Douglas Mental Health University Institute

Suicidality frequently leads to emergency department (ED) visits, yet few interventions are offered in EDs to mitigate suicide risk. This study uses a descriptive interpretative design to evaluate the key components for a successful use of such an intervention, the Stanley-Brown safety plan, in EDs. Semi-structured interviews were conducted with patients and ED clinicians and were analyzed using a thematic analysis approach. Participants’ perspectives revealed 6 key recommendations for a successful use of the safety plan in EDs: (1) personalize the content of the safety plan, (2) offer a variety of formats, (3) avoid periods of high emotional intensity, (4) engage a broad range of professionals in safety planning, (5) use limited time to make meaningful interventions, (6) propose alternative interventions. A change in the ED culture is needed to ensure that the management of suicidal patients in EDs includes brief therapeutic interventions like safety planning, to mitigate suicide risk.

Objective The Eating Disorder Examination Questionnaire (EDE‐Q) is a widely‐used measure of eating‐disorder symptoms. However, inconsistent replication of the subscale structure raises concern about validity. To provide a rigorous test of the EDE‐Q's dimensionality and item‐quality, we applied modern and classical test theory approaches to data obtained from a large, transdiagnostic sample of people with clinical eating disorders. Method We analyzed data from 1197 individuals ( M age = 27.9 years, SD = 10.08, 95% female) with various eating disorders, who had been assessed for treatment at a specialized program. Exploratory analyses (including Parallel Analyses), Confirmatory Factor Analyses (CFA) and graded‐response Item Response Theory (IRT) analyses, were conducted with Mplus. Results Factor analyses showed inappropriate fit to the original EDE‐Q subscales, as well as for alternative 1,2,3, and 4‐factor solutions. Parallel analyses suggested a one‐dimensional structure as best fit. IRT analyses showed substantial variability in EDE‐Q‐item quality and indicated that five items (fear of weight gain, feeling fat, desire to lose weight, importance of weight, importance of shape) were most pertinent to determining severity. The construct validity of the five EDE‐Q items was confirmed by a CFA, showing excellent fit. Discussion Our results suggest that EDE‐Q scores are best interpreted as spanning a one‐factor continuum. IRT results suggest that some items are more pertinent than others for determining eating‐disorder severity. Results could be useful for establishing short EDE‐Q versions, such as a five‐item version, which, in turn, would be helpful for measurement‐based clinical practice and for data‐collection in epidemiological and experimental studies.

Importance Nature-based therapeutic or preventive interventions for mental health are increasingly popular, but their effectiveness for improving mental health is not well documented. Objective To investigate the effectiveness of the Open Sky School Program (École à Ciel Ouvert), a 12-week nature-based intervention for elementary schoolchildren in grades 5 and 6, for reducing mental health symptoms. Design, Setting, and Participants This 2-arm, cluster randomized clinical trial was conducted from February 27 to June 16, 2023, in French-language elementary schools in Quebec, Canada, with green space within 1 km. Participants were teachers and students in grades 5 and 6. Intervention In the intervention group, for 2 hours per week for 12 weeks, classes were taught outdoors in a nearby park or wooded area. Teachers were encouraged to engage students in basic subjects and in 10 or more mental health activities (mindfulness, philosophy, and/or art therapy). Control group schools conducted classes as usual. Main Outcomes and Measures The primary outcome was change in student mental health (internalizing and externalizing symptoms, social problems) based on teacher- and student-reported 30-item Social Behavior Questionnaire (SBQ) scores (3-point scale) from baseline to the immediate postintervention follow-up, assessed in per-protocol and intent-to-treat mixed-model analyses. Secondary outcomes were student self-reported changes in depressive symptoms, positive or negative affect, pro-environmental efforts and/or attitudes, and nature connectedness. Results A total of 33 schools participated (53 teachers, 1015 students), including 16 schools (25 teachers, 515 students) in the intervention group and 17 schools (28 teachers, 500 students) in the control group. Student mean (SD) age was 10.9 (0.75) years; 507 (50.7%) were girls. Per-protocol and intent-to-treat mixed-model analyses showed no differences in mental health symptom change between groups; for example, the adjusted mean difference in SBQ scores between the intervention and control groups for externalizing symptoms was −0.04 (95% CI, −0.13 to 0.04) in the intent-to-treat analysis and −0.06 (95% CI, −0.16 to 0.04) in the per-protocol analysis. Post hoc analyses revealed low mental health symptoms at baseline, with low variability. Slightly greater reductions in symptoms were observed in the intervention group, but only for children with higher mental health symptoms at baseline ( P < .05 for interaction). For example, for children with internalizing symptoms 1 SD above the mean at baseline, internalizing symptoms decreased by 0.38 SD (mean change, −0.15; P < .001) in the intervention group vs the control group. Conclusions and Relevance In this large cluster randomized clinical trial in daily-life elementary school settings, 12 weeks of classes in green space for 2 hours per week did not reduce mental health symptoms in students aged 10 to 12 years in either the per-protocol or the intent-to-treat analysis. However, this low-cost, safe outdoor intervention may provide unmeasured or longer-term benefits for children with higher risk of mental health symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT05662436

