Evaluating chronic emotional dysregulation and irritability in relation to ADHD and depression genetic risk in children with ADHD / Joel T. NIGG in Journal of Child Psychology and Psychiatry, 61-2 (February 2020)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 61-2 (February 2020) . - p.205-214 Titre : Evaluating chronic emotional dysregulation and irritability in relation to ADHD and depression genetic risk in children with ADHD Type de document : Texte imprimé et/ou numérique Auteurs : Joel T. NIGG, Auteur ; Sarah L. KARALUNAS, Auteur ; Hanna C. GUSTAFSSON, Auteur ; Priya BHATT, Auteur ; Peter RYABININ, Auteur ; Michael A. MOONEY, Auteur ; Stephen V. FARAONE, Auteur ; Damien A. FAIR, Auteur ; Beth WILMOT, Auteur Article en page(s) : p.205-214 Langues : Anglais (eng) Mots-clés : Adhd  irritability  polygenic score  temperament Index. décimale : PER Périodiques Résumé : BACKGROUND: A central nosological problem concerns the etiological relationship of emotional dysregulation with ADHD. Molecular genetic risk scores provide a novel method for informing this question. METHODS: Participants were 514 community-recruited children of Northern European descent age 7-11 defined as ADHD or non-ADHD by detailed research evaluation. Parents-rated ADHD on standardized ratings and child temperament on the Temperament in Middle Childhood Questionnaire (TMCQ) and reported on ADHD and comorbid disorders by semi-structured clinical interview. Categorical and dimensional variables were created for ADHD, emotional dysregulation (implicating disruption of regulation of both anger-irritability and of positive valence surgency-sensation seeking), and irritability alone (anger dysregulation). Genome-wide polygenic risk scores (PRS) were computed for ADHD and depression genetic liability. Structural equation models and computationally derived emotion profiles guided analysis. RESULTS: The ADHD PRS was associated in variable-centered analyses with irritability (beta = .179, 95% CI = 0.087-0.280; DeltaR(2) = .034, p < .0002), but also with surgency/sensation seeking (B = .146, 95%CI = 0.052-0.240, DeltaR(2) =.022, p = .002). In person-centered analysis, the ADHD PRS was elevated in the emotion dysregulation ADHD group versus other ADHD children (OR = 1.44, 95% CI = 1.03-2.20, Nagelkerke DeltaR(2) = .013, p = .033) but did not differentiate irritable from surgent ADHD profiles. All effects were independent of variation in ADHD severity across traits or groups. The depression PRS was related to oppositional defiant disorder but not to ADHD emotion dysregulation. CONCLUSIONS: Irritability-anger and surgency-sensation seeking, as forms of negative and positively valenced dysregulated affect in ADHD populations, both relate principally to ADHD genetic risk and not mood-related genetic risk. En ligne : http://dx.doi.org/10.1111/jcpp.13132 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=415 [article] Evaluating chronic emotional dysregulation and irritability in relation to ADHD and depression genetic risk in children with ADHD [Texte imprimé et/ou numérique] / Joel T. NIGG, Auteur ; Sarah L. KARALUNAS, Auteur ; Hanna C. GUSTAFSSON, Auteur ; Priya BHATT, Auteur ; Peter RYABININ, Auteur ; Michael A. MOONEY, Auteur ; Stephen V. FARAONE, Auteur ; Damien A. FAIR, Auteur ; Beth WILMOT, Auteur . - p.205-214. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 61-2 (February 2020) . - p.205-214 Mots-clés : Adhd  irritability  polygenic score  temperament Index. décimale : PER Périodiques Résumé : BACKGROUND: A central nosological problem concerns the etiological relationship of emotional dysregulation with ADHD. Molecular genetic risk scores provide a novel method for informing this question. METHODS: Participants were 514 community-recruited children of Northern European descent age 7-11 defined as ADHD or non-ADHD by detailed research evaluation. Parents-rated ADHD on standardized ratings and child temperament on the Temperament in Middle Childhood Questionnaire (TMCQ) and reported on ADHD and comorbid disorders by semi-structured clinical interview. Categorical and dimensional variables were created for ADHD, emotional dysregulation (implicating disruption of regulation of both anger-irritability and of positive valence surgency-sensation seeking), and irritability alone (anger dysregulation). Genome-wide polygenic risk scores (PRS) were computed for ADHD and depression genetic liability. Structural equation models and computationally derived emotion profiles guided analysis. RESULTS: The ADHD PRS was associated in variable-centered analyses with irritability (beta = .179, 95% CI = 0.087-0.280; DeltaR(2) = .034, p < .0002), but also with surgency/sensation seeking (B = .146, 95%CI = 0.052-0.240, DeltaR(2) =.022, p = .002). In person-centered analysis, the ADHD PRS was elevated in the emotion dysregulation ADHD group versus other ADHD children (OR = 1.44, 95% CI = 1.03-2.20, Nagelkerke DeltaR(2) = .013, p = .033) but did not differentiate irritable from surgent ADHD profiles. All effects were independent of variation in ADHD severity across traits or groups. The depression PRS was related to oppositional defiant disorder but not to ADHD emotion dysregulation. CONCLUSIONS: Irritability-anger and surgency-sensation seeking, as forms of negative and positively valenced dysregulated affect in ADHD populations, both relate principally to ADHD genetic risk and not mood-related genetic risk. En ligne : http://dx.doi.org/10.1111/jcpp.13132 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=415

Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2 / Beth WILMOT in Journal of Child Psychology and Psychiatry, 57-2 (February 2016)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 57-2 (February 2016) . - p.152-160 Titre : Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2 Type de document : Texte imprimé et/ou numérique Auteurs : Beth WILMOT, Auteur ; Rebecca FRY, Auteur ; Lisa SMEESTER, Auteur ; Erica D. MUSSER, Auteur ; Jonathan MILL, Auteur ; Joel T. NIGG, Auteur Article en page(s) : p.152-160 Langues : Anglais (eng) Mots-clés : ADHD  methylation  epigenetic Index. décimale : PER Périodiques Résumé : Background Peripheral epigenetic marks hold promise for understanding psychiatric illness and may represent fingerprints of gene–environment interactions. We conducted an initial examination of CpG methylation variation in children with or without attention-deficit/hyperactivity disorder (ADHD). Methods Children age 7–12 were recruited, screened, evaluated and assigned to ADHD or non-ADHD groups by defined research criteria. Two independent age-matched samples were examined, a discovery set (n = 92, all boys, half control, half ADHD) and a confirmation set (n = 20, half ADHD, all boys). 5-methylcytosine levels were quantified in salivary DNA using the Illumina 450 K HumanMethylation array. Genes for which multiple probes were nominally significant and had a beta difference of at least 2% were evaluated for biological relevance and prioritized for confirmation and sequence validation. Gene pathways were explored and described. Results Two genes met the criteria for confirmation testing, VIPR2 and MYT1L; both had multiple probes meeting cutoffs and strong biological relevance. Probes on VIPR2 passed FDR correction in the confirmation set and were confirmed through bisulfite sequencing. Enrichment analysis suggested involvement of gene sets or pathways related to inflammatory processes and modulation of monoamine and cholinergic neurotransmission. Conclusions Although it is unknown to what extent CpG methylation seen in peripheral tissue reflect transcriptomic changes in the brain, these initial results indicate that peripheral DNA methylation markers in ADHD may be promising and suggest targeted hypotheses for future study in larger samples. En ligne : http://dx.doi.org/10.1111/jcpp.12457 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=280 [article] Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2 [Texte imprimé et/ou numérique] / Beth WILMOT, Auteur ; Rebecca FRY, Auteur ; Lisa SMEESTER, Auteur ; Erica D. MUSSER, Auteur ; Jonathan MILL, Auteur ; Joel T. NIGG, Auteur . - p.152-160. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 57-2 (February 2016) . - p.152-160 Mots-clés : ADHD  methylation  epigenetic Index. décimale : PER Périodiques Résumé : Background Peripheral epigenetic marks hold promise for understanding psychiatric illness and may represent fingerprints of gene–environment interactions. We conducted an initial examination of CpG methylation variation in children with or without attention-deficit/hyperactivity disorder (ADHD). Methods Children age 7–12 were recruited, screened, evaluated and assigned to ADHD or non-ADHD groups by defined research criteria. Two independent age-matched samples were examined, a discovery set (n = 92, all boys, half control, half ADHD) and a confirmation set (n = 20, half ADHD, all boys). 5-methylcytosine levels were quantified in salivary DNA using the Illumina 450 K HumanMethylation array. Genes for which multiple probes were nominally significant and had a beta difference of at least 2% were evaluated for biological relevance and prioritized for confirmation and sequence validation. Gene pathways were explored and described. Results Two genes met the criteria for confirmation testing, VIPR2 and MYT1L; both had multiple probes meeting cutoffs and strong biological relevance. Probes on VIPR2 passed FDR correction in the confirmation set and were confirmed through bisulfite sequencing. Enrichment analysis suggested involvement of gene sets or pathways related to inflammatory processes and modulation of monoamine and cholinergic neurotransmission. Conclusions Although it is unknown to what extent CpG methylation seen in peripheral tissue reflect transcriptomic changes in the brain, these initial results indicate that peripheral DNA methylation markers in ADHD may be promising and suggest targeted hypotheses for future study in larger samples. En ligne : http://dx.doi.org/10.1111/jcpp.12457 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=280

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