Comparison of three different eye-tracking tasks for distinguishing autistic from typically developing children and autistic symptom severity / J. KOU in Autism Research, 12-10 (October 2019)  

Public ISBD [article]  inAutism Research > 12-10 (October 2019) . - p.1529-1540 Titre : Comparison of three different eye-tracking tasks for distinguishing autistic from typically developing children and autistic symptom severity Type de document : Texte imprimé et/ou numérique Auteurs : J. KOU, Auteur ; J. LE, Auteur ; M. FU, Auteur ; C. LAN, Auteur ; Z. CHEN, Auteur ; Q. LI, Auteur ; W. ZHAO, Auteur ; L. XU, Auteur ; B. BECKER, Auteur ; K. M. KENDRICK, Auteur Article en page(s) : p.1529-1540 Langues : Anglais (eng) Mots-clés : Chinese children  attentional preference bias  autism spectrum disorder  dynamic social stimuli  eye-tracking Index. décimale : PER Périodiques Résumé : Altered patterns of visual social attention preference detected using eye-tracking and a variety of different paradigms are increasingly proposed as sensitive biomarkers for autism spectrum disorder. However, few eye-tracking studies have compared the relative efficacy of different paradigms to discriminate between autistic compared with typically developing children and their sensitivity to specific symptoms. To target this issue, the current study used three common eye-tracking protocols contrasting social versus nonsocial stimuli in young (2-7 years old) Chinese autistic (n = 35) and typically developing (n = 34) children matched for age and gender. Protocols included dancing people versus dynamic geometrical images, biological motion (dynamic light point walking human or cat) versus nonbiological motion (scrambled controls), and child playing with toy versus toy alone. Although all three paradigms differentiated autistic and typically developing children, the dancing people versus dynamic geometry pattern paradigm was the most effective, with autistic children showing marked reductions in visual preference for dancing people and correspondingly increased one for geometric patterns. Furthermore, this altered visual preference in autistic children was correlated with the Autism Diagnostic Observation Schedule social affect score and had the highest discrimination accuracy. Our results therefore indicate that decreased visual preference for dynamic social stimuli may be the most effective visual attention-based paradigm for use as a biomarker for autism in Chinese children. Clinical trial ID: NCT03286621 (clinicaltrials.gov); Clinical trial name: Development of Eye-tracking Based Markers for Autism in Young Children. Autism Res 2019, 12: 1529-1540. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Eye-tracking measures may be useful in aiding diagnosis and treatment of autism, although it is unclear which specific tasks are optimal. Here we compare the ability of three different social eye-gaze tasks to discriminate between autistic and typically developing young Chinese children and their sensitivity to specific autistic symptoms. Our results show that a dynamic task comparing visual preference for social (individuals dancing) versus geometric patterns is the most effective both for diagnosing autism and sensitivity to its social affect symptoms. En ligne : http://dx.doi.org/10.1002/aur.2174 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Comparison of three different eye-tracking tasks for distinguishing autistic from typically developing children and autistic symptom severity [Texte imprimé et/ou numérique] / J. KOU, Auteur ; J. LE, Auteur ; M. FU, Auteur ; C. LAN, Auteur ; Z. CHEN, Auteur ; Q. LI, Auteur ; W. ZHAO, Auteur ; L. XU, Auteur ; B. BECKER, Auteur ; K. M. KENDRICK, Auteur . - p.1529-1540. Langues : Anglais (eng) in Autism Research > 12-10 (October 2019) . - p.1529-1540 Mots-clés : Chinese children  attentional preference bias  autism spectrum disorder  dynamic social stimuli  eye-tracking Index. décimale : PER Périodiques Résumé : Altered patterns of visual social attention preference detected using eye-tracking and a variety of different paradigms are increasingly proposed as sensitive biomarkers for autism spectrum disorder. However, few eye-tracking studies have compared the relative efficacy of different paradigms to discriminate between autistic compared with typically developing children and their sensitivity to specific symptoms. To target this issue, the current study used three common eye-tracking protocols contrasting social versus nonsocial stimuli in young (2-7 years old) Chinese autistic (n = 35) and typically developing (n = 34) children matched for age and gender. Protocols included dancing people versus dynamic geometrical images, biological motion (dynamic light point walking human or cat) versus nonbiological motion (scrambled controls), and child playing with toy versus toy alone. Although all three paradigms differentiated autistic and typically developing children, the dancing people versus dynamic geometry pattern paradigm was the most effective, with autistic children showing marked reductions in visual preference for dancing people and correspondingly increased one for geometric patterns. Furthermore, this altered visual preference in autistic children was correlated with the Autism Diagnostic Observation Schedule social affect score and had the highest discrimination accuracy. Our results therefore indicate that decreased visual preference for dynamic social stimuli may be the most effective visual attention-based paradigm for use as a biomarker for autism in Chinese children. Clinical trial ID: NCT03286621 (clinicaltrials.gov); Clinical trial name: Development of Eye-tracking Based Markers for Autism in Young Children. Autism Res 2019, 12: 1529-1540. