Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation / Sarah J. GOODMAN in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation Type de document : texte imprimé Auteurs : Sarah J. GOODMAN, Auteur ; Christie L. BURTON, Auteur ; Darci T. BUTCHER, Auteur ; Michelle T. SIU, Auteur ; Mathieu LEMIRE, Auteur ; Eric CHATER-DIEHL, Auteur ; Andrei L. TURINSKY, Auteur ; Michael BRUDNO, Auteur ; Noam SORENI, Auteur ; David ROSENBERG, Auteur ; Kate D. FITZGERALD, Auteur ; Gregory L. HANNA, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Paul D. ARNOLD, Auteur ; Jennifer CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; Rosanna WEKSBERG, Auteur Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  DNA Methylation/genetics  Genetic Variation/genetics  Humans  Obsessive-Compulsive Disorder/genetics  Adhd  Biomarker  DNA methylation  Epigenetics  Ocd Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). METHODS: We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4-18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. RESULTS: Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. CONCLUSIONS: Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09324-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation [texte imprimé] / Sarah J. GOODMAN, Auteur ; Christie L. BURTON, Auteur ; Darci T. BUTCHER, Auteur ; Michelle T. SIU, Auteur ; Mathieu LEMIRE, Auteur ; Eric CHATER-DIEHL, Auteur ; Andrei L. TURINSKY, Auteur ; Michael BRUDNO, Auteur ; Noam SORENI, Auteur ; David ROSENBERG, Auteur ; Kate D. FITZGERALD, Auteur ; Gregory L. HANNA, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Paul D. ARNOLD, Auteur ; Jennifer CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; Rosanna WEKSBERG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  DNA Methylation/genetics  Genetic Variation/genetics  Humans  Obsessive-Compulsive Disorder/genetics  Adhd  Biomarker  DNA methylation  Epigenetics  Ocd Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). METHODS: We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4-18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. RESULTS: Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. CONCLUSIONS: Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09324-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Obsessive-compulsive disorder in children and youth: neurocognitive function in clinic and community samples / Russell SCHACHAR in Journal of Child Psychology and Psychiatry, 63-8 (August 2022)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 63-8 (August 2022) . - p.881-889 Titre : Obsessive-compulsive disorder in children and youth: neurocognitive function in clinic and community samples Type de document : texte imprimé Auteurs : Russell SCHACHAR, Auteur ; Annie DUPUIS, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Stelios GEORGIADES, Auteur ; Noam SORENI, Auteur ; Paul D. ARNOLD, Auteur ; Christie L. BURTON, Auteur ; Jennifer CROSBIE, Auteur Article en page(s) : p.881-889 Langues : Anglais (eng) Mots-clés : Adolescent  Attention  Child  Comorbidity  Humans  Obsessive-Compulsive Disorder/diagnosis  Phenotype  Reaction Time/physiology  Ocd  Stop-signal task  executive function  neurocognition Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurocognitive impairments are common in OCD, although not well studied in children and youth with the disorder. METHOD: Using the stop-signal task (SST), we measured response inhibition (stop-signal reaction time-SSRT), sustained attention (reaction time variability-RTV), reaction time (RT), and performance monitoring (post-error slowing-PES) in OCD cases and controls from two samples of children and youth. A Clinic OCD group (n=171, aged 7-17years) was recruited from a specialty clinic after rigorous assessment. A typically developing (Clinic TD, n=157) group was enlisted through advertisement. A community OCD sample (Community OCD, n=147) and controls (Community TD n=13,832, aged 6-17 years) were recruited at a science museum. We also identified a community group with high OCD traits without an OCD diagnosis (Community High Trait; n=125). RESULTS: Clinic OCD participants had longer SSRT and greater RTV than Clinic TD. These effects were greater in younger OCD participants and, for SSRT, in those on medication for OCD. The Community OCD group did not differ from Controls but was similar to the Clinic OCD group in ADHD and ASD comorbidity and medication usage. The Community High Trait group had longer SSRT and atypical PES suggesting that symptom severity predicts neurocognitive function. No group differences were found in RT. CONCLUSIONS: In the largest study of neurocognitive performance in children with OCD to date, we found impaired response inhibition and sustained attention in OCD participants in comparison to typically developing peers. Performance was worse in younger OCD participants. In the community sample, participants with high OCD trait scores but no OCD diagnosis had impaired response inhibition and error processing, suggesting that OCD might be under-recognized. En ligne : http://dx.doi.org/10.1111/jcpp.13533 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 [article] Obsessive-compulsive disorder in children and youth: neurocognitive function in clinic and community samples [texte imprimé] / Russell SCHACHAR, Auteur ; Annie DUPUIS, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Stelios GEORGIADES, Auteur ; Noam SORENI, Auteur ; Paul D. ARNOLD, Auteur ; Christie L. BURTON, Auteur ; Jennifer CROSBIE, Auteur . - p.881-889. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 63-8 (August 2022) . - p.881-889 Mots-clés : Adolescent  Attention  Child  Comorbidity  Humans  Obsessive-Compulsive Disorder/diagnosis  Phenotype  Reaction Time/physiology  Ocd  Stop-signal task  executive function  neurocognition Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurocognitive impairments are common in OCD, although not well studied in children and youth with the disorder. METHOD: Using the stop-signal task (SST), we measured response inhibition (stop-signal reaction time-SSRT), sustained attention (reaction time variability-RTV), reaction time (RT), and performance monitoring (post-error slowing-PES) in OCD cases and controls from two samples of children and youth. A Clinic OCD group (n=171, aged 7-17years) was recruited from a specialty clinic after rigorous assessment. A typically developing (Clinic TD, n=157) group was enlisted through advertisement. A community OCD sample (Community OCD, n=147) and controls (Community TD n=13,832, aged 6-17 years) were recruited at a science museum. We also identified a community group with high OCD traits without an OCD diagnosis (Community High Trait; n=125). RESULTS: Clinic OCD participants had longer SSRT and greater RTV than Clinic TD. These effects were greater in younger OCD participants and, for SSRT, in those on medication for OCD. The Community OCD group did not differ from Controls but was similar to the Clinic OCD group in ADHD and ASD comorbidity and medication usage. The Community High Trait group had longer SSRT and atypical PES suggesting that symptom severity predicts neurocognitive function. No group differences were found in RT. CONCLUSIONS: In the largest study of neurocognitive performance in children with OCD to date, we found impaired response inhibition and sustained attention in OCD participants in comparison to typically developing peers. Performance was worse in younger OCD participants. In the community sample, participants with high OCD trait scores but no OCD diagnosis had impaired response inhibition and error processing, suggesting that OCD might be under-recognized. En ligne : http://dx.doi.org/10.1111/jcpp.13533 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation / MatthewJ GAZZELLONE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.36 Titre : Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation Type de document : texte imprimé Auteurs : MatthewJ GAZZELLONE, Auteur ; Mehdi ZARREI, Auteur ; Christie L. BURTON, Auteur ; Susan WALKER, Auteur ; Mohammed UDDIN, Auteur ; S.M. SHAHEEN, Auteur ; Julie COSTE, Auteur ; Rageen RAJENDRAM, Auteur ; Reva J. SCHACHTER, Auteur ; Marlena COLASANTO, Auteur ; Gregory L. HANNA, Auteur ; David R. ROSENBERG, Auteur ; Noam SORENI, Auteur ; Kate D. FITZGERALD, Auteur ; Christian R. MARSHALL, Auteur ; Janet A. BUCHANAN, Auteur ; Daniele MERICO, Auteur ; Paul D. ARNOLD, Auteur ; Stephen SCHERER, Auteur Article en page(s) : p.36 Langues : Anglais (eng) Mots-clés : Copy number variation  Obsessive-compulsive disorder  Pediatrics  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : 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 x 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. En ligne : http://dx.doi.org/10.1186/s11689-016-9170-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation [texte imprimé] / MatthewJ GAZZELLONE, Auteur ; Mehdi ZARREI, Auteur ; Christie L. BURTON, Auteur ; Susan WALKER, Auteur ; Mohammed UDDIN, Auteur ; S.M. SHAHEEN, Auteur ; Julie COSTE, Auteur ; Rageen RAJENDRAM, Auteur ; Reva J. SCHACHTER, Auteur ; Marlena COLASANTO, Auteur ; Gregory L. HANNA, Auteur ; David R. ROSENBERG, Auteur ; Noam SORENI, Auteur ; Kate D. FITZGERALD, Auteur ; Christian R. MARSHALL, Auteur ; Janet A. BUCHANAN, Auteur ; Daniele MERICO, Auteur ; Paul D. ARNOLD, Auteur ; Stephen SCHERER, Auteur . - p.36. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.36 Mots-clés : Copy number variation  Obsessive-compulsive disorder  Pediatrics  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : 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 x 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. En ligne : http://dx.doi.org/10.1186/s11689-016-9170-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

---

1 (1 - 3 / 3) Par page : 25 50 100 200