Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets / Merel C. POSTEMA in Journal of Child Psychology and Psychiatry, 62-10 (October 2021)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 62-10 (October 2021) . - p.1202-1219 Titre : Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets Type de document : texte imprimé Auteurs : Merel C. POSTEMA, Auteur ; Martine HOOGMAN, Auteur ; Sara AMBROSINO, Auteur ; Philip ASHERSON, Auteur ; Tobias BANASCHEWSKI, Auteur ; Cibele E. BANDEIRA, Auteur ; Alexandr BARANOV, Auteur ; Claiton H.D. BAU, Auteur ; Sarah BAUMEISTER, Auteur ; Ramona BAUR-STREUBEL, Auteur ; Mark A. BELLGROVE, Auteur ; Joseph BIEDERMAN, Auteur ; Janita B. BRALTEN, Auteur ; Daniel BRANDEIS, Auteur ; Silvia BREM, Auteur ; Jan K. BUITELAAR, Auteur ; Geraldo F. BUSATTO, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; Mara CERCIGNANI, Auteur ; Tiffany M. CHAIM-AVANCINI, Auteur ; Kaylita C. CHANTILUKE, Auteur ; Anastasia CHRISTAKOU, Auteur ; David COGHILL, Auteur ; Annette CONZELMANN, Auteur ; Ana I. CUBILLO, Auteur ; Renata B. CUPERTINO, Auteur ; Patrick DE ZEEUW, Auteur ; Alysa E. DOYLE, Auteur ; Sarah DURSTON, Auteur ; Eric A. EARL, Auteur ; Jeffery N. EPSTEIN, Auteur ; Thomas ETHOFER, Auteur ; Damien A. FAIR, Auteur ; Andreas J. FALLGATTER, Auteur ; Stephen V. FARAONE, Auteur ; Thomas FRODL, Auteur ; Matt C. GABEL, Auteur ; Tinatin GOGBERASHVILI, Auteur ; Eugenio H. GREVET, Auteur ; Jan HAAVIK, Auteur ; Neil A. HARRISON, Auteur ; Catharina A. HARTMAN, Auteur ; Dirk J. HESLENFELD, Auteur ; Pieter J. HOEKSTRA, Auteur ; Sarah HOHMANN, Auteur ; Marie F. HØVIK, Auteur ; Terry L. JERNIGAN, Auteur ; Bernd KARDATZKI, Auteur ; Georgii KARKASHADZE, Auteur ; Clare KELLY, Auteur ; Gregor KOHLS, Auteur ; Kerstin KONRAD, Auteur ; Jonna KUNTSI, Auteur ; Luisa LÁZARO, Auteur ; Sara LERA-MIGUEL, Auteur ; Klaus-Peter LESCH, Auteur ; Mario R. LOUZA, Auteur ; Astri J. LUNDERVOLD, Auteur ; Charles B MALPAS, Auteur ; Paulo MATTOS, Auteur ; Hazel MCCARTHY, Auteur ; Leyla NAMAZOVA-BARANOVA, Auteur ; Rosa NICOLAU, Auteur ; Joel T. NIGG, Auteur ; Stephanie NOVOTNY, Auteur ; Eileen OBERWELLAND WEISS, Auteur ; Ruth L. O'GORMAN TUURA, Auteur ; Jaap OOSTERLAAN, Auteur ; Bob ORANJE, Auteur ; Yannis PALOYELIS, Auteur ; Paul PAULI, Auteur ; Felipe A. PICON, Auteur ; Kerstin J. PLESSEN, Auteur ; Josep Antoni RAMOS-QUIROGA, Auteur ; Andreas REIF, Auteur ; Liesbeth RENEMAN, Auteur ; Pedro G.P. ROSA, Auteur ; Katya RUBIA, Auteur ; Anouk SCHRANTEE, Auteur ; Lizanne SCHWEREN, Auteur ; Jochen SEITZ, Auteur ; Philip SHAW, Auteur ; Tim J. SILK, Auteur ; Norbert SKOKAUSKAS, Auteur ; Juan C. SOLIVA VILA, Auteur ; Michael C. STEVENS, Auteur ; Gustavo SUDRE, Auteur ; Leanne TAMM, Auteur ; Fernanda TOVAR-MOLL, Auteur ; Theo G.M. VAN ERP, Auteur ; Alasdair VANCE, Auteur ; Oscar VILARROYA, Auteur ; Yolanda VIVES-GILABERT, Auteur ; Georg G. VON POLIER, Auteur ; Susanne WALITZA, Auteur ; Yuliya N. YONCHEVA, Auteur ; Marcus V. ZANETTI, Auteur ; Georg C. ZIEGLER, Auteur ; David C. GLAHN, Auteur ; Neda JAHANSHAD, Auteur Année de publication : 2021 Article en page(s) : p.1202-1219 Langues : Anglais (eng) Mots-clés : Attention-deficit  brain asymmetry  brain laterality  hyperactivity disorder  large-scale data  structural MRI Index. décimale : PER Périodiques Résumé : Objective Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. Results There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study-wide correction for multiple testing. Conclusion Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait. En ligne : https://doi.org/10.1111/jcpp.13396 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=462 [article] Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets [texte imprimé] / Merel C. POSTEMA, Auteur ; Martine HOOGMAN, Auteur ; Sara AMBROSINO, Auteur ; Philip ASHERSON, Auteur ; Tobias BANASCHEWSKI, Auteur ; Cibele E. BANDEIRA, Auteur ; Alexandr BARANOV, Auteur ; Claiton H.D. BAU, Auteur ; Sarah BAUMEISTER, Auteur ; Ramona BAUR-STREUBEL, Auteur ; Mark A. BELLGROVE, Auteur ; Joseph BIEDERMAN, Auteur ; Janita