Dépouillements

Commentary on "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" / George M. ANDERSON in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 20p. Titre : Commentary on "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" Type de document : Texte imprimé et/ou numérique Auteurs : George M. ANDERSON, Auteur ; Edwin H. Jr COOK, Auteur Article en page(s) : 20p. Langues : Anglais (eng) Mots-clés : 5-ht  Autism  Hyperserotonemia  Platelet aggregation  Platelet count  Platelet functioning  Platelet release  Serotonin Index. décimale : PER Périodiques Résumé : We comment on the recent report entitled "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" [Molecular Autism 2015;6:57]. We find it commendable that the authors have investigated platelet factors potentially involved in the well-replicated observation of platelet hyperserotonemia in autism. However, we believe the results need a fuller discussion in the context of prior studies, think that certain aspects of the interpretation need to be reassessed, and attempt to provide a framework for further research in this area. En ligne : http://dx.doi.org/10.1186/s13229-016-0086-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Commentary on "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" [Texte imprimé et/ou numérique] / George M. ANDERSON, Auteur ; Edwin H. Jr COOK, Auteur . - 20p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 20p. Mots-clés : 5-ht  Autism  Hyperserotonemia  Platelet aggregation  Platelet count  Platelet functioning  Platelet release  Serotonin Index. décimale : PER Périodiques Résumé : We comment on the recent report entitled "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" [Molecular Autism 2015;6:57]. We find it commendable that the authors have investigated platelet factors potentially involved in the well-replicated observation of platelet hyperserotonemia in autism. However, we believe the results need a fuller discussion in the context of prior studies, think that certain aspects of the interpretation need to be reassessed, and attempt to provide a framework for further research in this area. En ligne : http://dx.doi.org/10.1186/s13229-016-0086-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Overexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment / A. BANERJEE in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 16p. Titre : Overexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment Type de document : Texte imprimé et/ou numérique Auteurs : A. BANERJEE, Auteur ; J. A. LUONG, Auteur ; A. HO, Auteur ; A. O. SAIB, Auteur ; J. E. PLOSKI, Auteur Article en page(s) : 16p. Langues : Anglais (eng) Mots-clés : Acoustic Stimulation  Animals  Autism Spectrum Disorder/etiology  Basolateral Nuclear Complex/drug effects/metabolism  Carrier Proteins/biosynthesis/genetics/physiology  Conditioning, Classical/physiology  Disease Models, Animal  Electroshock  Exploratory Behavior/drug effects/physiology  Fear/drug effects/physiology  Female  Freezing Reaction, Cataleptic  Gene Expression Regulation/drug effects  Genetic Vectors/administration & dosage/genetics  Homer Scaffolding Proteins  Nerve Tissue Proteins/biosynthesis/genetics/physiology  Pregnancy  Prenatal Exposure Delayed Effects  RNA, Messenger/biosynthesis  Rats  Recombinant Fusion Proteins/biosynthesis/genetics  Social Behavior  Teratogens/pharmacology  Transduction, Genetic  Valproic Acid/pharmacology  Amygdala  Autism  Emotion  Homer1a  Learning  Memory  Pavlovian fear conditioning  Valproic acid Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASDs) represent a heterogeneous group of disorders with a wide range of behavioral impairments including social and communication deficits. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety, and some studies indicate that a subset of ASD individuals have a reduced ability to be fear conditioned. Deciphering the molecular basis of ASD has been considerably challenging and it currently remains poorly understood. In this study we examined the molecular basis of autism-like impairments in an environmentally induced animal model of ASD, where pregnant rats are exposed to the known teratogen, valproic acid (VPA), on day 12.5 of gestation and the subsequent progeny exhibit ASD-like symptoms. We focused our analysis on the basal and lateral nucleus of the amygdala (BLA), a region of the brain found to be associated with ASD pathology. METHODS: We performed whole genome gene expression analysis on the BLA using DNA microarrays to examine differences in gene expression within the amygdala of VPA-exposed animals. We validated one VPA-dysregulated candidate gene (Homer1a) using both quantitative PCR (qRT-PCR) and western blot. Finally, we overexpressed Homer1a within the basal and lateral amygdala of naive animals utilizing adeno-associated viruses (AAV) and subsequently examined these animals in a battery of behavioral tests associated with ASD, including auditory fear conditioning, social interaction and open field. RESULTS: Our microarray data indicated that Homer1a was one of the genes which exhibited a significant upregulation within the amygdala. We observed an increase in Homer1a messenger RNA (mRNA) and protein in multiple cohorts of VPA-exposed animals indicating that dysregulation of Homer1a levels might underlie some of the symptoms exhibited by VPA-exposed animals. To test this hypothesis, we overexpressed Homer1a within BLA neurons utilizing a viral-mediated approach and found that overexpression of Homer1a impaired auditory fear conditioning and reduced social interaction, while having no influence on open-field behavior. CONCLUSIONS: This study indicates that dysregulation of amygdala Homer1a might contribute to some autism-like symptoms induced by VPA exposure. These findings are interesting in part because Homer1a influences the functioning of Shank3, metabotropic glutamate receptors (mGluR5), and Homer1, and these proteins have previously been associated with ASD, indicating that these differing models of ASD may have a similar molecular basis. En ligne : http://dx.doi.org/10.1186/s13229-016-0077-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Overexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment [Texte imprimé et/ou numérique] / A. BANERJEE, Auteur ; J. A. LUONG, Auteur ; A. HO, Auteur ; A. O. SAIB, Auteur ; J. E. PLOSKI, Auteur . - 16p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 16p. Mots-clés : Acoustic Stimulation  Animals  Autism Spectrum Disorder/etiology  Basolateral Nuclear Complex/drug effects/metabolism  Carrier Proteins/biosynthesis/genetics/physiology  Conditioning, Classical/physiology  Disease Models, Animal  Electroshock  Exploratory Behavior/drug effects/physiology  Fear/drug effects/physiology  Female  Freezing Reaction, Cataleptic  Gene Expression Regulation/drug effects  Genetic Vectors/administration & dosage/genetics  Homer Scaffolding Proteins  Nerve Tissue Proteins/biosynthesis/genetics/physiology  Pregnancy  Prenatal Exposure Delayed Effects  RNA, Messenger/biosynthesis  Rats  Recombinant Fusion Proteins/biosynthesis/genetics  Social Behavior  Teratogens/pharmacology  Transduction, Genetic  Valproic Acid/pharmacology  Amygdala  Autism  Emotion  Homer1a  Learning  Memory  Pavlovian fear conditioning  Valproic acid Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASDs) represent a heterogeneous group of disorders with a wide range of behavioral impairments including social and communication deficits. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety, and some studies indicate that a subset of ASD individuals have a reduced ability to be fear conditioned. Deciphering the molecular basis of ASD has been considerably challenging and it currently remains poorly understood. In this study we examined the molecular basis of autism-like impairments in an environmentally induced animal model of ASD, where pregnant rats are exposed to the known teratogen, valproic acid (VPA), on day 12.5 of gestation and the subsequent progeny exhibit ASD-like symptoms. We focused our analysis on the basal and lateral nucleus of the amygdala (BLA), a region of the brain found to be associated with ASD pathology. METHODS: We performed whole genome gene expression analysis on the BLA using DNA microarrays to examine differences in gene expression within the amygdala of VPA-exposed animals. We validated one VPA-dysregulated candidate gene (Homer1a) using both quantitative PCR (qRT-PCR) and western blot. Finally, we overexpressed Homer1a within the basal and lateral amygdala of naive animals utilizing adeno-associated viruses (AAV) and subsequently examined these animals in a battery of behavioral tests associated with ASD, including auditory fear conditioning, social interaction and open field. RESULTS: Our microarray data indicated that Homer1a was one of the genes which exhibited a significant upregulation within the amygdala. We observed an increase in Homer1a messenger RNA (mRNA) and protein in multiple cohorts of VPA-exposed animals indicating that dysregulation of Homer1a levels might underlie some of the symptoms exhibited by VPA-exposed animals. To test this hypothesis, we overexpressed Homer1a within BLA neurons utilizing a viral-mediated approach and found that overexpression of Homer1a impaired auditory fear conditioning and reduced social interaction, while having no influence on open-field behavior. CONCLUSIONS: This study indicates that dysregulation of amygdala Homer1a might contribute to some autism-like symptoms induced by VPA exposure. These findings are interesting in part because Homer1a influences the functioning of Shank3, metabotropic glutamate receptors (mGluR5), and Homer1, and these proteins have previously been associated with ASD, indicating that these differing models of ASD may have a similar molecular basis. En ligne : http://dx.doi.org/10.1186/s13229-016-0077-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Erratum to: Sex differences in the association between infant markers and later autistic traits / Rachael BEDFORD in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 33p. Titre : Erratum to: Sex differences in the association between infant markers and later autistic traits Type de document : Texte imprimé et/ou numérique Auteurs : Rachael BEDFORD, Auteur ; E. J. JONES, Auteur ; M. H. JOHNSON, Auteur ; A. PICKLES, Auteur ; Tony CHARMAN, Auteur ; T. GLIGA, Auteur Article en page(s) : 33p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-016-0094-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Erratum to: Sex differences in the association between infant markers and later autistic traits [Texte imprimé et/ou numérique] / Rachael BEDFORD, Auteur ; E. J. JONES, Auteur ; M. H. JOHNSON, Auteur ; A. PICKLES, Auteur ; Tony CHARMAN, Auteur ; T. GLIGA, Auteur . - 33p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 33p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-016-0094-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Sex differences in the association between infant markers and later autistic traits / Rachael BEDFORD in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 21p. Titre : Sex differences in the association between infant markers and later autistic traits Type de document : Texte imprimé et/ou numérique Auteurs : Rachael BEDFORD, Auteur ; E. J. JONES, Auteur ; M. H. JOHNSON, Auteur ; A. PICKLES, Auteur ; Tony CHARMAN, Auteur ; T. GLIGA, Auteur Article en page(s) : 21p. Langues : Anglais (eng) Mots-clés : Attention/physiology  Autism Spectrum Disorder/diagnosis/pathology  Female  Fixation, Ocular/physiology  Humans  Infant  Male  Phenotype  Risk Factors  Severity of Illness Index  Sex Factors  Siblings  Surveys and Questionnaires  Video Recording  Autism  Differential liability  High risk  Infants  Sex difference Index. décimale : PER Périodiques Résumé : BACKGROUND: Although it is well established that the prevalence of autism spectrum disorder (ASD) is higher in males than females, there is relatively little understanding of the underlying mechanisms and their developmental time course. Sex-specific protective or risk factors have often been invoked to explain these differences, but such factors are yet to be identified. METHODS: We take a developmental approach, using a prospective sample of 104 infants at high and low familial risk for ASD, to characterise sex differences in infant markers known to predict emerging autism symptoms. We examine three markers previously shown to be associated with later autistic social-communication symptoms: the Autism Observation Scale for Infants (AOSI) total score, attention disengagement speed and gaze following behaviour. Our aim was to test whether sex differences were already present in these markers at 1 year of age, which would suggest sex-specific mechanisms of risk or protection. RESULTS: While no sex differences were found in any of the three markers investigated, we found sex differences in their relationship to 3-year autism traits; all three markers significantly predicted later autism traits only in the boys. CONCLUSIONS: Previously identified 'early autism markers' were associated with later autism symptoms only in boys. This suggests that there may be additional moderating risk or protective factors which remain to be identified. Our findings have important implications for prospective studies in terms of directly testing for the moderating effect of sex on emerging autistic traits. En ligne : http://dx.doi.org/10.1186/s13229-016-0081-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Sex differences in the association between infant markers and later autistic traits [Texte imprimé et/ou numérique] / Rachael BEDFORD, Auteur ; E. J. JONES, Auteur ; M. H. JOHNSON, Auteur ; A. PICKLES, Auteur ; Tony CHARMAN, Auteur ; T. GLIGA, Auteur . - 21p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 21p. Mots-clés : Attention/physiology  Autism Spectrum Disorder/diagnosis/pathology  Female  Fixation, Ocular/physiology  Humans  Infant  Male  Phenotype  Risk Factors  Severity of Illness Index  Sex Factors  Siblings  Surveys and Questionnaires  Video Recording  Autism  Differential liability  High risk  Infants  Sex difference Index. décimale : PER Périodiques Résumé : BACKGROUND: Although it is well established that the prevalence of autism spectrum disorder (ASD) is higher in males than females, there is relatively little understanding of the underlying mechanisms and their developmental time course. Sex-specific protective or risk factors have often been invoked to explain these differences, but such factors are yet to be identified. METHODS: We take a developmental approach, using a prospective sample of 104 infants at high and low familial risk for ASD, to characterise sex differences in infant markers known to predict emerging autism symptoms. We examine three markers previously shown to be associated with later autistic social-communication symptoms: the Autism Observation Scale for Infants (AOSI) total score, attention disengagement speed and gaze following behaviour. Our aim was to test whether sex differences were already present in these markers at 1 year of age, which would suggest sex-specific mechanisms of risk or protection. RESULTS: While no sex differences were found in any of the three markers investigated, we found sex differences in their relationship to 3-year autism traits; all three markers significantly predicted later autism traits only in the boys. CONCLUSIONS: Previously identified 'early autism markers' were associated with later autism symptoms only in boys. This suggests that there may be additional moderating risk or protective factors which remain to be identified. Our findings have important implications for prospective studies in terms of directly testing for the moderating effect of sex on emerging autistic traits. En ligne : http://dx.doi.org/10.1186/s13229-016-0081-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density / S. R. BERKOWICZ in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 22p. Titre : Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density Type de document : Texte imprimé et/ou numérique Auteurs : S. R. BERKOWICZ, Auteur ; T. J. FEATHERBY, Auteur ; Z. QU, Auteur ; A. GIOUSOH, Auteur ; N. A. BORG, Auteur ; J. I. HENG, Auteur ; J. C. WHISSTOCK, Auteur ; P. I. BIRD, Auteur Article en page(s) : 22p. Langues : Anglais (eng) Mots-clés : Animals  Attention Deficit Disorder with Hyperactivity/metabolism/pathology  Autism Spectrum Disorder/metabolism/pathology  Behavior, Animal  Brain/metabolism/pathology  Disease Models, Animal  Female  Genotype  Glycoproteins/genetics/metabolism  Interneurons/metabolism  Male  Memory, Short-Term  Mice  Mice, Inbred C57BL  Mice, Knockout  Motor Activity  Nerve Tissue Proteins/deficiency/genetics/metabolism  Parvalbumins/genetics/metabolism  Phenotype  Real-Time