Purpose Immunohistochemical (IHC) and histochemical (HC) staining techniques are widely used on human brains that are post-fixed in formalin and stored in brain banks worldwide for varying durations, from months to decades. Understanding the effects of prolonged post-fixation, postmortem interval (PMI), and age on these staining procedures is important for accurately interpreting their outcomes, thereby improving the diagnosis and research of brain disorders afflicting millions of people worldwide. Methods In this study, we conducted both IHC and HC staining on the prefrontal cortex of postmortem human brains post-fixed for 1, 5, 10, 15, and 20 years. For IHC staining, we used two antibodies for each marker: the neuron marker neuronal nuclear antigen (NeuN), the astrocyte marker glial fibrillary acidic protein (GFAP), and the microglia marker ionized calcium-binding adaptor molecule 1 (Iba1). For HC staining, we conducted hematoxylin and eosin Y (H&E), cresyl violet (CV), and Luxol fast blue (LFB) stains to examine neuropils, neurons, and myelin, respectively. Results We observed that the intensity of NeuN, Iba1, CV, or LFB staining was negatively correlated with post-fixation durations. Conversely, we detected a positive correlation between the intensity of GFAP and H&E staining and post-fixation durations. Moreover, there was no correlation between the intensity of NeuN, GFAP, Iba1, H&E, CV, and LFB staining and PMI. Additionally, no correlation was found between these staining intensities and age, except for the intensity of GFAP immunostained by one antiserum, which was negatively correlated with age. Conclusion Taken together, these findings suggest that prolonged post-fixation has both positive and negative effects, while age and PMI exert limited influence on these IHC and HC parameters. Therefore, it is essential to consider these differential changes when interpreting results derived from tissues with extended post-fixation durations. Furthermore, if feasible, we recommend conducting IHC and HC staining on human brains with the same post-fixation time spans and using the most optimal antibodies to mitigate the impact on subsequent analyses.

Attention-deficit/hyperactivity disorder (ADHD) has a significant impact on psychosocial and occupational functioning. Sixty-five percent of children with ADHD continue to meet full or partial diagnostic criteria for ADHD in adulthood, and an estimated 4% of the workforce has a diagnosis of ADHD. We performed a systematic literature review to understand the experience of ADHD in the workplace. Articles were included in the systematic literature review if they reported results on employment outcomes of adults with ADHD. Methodological quality assessment was evaluated using the Mixed Methods Appraisal Tool. Seventy-nine studies were included in this systematic literature review ( n ADHD = 68,275). Results were synthesized into four categories: challenges, strengths, adaptations, and sex differences. Eight themes were included: ADHD symptoms at work, workplace performance, job satisfaction, maladaptive work thoughts and behaviors, interpersonal relationships at work, personal strengths, embracing ADHD, person-environment fit, and accommodations and support. Workers with ADHD can adapt and thrive in employment with the right person-environment fit, and accommodations and support. Many challenges related to ADHD can be remodeled into assets in a workplace environment that promotes flexible working practices and openness to neurodiversity.

