Suicidal Ideation Amongst University Students During the COVID-19 Pandemic: Time Trends and Risk Factors.

OBJECTIVE: Examine time trends in suicidal ideation in post-secondary students over the first three waves of the COVID-19 pandemic in Canada and identify subpopulations of students with increased risk. METHOD: We analysed 14 months of data collected through repeated cross-sectional deployment of the World Health Organization (WHO) World Mental Health-International College Student (WMH-ICS) survey at the University of British Columbia. Estimated log odds weekly trends of 30-day suicidal ideation (yes/no) were plotted against time with adjustments for demographics using binary logistic generalized additive model (GAM). Risk factors for 30-day suicidal ideation frequency (four categories) were examined using the ordered logistic GAM, with a cubic smoothing spline for modelling time trend in obervation weeks and accounting for demographics. RESULTS: Nearly one-fifth (18.9%) of students experienced suicidal ideation in the previous 30 days. While the estimated log odds suggested that binary suicidal ideation was relatively stable across the course of the pandemic, an initial drop followed by an increasing trend was observed. Risk factors for suicidal ideation frequency during the pandemic included identifying as Chinese or as another non-Indigenous ethnic minority; experiencing current symptoms of depression or anxiety; having a history of suicidal planning or attempts; and feeling overwhelmed but unable to get help as a result of COVID-19. Older age was identified as a protective factor. CONCLUSIONS: The general university student population in our study was relatively resilient with respect to suicidal ideation during the first three waves of the pandemic, but trends indicate the possibility of delayed impact. Specific sub-populations were found to be at increased risk and should be considered for targeted support. Further analyses should be undertaken to continue monitoring suicidality trends throughout the remainder of the pandemic and beyond.

The World Mental Health International College Student Survey in Canada: Protocol for a Mental Health and Substance Use Trend Study.

BACKGROUND: The World Health Organization World Mental Health International College Student (WMH-ICS) initiative aims to screen for mental health and substance use problems among postsecondary students on a global scale as well as to develop and evaluate evidence-based preventive and ameliorative interventions for this population. This protocol paper presents the Canadian version of the WMH-ICS survey, detailing the adapted survey instrument, the unique weekly cross-sectional administration, the multitiered recruitment strategy, and the associated risk mitigation protocols. OBJECTIVE: This paper aims to provide a methodological resource for researchers conducting cross-national comparisons of WMH-ICS data, as well as to serve as a useful guide for those interested in replicating the outlined cross-sectional methodology to better understand how mental health and substance use vary over time among university students. METHODS: The online survey is based on the WMH-ICS survey instrument, modified to the Canadian context by the addition of questions pertaining to Canadian-based guidelines and the translation of the survey to Canadian French. The survey is administered through the Qualtrics survey platform and is sent to an independent stratified random sample of 350 students per site weekly, followed by two reminder emails. Upon survey closure every week, a random subsample of 70 nonresponders are followed up with via phone or through a personal email in an effort to decrease nonresponder bias. The survey is accompanied by an extensive risk mitigation protocol that stratifies respondents by the level of need and provides tailored service recommendations, including a facilitated expedited appointment to student counseling services for those at increased risk of suicide. The anticipated sample size is approximately 5500 students per site per year. RESULTS: In February 2020, the Canadian survey was deployed at the University of British Columbia. This was followed by deployment at Simon Fraser University (November 2020), McMaster University (January 2021), and the University of Toronto (January 2022). Data collection at all 4 sites is ongoing. As of May 6, 2022, 29,503 responses have been collected. CONCLUSIONS: Based on international collaboration, the Canadian version of the WMH-ICS survey incorporates a novel methodological approach centered on the weekly administration of a comprehensive cross-sectional survey to independent stratified random samples of university students. After 27 months of consecutive survey administration, we have developed and refined a survey protocol that has proven effective in engaging students at four Canadian institutions, allowing us to track how mental health and substance use vary over time using an internationally developed university student survey based on the criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/35168.

The L1624Q Variant in SCN1A Causes Familial Epilepsy Through a Mixed Gain and Loss of Channel Function.