Polymerase Chain Reaction  Vocalization, Animal  Autism spectrum disorder  Brinp1  Cortex  Hyperactivity  Interneuron  Knock-out  Neurodevelopment  Parvalbumin Index. décimale : PER Périodiques Résumé : BACKGROUND: BMP/RA-inducible neural-specific protein 1 (Brinp1) is highly conserved in vertebrates, and continuously expressed in the neocortex, hippocampus, olfactory bulb and cerebellum from mid-embryonic development through to adulthood. METHODS: Brinp1 knock-out (Brinp1(-/-)) mice were generated by Cre-recombinase-mediated removal of the third exon of Brinp1. Knock-out mice were characterised by behavioural phenotyping, immunohistochemistry and expression analysis of the developing and adult brain. RESULTS: Absence of Brinp1 during development results in a behavioural phenotype resembling autism spectrum disorder (ASD), in which knock-out mice show reduced sociability and changes in vocalisation capacity. In addition, Brinp1(-/-) mice exhibit hyper-locomotor activity, have impaired short-term memory, and exhibit poor reproductive success. Brinp1(-/-) mice show increased density of parvalbumin-expressing interneurons in the adult mouse brain. Brinp1(-/-) mice do not show signs of altered neural precursor proliferation or increased apoptosis during late embryonic brain development. The expression of the related neuronal migration genes Astn1 and Astn2 is increased in the brains of Brinp1(-/-) mice, suggesting that they may ameliorate the effects of Brinp1 loss. CONCLUSIONS: Brinp1 plays an important role in normal brain development and function by influencing neuronal distribution within the cortex. The increased cortical PV-positive interneuron density and altered behaviour of Brinp1(-/-) mice resemble features of a subset of human neurological disorders; namely autism spectrum disorder (ASD) and the hyperactivity aspect of attention deficit hyperactivity disorder (ADHD). En ligne : http://dx.doi.org/10.1186/s13229-016-0079-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density [Texte imprimé et/ou numérique] / S. R. BERKOWICZ, Auteur ; T. J. FEATHERBY, Auteur ; Z. QU, Auteur ; A. GIOUSOH, Auteur ; N. A. BORG, Auteur ; J. I. HENG, Auteur ; J. C. WHISSTOCK, Auteur ; P. I. BIRD, Auteur . - 22p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 22p. Mots-clés : Animals  Attention Deficit Disorder with Hyperactivity/metabolism/pathology  Autism Spectrum Disorder/metabolism/pathology  Behavior, Animal  Brain/metabolism/pathology  Disease Models, Animal  Female  Genotype  Glycoproteins/genetics/metabolism  Interneurons/metabolism  Male  Memory, Short-Term  Mice  Mice, Inbred C57BL  Mice, Knockout  Motor Activity  Nerve Tissue Proteins/deficiency/genetics/metabolism  Parvalbumins/genetics/metabolism  Phenotype  Real-Time Polymerase Chain Reaction  Vocalization, Animal  Autism spectrum disorder  Brinp1  Cortex  Hyperactivity  Interneuron  Knock-out  Neurodevelopment  Parvalbumin Index. décimale : PER Périodiques Résumé : BACKGROUND: BMP/RA-inducible neural-specific protein 1 (Brinp1) is highly conserved in vertebrates, and continuously expressed in the neocortex, hippocampus, olfactory bulb and cerebellum from mid-embryonic development through to adulthood. METHODS: Brinp1 knock-out (Brinp1(-/-)) mice were generated by Cre-recombinase-mediated removal of the third exon of Brinp1. Knock-out mice were characterised by behavioural phenotyping, immunohistochemistry and expression analysis of the developing and adult brain. RESULTS: Absence of Brinp1 during development results in a behavioural phenotype resembling autism spectrum disorder (ASD), in which knock-out mice show reduced sociability and changes in vocalisation capacity. In addition, Brinp1(-/-) mice exhibit hyper-locomotor activity, have impaired short-term memory, and exhibit poor reproductive success. Brinp1(-/-) mice show increased density of parvalbumin-expressing interneurons in the adult mouse brain. Brinp1(-/-) mice do not show signs of altered neural precursor proliferation or increased apoptosis during late embryonic brain development. The expression of the related neuronal migration genes Astn1 and Astn2 is increased in the brains of Brinp1(-/-) mice, suggesting that they may ameliorate the effects of Brinp1 loss. CONCLUSIONS: Brinp1 plays an important role in normal brain development and function by influencing neuronal distribution within the cortex. The increased cortical PV-positive interneuron density and altered behaviour of Brinp1(-/-) mice resemble features of a subset of human neurological disorders; namely autism spectrum disorder (ASD) and the hyperactivity aspect of attention deficit hyperactivity disorder (ADHD). En ligne : http://dx.doi.org/10.1186/s13229-016-0079-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Synaptic vesicle dynamic changes in a model of fragile X / Jantine A.C. BROEK in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 17p. Titre : Synaptic vesicle dynamic changes in a model of fragile X Type de document : Texte imprimé et/ou numérique Auteurs : Jantine A.C. BROEK, Auteur ; Z. LIN, Auteur ; H. M. DE GRUITER, Auteur ; H. VAN 'T SPIJKER, Auteur ; E. D. HAASDIJK, Auteur ; David COX, Auteur ; S. OZCAN, Auteur ; G. W. A. VAN CAPPELLEN, Auteur ; A. B. HOUTSMULLER, Auteur ; R. WILLEMSEN, Auteur ; C. I. DE ZEEUW, Auteur ; S. BAHN, Auteur Article en page(s) : 17p. Langues : Anglais (eng) Mots-clés : Animals  Animals, Congenic  Cells, Cultured  Cerebellum/pathology/physiopathology  Fluorescent Dyes  Fragile X Mental Retardation Protein/genetics/physiology  Fragile X Syndrome/genetics/metabolism/physiopathology  Hippocampus/pathology/physiopathology  Intravital Microscopy  Male  Mass Spectrometry/methods  Mice  Mice, Inbred C57BL  Mice, Knockout  Mice, Neurologic Mutants  Microscopy, Electron  Models, Animal  Nerve Tissue Proteins/analysis  Presynaptic Terminals/secretion  Proteome  Purkinje Cells/physiology/ultrastructure  Pyridinium Compounds  Quaternary Ammonium Compounds  Signal Transduction  Synaptic Transmission  Synaptic Vesicles/metabolism  Synaptosomes/metabolism  Electron microscopy  Fragile X syndrome (FXS)  Mass spectrometry (MS)  Quantitative live-cell imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. METHODS: Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MS(E)) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. RESULTS: Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. CONCLUSIONS: Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS. En ligne : http://dx.doi.org/10.1186/s13229-016-0080-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Synaptic vesicle dynamic changes in a model of fragile X [Texte imprimé et/ou numérique] / Jantine A.C. BROEK, Auteur ; Z. LIN, Auteur ; H. M. DE GRUITER, Auteur ; H. VAN 'T SPIJKER, Auteur ; E. D. HAASDIJK, Auteur ; David COX, Auteur ; S. OZCAN, Auteur ; G. W. A. VAN CAPPELLEN, Auteur ; A. B. HOUTSMULLER, Auteur ; R. WILLEMSEN, Auteur ; C. I. DE ZEEUW, Auteur ; S. BAHN, Auteur . - 17p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 17p. Mots-clés : Animals  Animals, Congenic  Cells, Cultured  Cerebellum/pathology/physiopathology  Fluorescent Dyes  Fragile X Mental Retardation Protein/genetics/physiology  Fragile X Syndrome/genetics/metabolism/physiopathology  Hippocampus/pathology/physiopathology  Intravital Microscopy  Male  Mass Spectrometry/methods  Mice  Mice, Inbred C57BL  Mice, Knockout  Mice, Neurologic Mutants  Microscopy, Electron  Models, Animal  Nerve Tissue Proteins/analysis  Presynaptic Terminals/secretion  Proteome  Purkinje Cells/physiology/ultrastructure  Pyridinium Compounds  Quaternary Ammonium Compounds  Signal Transduction  Synaptic Transmission  Synaptic Vesicles/metabolism  Synaptosomes/metabolism  Electron microscopy  Fragile X syndrome (FXS)  Mass spectrometry (MS)  Quantitative live-cell imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. METHODS: Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MS(E)) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. RESULTS: Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. CONCLUSIONS: Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS. En ligne : http://dx.doi.org/10.1186/s13229-016-0080-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression / Emily L. CASANOVA in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 18p. Titre : Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression Type de document : Texte imprimé et/ou numérique Auteurs : Emily