Executive functioning and local-global visual processing: candidate endophenotypes for autism spectrum disorder? / Lien VAN EYLEN in Journal of Child Psychology and Psychiatry, 58-3 (March 2017)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 58-3 (March 2017) . - p.258-269 Titre : Executive functioning and local-global visual processing: candidate endophenotypes for autism spectrum disorder? Type de document : texte imprimé Auteurs : Lien VAN EYLEN, Auteur ; Bart BOETS, Auteur ; Nele COSEMANS, Auteur ; Hilde PEETERS, Auteur ; Jean STEYAERT, Auteur ; Johan WAGEMANS, Auteur ; Ilse NOENS, Auteur Article en page(s) : p.258-269 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  relatives  intermediate phenotype  executive functioning  central coherence Index. décimale : PER Périodiques Résumé : Background Heterogeneity within autism spectrum disorder (ASD) hampers insight in the etiology and stimulates the search for endophenotypes. Endophenotypes should meet several criteria, the most important being the association with ASD and the higher occurrence rate in unaffected ASD relatives than in the general population. We evaluated these criteria for executive functioning (EF) and local-global (L-G) visual processing. Methods By administering an extensive cognitive battery which increases the validity of the measures, we examined which of the cognitive anomalies shown by ASD probands also occur in their unaffected relatives (n = 113) compared to typically developing (TD) controls (n = 100). Microarrays were performed, so we could exclude relatives from probands with a de novo mutation in a known ASD susceptibility copy number variant, thus increasing the probability that genetic risk variants are shared by the ASD relatives. An overview of studies investigating EF and L-G processing in ASD relatives was also provided. Results For EF, ASD relatives – like ASD probands – showed impairments in response inhibition, cognitive flexibility and generativity (specifically, ideational fluency), and EF impairments in daily life. For L-G visual processing, the ASD relatives showed no anomalies on the tasks, but they reported more attention to detail in daily life. Group differences were similar for siblings and for parents of ASD probands, and yielded larger effect sizes in a multiplex subsample. The group effect sizes for the comparison between ASD probands and TD individuals were generally larger than those of the ASD relatives compared to TD individuals. Conclusions Impaired cognitive flexibility, ideational fluency and response inhibition are strong candidate endophenotypes for ASD. They could help to delineate etiologically more homogeneous subgroups, which is clinically important to allow assigning ASD probands to different, more targeted, interventions. En ligne : http://dx.doi.org/10.1111/jcpp.12637 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303 [article] Executive functioning and local-global visual processing: candidate endophenotypes for autism spectrum disorder? [texte imprimé] / Lien VAN EYLEN, Auteur ; Bart BOETS, Auteur ; Nele COSEMANS, Auteur ; Hilde PEETERS, Auteur ; Jean STEYAERT, Auteur ; Johan WAGEMANS, Auteur ; Ilse NOENS, Auteur . - p.258-269. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 58-3 (March 2017) . - p.258-269 Mots-clés : Autism spectrum disorder  relatives  intermediate phenotype  executive functioning  central coherence Index. décimale : PER Périodiques Résumé : Background Heterogeneity within autism spectrum disorder (ASD) hampers insight in the etiology and stimulates the search for endophenotypes. Endophenotypes should meet several criteria, the most important being the association with ASD and the higher occurrence rate in unaffected ASD relatives than in the general population. We evaluated these criteria for executive functioning (EF) and local-global (L-G) visual processing. Methods By administering an extensive cognitive battery which increases the validity of the measures, we examined which of the cognitive anomalies shown by ASD probands also occur in their unaffected relatives (n = 113) compared to typically developing (TD) controls (n = 100). Microarrays were performed, so we could exclude relatives from probands with a de novo mutation in a known ASD susceptibility copy number variant, thus increasing the probability that genetic risk variants are shared by the ASD relatives. An overview of studies investigating EF and L-G processing in ASD relatives was also provided. Results For