Explore the vast range of titles available.

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive–compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi‐site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA‐OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

Cheek swabs, heterogeneous samples consisting primarily of buccal epithelial cells, are widely used in pediatric DNA methylation studies and biomarker creation. However, the decrease in buccal proportion with age in adults remains unexamined in childhood. We analyzed cheek swabs from 4626 typically developing children 2-months to 20-years-old. Estimated buccal proportion declined throughout childhood with both increasing chronological and predicted epigenetic age. However, buccal proportion did not associate with age throughout adolescence. Variability in buccal proportion increased with age through the entire developmental range. These trends held inversely true for neutrophil proportions. Correcting for buccal proportion attenuated the weak association with PedBE age acceleration to non-significance during initial estimation. Notably, correcting for buccal proportion attenuated the association of PedBE age acceleration with obsessive-compulsive disorder and strengthened the association with diurnal cortisol slope. Thus, the age-related change in children’s oral cells is a crucial consideration for cell type-sensitive research. Cheek swabs are widely used in pediatric epigenetic studies, but changes in their cellular composition with age are unclear. Here the authors show that buccal epithelial cells decline with age until adolescence, then stabilize, while variability increases with age, impacting the precision of tools like the PedBE clock in pediatric epigenetics.

Background: It is not uncommon to find obsessive-compulsive symptoms (OCS) in patients treated with clozapine. These symptoms are attributed to anti-serotonergic effects of clozapine. The objective of this study was to conduct a systematic review of reported cases of clozapine-associated OCS to better understand the nature and management of these symptoms. Methods: MEDLINE, Embase, and PsycINFO databases were searched with no publication year or language restrictions. Studies reporting cases of clozapine-associated OCS, either de novo or exacerbation of preexisting OCS, were included. The final search date was July 11, 2019. Results: Fifty-seven studies, involving 107 cases (75 de novo, 32 exacerbated OCS), were included. Clozapine triggered moderate-severe OCS at varying doses (100–900 mg/day) and treatment durations (median 6 months, interquartile range 2–24 months). Higher severity was significantly associated with preexisting OCS, poorer insight into OCS, and active psychosis at the time of OCS. Common strategies to treat clozapine-associated OCS included adding selective serotonin reuptake inhibitors, clomipramine, or aripiprazole, often accompanied by clozapine dose reduction. The rate of response to antidepressants was 49% (29/59), where younger age, shorter duration of underlying illness, shorter cloza­pine treatment duration, better insight into OCS, and presence of taboo thoughts were significantly associated with antidepressant response. Subsequent clozapine dose reduction was effective in many non-responders, where aripiprazole was simultaneously added in 50% (8/16). Conclusions: Clozapine can trigger severe OCS. Adding aripiprazole with/without clozapine dose reduction may be a good alternative to antidepressants for managing clozapine-associated OCS. Clinicians should be more vigilant about these adverse effects and administer appropriate treatments.

Understanding the psychosocial status of children and adolescents during the COVID-19 pandemic is vital to the appropriate and adequate allocation of social supports and mental health resources. This study evaluates the burden of mental health concerns and the impact of demographic factors while tracking mental health service recommendations to inform community service needs. MyHEARTSMAP is a digital self-assessment mental health evaluation completed by children and their guardian throughout British Columbia between August 2020 to July 2021. Severity of mental health concerns was evaluated across psychiatric, social, functioning, and youth health domains. Proportional odds modelling evaluated the impact of demographic factors on severity. Recommendations for support services were provided based on the evaluation. We recruited 541 families who completed 424 psychosocial assessments on individual children. Some degree of difficulty across the psychiatric, social, or functional domains was reported for more than half of children and adolescents. Older youth and those not attending any formal school or education program were more likely to report greater psychiatric difficulty. Girls experienced greater social concerns, and children attending full-time school at-home were more likely to identify difficulty within the youth health domain but were not more likely to have psychiatric difficulties. Considerations to access community mental health service were triggered in the majority (74%) of cases. Psychosocial concerns are highly prevalent amongst children and adolescents during the COVID-19 pandemic. Based on identified needs of this cohort, additional community health supports are required, particularly for higher risk groups.