A novel radiotracer, [¹¹C]SL25.1188, targets monoamine oxidase-B (MAO-B) enzyme, found primarily in astrocytes, which metabolizes monoamines (including dopamine), particularly in subcortical regions. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. We aimed to test whether levels of MAO-B, an index of astrocyte function are low in the living brains of early psychosis and their high-risk states. Thirty-eight participants including antipsychotic-free/minimally exposed clinical participants with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-min positron emission tomography (PET) scan with [¹¹C]SL25.1188, to measure MAO-B VT, an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B VT (F(2,37.42) = 4.56, p = 0.02, Cohen’s f = 0.49), controlling for tobacco (F (1,37.42) = 5.37, p = 0.03) and cannabis use (F(1,37.42) = 5.11, p = 0.03) with significantly lower MAO-B VT in CHR compared to HV (Cohen’s d = 0.99). We report a significant cannabis effect on MAO-B VT (F(1,39.19) = 12.57, p = 0.001, Cohen’s f = 0.57), with a significant group-by-cannabis interaction (F(2,37.30) = 3.82, p = 0.03, Cohen’s f = 0.45), indicating lower MAO-B VT in cannabis-using clinical groups. Lower MAO-B VT levels were more robust in striatal than cortical regions, in both clinical groups (F(12,46.84) = 2.08, p = 0.04, Cohen’s f = 0.73) and in cannabis users (F(6,46.84) = 6.42, p < 0.001, Cohen’s f = 0.91). Lower MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP clinical populations. Lower MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.

Background Urbanicity is a well‐established risk factor for psychosis. Our recent multi‐national study found an association between urbanicity and clinical psychosis in Northern Europe but not in Southern Europe. In this study, we hypothesized that the effect of current urbanicity on variation of schizotypy would be greater in North‐western Europe countries than in Southern Europe ones. Methods We recruited 1080 individuals representative of the populations aged 18–64 of 14 different sites within 5 countries, classified as either North‐western Europe (England, France, and The Netherlands) with Southern Europe (Spain and Italy). Our main outcome was schizotypy, assessed through the Structured Interview for Schizotypy‐Revised. Our main exposure was current urbanicity, operationalized as local population density. A priori confounders were age, sex, ethnic minority status, childhood maltreatment, and social capital. Schizotypy variation was assessed using multi‐level regression analysis. To test the differential effect of urbanicity between North‐western and Southern European, we added an interaction term between population density and region of recruitment. Results Population density was associated with schizotypy ( β = 0.248,95%CI = 0.122–0.375; p < 0.001). The addition of the interaction term improved the model fit (likelihood test ratio: χ ² = 6.85; p = 0.009). The effect of urbanicity on schizotypy was substantially stronger in North‐western Europe ( β = 0.620,95%CI = 0.362–0.877; p < 0.001) compared with Southern Europe ( β = 0.190,95%CI = 0.083–0.297; p = 0.001). Conclusions The association between urbanicity and both subclinical schizotypy and clinical psychosis, rather than being universal, is context‐specific. Considering that urbanization is a rapid and global process, further research is needed to disentangle the specific factors underlying this relationship.

Background Harsh parenting in early childhood is related to offspring's adverse behavioral outcomes. Due to the scarcity of longitudinal neuroimaging data, few studies have explored the neurobiological underpinnings of this association, focusing on within-person variability. This study examined the temporal associations among harsh parenting, later behavioral problems, and the developmental trajectories of amygdala volume and amygdala resting-state functional connectivity (RSFC) profiles, using longitudinal neuroimaging data. Methods The study was embedded in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. T1-weighted (296 children, 642 scans) and resting-state functional scans (256 children, 509 scans) were collected at ages 4.5, 6, 7.5, and 10.5 years. Amygdala volume and RSFC between the amygdala and six brain regions that have leading roles in emotional regulation were extracted. Harsh parenting at 4.5 years and child behavioral problems at 10.5 years were assessed via parent-report questionnaires. Linear regression and linear mixed models were applied. Results Harsh parenting was associated with more severe externalizing problems in girls ( β = 0.24, 95% CI 0.08–0.40) but not boys ( p int = 0.07). In the overall sample, harsh parenting was associated with the developmental trajectories of amygdala-ACC, amygdala-OFC, and amygdala-DLPFC RSFC. In addition, the developmental trajectory of amygdala-ACC RSFC mediated the harsh parenting–externalizing problems association in girls (indirect effect = 0.06, 95% CI 0.01–0.14). Conclusions Harsh parenting in early childhood was associated with amygdala neurocircuitry development and behavioral problems. The developmental trajectory of amygdala-ACC RSFC is a potential neural mechanism linking harsh parenting and externalizing problems in girls.