EF, ASD relatives – like ASD probands – showed impairments in response inhibition, cognitive flexibility and generativity (specifically, ideational fluency), and EF impairments in daily life. For L-G visual processing, the ASD relatives showed no anomalies on the tasks, but they reported more attention to detail in daily life. Group differences were similar for siblings and for parents of ASD probands, and yielded larger effect sizes in a multiplex subsample. The group effect sizes for the comparison between ASD probands and TD individuals were generally larger than those of the ASD relatives compared to TD individuals. Conclusions Impaired cognitive flexibility, ideational fluency and response inhibition are strong candidate endophenotypes for ASD. They could help to delineate etiologically more homogeneous subgroups, which is clinically important to allow assigning ASD probands to different, more targeted, interventions. En ligne : http://dx.doi.org/10.1111/jcpp.12637 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303

Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells / Sahar AVAZZADEH in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 52 p. Titre : Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells Type de document : texte imprimé Auteurs : Sahar AVAZZADEH, Auteur ; Katya MCDONAGH, Auteur ; Jamie REILLY, Auteur ; Yao WANG, Auteur ; Stephanie D. BOOMKAMP, Auteur ; Veronica MCINERNEY, Auteur ; Janusz KRAWCZYK, Auteur ; Jacqueline FITZGERALD, Auteur ; Niamh FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Amirhossein JALALI, Auteur ; Eva B. FORMAN, Auteur ; Sally A. LYNCH, Auteur ; Sean ENNIS, Auteur ; Nele COSEMANS, Auteur ; Hilde PEETERS, Auteur ; Peter DOCKERY, Auteur ; Timothy O'BRIEN, Auteur ; Leo R. QUINLAN, Auteur ; Louise GALLAGHER, Auteur ; Sanbing SHEN, Auteur Article en page(s) : 52 p. Langues : Anglais (eng) Mots-clés : Autism  Calcium signaling  Induced pluripotent stem cells  NRXN1alpha  Neurons  Transcriptome Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1alpha (+/-) deletions. Seven control and six NRXN1alpha (+/-) iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca(2+)) imaging was performed using Fluo4-AM, and the properties of Ca(2+) transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1alpha (+/-) neurons. Results: NRXN1alpha (+/-) neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca(2+) transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1alpha (+/-) neurons identified by STRING and GSEA analyses. Conclusions: This is the first report to show that human NRXN1alpha (+/-) neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca(2+) transients, which may facilitate the development of drug screening assays for the treatment of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0303-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells [texte imprimé] / Sahar AVAZZADEH, Auteur ; Katya MCDONAGH, Auteur ; Jamie REILLY, Auteur ; Yao WANG, Auteur ; Stephanie D. BOOMKAMP, Auteur ; Veronica MCINERNEY, Auteur ; Janusz KRAWCZYK, Auteur ; Jacqueline FITZGERALD, Auteur ; Niamh FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Amirhossein JALALI, Auteur ; Eva B. FORMAN, Auteur ; Sally A. LYNCH, Auteur ; Sean ENNIS, Auteur ; Nele COSEMANS, Auteur ; Hilde PEETERS, Auteur ; Peter DOCKERY, Auteur ; Timothy O'BRIEN, Auteur ; Leo R. QUINLAN, Auteur ; Louise GALLAGHER, Auteur ; Sanbing SHEN, Auteur . - 52 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 52 p. Mots-clés : Autism  Calcium signaling  Induced pluripotent stem cells  NRXN1alpha  Neurons  Transcriptome Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1alpha (+/-) deletions. Seven control and six NRXN1alpha (+/-) iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca(2+)) imaging was performed using Fluo4-AM, and the properties of Ca(2+) transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1alpha (+/-) neurons. Results: NRXN1alpha (+/-) neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca(2+) transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1alpha (+/-) neurons identified by STRING and GSEA analyses. Conclusions: This is the first report to show that human NRXN1alpha (+/-) neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca(2+) transients, which may facilitate the development of drug screening assays for the treatment of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0303-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

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