IntroductionPostpartum depression and anxiety (PPDA) is experienced by up to 20% of families in the first year. The condition impacts not only parents but also their developing child. While mindfulness-based interventions (MBI) have shown to be beneficial for this population, many parents do not have access to treatment or find it challenging to commit or complete the treatment. The COVID-19 pandemic has heightened some of the challenges that parents face. The ability to find time for needed self-care and health interventions is also affected by limited childcare support. The opportunity to attend a group online may significantly improve the accessibility to group MBI but may also bring challenges. This study aims to examine the feasibility and acceptability of online MBI groups for parents in families affected with PPDA.Methods and analysisIn this feasibility study, participants will include mothers diagnosed with PPDA and their partners. Two online MBI groups will run simultaneously for 8 weeks: one for mothers with PPDA and another one for their partners. The primary outcome will be feasibility of conducting the online groups, assessed from the facilitators’ perspective, participants’ perspective and attrition throughout the study. The participants’ perspectives on feasibility will be assessed by questions including how difficult it was for them to make it to the sessions, specific obstacles encountered and their scheduling preferences. The facilitators’ perspective will be assessed by frequency of technical difficulties encountered, of disruptions in the online sessions and of episodes where parents leave the screen (eg, to calm their child). Secondary outcomes will include mental health, couple relationship, satisfaction and acceptability which will also be evaluated through participant questionnaires.Ethics and disseminationThe study has received ethics approval from the University of British Columbia Children’s and Women’s Research Ethics Board. Study results will be disseminated through peer-reviewed journals and conferences.Trial registration numberNCT04617132.

Given diverse symptom expression and high rates of comorbid conditions, the present study explored underlying commonalities among OCD-affected children and adolescents to better conceptualize disorder presentation and associated features. Data from 830 OCD-affected participants presenting to OCD specialty centers was aggregated. Dependent mixture modeling was used to examine latent clusters based on their age- and gender adjusted symptom severity (as measured by the Children’s Yale-Brown Obsessive-Compulsive Scale; CY-BOCS), symptom type (as measured by factor scores calculated from the CY-BOCS symptom checklist), and comorbid diagnoses (as assessed via diagnostic interviews). Fit statistics favored a four-cluster model with groups distinguished primarily by symptom expression and comorbidity type. Fit indices for 3–7 cluster models were only marginally different and characteristics of the clusters remained largely stable between solutions with small clusters of distinct presentations added in more complex models. Rather than identifying a single classification system, the findings support the utility of integrating dimensional, developmental, and transdiagnostic information in the conceptualization of OCD-affected children and adolescents. Identified clusters point to the centrality of contamination concerns to OCD, relationships between broader symptom expression and higher levels of comorbidity, and the potential for complex/neurodevelopmental presentations.

Objective: To evaluate the lifetime prevalence of infectious, inflammatory, and autoimmune disorders in a multisite study of probands with childhood-onset obsessive compulsive disorder (OCD) and their first-degree relatives. Methods: Medical questionnaires were completed by 1401 probands and 1045 first-degree relatives in the OCD Collaborative Genetics Association Study. Lifetime prevalence of immune-related diseases was compared with the highest available population estimate and reported as a point estimate with 95% adjusted Wald interval. Worst-episode OCD severity and symptom dimensions were assessed with the Yale–Brown Obsessive Compulsive Scale (YBOCS) and Symptom Checklist (YBOCS-CL). Results: Probands reported higher-than-expected prevalence of scarlet fever (4.0 [3.1–5.2]% vs. 1.0%–2.0%, z = 1.491, p < 0.001, n = 1389), encephalitis or meningitis (1.4 [0.9–2.1]% vs. 0.1%–0.4%, z = 5.913, p < 0.001, n = 1393), rheumatoid arthritis (1.1 [0.6–2.0]% vs. 0.2%–0.4%, z = 3.416, p < 0.001, n = 949) and rheumatic fever (0.6 [0.3–1.2]% vs. 0.1%–0.2%, z = 3.338, p < 0.001, n = 1390), but not systemic lupus erythematosus, diabetes, asthma, multiple sclerosis, psoriasis, or inflammatory bowel disease. First-degree relatives reported similarly elevated rates of scarlet fever, rheumatic fever, and encephalitis or meningitis independent of OCD status. There was no association between worst-episode severity and immune-related comorbidities, although probands reporting frequent ear or throat infections had increased severity of cleaning-/contamination-related symptoms (mean factor score 2.5 ± 0.9 vs. 2.3 ± 1.0, t = 3.183, p = 0.002, n = 822). Conclusion: These data suggest high rates of streptococcal-related and other immune-mediated diseases in patients with childhood-onset OCD and are consistent with epidemiological studies in adults noting familial clustering. Limitations include potential reporting bias and absence of a control group, underscoring the need for further prospective studies characterizing medical and psychiatric disease clusters and their interactions in children. Such studies may ultimately improve our understanding of OCD pathogenesis and aid in the development of adjunctive immune-modulating therapeutic strategies.