Autism spectrum disorder prevalence more than quadrupled in the United States between 2000 and 2020. Ice storm-related prenatal maternal stress (PNMS) predicts autistic-like trait severity in children exposed early in gestation. The objective was to determine the extent to which PNMS influences the severity and trajectory of autistic-like traits in prenatally flood-exposed children at ages 4–7 years and to test moderation by sex and gestational timing. Soon after the June 2008 floods in Iowa, USA, 268 women pregnant during the disaster were assessed for objective hardship, subjective distress, and cognitive appraisal of the experience. When their children were 4, 5½, and 7 years old, mothers completed the Social Communication Questionnaire (SCQ) to assess their children’s autistic-like traits; 137 mothers completed the SCQ for at least one age. The final longitudinal multilevel model showed that the greater the maternal subjective distress, the more severe the child’s autistic-like traits, controlling for objective hardship. The effect of PNMS on rate of change was not significant, and there were no significant main effects or interactions involving sex or timing. Prenatal maternal subjective distress, but not objective hardship or cognitive appraisal, predicted more severe autistic-like traits at age 4, and this effect remained stable through age 7.

Youth suicidality is characterized by its transient nature and diverse causal pathways. Currently, a unified approach searching for final common pathway towards youth suicide has proven unsuccessful. Therefore an exploration of its heterogeneity across different levels is needed. Utilizing 1,624 children with suicidal thoughts and behaviors (STB) and 3,224 healthy controls from the ABCD Study, we first clustered children with STB based on thirty-four cognitive and psychopathological measures capturing suicide-related risk-moderating traits. We then compared environmental and genetic risk factors, and neuroanatomical characteristics of each subtype with controls. We identified five distinct STB subtypes, each revealing unique neuroanatomy, environmental/genetic risks, and persistence patterns. Subtype 1 (Depressive, 9.6%) exhibited the most severe depressive symptoms. Subtype 2 (Externalizing, 20.1%) displayed anatomical and functional alterations in frontoparietal network and increased genetic risk for ADHD. Subtype 3 (Cognitive Deficit, 20.4%) demonstrated lower cognitive performance and widespread white-matter deficits. Subtype 4 (Mild Psychotic, 22.2%) had higher prodromal psychotic symptoms, often unnoticed by parents. Subtype 5 (High Functioning, 27.6%) showed larger total brain volume, better cognition, and higher socio-economic status, contrasting subtypes 1-4. Only Subtypes 1 and 2 demonstrate persistent STB features at 2-year follow-up. Our results suggested that youth suicidal behaviour may result from several distinct bio-behavioral pathways that are identifiable through co-occurring psychopathology, and provide insights into the underlying neural mechanisms and corresponding intervention strategies.

Amyloid accumulation in Alzheimer’s disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD (AppNL-G-F/hMapt), monitoring brain connectivity by means of resting-state fMRI. While the 4-month-old AD mice are indistinguishable from wild-type controls (WT), decreased connectivity in the default-mode network is significant for the AD mice relative to WT mice by 6 months of age and is pronounced by 9 months of age. In a second cohort of 20-month-old mice with persistent functional connectivity deficits for AD relative to WT, we assess the impact of two-months of oral treatment with a silent allosteric modulator of mGluR5 (BMS-984923/ALX001) known to rescue synaptic density. Functional connectivity deficits in the aged AD mice are reversed by the mGluR5-directed treatment. The longitudinal application of fMRI has enabled us to define the preclinical time trajectory of AD-related changes in functional connectivity, and to demonstrate a translatable metric for monitoring disease emergence, progression, and response to synapse-rescuing treatment.