B. BRALTEN, Auteur ; Daniel BRANDEIS, Auteur ; Silvia BREM, Auteur ; Jan K. BUITELAAR, Auteur ; Geraldo F. BUSATTO, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; Mara CERCIGNANI, Auteur ; Tiffany M. CHAIM-AVANCINI, Auteur ; Kaylita C. CHANTILUKE, Auteur ; Anastasia CHRISTAKOU, Auteur ; David COGHILL, Auteur ; Annette CONZELMANN, Auteur ; Ana I. CUBILLO, Auteur ; Renata B. CUPERTINO, Auteur ; Patrick DE ZEEUW, Auteur ; Alysa E. DOYLE, Auteur ; Sarah DURSTON, Auteur ; Eric A. EARL, Auteur ; Jeffery N. EPSTEIN, Auteur ; Thomas ETHOFER, Auteur ; Damien A. FAIR, Auteur ; Andreas J. FALLGATTER, Auteur ; Stephen V. FARAONE, Auteur ; Thomas FRODL, Auteur ; Matt C. GABEL, Auteur ; Tinatin GOGBERASHVILI, Auteur ; Eugenio H. GREVET, Auteur ; Jan HAAVIK, Auteur ; Neil A. HARRISON, Auteur ; Catharina A. HARTMAN, Auteur ; Dirk J. HESLENFELD, Auteur ; Pieter J. HOEKSTRA, Auteur ; Sarah HOHMANN, Auteur ; Marie F. HØVIK, Auteur ; Terry L. JERNIGAN, Auteur ; Bernd KARDATZKI, Auteur ; Georgii KARKASHADZE, Auteur ; Clare KELLY, Auteur ; Gregor KOHLS, Auteur ; Kerstin KONRAD, Auteur ; Jonna KUNTSI, Auteur ; Luisa LÁZARO, Auteur ; Sara LERA-MIGUEL, Auteur ; Klaus-Peter LESCH, Auteur ; Mario R. LOUZA, Auteur ; Astri J. LUNDERVOLD, Auteur ; Charles B MALPAS, Auteur ; Paulo MATTOS, Auteur ; Hazel MCCARTHY, Auteur ; Leyla NAMAZOVA-BARANOVA, Auteur ; Rosa NICOLAU, Auteur ; Joel T. NIGG, Auteur ; Stephanie NOVOTNY, Auteur ; Eileen OBERWELLAND WEISS, Auteur ; Ruth L. O'GORMAN TUURA, Auteur ; Jaap OOSTERLAAN, Auteur ; Bob ORANJE, Auteur ; Yannis PALOYELIS, Auteur ; Paul PAULI, Auteur ; Felipe A. PICON, Auteur ; Kerstin J. PLESSEN, Auteur ; Josep Antoni RAMOS-QUIROGA, Auteur ; Andreas REIF, Auteur ; Liesbeth RENEMAN, Auteur ; Pedro G.P. ROSA, Auteur ; Katya RUBIA, Auteur ; Anouk SCHRANTEE, Auteur ; Lizanne SCHWEREN, Auteur ; Jochen SEITZ, Auteur ; Philip SHAW, Auteur ; Tim J. SILK, Auteur ; Norbert SKOKAUSKAS, Auteur ; Juan C. SOLIVA VILA, Auteur ; Michael C. STEVENS, Auteur ; Gustavo SUDRE, Auteur ; Leanne TAMM, Auteur ; Fernanda TOVAR-MOLL, Auteur ; Theo G.M. VAN ERP, Auteur ; Alasdair VANCE, Auteur ; Oscar VILARROYA, Auteur ; Yolanda VIVES-GILABERT, Auteur ; Georg G. VON POLIER, Auteur ; Susanne WALITZA, Auteur ; Yuliya N. YONCHEVA, Auteur ; Marcus V. ZANETTI, Auteur ; Georg C. ZIEGLER, Auteur ; David C. GLAHN, Auteur ; Neda JAHANSHAD, Auteur . - 2021 . - p.1202-1219. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 62-10 (October 2021) . - p.1202-1219 Mots-clés : Attention-deficit  brain asymmetry  brain laterality  hyperactivity disorder  large-scale data  structural MRI Index. décimale : PER Périodiques Résumé : Objective Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. Results There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study-wide correction for multiple testing. Conclusion Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait. En ligne : https://doi.org/10.1111/jcpp.13396 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=462

Sex differences in parent-offspring recurrence of attention-deficit/hyperactivity disorder / Berit S. SOLBERG in Journal of Child Psychology and Psychiatry, 62-8 (August 2021)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 62-8 (August 2021) . - p.1010-1018 Titre : Sex differences in parent-offspring recurrence of attention-deficit/hyperactivity disorder Type de document : texte imprimé Auteurs : Berit S. SOLBERG, Auteur ; Tor-Arne HEGVIK, Auteur ; Anne HALMØY, Auteur ; Rolv SKJAERVEN, Auteur ; Anders ENGELAND, Auteur ; Jan HAAVIK, Auteur ; Kari KLUNGSØYR, Auteur Article en page(s) : p.1010-1018 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/epidemiology  Depressive Disorder, Major  Fathers  Female  Humans  Male  Norway/epidemiology  Parents  Risk Factors  Sex Characteristics  Attention-deficit/hyperactivity disorder  epidemiology  intergenerational recurrence risk  parent-of-origin  sex differences Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder sharing genetic risk factors with other common psychiatric disorders. However, intergenerational