Variants of the SCN1A gene encoding the neuronal voltage-gated sodium channel NaV1.1 cause over 85% of all cases of Dravet syndrome, a severe and often pharmacoresistent epileptic encephalopathy with mostly infantile onset. But with the increased availability of genetic testing for patients with epilepsy, variants in SCN1A have now also been described in a range of other epilepsy phenotypes. The vast majority of these epilepsy-associated variants are de novo, and most are either nonsense variants that truncate the channel or missense variants that are presumed to cause loss of channel function. However, biophysical analysis has revealed a significant subset of missense mutations that result in increased excitability, further complicating approaches to precision pharmacotherapy for patients with SCN1A variants and epilepsy. We describe clinical and biophysical data of a familial SCN1A variant encoding the NaV1.1 L1624Q mutant. This substitution is located on the extracellular linker between S3 and S4 of Domain IV of NaV1.1 and is a rare case of a familial SCN1A variant causing an autosomal dominant frontal lobe epilepsy. We expressed wild-type (WT) and L1642Q channels in CHO cells. Using patch-clamp to characterize channel properties at several temperatures, we show that the L1624Q variant increases persistent current, accelerates fast inactivation onset and decreases current density. While SCN1A-associated epilepsy is typically considered a loss-of-function disease, our results put L1624Q into a growing set of mixed gain and loss-of-function variants in SCN1A responsible for epilepsy.

Functional Genomics of Epilepsy and Associated Neurodevelopmental Disorders Using Simple Animal Models: From Genes, Molecules to Brain Networks.

The genetic diagnosis of patients with seizure disorders has been improved significantly by the development of affordable next-generation sequencing technologies. Indeed, in the last 20 years, dozens of causative genes and thousands of associated variants have been described and, for many patients, are now considered responsible for their disease. However, the functional consequences of these mutations are often not studied in vivo, despite such studies being central to understanding pathogenic mechanisms and identifying novel therapeutic avenues. One main roadblock to functionally characterizing pathogenic mutations is generating and characterizing in vivo mammalian models carrying clinically relevant variants in specific genes identified in patients. Although the emergence of new mutagenesis techniques facilitates the production of rodent mutants, the fact that early development occurs internally hampers the investigation of gene function during neurodevelopment. In this context, functional genomics studies using simple animal models such as flies or fish are advantageous since they open a dynamic window of investigation throughout embryonic development. In this review, we will summarize how the use of simple animal models can fill the gap between genetic diagnosis and functional and phenotypic correlates of gene function in vivo. In particular, we will discuss how these simple animals offer the possibility to study gene function at multiple scales, from molecular function (i.e., ion channel activity), to cellular circuit and brain network dynamics. As a result, simple model systems offer alternative avenues of investigation to model aspects of the disease phenotype not currently possible in rodents, which can help to unravel the pathogenic substratum in vivo.

An Efficacy Trial of Carescapes: Home-Based Child-Care Practices and Children's Social Outcomes.

This study reported findings from a longitudinal randomized controlled trial of Carescapes, a professional development program for home-based child-care providers in promoting children's social competence. Participants included 134 child-care providers and 310 children, ages 3-5 years, in Oregon. The Carescapes intervention group made significant improvements in observed caregiver responsiveness and monitoring, and showed decreased caregiver-reported child problem behavior and improved parent-reported peer relationships compared to the control group. Increased caregiver-reported cooperation skills were found for the intervention group at follow-up. No differences in condition were found for kindergarten teacher-reported social-behavioral, classroom, and academic skills. Moderation effects on children's behavior and peer relations were found for child age and exposure to the intervention child care.

Unrelated donor and HLA-identical sibling haematopoietic stem cell transplantation cure chronic granulomatous disease with good long-term outcome and growth.

Chronic granulomatous disease (CGD) causes recurrent infection and inflammatory disease. Despite antimicrobial prophylaxis, patients experience frequent hospitalisations and 50% mortality by 30 years. Haematopoietic stem cell transplantation (HSCT) can cure CGD with resolution of infection and colitis. This study reports the survival and long-term outcome in 20 conditioned patients treated between 1998 and 2007, using 10 matched sibling (MSD) and 10 unrelated donors (URD). Age at HSCT, graft-versus-host disease (GvHD), growth, and outcome were analysed. Fourteen had > or = 1 invasive infection, 10 had colitis and seven had growth failure before HSCT. Median age at transplantation was 75 months (range 15 months-21 years). Eighteen (90%) were alive 4-117 months (median 61) after HSCT with normal neutrophil function. Two died from disseminated fungal infection. Two experienced significant chronic GvHD, with continuing sequelae in 1. Colitis resolved within 8 weeks of HSCT. Mean weight and height for age Z scores on recovery from HSCT rose significantly (P < 0.001). HSCT with MSD or URD gave excellent engraftment and survival, remission of colitis and catch-up growth, with low incidence of significant GvHD. Transplant-associated complications were restricted to those with pre-existing infection or inflammation, supporting the argument for early HSCT for more CGD patients with a well matched donor.