L. CASANOVA, Auteur ; J. L. SHARP, Auteur ; H. CHAKRABORTY, Auteur ; N. S. SUMI, Auteur ; Manuel F. CASANOVA, Auteur Article en page(s) : 18p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/epidemiology/genetics/psychology  Autistic Disorder/epidemiology/genetics/psychology  Body Patterning/genetics  Cell Nucleus/metabolism  Chromatin Assembly and Disassembly/genetics  Comorbidity  Databases, Genetic  Epigenomics  Epilepsy/epidemiology/genetics/psychology  Gene Expression Regulation  Gene Ontology  Genetic Association Studies  Humans  Intellectual Disability/epidemiology/genetics  Nerve Tissue Proteins/genetics/physiology  Neurogenesis/genetics  Nuclear Proteins/genetics/physiology  Penetrance  Protein Interaction Maps/genetics  Risk  Syndrome  Body patterning  Chromatin assembly and disassembly  Epilepsy  Mental retardation  Regulation of gene expression Index. décimale : PER Périodiques Résumé : BACKGROUND: Intellectual disability (ID), autism, and epilepsy share frequent yet variable comorbidities with one another. In order to better understand potential genetic divergence underlying this variable risk, we studied genes responsible for monogenic IDs, grouped according to their autism and epilepsy comorbidities. METHODS: Utilizing 465 different forms of ID with known molecular origins, we accessed available genetic databases in conjunction with gene ontology (GO) to determine whether the genetics underlying ID diverge according to its comorbidities with autism and epilepsy and if genes highly penetrant for autism or epilepsy share distinctive features that set them apart from genes that confer comparatively variable or no apparent risk. RESULTS: The genetics of ID with autism are relatively enriched in terms associated with nervous system-specific processes and structural morphogenesis. In contrast, we find that ID with highly comorbid epilepsy (HCE) is modestly associated with lipid metabolic processes while ID without autism or epilepsy comorbidity (ID only) is enriched at the Golgi membrane. Highly comorbid autism (HCA) genes, on the other hand, are strongly enriched within the nucleus, are typically involved in regulation of gene expression, and, along with IDs with more variable autism, share strong ties with a core protein-protein interaction (PPI) network integral to basic patterning of the CNS. CONCLUSIONS: According to GO terminology, autism-related gene products are integral to neural development. While it is difficult to draw firm conclusions regarding IDs unassociated with autism, it is clear that the majority of HCA genes are tightly linked with general dysregulation of gene expression, suggesting that disturbances to the chronology of neural maturation and patterning may be key in conferring susceptibility to autism spectrum conditions. En ligne : http://dx.doi.org/10.1186/s13229-016-0082-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression [Texte imprimé et/ou numérique] / Emily L. CASANOVA, Auteur ; J. L. SHARP, Auteur ; H. CHAKRABORTY, Auteur ; N. S. SUMI, Auteur ; Manuel F. CASANOVA, Auteur . - 18p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 18p. Mots-clés : Autism Spectrum Disorder/epidemiology/genetics/psychology  Autistic Disorder/epidemiology/genetics/psychology  Body Patterning/genetics  Cell Nucleus/metabolism  Chromatin Assembly and Disassembly/genetics  Comorbidity  Databases, Genetic  Epigenomics  Epilepsy/epidemiology/genetics/psychology  Gene Expression Regulation  Gene Ontology  Genetic Association Studies  Humans  Intellectual Disability/epidemiology/genetics  Nerve Tissue Proteins/genetics/physiology  Neurogenesis/genetics  Nuclear Proteins/genetics/physiology  Penetrance  Protein Interaction Maps/genetics  Risk  Syndrome  Body patterning  Chromatin assembly and disassembly  Epilepsy  Mental retardation  Regulation of gene expression Index. décimale : PER Périodiques Résumé : BACKGROUND: Intellectual disability (ID), autism, and epilepsy share frequent yet variable comorbidities with one another. In order to better understand potential genetic divergence underlying this variable risk, we studied genes responsible for monogenic IDs, grouped according to their autism and epilepsy comorbidities. METHODS: Utilizing 465 different forms of ID with known molecular origins, we accessed available genetic databases in conjunction with gene ontology (GO) to determine whether the genetics underlying ID diverge according to its comorbidities with autism and epilepsy and if genes highly penetrant for autism or epilepsy share distinctive features that set them apart from genes that confer comparatively variable or no apparent risk. RESULTS: The genetics of ID with autism are relatively enriched in terms associated with nervous system-specific processes and structural morphogenesis. In contrast, we find that ID with highly comorbid epilepsy (HCE) is modestly associated with lipid metabolic processes while ID without autism or epilepsy comorbidity (ID only) is enriched at the Golgi membrane. Highly comorbid autism (HCA) genes, on the other hand, are strongly enriched within the nucleus, are typically involved in regulation of gene expression, and, along with IDs with more variable autism, share strong ties with a core protein-protein interaction (PPI) network integral to basic patterning of the CNS. CONCLUSIONS: According to GO terminology, autism-related gene products are integral to neural development. While it is difficult to draw firm conclusions regarding IDs unassociated with autism, it is clear that the majority of HCA genes are tightly linked with general dysregulation of gene expression, suggesting that disturbances to the chronology of neural maturation and patterning may be key in conferring susceptibility to autism spectrum conditions. En ligne : http://dx.doi.org/10.1186/s13229-016-0082-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Dyspraxia and autistic traits in adults with and without autism spectrum conditions / Sarah A. CASSIDY in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 48p. Titre : Dyspraxia and autistic traits in adults with and without autism spectrum conditions Type de document : Texte imprimé et/ou numérique Auteurs : Sarah A. CASSIDY, Auteur ; P. HANNANT, Auteur ; Teresa TAVASSOLI, Auteur ; Carrie ALLISON, Auteur ; P. SMITH, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 48p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Aged  Apraxias/complications/physiopathology/psychology  Autism Spectrum Disorder/complications/physiopathology/psychology  Autistic Disorder/complications/physiopathology/psychology  Case-Control Studies  Empathy  Female  Humans  Male  Middle Aged  Phenotype  Psychological Tests  Psychomotor Performance  Social Skills  Surveys and Questionnaires  Autism spectrum conditions  Autistic traits  Co-morbidity  Dyspraxia Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum conditions (ASC) are frequently associated with motor coordination difficulties. However, no studies have explored the prevalence of dyspraxia in a large sample of individuals with and without ASC or associations between dyspraxia and autistic traits in these individuals. METHODS: Two thousand eight hundred seventy-one adults (with ASC) and 10,706 controls (without ASC) self-reported whether they have been diagnosed with dyspraxia. A subsample of participants then completed the Autism Spectrum Quotient (AQ; 1237 ASC and 6765 controls) and the Empathy Quotient (EQ; 1147 ASC and 6129 controls) online through the Autism Research Centre website. The prevalence of dyspraxia was compared between those with and without ASC. AQ and EQ scores were compared across the four groups: (1) adults with ASC with dyspraxia, (2) adults with ASC without dyspraxia, (3) controls with dyspraxia, and (4) controls without dyspraxia. RESULTS: Adults with ASC were significantly more likely to report a diagnosis of dyspraxia (6.9%) than those without ASC (0.8%). In the ASC group, those with co-morbid diagnosis of dyspraxia did not have significantly different AQ or EQ scores than those without co-morbid dyspraxia. However, in the control group (without ASC), those with dyspraxia had significantly higher AQ and lower EQ scores than those without dyspraxia. CONCLUSIONS: Dyspraxia is significantly more prevalent in adults with ASC compared to controls, confirming reports that motor coordination difficulties are significantly more common in this group. Interestingly, in the general