recurrence patterns of ADHD from parents to sons and daughters are not known. We aimed to examine the risk of ADHD in offspring of parents with ADHD and parents with other psychiatric disorders by parental and offspring sex, using parents without the specific disorders as comparison. METHODS: In a generation study linking data from several population-based registries, all Norwegians born 1967-2011 (n = 2,486,088; Medical Birth Registry of Norway) and their parents were followed to 2015. To estimate intergenerational recurrence risk, we calculated prevalence differences (PD) and the relative risk (RR) of ADHD in offspring by parental ADHD, bipolar disorder (BD), schizophrenia spectrum disorder (SCZ), major depression (MDD), all by parental and offspring sex. RESULTS: The absolute prevalence of ADHD in offspring of parents with ADHD was very high, especially in sons of two affected parents (41.5% and 25.1% in sons and daughters, respectively), and far higher than in offspring of parents with BD, SCZ or MDD. Intergenerational recurrence risks were higher for maternal than paternal ADHD (RR(maternal) 8.4, 95% confidence interval (CI) 8.2-8.6 vs. RR(paternal) 6.2, 6.0-6.4) and this was also true on the absolute scale (PD(maternal) 21.1% (20.5-21.7) vs. PD(paternal) 14.8% (14.3-15.4)). RRs were higher in daughters, while PDs higher in sons. Parental SCZ, BD and MDD were associated with an approximately doubled risk of offspring ADHD compared to parents without the respective disorders, and estimates did not differ significantly between daughters and sons. CONCLUSIONS: The intergenerational recurrence risks of ADHD were high and higher from mothers with ADHD than fathers with ADHD. Other parental psychiatric disorders also conferred increased risk of offspring ADHD, but far lower, indicating a sex- and diagnosis-specific intergenerational recurrence risk in parents with ADHD. En ligne : http://dx.doi.org/10.1111/jcpp.13368 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456 [article] Sex differences in parent-offspring recurrence of attention-deficit/hyperactivity disorder [texte imprimé] / Berit S. SOLBERG, Auteur ; Tor-Arne HEGVIK, Auteur ; Anne HALMØY, Auteur ; Rolv SKJAERVEN, Auteur ; Anders ENGELAND, Auteur ; Jan HAAVIK, Auteur ; Kari KLUNGSØYR, Auteur . - p.1010-1018. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 62-8 (August 2021) . - p.1010-1018 Mots-clés : Attention Deficit Disorder with Hyperactivity/epidemiology  Depressive Disorder, Major  Fathers  Female  Humans  Male  Norway/epidemiology  Parents  Risk Factors  Sex Characteristics  Attention-deficit/hyperactivity disorder  epidemiology  intergenerational recurrence risk  parent-of-origin  sex differences Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder sharing genetic risk factors with other common psychiatric disorders. However, intergenerational recurrence patterns of ADHD from parents to sons and daughters are not known. We aimed to examine the risk of ADHD in offspring of parents with ADHD and parents with other psychiatric disorders by parental and offspring sex, using parents without the specific disorders as comparison. METHODS: In a generation study linking data from several population-based registries, all Norwegians born 1967-2011 (n = 2,486,088; Medical Birth Registry of Norway) and their parents were followed to 2015. To estimate intergenerational recurrence risk, we calculated prevalence differences (PD) and the relative risk (RR) of ADHD in offspring by parental ADHD, bipolar disorder (BD), schizophrenia spectrum disorder (SCZ), major depression (MDD), all by parental and offspring sex. RESULTS: The absolute prevalence of ADHD in offspring of parents with ADHD was very high, especially in sons of two affected parents (41.5% and 25.1% in sons and daughters, respectively), and far higher than in offspring of parents with BD, SCZ or MDD. Intergenerational recurrence risks were higher for maternal than paternal ADHD (RR(maternal) 8.4, 95% confidence interval (CI) 8.2-8.6 vs. RR(paternal) 