Cerebral asymmetry is fundamental to various cognitive functions but is often disrupted in neuropsychiatric disorders. While adolescent brain growth has been extensively studied, the maturation of brain asymmetry in children and its influencing factors remain poorly understood. Using longitudinal data from 11,000 children aged 10–14 in the ABCD Study, we mapped the developmental trajectory of structural brain asymmetry and revealed significant age-related, modality-specific development patterns, particularly linked to crystallized intelligence and general psychiatric risks. Genetically, structural asymmetry were related to synaptic processes and neurogenesis, likely through asymmetric synaptic pruning. At the macrostructural level, corpus callosum integrity emerged as a key factor in modulating longitudinal asymmetry. Environmentally, favorable perinatal conditions were associated with prolonged corpus callosum development, affecting future asymmetry patterns and cognitive outcomes. These findings underscore the dynamic yet predictable interactions between brain structural asymmetry, its determinants, and cognitive and psychiatric outcomes during this pivotal developmental stage. Our results provide empirical support for the adaptive plasticity theory in cerebral asymmetry and offer new insights into both cognitive maturation and potential risk for early-onset psychiatric disorder risks.

Structural and functional changes of the brain are assumed to contribute to excessive cocaine intake, craving, and relapse in cocaine use disorder (CUD). Epigenetic and transcriptional changes were hypothesized as a molecular basis for CUD-associated brain alterations. Here we performed a multi-omics study of CUD by integrating epigenome-wide methylomic (N = 42) and transcriptomic (N = 25) data from the same individuals using postmortem brain tissue of Brodmann Area 9 (BA9). Of the N = 1 057 differentially expressed genes (p < 0.05), one gene, ZFAND2A, was significantly upregulated in CUD at transcriptome-wide significance (q < 0.05). Differential alternative splicing (AS) analysis revealed N = 98 alternatively spliced transcripts enriched in axon and dendrite extension pathways. Strong convergent overlap in CUD-associated expression deregulation was found between our BA9 cohort and independent replication datasets. Epigenomic, transcriptomic, and AS changes in BA9 converged at two genes, ZBTB4 and INPP5E. In pathway analyses, synaptic signaling, neuron morphogenesis, and fatty acid metabolism emerged as the most prominently deregulated biological processes. Drug repositioning analysis revealed glucocorticoid receptor targeting drugs as most potent in reversing the CUD expression profile. Our study highlights the value of multi-omics approaches for an in-depth molecular characterization and provides insights into the relationship between CUD-associated epigenomic and transcriptomic signatures in the human prefrontal cortex.

Background The legacy of structural and colonial violence has disrupted attachment which has led to the breakdown of healthy relationships within some Indigenous families and communities. A key component of re-establishing attachment is through addressing the effect of historical and on-going colonalism (e.g., intergenerational trauma, cultural connectedness) on individual, family, and community relationships. Methods We conducted a descriptive environmental scan of web-based resources and complemented it with community reports from conversations with key Indigenous stakeholders, to identify and describe what programs are available to Indigenous youth within community settings that focus on fostering healthy relations. Qualitative descriptive summaries were used to synthesize information, summary statistics and frequencies described commonalities across programs, and pattern analysis identified patterns within the data based on demographic factors. In total, forty-seven programs were found across thirty-four organizations. Findings Programs integrated cultivating healthy relationships by focusing on skill training (55%), Indigenous cultural education and activities (42%), and mentorship (25%). Programs described the relationships they focused on in broad terms such as healthy relationships, intergenerational relations, and relationships with the land. Programs differed based on gender and age; programs designed for girls focused on self-empowerment and those for boys on violence prevention training. Programs for younger youth aimed to foster positive identity, those for teenagers on relationship building, and those for older youth on promoting mental health. Conclusion These findings highlight distinct features of healthy relationship programming for Indigenous youth in Canada and offers promising avenues in the future development of such programming based on age and gender. These findings may be of interest to healthcare service research or decision-makers looking to develop healthy relationship programs in Indigenous contexts to develop culturally-relevant and trauma-informed programming to address the effects of historical and on-going colonalism.