population, dyspraxia was associated with significantly higher autistic traits and lower empathy. These results suggest that motor coordination skills are important for effective social skills and empathy. En ligne : http://dx.doi.org/10.1186/s13229-016-0112-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Dyspraxia and autistic traits in adults with and without autism spectrum conditions [Texte imprimé et/ou numérique] / Sarah A. CASSIDY, Auteur ; P. HANNANT, Auteur ; Teresa TAVASSOLI, Auteur ; Carrie ALLISON, Auteur ; P. SMITH, Auteur ; Simon BARON-COHEN, Auteur . - 48p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 48p. Mots-clés : Adolescent  Adult  Aged  Apraxias/complications/physiopathology/psychology  Autism Spectrum Disorder/complications/physiopathology/psychology  Autistic Disorder/complications/physiopathology/psychology  Case-Control Studies  Empathy  Female  Humans  Male  Middle Aged  Phenotype  Psychological Tests  Psychomotor Performance  Social Skills  Surveys and Questionnaires  Autism spectrum conditions  Autistic traits  Co-morbidity  Dyspraxia Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum conditions (ASC) are frequently associated with motor coordination difficulties. However, no studies have explored the prevalence of dyspraxia in a large sample of individuals with and without ASC or associations between dyspraxia and autistic traits in these individuals. METHODS: Two thousand eight hundred seventy-one adults (with ASC) and 10,706 controls (without ASC) self-reported whether they have been diagnosed with dyspraxia. A subsample of participants then completed the Autism Spectrum Quotient (AQ; 1237 ASC and 6765 controls) and the Empathy Quotient (EQ; 1147 ASC and 6129 controls) online through the Autism Research Centre website. The prevalence of dyspraxia was compared between those with and without ASC. AQ and EQ scores were compared across the four groups: (1) adults with ASC with dyspraxia, (2) adults with ASC without dyspraxia, (3) controls with dyspraxia, and (4) controls without dyspraxia. RESULTS: Adults with ASC were significantly more likely to report a diagnosis of dyspraxia (6.9%) than those without ASC (0.8%). In the ASC group, those with co-morbid diagnosis of dyspraxia did not have significantly different AQ or EQ scores than those without co-morbid dyspraxia. However, in the control group (without ASC), those with dyspraxia had significantly higher AQ and lower EQ scores than those without dyspraxia. CONCLUSIONS: Dyspraxia is significantly more prevalent in adults with ASC compared to controls, confirming reports that motor coordination difficulties are significantly more common in this group. Interestingly, in the general population, dyspraxia was associated with significantly higher autistic traits and lower empathy. These results suggest that motor coordination skills are important for effective social skills and empathy. En ligne : http://dx.doi.org/10.1186/s13229-016-0112-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Data from the Baby Siblings Research Consortium confirm and specify the nature of the female protective effect in autism: A commentary on Messinger et al / John N. CONSTANTINO in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 32p. Titre : Data from the Baby Siblings Research Consortium confirm and specify the nature of the female protective effect in autism: A commentary on Messinger et al Type de document : Texte imprimé et/ou numérique Auteurs : John N. CONSTANTINO, Auteur Article en page(s) : 32p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Compensatory  Female protective effect  Resilience  Sex Index. décimale : PER Périodiques Résumé : Sibling recurrence data from the Baby Siblings Research Consortium (BSRC) recapitulate results from very large clinical family studies that demonstrate the absence of the Carter effect and provide clarification of the nature of the female protective effect in ASD. This legacy prospective data collection confirmed marked differences in the proportions of males versus females who lie along deviant trajectories of social development in the setting of inherited liability to autism--a phenomenon which defines the female protective effect--and demonstrate that among affected children, sex differences are modest and homologous to those observed among non-ASD children. En ligne : http://dx.doi.org/10.1186/s13229-016-0092-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Data from the Baby Siblings Research Consortium confirm and specify the nature of the female protective effect in autism: A commentary on Messinger et al [Texte imprimé et/ou numérique] / John N. CONSTANTINO, Auteur . - 32p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 32p. Mots-clés : Autism spectrum disorder  Compensatory  Female protective effect  Resilience  Sex Index. décimale : PER Périodiques Résumé : Sibling recurrence data from the Baby Siblings Research Consortium (BSRC) recapitulate results from very large clinical family studies that demonstrate the absence of the Carter effect and provide clarification of the nature of the female protective effect in ASD. This legacy prospective data collection confirmed marked differences in the proportions of males versus females who lie along deviant trajectories of social development in the setting of inherited liability to autism--a phenomenon which defines the female protective effect--and demonstrate that among affected children, sex differences are modest and homologous to those observed among non-ASD children. En ligne : http://dx.doi.org/10.1186/s13229-016-0092-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Visual preference for social stimuli in individuals with autism or neurodevelopmental disorders: an eye-tracking study / Hayley CRAWFORD in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 24p. Titre : Visual preference for social stimuli in individuals with autism or neurodevelopmental disorders: an eye-tracking study Type de document : Texte imprimé et/ou numérique Auteurs : Hayley CRAWFORD, Auteur ; J. MOSS, Auteur ; C. OLIVER, Auteur ; N. ELLIOTT, Auteur ; George M. ANDERSON, Auteur ; J. P. MCCLEERY, Auteur Article en page(s) : 24p. Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder/physiopathology  Case-Control Studies  De Lange Syndrome/physiopathology  Eye Movements/physiology  Female  Fragile X Syndrome/physiopathology  Humans  Male  Photic Stimulation  Rubinstein-Taybi Syndrome/physiopathology  Social Behavior  Visual Perception/physiology  Autism spectrum disorder  Cornelia de Lange syndrome  Eye-tracking  Fragile X syndrome  Rubinstein-Taybi syndrome  Social attention Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent research has identified differences in relative attention to competing social versus non-social video stimuli in individuals with autism spectrum disorder (ASD). Whether attentional allocation is influenced by the potential threat of stimuli has yet to be investigated. This is manipulated in the current study by the extent to which the stimuli are moving towards or moving past the viewer. Furthermore, little is known about whether such differences exist across other neurodevelopmental disorders. This study aims to determine if adolescents with ASD demonstrate differences in attentional allocation to competing pairs of social and non-social video stimuli, where the actor or object either moves towards or moves past the viewer, in comparison to individuals without ASD, and to determine if individuals with three genetic syndromes associated with differing social phenotypes demonstrate differences in attentional allocation to the same stimuli. METHODS: In study 1, adolescents with ASD and control participants were presented with social and non-social video stimuli in two formats (moving towards or moving past the viewer) whilst their eye movements were recorded. This paradigm was then employed with groups of individuals with fragile X, Cornelia de Lange, and Rubinstein-Taybi syndromes who were matched with one another on chronological age, global adaptive behaviour, and verbal adaptive behaviour (study 2). RESULTS: Adolescents with ASD demonstrated reduced looking-time to social versus non-social videos only when stimuli were moving towards them. Individuals in the three genetic syndrome groups showed similar looking-time but differences in fixation latency for social stimuli moving towards them. Across both studies, we observed