6.2, 6.0-6.4) and this was also true on the absolute scale (PD(maternal) 21.1% (20.5-21.7) vs. PD(paternal) 14.8% (14.3-15.4)). RRs were higher in daughters, while PDs higher in sons. Parental SCZ, BD and MDD were associated with an approximately doubled risk of offspring ADHD compared to parents without the respective disorders, and estimates did not differ significantly between daughters and sons. CONCLUSIONS: The intergenerational recurrence risks of ADHD were high and higher from mothers with ADHD than fathers with ADHD. Other parental psychiatric disorders also conferred increased risk of offspring ADHD, but far lower, indicating a sex- and diagnosis-specific intergenerational recurrence risk in parents with ADHD. En ligne : http://dx.doi.org/10.1111/jcpp.13368 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456

SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder / Sören MERKER in Journal of Child Psychology and Psychiatry, 58-7 (July 2017)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 58-7 (July 2017) . - p.798-809 Titre : SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder Type de document : texte imprimé Auteurs : Sören MERKER, Auteur ; Andreas REIF, Auteur ; Georg C. ZIEGLER, Auteur ; Heike WEBER, Auteur ; Ute MAYER, Auteur ; Ann-Christine EHLIS, Auteur ; Annette CONZELMANN, Auteur ; Stefan JOHANSSON, Auteur ; Clemens MÜLLER-REIBLE, Auteur ; Indrajit NANDA, Auteur ; Thomas HAAF, Auteur ; Reinhard ULLMANN, Auteur ; Marcel ROMANOS, Auteur ; Andreas J. FALLGATTER, Auteur ; Paul PAULI, Auteur ; Tatyana STREKALOVA, Auteur ; Charline JANSCH, Auteur ; Alejandro ARIAS-VASQUEZ, Auteur ; Jan HAAVIK, Auteur ; Marta RIBASES, Auteur ; Josep Antoni RAMOS-QUIROGA, Auteur ; Jan K. BUITELAAR, Auteur ; Barbara FRANKE, Auteur ; Klaus-Peter LESCH, Auteur Article en page(s) : p.798-809 Langues : Anglais (eng) Mots-clés : Attention-deficit/hyperactivity disorder  glucose transporter  SLC2A3  single-nucleotide polymorphisms  duplication  copy number variants  energy homeostasis  frontostriatal network Index. décimale : PER Périodiques Résumé : Background Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory–inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Methods Case–control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Results Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Conclusions Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. En ligne : http://dx.doi.org/10.1111/jcpp.12702 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=316 [article] SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder [texte imprimé] / Sören MERKER, Auteur ; Andreas REIF, Auteur ; Georg C. ZIEGLER, Auteur ; Heike WEBER, Auteur ; Ute MAYER, Auteur ; Ann-Christine EHLIS, Auteur ; Annette CONZELMANN, Auteur ; Stefan JOHANSSON, Auteur ; Clemens MÜLLER-REIBLE, Auteur ; Indrajit NANDA, Auteur ; Thomas HAAF, Auteur ; Reinhard ULLMANN, Auteur ; Marcel ROMANOS, Auteur ; Andreas J. FALLGATTER, Auteur ; Paul PAULI, Auteur ; Tatyana STREKALOVA, Auteur ; Charline JANSCH, Auteur ; Alejandro ARIAS-VASQUEZ, Auteur ; Jan HAAVIK, Auteur ; Marta RIBASES, Auteur ; Josep Antoni RAMOS-QUIROGA, Auteur ; Jan K. BUITELAAR, Auteur ; Barbara FRANKE, Auteur ; Klaus-Peter LESCH, Auteur . - p.798-809. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 58-7 (July 2017) . - p.798-809 Mots-clés : Attention-deficit/hyperactivity disorder  glucose transporter  SLC2A3  single-nucleotide polymorphisms  duplication  copy number variants  energy homeostasis  frontostriatal network Index. décimale : PER Périodiques Résumé : Background Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory–inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Methods Case–control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Results Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Conclusions Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. En ligne : http://dx.doi.org/10.1111/jcpp.12702 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=316

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