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Eye-tracking measures may be useful in aiding diagnosis and treatment of autism, although it is unclear which specific tasks are optimal. Here we compare the ability of three different social eye-gaze tasks to discriminate between autistic and typically developing young Chinese children and their sensitivity to specific autistic symptoms. Our results show that a dynamic task comparing visual preference for social (individuals dancing) versus geometric patterns is the most effective both for diagnosing autism and sensitivity to its social affect symptoms. En ligne : http://dx.doi.org/10.1002/aur.2174 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors / C. X. LIU in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 23p. Titre : CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors Type de document : Texte imprimé et/ou numérique Auteurs : C. X. LIU, Auteur ; C. Y. LI, Auteur ; C. C. HU, Auteur ; Y. WANG, Auteur ; J. LIN, Auteur ; Y. H. JIANG, Auteur ; Q. LI, Auteur ; X. XU, Auteur Article en page(s) : 23p. Langues : Anglais (eng) Mots-clés : Asd  Animal model  CRISPR/Cas9  Social behavior  Zebrafish  shank3 Index. décimale : PER Périodiques Résumé : Background: Human genetic and genomic studies have supported a strong causal role of SHANK3 deficiency in autism spectrum disorder (ASD). However, the molecular mechanism underlying SHANK3 deficiency resulting in ASD is not fully understood. Recently, the zebrafish has become an attractive organism to model ASD because of its high efficiency of genetic manipulation and robust behavioral phenotypes. The orthologous gene to human SHANK3 is duplicated in the zebrafish genome and has two homologs, shank3a and shank3b. Previous studies have reported shank3 morphants in zebrafish using the morpholino method. Here, we report the generation and characterization of shank3b mutant zebrafish in larval and adult stages using the CRISPR/Cas9 genome editing technique. Methods: CRISPR/Cas9 was applied to generate a shank3b loss-of-function mutation (shank3b(-/-) ) in zebrafish. A series of morphological measurements, behavioral tests, and molecular analyses were performed to systematically characterize the behavioral and molecular changes in shank3b mutant zebrafish. Results: shank3b(-/-) zebrafish exhibited abnormal morphology in early development. They showed reduced locomotor activity both as larvae and adults, reduced social interaction and time spent near conspecifics, and significant repetitive swimming behaviors. Additionally, the levels of both postsynaptic homer1 and presynaptic synaptophysin were significantly reduced in the adult brain of shank3b-deficient zebrafish. Conclusions: We generated the first inheritable shank3b mutant zebrafish model using CRISPR/Cas9 gene editing approach. shank3b(-/-) zebrafish displayed robust autism-like behaviors and altered levels of the synaptic proteins homer1 and synaptophysin. The versatility of zebrafish as a model for studying neurodevelopment and conducting drug screening will likely have a significant contribution to future studies of human SHANK3 function and ASD. En ligne : http://dx.doi.org/10.1186/s13229-018-0204-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 [article] CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors [Texte imprimé et/ou numérique] / C. X. LIU, Auteur ; C. Y. LI, Auteur ; C. C. HU, Auteur ; Y. WANG, Auteur ; J. LIN, Auteur ; Y. H. JIANG, Auteur ; Q. LI, Auteur ; X. XU, Auteur . - 23p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 23p. Mots-clés : Asd  Animal model  CRISPR/Cas9  Social behavior  Zebrafish  shank3 Index. décimale : PER Périodiques Résumé : Background: Human genetic and genomic studies have supported a strong causal role of SHANK3 deficiency in autism spectrum disorder (ASD). However, the molecular mechanism underlying SHANK3 deficiency resulting in ASD is not fully understood. Recently, the zebrafish has become an attractive organism to model ASD because of its high efficiency of genetic manipulation and robust behavioral phenotypes. The orthologous gene to human SHANK3 is duplicated in the zebrafish genome and has two homologs, shank3a and shank3b. Previous studies have reported shank3 