Background Anxiety disorders are the most common psychiatric problems among Canadian youth and typically have an onset in childhood or adolescence. They are characterized by high rates of relapse and chronicity, often resulting in substantial impairment across the lifespan. Genetic factors play an important role in the vulnerability toward anxiety disorders. However, genetic contribution to anxiety in youth is not well understood and can change across developmental stages. Large-scale genetic studies of youth are needed with detailed assessments of symptoms of anxiety disorders and their major comorbidities to inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Methods The Genetic Architecture of Youth Anxiety (GAYA) study is a Pan-Canadian effort of clinical and genetic experts with specific recruitment sites in Calgary, Halifax, Hamilton, Toronto, and Vancouver. Youth aged 10–19 ( n  = 13,000) will be recruited from both clinical and community settings and will provide saliva samples, complete online questionnaires on demographics, symptoms of mental health concerns, and behavioural inhibition, and complete neurocognitive tasks. A subset of youth will be offered access to a self-managed Internet-based cognitive behavioral therapy resource. Analyses will focus on the identification of novel genetic risk loci for anxiety disorders in youth and assess how much of the genetic risk for anxiety disorders is unique or shared across the life span. Discussion Results will substantially inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Given that the GAYA study will be the biggest genomic study of anxiety disorders in youth in Canada, this project will further foster collaborations nationally and across the world.

Background Canadians endured unprecedented mental health (MH) and support access challenges during the first COVID-19 wave. Identifying groups of individuals who remain at risk beyond the acute pandemic phase is key to guiding systemic intervention efforts and policy. We hypothesized that determinants of three complementary, clinically actionable psychiatric outcomes would differ across Canadian age groups. Methods The Personal Impacts of COVID-19 Survey (PICS) was iteratively developed with stakeholder feedback, incorporating validated, age-appropriate measures. Baseline, cross-sectional online data collected between November 2020-July 2021 was used in analyses. Age group-specific determinants were sought for three key baseline MH outcomes: (1) current probable depression, generalized anxiety disorder, obsessive–compulsive disorder and/or suicide attempt during COVID-19, (2) increased severity of any lifetime psychiatric diagnosis, and (3) inadequate MH support access during COVID-19. Multivariable logistic regression models were constructed for children, youth (self- and parent-report), young adults (19–29 years) and adults over 29 years, using survey type as a covariate. Statistical significance was defined by 95% confidence interval excluding an odds ratio of one. Results Data from 3140 baseline surveys were analyzed. Late adolescence and early adulthood were identified as life phases with the worst MH outcomes. Poverty, limited education, home maker/caregiver roles, female and non-binary gender, LGBTQ2S + status and special educational, psychiatric and medical conditions were differentially identified as determinants across age groups. Interpretation Negative psychiatric impacts of COVID-19 on Canadians that include poor access to MH support clearly persisted beyond the first wave, widening pre-existing inequity gaps. This should guide policy makers and clinicians in current and future prioritization efforts.

Obsessive compulsive disorder (OCD) is substantially heritable, but few molecular genetic risk factors have been identified. Knockout mice lacking SLIT and NTRK-Like Family, Member 5 (SLITRK5) display OCD-like phenotypes including serotonin reuptake inhibitor-sensitive pathologic grooming, and corticostriatal dysfunction. Thus, mutations that impair SLITRK5 function may contribute to the genetic risk for OCD. We re-sequenced the protein-coding sequence of the human SLITRK5 gene (SLITRK5) in three hundred and seventy seven OCD subjects and compared rare non-synonymous mutations (RNMs) in that sample with similar mutations in the 1000 Genomes database. We also performed in silico assessments and in vitro functional synaptogenesis assays on the Slitrk5 mutations identified. We identified four RNM's among these OCD subjects. There were no significant differences in the prevalence or in silico effects of rare non-synonymous mutations in the OCD sample versus controls. Direct functional testing of recombinant SLITRK5 proteins found that all mutations identified in OCD subjects impaired synaptogenic activity whereas none of the pseudo-matched mutations identified in 1000 Genomes controls had significant effects on SLITRK5 function (Fisher's exact test P = 0.028). These results demonstrate that rare functional mutations in SLITRK5 contribute to the genetic risk for OCD in human populations. They also highlight the importance of biological characterization of allelic effects in understanding genotype-phenotype relationships as there were no statistical differences in overall prevalence or bioinformatically predicted effects of OCD case versus control mutations. Finally, these results converge with others to highlight the role of aberrant synaptic function in corticostriatal neurons in the pathophysiology of OCD.