Background Research suggests a putative role of the glucocorticoid stress hormone cortisol in the accumulation of adiposity. However, obesity and weight fluctuations may also wear and tear physiological systems promoting adaptation, affecting cortisol secretion. This possibility remains scarcely investigated in longitudinal research. This study tests whether trajectories of body mass index (BMI) across the first 15 years of life are associated with hair cortisol concentration (HCC) measured two years later and whether variability in BMI and timing matter. Methods BMI (kg/m²) was prospectively measured at twelve occasions between age 5 months and 15 years. Hair was sampled at age 17 in 565 participants. Sex, family socioeconomic status, and BMI measured concurrently to HCC were considered as control variables. Results Latent class analyses identified three BMI trajectories: “low-stable” (59.2%, n = 946), “moderate” (32.6%, n = 507), and “high-rising” (8.2%, n = 128). BMI variability was computed by dividing the standard deviation of an individual’s BMI measurements by the mean of these measurements. Findings revealed linear effects, such that higher HCC was noted for participants with moderate BMI trajectories in comparison to low-stable youth (β = 0.10, p = 0.03, 95% confidence interval (CI) = [0.02–0.40]); however, this association was not detected in the high-rising BMI youth (β = −0.02, p = 0.71, 95% CI = [−0.47–0.32]). Higher BMI variability across development predicted higher cortisol (β = 0.17, p = 0.003, 95% CI = [0.10–4.91]), additively to the contribution of BMI trajectories. BMI variability in childhood was responsible for that finding, possibly suggesting a timing effect. Conclusions This study strengthens empirical support for BMI-HCC association and suggests that more attention should be devoted to BMI fluctuations in addition to persistent trajectories of BMI.

Background Early intervention services (EIS) for psychosis have proven highly effective in treating first episode psychosis. Yet, retention or “engagement” in EIS remains highly variable. Dis/engagement as a contested concept and fluid process involving relationships between service providers and service users remains poorly understood. This study aimed to critically evaluate and explain the dynamic interplay of service provider-user relationships in effecting dis/engagement from an early intervention program for psychosis. Methods Forty study participants, 16 service providers and 24 service users (19 current and 5 disengaged) from a Canadian EIS program, were administered semi-structured interviews. Qualitative analysis was conducted using grounded theory methods, with findings captured and reconceptualized in a novel explanatory model. Findings A model of engagement with eight major domains of engagement in EIS positioned along a control-autonomy spectrum was developed from the findings, with Clinical engagement (attendance) and Life engagement (life activities) at opposite ends of the spectrum, interspersed by six intermediate domains: Medication/treatment, Symptoms/illness, Mental health, Physical health/wellness, Communication, and Relationships, each domain bearing uniquely on engagement. Conclusions An examination of service user and service provider perspectives on the various domains identified in the spectrum model, and their dynamic interplay, reveals the complexity of choices faced by service users in engaging and not engaging with services.

Background Schizophrenia spectrum and other psychotic disorders (SSPD) are among the most debilitating of all mental disorders. While the evidence for psychosocial interventions such as cognitive behavioral therapy and peer support has significantly improved, access to these services remains limited. This paper describes a protocol for a pragmatic feasibility study of a digital mental health intervention (HoryzonsCa) that provides access to evidence-based psychosocial interventions, social networking, and clinical and peer support services through a secured, web-based platform for adults diagnosed with SSPD. Objective The objectives are: (1) Adapt and translate HoryzonsCa for implementation in English and French; (2) Develop an implementation and training strategy; (3) Assess the acceptability, safety, and demand of HoryzonsCa; (4) Assess clinical outcomes and perceived impacts; (5) Examine the experiences and process of adapting and implementing HoryzonsCa; (6) Explore the role of sociocultural and demographic factors on HoryzonsCa outcomes and implementation. Methods This feasibility study will use a single-group, pre-post, mixed-methods (QUAN–QUAL convergent) research design, with assessments at baseline and 12 weeks. The study aims to recruit 100 individuals (ages 18–50) diagnosed with SSPD from two healthcare settings in Canada. Data collection includes interview-based psychometric measures, self-reports, focus groups, and interviews with participants. The study will also collect qualitative data from moderators and the research team, and will be conducted entirely remotely. Conclusions This study has been prospectively registered and is underway. It will provide timely information on the feasibility and potential impacts of using digital mental health services for individuals with chronic mental health conditions. Trial Registration ISRCTN12561259; https://doi.org/10.1186/ISRCTN12561259 (250/max 250 words)