morphants in zebrafish using the morpholino method. Here, we report the generation and characterization of shank3b mutant zebrafish in larval and adult stages using the CRISPR/Cas9 genome editing technique. Methods: CRISPR/Cas9 was applied to generate a shank3b loss-of-function mutation (shank3b(-/-) ) in zebrafish. A series of morphological measurements, behavioral tests, and molecular analyses were performed to systematically characterize the behavioral and molecular changes in shank3b mutant zebrafish. Results: shank3b(-/-) zebrafish exhibited abnormal morphology in early development. They showed reduced locomotor activity both as larvae and adults, reduced social interaction and time spent near conspecifics, and significant repetitive swimming behaviors. Additionally, the levels of both postsynaptic homer1 and presynaptic synaptophysin were significantly reduced in the adult brain of shank3b-deficient zebrafish. Conclusions: We generated the first inheritable shank3b mutant zebrafish model using CRISPR/Cas9 gene editing approach. shank3b(-/-) zebrafish displayed robust autism-like behaviors and altered levels of the synaptic proteins homer1 and synaptophysin. The versatility of zebrafish as a model for studying neurodevelopment and conducting drug screening will likely have a significant contribution to future studies of human SHANK3 function and ASD. En ligne : http://dx.doi.org/10.1186/s13229-018-0204-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354

Glutathione pathway gene variation and risk of autism spectrum disorders / K. BOWERS in Journal of Neurodevelopmental Disorders, 3-2 (June 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-2 (June 2011) . - p.132-43 Titre : Glutathione pathway gene variation and risk of autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : K. BOWERS, Auteur ; Q. LI, Auteur ; Jan BRESSLER, Auteur ; D. AVRAMOPOULOS, Auteur ; C. NEWSCHAFFER, Auteur ; M. D. FALLIN, Auteur Article en page(s) : p.132-43 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Despite evidence that autism is highly heritable with estimates of 15 or more genes involved, few studies have directly examined associations of multiple gene interactions. Since inability to effectively combat oxidative stress has been suggested as a mechanism of autism, we examined genetic variation 42 genes (308 single-nucleotide polymorphisms (SNPs)) related to glutathione, the most important antioxidant in the brain, for both marginal association and multi-gene interaction among 318 case-parent trios from The Autism Genetic Resource Exchange. Models of multi-SNP interactions were estimated using the trio Logic Regression method. A three-SNP joint effect was observed for genotype combinations of SNPs in glutaredoxin, glutaredoxin 3 (GLRX3), and cystathione gamma lyase (CTH); OR = 3.78, 95% CI: 2.36, 6.04. Marginal associations were observed for four genes including two involved in the three-way interaction: CTH, alcohol dehydrogenase 5, gamma-glutamylcysteine synthetase, catalytic subunit and GLRX3. These results suggest that variation in genes involved in counterbalancing oxidative stress may contribute to autism, though replication is necessary. En ligne : http://dx.doi.org/10.1007/s11689-011-9077-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Glutathione pathway gene variation and risk of autism spectrum disorders [Texte imprimé et/ou numérique] / K. BOWERS, Auteur ; Q. LI, Auteur ; Jan BRESSLER, Auteur ; D. AVRAMOPOULOS, Auteur ; C. NEWSCHAFFER, Auteur ; M. D. FALLIN, Auteur . - p.132-43. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-2 (June 2011) . - p.132-43 Index. décimale : PER Périodiques Résumé : Despite evidence that autism is highly heritable with estimates of 15 or more genes involved, few studies have directly examined associations of multiple gene interactions. Since inability to effectively combat oxidative stress has been suggested as a mechanism of autism, we examined genetic variation 42 genes (308 single-nucleotide polymorphisms (SNPs)) related to glutathione, the most important antioxidant in the brain, for both marginal association and multi-gene interaction among 318 case-parent trios from The Autism Genetic Resource Exchange. Models of multi-SNP interactions were estimated using the trio Logic Regression method. A three-SNP joint effect was observed for genotype combinations of SNPs in glutaredoxin, glutaredoxin 3 (GLRX3), and cystathione gamma lyase (CTH); OR = 3.78, 95% CI: 2.36, 6.04. Marginal associations were observed for four genes including two involved in the three-way interaction: CTH, alcohol dehydrogenase 5, gamma-glutamylcysteine synthetase, catalytic subunit and GLRX3. These results suggest that variation in genes involved in counterbalancing oxidative stress may contribute to autism, though replication is necessary. En ligne : http://dx.doi.org/10.1007/s11689-011-9077-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

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