. The OFF-OFF group had a numerically lower HDRS-17 score compared to the ON-ON group at the end of the RCT. No unexpected adverse events occurred. During the open-label phase, participants showed sustained reduction in HDRS-17 scores at 12, 18, and 24 months post-implantation, with successive observed-case response rates of 65.7%, 69%, and 73.1%, respectively. Improvements in life functioning were also noted.ConclusionsThis trial represents the largest single-centre, sham-controlled study of SCG DBS for TRD in the literature. Although the RCT showed no significant group differences, most participants achieved response during the open-label phase. Safety outcomes aligned with previous trials. Future RCTs should integrate insights from the past decade of DBS for TRD research to optimize outcomes. Key considerations include selecting DBS contact locations that ensure engagement of critical white matter tracts, employing novel and sufficiently long clinical trial designs to account for the non-specific effects of the DBS procedure, as well as incorporating biomarkers to guide DBS programming.

ObjectiveCognitive impairment is a core feature of schizophrenia spectrum disorders. Our previous study on a first-episode psychosis cohort showed that symptoms related to impoverished/disorganized communication and motor impoverishment predicted verbal and working memory scores, respectively. This study aimed to explore those predictors in people across the range of illness chronicity.MethodsWe employed iterative Constrained Principal Component Analysis (iCPCA) to investigate the relationship between 15 cognitive measures from the MATRICS battery, including processing speed, attention, working, verbal and nonverbal memory, reasoning, and problem-solving, and 27 Positive and Negative Syndrome Scale (PANSS) items in 198 outpatients from two sites in Australia and one in Canada. The iCPCA method was used to determine symptoms that reliably predict specific combinations of cognitive measures while controlling Type I errors.ResultsWe found that a verbal memory and learning component was predicted by the PANSS item , and a visual attention/working memory component was linked to the PANSS item .ConclusionsThese accord with our previous findings in an early psychosis sample, that is, negative symptoms of diminished expression are key predictors of cognitive abilities in schizophrenia. Namely, communication and motor impoverishments predicted lower scores on tests of verbal memory, learning, visual attention, and working memory. These findings may inform personalized treatment approaches targeting cognitive deficits and negative symptoms in schizophrenia.

ObjectiveUnderstanding differences in outpatient care before and after mental health hospitalization for adolescents from diverse backgrounds is critical to ensuring effective and responsive care. The objective of the current study was to examine outpatient mental health care in the two years before and 30 days after a mental health hospitalization for adolescents from immigrant, refugee and non-immigrant backgrounds.MethodThis retrospective, population-based cohort study, conducted in British Columbia (BC), Canada, analyzed linked health service utilization data (practitioner billings, hospitalizations) and migration records to track outpatient care before and after mental health hospitalization. The study included adolescents (ages 10-18) with an unscheduled/urgent mental health hospitalization between January 1, 2008 and December 31, 2016 (n = 5,314) from a cohort of adolescents in 10 of the largest school districts in BC (between 1996 and 2016). The main analyses examined outpatient mental health visits (e.g., general practitioner/psychiatrist) (i) in the two years before hospitalization and (ii) in the 30 days after discharge. Sub-analyses focused on outpatient visits with psychiatrists.ResultsOverall, 30.4% had no outpatient mental health visit in the two years before hospitalization and 45.1% had none in the 30 days following discharge. First-generation immigrants and refugees and second-generation immigrant adolescents were significantly less likely than non-immigrants to have had an outpatient mental health visit in the two years before mental health hospitalization (aOR = 0.79, 95% CI, 0.63 to 0.98; aOR = 0.75, 95% CI, 0.61 to 0.93; aOR = 0.40, 95% CI, 0.26 to 0.64). Second-generation immigrant adolescents were significantly more likely than non-immigrants to have had any outpatient mental health visit in the 30 days following hospitalization (aOR = 1.34, 95% CI, 1.09 to 1.65).ConclusionsResults suggest outpatient care before and after mental health hospitalizations is limited for many adolescents in BC and differed by migration background. Implications for meeting standards of care are discussed.

Anticonvulsants are an essential treatment for bipolar disorder; however, there is relatively little known about their use in older age bipolar disorder (OABD). In this paper, which leverages a large international dataset, we aim to 1) describe the use of anticonvulsants in OABD compared to younger age bipolar disorder (YABD; ages <50 years old) and 2) explore any demographic/clinical correlates.

ObjectivePatients with intellectual and developmental disabilities (IDDs) and psychiatric disorders are at higher risk for prolonged hospitalisations. The aim of this study was to examine the prevalence of IDD among long-stay inpatients in Ontario psychiatric beds, and compare the demographic and clinical profiles of long-stay inpatients with and without IDD.MethodsThis Ontario population-based cross-sectional study used linked health administrative databases. All patients over 18 years of age occupying a non-forensic psychiatric inpatient bed in Ontario on September 30th, 2023 were included in the analysis. We examined prevalence of IDD among patients with a length of stay (LOS) ≥ 365 days ('long-stay patients'). Standardised differences were used to compare demographic, clinical, functional, and health care utilisation characteristics between patients with and without IDD.ResultsOf the 1,466 long-stay patients in an Ontario non-forensic psychiatric inpatient bed, 22.0% had IDD. They were younger (mean age 44.3 vs. 47.6) and a higher proportion were male (64.3% vs. 50.1%). In the 2 years prior to admission, a higher proportion of long-stay patients with IDD had a psychotic disorder (73.3% vs. 54.0%), and they had a higher median number of ED visits (5 vs. 3). Long-stay inpatients with IDD were more likely to have difficulty with activities of daily living (39.8% vs. 15.0%), moderate/severe cognitive impairment (63.0% vs. 29.9%) and fewer social contacts in place to support discharge (59.3% vs. 48.6%). While in hospital, a greater proportion of long-stay patients with IDD were subject to restraints (12.4% vs. 8.0%) and seclusion (20.2% vs. 11.2%).ConclusionsAdults with IDD account for more than one in five long-stay psychiatric inpatients and have unique needs including greater cognitive impairment and difficulty caring for themselves. Successful transitions out of hospital require specialised resources and cross-sectoral collaboration.