Several studies have highlighted increased psychosis risk in migrant and minority ethnic populations. Migration before age 18 appears to increase risk, but further evidence is required. We investigated this issue in a European case-control study. We hypothesized that migration during two key socio-developmental periods, childhood and adolescence, would be most strongly associated with increased odds of psychosis, and that this would be more pronounced for racialised minorities. We used data from five countries in the EUropean network of national schizophrenia networks studying Gene-Environment Interactions [EU-GEI] study. We examined the association between migration in infancy (0–4 years), childhood (5–10 years), adolescence (11–17 years) or adulthood (18+ years) and first episode psychotic disorder. We fitted unadjusted and adjusted logistic regression models to estimate odds ratios [OR] and 95% confidence intervals [95%CI] for associations between age-at-migration and psychosis. In stratified models, we also examined whether these associations varied by ethnicity. The sample consisted of 937 cases and 1,195 controls. Migration at all ages, including infancy (OR: 2.03, 95%CI: 1.01–4.10), childhood (OR: 2.07, 95%CI: 1.04–4.14), adolescence (OR: 3.26, 95%CI: 1.89–5.63) and adulthood (OR: 1.71, 95%CI: 1.21–2.41), was associated with increased odds of psychosis compared with the white majority non-migrant group, after adjustment for all confounders except ethnoracial identity. After additional adjustment for ethnoracial identity, only migration during adolescence remained associated with psychosis (OR 1.94, 95%CI: 1.11–3.36). In stratified analyses, migration during adolescence was associated with increased odds of psychosis in Black (OR: 6.52, 95%CI: 3.00–14.20) and North African (OR: 16.43, 95%CI: 1.88–143.51) groups.Migration during adolescence increased psychosis risk, particularly in racially minoritised young people. This suggests that development of interventions for minoritised young migrants that alleviate stressors associated with migration and acculturation are warranted.

Apolipoprotein B (APOB), a receptor-binding protein present in cholesterol-rich lipoproteins, has been implicated in Alzheimer's disease (AD). High levels of APOB-containing low-density lipoproteins (LDL) are linked to the pathogenesis of both early-onset familial and late-onset sporadic AD. Rare coding mutations in the APOB gene are associated with familial AD, suggesting a role for APOB-bound lipoproteins in the central nervous system. This research explores APOB gene regulation across the AD spectrum using four cohorts: BRAINEAC (elderly control brains), DBCBB (controls, AD brains), ROSMAP (controls, MCI, AD brains), and ADNI (control, MCI, AD clinical subjects). APOB protein levels, measured via mass spectrometry and ELISA, positively correlated with AD pathology indices and cognition, while APOB mRNA levels showed negative correlations. Brain APOB protein levels are also correlated with cortical Aβ levels. A common coding variant in the APOB gene locus affected its expression but didn't impact AD risk or brain cholesterol concentrations, except for 24-S-hydroxycholesterol. Polymorphisms in the CYP27A1 gene, notably rs4674344, were associated with APOB protein levels. A negative correlation was observed between brain APOB gene expression and AD biomarker levels. CSF APOB correlated with Tau pathology in presymptomatic subjects, while cortical APOB was strongly associated with cortical Aβ deposition in late-stage AD. The study discusses the potential link between blood-brain barrier dysfunction and AD symptoms in relation to APOB neurobiology. Overall, APOB's involvement in lipoprotein metabolism appears to influence AD pathology across different stages of the disease.