Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation

Abstract Background Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. Methods We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. Results We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 × 10−03; FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten “CNV positive” trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. Conclusions Our findings suggest that rare CNVs may contribute to the etiology of OCD.http://deepblue.lib.umich.edu/bitstream/2027.42/134675/1/11689_2016_Article_9170.pd

A Comparative Study of Repetitive Behaviours in Pediatric Obsessive-compulsive Disorder and Autism Spectrum Disorder

Repetitive behaviours are a core feature and source of impairment in two neurodevelopmental disorders: obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD). However, few studies have systematically examined repetitive behaviours across these two disorders. As part of the Province of Ontario Neurodevelopmental Disorders network we compared repetitive behaviour subtypes in children and adolescents with OCD and ASD using several instruments. Findings revealed marked heterogeneity of repetitive behaviour subtypes in children and adolescents with OCD and ASD. Results suggest repetitive behaviour subtypes that are more common in OCD, ASD, and equally prevalent across disorders. Findings will help guide future pathophysiological studies by localizing dimensional traits of repetitive behaviours across disorders.M.Sc

Effect of Professional Training on Child Protection Workers' Conceptualization and Self-Efficacy in Domestic Violence Cases

Child exposure to domestic violence (DV) is a recognized form of child maltreatment. In Ontario, more cases are referred to child protection as a result of concerns of DV than for any other form of maltreatment. Child protection workers often do not understand the dynamics of DV and are not well equipped with the tools or knowledge to refer families to appropriate interventions. We examined the efficacy of professional training to improve worker responses to mothers who have experienced DV and fathers who have perpetrated DV. Findings revealed marked differences in workers' capacity and self-efficacy for conceptualizing the risks and needs of mothers and fathers. Professional training resulted in improvements to worker's conceptualization of mothers' risk and needs as they intersected with DV, not fathers'. Results will help lay the groundwork for future studies aimed at improving workers' knowledge and response to families in circumstances of DV.M.A

The longitudinal association between temperament and physical activity in young children

Objective: To examine the longitudinal association of negative affect and physical activity in a population of preschool children. Study Design: Participants included 763 children (53% male) attending scheduled health supervision visits in their primary care physicians’ offices. Data were collected at two time points at mean ages 27 (SD = 5.4) and 47 (SD = 6.2) months. Negative affect (NA) was measured using the Negative Affectivity (frustration/anger, decreased soothability) domain of the Children’s Behaviour Questionnaire. Physical Activity (PA) was assessed using a parent-report questionnaire. Multiple regression analyses tested the association between NA and PA, adjusting for child age, sex, z-BMI, PA at Time 1, maternal education, household income, and season, and examined for sex differences in the relationship between NA and PA. Results: The longitudinal association between NA at Time 1 and PA at Time 2 was moderated by sex (p<.001). After adjusting for covariates, females with greater NA at Time 1 had decreased PA at Time 2 (p=.01), whereas males with greater NA at Time 1 had increased PA at Time 2 (p=.01). Specifically, among females, every 1 unit increase in NA at Time 1 was associated with a 9.9 minute/day decrease in PA at Time 2 (95% CI: -17.1,-2.8). Conclusions: NA and PA were associated early in childhood and the effects of NA on PA were gender specific. These findings underscore the importance of longitudinal and gender-specific analyses in mood-obesity research

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation

Abstract Background Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. Methods We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. Results We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 × 10−03; FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten “CNV positive” trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. Conclusions Our findings suggest that rare CNVs may contribute to the etiology of OCD