within- and between-group differences in attention to social stimuli that were moving towards versus moving past the viewer. CONCLUSIONS: Taken together, these results provide strong evidence to suggest differential visual attention to competing social versus non-social video stimuli in populations with clinically relevant, genetically mediated differences in socio-behavioural phenotypes. En ligne : http://dx.doi.org/10.1186/s13229-016-0084-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Visual preference for social stimuli in individuals with autism or neurodevelopmental disorders: an eye-tracking study [Texte imprimé et/ou numérique] / Hayley CRAWFORD, Auteur ; J. MOSS, Auteur ; C. OLIVER, Auteur ; N. ELLIOTT, Auteur ; George M. ANDERSON, Auteur ; J. P. MCCLEERY, Auteur . - 24p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 24p. Mots-clés : Adolescent  Autism Spectrum Disorder/physiopathology  Case-Control Studies  De Lange Syndrome/physiopathology  Eye Movements/physiology  Female  Fragile X Syndrome/physiopathology  Humans  Male  Photic Stimulation  Rubinstein-Taybi Syndrome/physiopathology  Social Behavior  Visual Perception/physiology  Autism spectrum disorder  Cornelia de Lange syndrome  Eye-tracking  Fragile X syndrome  Rubinstein-Taybi syndrome  Social attention Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent research has identified differences in relative attention to competing social versus non-social video stimuli in individuals with autism spectrum disorder (ASD). Whether attentional allocation is influenced by the potential threat of stimuli has yet to be investigated. This is manipulated in the current study by the extent to which the stimuli are moving towards or moving past the viewer. Furthermore, little is known about whether such differences exist across other neurodevelopmental disorders. This study aims to determine if adolescents with ASD demonstrate differences in attentional allocation to competing pairs of social and non-social video stimuli, where the actor or object either moves towards or moves past the viewer, in comparison to individuals without ASD, and to determine if individuals with three genetic syndromes associated with differing social phenotypes demonstrate differences in attentional allocation to the same stimuli. METHODS: In study 1, adolescents with ASD and control participants were presented with social and non-social video stimuli in two formats (moving towards or moving past the viewer) whilst their eye movements were recorded. This paradigm was then employed with groups of individuals with fragile X, Cornelia de Lange, and Rubinstein-Taybi syndromes who were matched with one another on chronological age, global adaptive behaviour, and verbal adaptive behaviour (study 2). RESULTS: Adolescents with ASD demonstrated reduced looking-time to social versus non-social videos only when stimuli were moving towards them. Individuals in the three genetic syndrome groups showed similar looking-time but differences in fixation latency for social stimuli moving towards them. Across both studies, we observed within- and between-group differences in attention to social stimuli that were moving towards versus moving past the viewer. CONCLUSIONS: Taken together, these results provide strong evidence to suggest differential visual attention to competing social versus non-social video stimuli in populations with clinically relevant, genetically mediated differences in socio-behavioural phenotypes. En ligne : http://dx.doi.org/10.1186/s13229-016-0084-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity / C. C. DOUGHERTY in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 28p. Titre : Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity Type de document : Texte imprimé et/ou numérique Auteurs : C. C. DOUGHERTY, Auteur ; D. W. EVANS, Auteur ; G. J. KATUWAL, Auteur ; A. M. MICHAEL, Auteur Article en page(s) : 28p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Algorithms  Autism Spectrum Disorder/diagnostic imaging/pathology  Child  Cross-Sectional Studies  Humans  Image Processing, Computer-Assisted  Magnetic Resonance Imaging  Male  Severity of Illness Index  Temporal Lobe/anatomy & histology  Young Adult  Asymmetry  Autism spectrum disorder  Development  Fusiform gyrus  Structural imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: While asymmetry in the fusiform gyrus (FFG) has been reported in functional and structural studies in typically developing controls (TDC), few studies have examined FFG asymmetry in autism spectrum disorder (ASD) subjects and those studies are limited by small sample sizes, and confounded by cognitive ability or handedness. No previous work has examined FFG surface area or cortical thickness asymmetry in ASD; nor do we understand the trajectory of FFG asymmetry over time. Finally, it is not known how FFG structural asymmetry relates to ASD symptom severity. METHODS: In this study, we examined FFG volume, surface area, and cortical thickness asymmetry, as well as their cross-sectional trajectories in a large sample of right-handed males aged 7 to 25 years with 128 ASD and 127 TDC subjects using general linear models. In addition, we examined the relationship between FFG asymmetry and ASD severity using the Autism Diagnostic Observation Schedule (ADOS) and Gotham autism severity scores. RESULTS: Findings revealed that while group differences were evident with mean leftward asymmetry in ASD and mean near symmetry in TDC volume and surface area, asymmetry for both groups existed on a spectrum encompassing leftward and rightward asymmetry. In ASD subjects, volume asymmetry was negatively associated with ADOS and autism severity score symptom measures, with a subset of rightward asymmetric patients being most severely affected. We also observed differential trajectory of surface area asymmetry: ASD subjects exhibited a change from leftward asymmetry toward symmetry from age 7 to 25, whereas TDCs exhibited the reverse trend with a change from near symmetry toward leftward symmetry over the observed age range. CONCLUSIONS: Abnormalities in FFG structural asymmetry are related to symptom severity in ASD and show differential developmental trajectory compared to TDC. This study is the first to note these findings. These results may have important implications for understanding the role of FFG asymmetry in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0089-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity [Texte imprimé et/ou numérique] / C. C. DOUGHERTY, Auteur ; D. W. EVANS, Auteur ; G. J. KATUWAL, Auteur ; A. M. MICHAEL, Auteur . - 28p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 28p. Mots-clés : Adolescent  Adult  Algorithms  Autism Spectrum Disorder/diagnostic imaging/pathology  Child  Cross-Sectional Studies  Humans  Image Processing, Computer-Assisted  Magnetic Resonance Imaging  Male  Severity of Illness Index  Temporal Lobe/anatomy & histology  Young Adult  Asymmetry  Autism spectrum disorder  Development  Fusiform gyrus  Structural imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: While asymmetry in the fusiform gyrus (FFG) has been reported in functional and structural studies in typically developing controls (TDC), few studies have examined FFG asymmetry in autism spectrum disorder (ASD) subjects and those studies are limited by small sample sizes, and confounded by cognitive ability or handedness. No previous work has examined FFG surface area or cortical thickness asymmetry in ASD; nor do we understand the trajectory of FFG asymmetry over time. Finally, it is not known how FFG structural asymmetry relates to ASD symptom severity. METHODS: In this study, we examined FFG volume, surface area, and cortical thickness asymmetry, as well as their cross-sectional trajectories in a large sample of right-handed males aged 7 to 25 years with 128 ASD and 127 TDC subjects using general linear models. In addition, we examined the relationship between FFG asymmetry and ASD severity using the Autism Diagnostic Observation Schedule (ADOS) and Gotham autism severity scores. RESULTS: Findings revealed that while group differences were evident with mean leftward asymmetry in ASD and mean near symmetry in TDC volume and surface area, asymmetry for both groups existed on a spectrum encompassing leftward and rightward asymmetry. In ASD subjects, volume asymmetry was negatively associated with ADOS and autism severity score symptom measures, with a subset of rightward asymmetric patients being most severely affected. We also observed differential trajectory of surface area asymmetry: ASD subjects exhibited a change from leftward asymmetry toward symmetry from age 7 to 25, whereas TDCs exhibited the reverse trend with a change from near symmetry toward leftward symmetry over the observed age range. CONCLUSIONS: Abnormalities in FFG structural asymmetry are related to symptom severity in ASD and show differential developmental trajectory compared to TDC. This study is the first to note these findings. These results may have important implications for understanding the role of FFG asymmetry in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0089-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Effect of co-twin gender on neurodevelopmental symptoms: a twin register study / J. M. ERIKSSON in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 8p. Titre : Effect of co-twin gender on neurodevelopmental symptoms: a twin register study Type de document : Texte imprimé et/ou numérique Auteurs : J. M. ERIKSSON, Auteur ; S. LUNDSTRÖM, Auteur ; P. LICHTENSTEIN, Auteur ; Susanne BEJEROT, Auteur ; E. ERIKSSON, Auteur Article en page(s) : 8p. Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics/physiopathology  Autism Spectrum Disorder/genetics/physiopathology  Child  Comorbidity  Diseases in Twins  Female  Follow-Up Studies  Gender Identity  Humans  Interview, Psychological  Male  Neurodevelopmental Disorders/genetics/physiopathology  Parents  Pregnancy  Prenatal Exposure Delayed Effects  Sex Characteristics  Stereotyped Behavior  Sweden/epidemiology  Testosterone/physiology  Tic Disorders/genetics/physiopathology  Twins, Dizygotic/psychology  Asperger syndrome  Attention-deficit hyperactivity disorders  Autistic disorder  Symptom assessment  Twin study Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders thought to have both genetic and environmental causes. It has been hypothesized that exposure to elevated levels of prenatal testosterone is associated with elevated traits of ASD and ADHD. Assuming that testosterone levels from a dizygotic male twin fetus may lead to enhanced testosterone exposure of its co-twins, we aimed to test the prenatal testosterone hypothesis by comparing same-sex with opposite-sex dizygotic twins with respect to neurodevelopmental symptoms. METHODS: Neuropsychiatric traits were assessed in a population-based twin cohort from the Child and Adolescent Twin Study in Sweden (CATSS). Parental interviews were conducted for 16,312 dizygotic twins, 9 and 12 years old, with the Autism-Tics, ADHD, and other Comorbidities inventory (A-TAC). RESULTS: Girls with a female co-twin had an increased risk of reaching the cut-off score for ADHD compared with girls with a male co-twin. Both boys and girls with a female co-twin displayed a larger number of traits related to attention deficit and repetitive and stereotyped behaviors than those with a male twin. In girls, this also extended to social interaction and the combined measures for ASD and ADHD, however, with small effect sizes. CONCLUSIONS: Our results are reverse to what would have been expected from the prenatal testosterone hypothesis but consistent with a previous study of ASD and ADHD traits in dizygotic twins. The seemingly protective effect for girls of having a twin brother may be an effect of parent report bias, but may also be an unexpected effect of sharing the intrauterine environment with a male co-twin. En ligne : http://dx.doi.org/10.1186/s13229-016-0074-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Effect of co-twin gender on neurodevelopmental symptoms: a twin register study [Texte imprimé et/ou numérique] / J. M. ERIKSSON, Auteur ; S. LUNDSTRÖM, Auteur ; P. LICHTENSTEIN, Auteur ; Susanne BEJEROT, Auteur ; E. ERIKSSON, Auteur . - 8p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 8p. Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics/physiopathology  Autism Spectrum Disorder/genetics/physiopathology  Child  Comorbidity  Diseases in Twins  Female  Follow-Up Studies  Gender Identity  Humans  Interview, Psychological  Male  Neurodevelopmental Disorders/genetics/physiopathology  Parents  Pregnancy  Prenatal Exposure Delayed Effects  Sex Characteristics  Stereotyped Behavior  Sweden/epidemiology  Testosterone/physiology  Tic Disorders/genetics/physiopathology  Twins, Dizygotic/psychology  Asperger syndrome  Attention-deficit hyperactivity disorders  Autistic disorder  Symptom assessment  Twin study Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders thought to have both genetic and environmental causes. It has been hypothesized that exposure to elevated levels of prenatal testosterone is associated with elevated traits of ASD and ADHD. Assuming that testosterone levels from a dizygotic male twin fetus may lead to enhanced testosterone exposure of its co-twins, we aimed to test the prenatal testosterone hypothesis by comparing same-sex with opposite-sex dizygotic twins with respect to neurodevelopmental symptoms. METHODS: Neuropsychiatric traits were assessed in a population-based twin cohort from the Child and Adolescent Twin Study in Sweden (CATSS). Parental interviews were conducted for 16,312 dizygotic twins, 9 and 12 years old, with the Autism-Tics, ADHD, and other Comorbidities inventory (A-TAC). RESULTS: Girls with a female co-twin had an increased risk of reaching the cut-off score for ADHD compared with girls with a male co-twin. Both boys and girls with a female co-twin displayed a larger number of traits related to attention deficit and repetitive and stereotyped behaviors than those with a male twin. In girls, this also extended to social interaction and the combined measures for ASD and ADHD, however, with small effect sizes. CONCLUSIONS: Our results are reverse to what would have been expected from the prenatal testosterone hypothesis but consistent with a previous study of ASD and ADHD traits in dizygotic twins. The seemingly protective effect for girls of having a twin brother may be an effect of parent report bias, but may also be an unexpected effect of sharing the intrauterine environment with a male co-twin. En ligne : http://dx.doi.org/10.1186/s13229-016-0074-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders / M. FIORENTINO in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 49p. Titre : Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : M. FIORENTINO, Auteur ; A. SAPONE, Auteur ; S. SENGER, Auteur ; S. S. CAMHI, Auteur ; S. M. KADZIELSKI, Auteur ; Timothy M. BUIE, Auteur ; D. L. KELLY, Auteur ; N. CASCELLA, Auteur ; A. FASANO, Auteur Article en page(s) : 49p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/genetics/immunology/metabolism/pathology  Biopsy  Blood-Brain Barrier/immunology/metabolism/pathology  Case-Control Studies  Cerebellum/immunology/metabolism/pathology  Cerebral Cortex/immunology/metabolism/pathology  Child  Child, Preschool  Claudin-3/genetics/immunology  Claudin-5/genetics/immunology  Claudins/genetics/immunology  DNA-Binding Proteins/genetics/immunology  Duodenum/immunology/metabolism/pathology  Female  Gene Expression  Humans  Interleukin-1beta/genetics/immunology  Interleukin-8/genetics/immunology  MARVEL Domain Containing 2 Protein/genetics/immunology  Male  Matrix Metalloproteinase 9/genetics/immunology  Middle Aged  Permeability  Schizophrenia/genetics/immunology/metabolism/pathology  Tight Junctions/immunology/metabolism/pathology  Autism spectrum disorders  Blood-brain barrier  Duodenal biopsies  Gut permeability  Gut-brain axis  Neuroinflammation  Postmortem brain  Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. METHODS: Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. RESULTS: Claudin (CLDN)-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3, tricellulin, and MMP-9 were higher in the ASD cortex. IL-8, tPA, and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components (CLDN-1, OCLN, TRIC), whereas 66% had increased pore-forming CLDNs (CLDN-2, -10, -15) compared to controls. CONCLUSIONS: In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies. En ligne : http://dx.doi.org/10.1186/s13229-016-0110-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders [Texte imprimé et/ou numérique] / M. FIORENTINO, Auteur ; A. SAPONE, Auteur ; S. SENGER, Auteur ; S. S. CAMHI, Auteur ; S. M. KADZIELSKI, Auteur ; Timothy M. BUIE, Auteur ; D. L. KELLY, Auteur ; N. CASCELLA, Auteur ; A. FASANO, Auteur . - 49p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 49p. Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/genetics/immunology/metabolism/pathology  Biopsy  Blood-Brain Barrier/immunology/metabolism/pathology  Case-Control Studies  Cerebellum/immunology/metabolism/pathology  Cerebral Cortex/immunology/metabolism/pathology  Child  Child, Preschool  Claudin-3/genetics/immunology  Claudin-5/genetics/immunology  Claudins/genetics/immunology  DNA-Binding Proteins/genetics/immunology  Duodenum/immunology/metabolism/pathology  Female  Gene Expression  Humans  Interleukin-1beta/genetics/immunology  Interleukin-8/genetics/immunology  MARVEL Domain Containing 2 Protein/genetics/immunology  Male  Matrix Metalloproteinase 9/genetics/immunology  Middle Aged  Permeability  Schizophrenia/genetics/immunology/metabolism/pathology  Tight Junctions/immunology/metabolism/pathology  Autism spectrum disorders  Blood-brain barrier  Duodenal biopsies  Gut permeability  Gut-brain axis  Neuroinflammation  Postmortem brain  Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. METHODS: Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. RESULTS: Claudin (CLDN)-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3, tricellulin, and MMP-9 were higher in the ASD cortex. IL-8, tPA, and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components (CLDN-1, OCLN, TRIC), whereas 66% had increased pore-forming CLDNs (CLDN-2, -10, -15) compared to controls. CONCLUSIONS: In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies. En ligne : http://dx.doi.org/10.1186/s13229-016-0110-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Atypical lateralization of motor circuit functional connectivity in children with autism is associated with motor deficits / D. L. FLORIS in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 35p. Titre : Atypical lateralization of motor circuit functional connectivity in children with autism is associated with motor deficits Type de document : Texte imprimé et/ou numérique Auteurs : D. L. FLORIS, Auteur ; A. D. BARBER, Auteur ; M. B. NEBEL, Auteur ; M. MARTINELLI, Auteur ; Meng-Chuan LAI, Auteur ; D. CROCETTI, Auteur ; Simon BARON-COHEN, Auteur ; J. SUCKLING, Auteur ; J. J. PEKAR, Auteur ; S. H. MOSTOFSKY, Auteur Article en page(s) : 35p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/physiopathology  Brain/diagnostic imaging/physiopathology  Case-Control Studies  Child  Female  Functional Laterality/physiology  Humans  Image Processing, Computer-Assisted  Language  Magnetic Resonance Imaging  Male  Neuropsychological Tests  Autism  Hemispheric specialization  Intrinsic functional connectivity  Lateralization  Motor deficits Index. décimale : PER Périodiques Résumé : BACKGROUND: Atypical lateralization of language-related functions has been repeatedly found in individuals with autism spectrum conditions (ASC). Few studies have, however, investigated deviations from typically occurring asymmetry of other lateralized cognitive and behavioural domains. Motor deficits are among the earliest and most prominent symptoms in individuals with ASC and precede core social and communicative symptoms. METHODS: Here, we investigate whether motor circuit connectivity is (1) atypically lateralized in children with ASC and (2) whether this relates to core autistic symptoms and motor performance. Participants comprised 44 right-handed high-functioning children with autism (36 males, 8 females) and 80 typically developing control children (58 males, 22 females) matched on age, sex and performance IQ. We examined lateralization of functional motor circuit connectivity based on homotopic seeds derived from peak activations during a finger tapping paradigm. Motor performance was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS). RESULTS: Children with ASC showed rightward lateralization in mean motor circuit connectivity compared to typically developing children, and this was associated with poorer performance on all three PANESS measures. CONCLUSIONS: Our findings reveal that atypical lateralization in ASC is not restricted to language functions but is also present in circuits subserving motor functions and may underlie motor deficits in children with ASC. Future studies should investigate whether this is an age-invariant finding extending to adolescents and adults and whether these asymmetries relate to atypical lateralization in the language domain. En ligne : http://dx.doi.org/10.1186/s13229-016-0096-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Atypical lateralization of motor circuit functional connectivity in children with autism is associated with motor deficits [Texte imprimé et/ou numérique] / D. L. FLORIS, Auteur ; A. D. BARBER, Auteur ; M. B. NEBEL, Auteur ; M. MARTINELLI, Auteur ; Meng-Chuan LAI, Auteur ; D. CROCETTI, Auteur ; Simon BARON-COHEN, Auteur ; J. SUCKLING, Auteur ; J. J. PEKAR, Auteur ; S. H. MOSTOFSKY, Auteur . - 35p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 35p. Mots-clés : Autism Spectrum Disorder/physiopathology  Brain/diagnostic imaging/physiopathology  Case-Control Studies  Child  Female  Functional Laterality/physiology  Humans  Image Processing, Computer-Assisted  Language  Magnetic Resonance Imaging  Male  Neuropsychological Tests  Autism  Hemispheric specialization  Intrinsic functional connectivity  Lateralization  Motor deficits Index. décimale : PER Périodiques Résumé : BACKGROUND: Atypical lateralization of language-related functions has been repeatedly found in individuals with autism spectrum conditions (ASC). Few studies have, however, investigated deviations from typically occurring asymmetry of other lateralized cognitive and behavioural domains. Motor deficits are among the earliest and most prominent symptoms in individuals with ASC and precede core social and communicative symptoms. METHODS: Here, we investigate whether motor circuit connectivity is (1) atypically lateralized in children with ASC and (2) whether this relates to core autistic symptoms and motor performance. Participants comprised 44 right-handed high-functioning children with autism (36 males, 8 females) and 80 typically developing control children (58 males, 22 females) matched on age, sex and performance IQ. We examined lateralization of functional motor circuit connectivity based on homotopic seeds derived from peak activations during a finger tapping paradigm. Motor performance was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS). RESULTS: Children with ASC showed rightward lateralization in mean motor circuit connectivity compared to typically developing children, and this was associated with poorer performance on all three PANESS measures. CONCLUSIONS: Our findings reveal that atypical lateralization in ASC is not restricted to language functions but is also present in circuits subserving motor functions and may underlie motor deficits in children with ASC. Future studies should investigate whether this is an age-invariant finding extending to adolescents and adults and whether these asymmetries relate to atypical lateralization in the language domain. En ligne : http://dx.doi.org/10.1186/s13229-016-0096-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Mimetic desire in autism spectrum disorder / Baudouin FORGEOT D'ARC in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 45p. Titre : Mimetic desire in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Baudouin FORGEOT D'ARC, Auteur ; F. VINCKIER, Auteur ; M. LEBRETON, Auteur ; I. SOULIERES, Auteur ; Laurent MOTTRON, Auteur ; M. PESSIGLIONE, Auteur Article en page(s) : 45p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Anhedonia  Autism Spectrum Disorder/physiopathology/psychology  Case-Control Studies  Female  Humans  Imitative Behavior/physiology  Judgment  Male  Motivation/physiology  Psychological Tests  Social Perception  Autism  Brain valuation system  Mimetic desire  Mirror neuron system  Restricted interests  Social cognition  Social influence  Social motivation Index. décimale : PER Périodiques Résumé : Mimetic desire (MD), the spontaneous propensity to pursue goals that others pursue, is a case of social influence that is believed to shape preferences. Autism spectrum disorder (ASD) is defined by both atypical interests and altered social interaction. We investigated whether MD is lower in adults with ASD compared to typically developed adults and whether MD correlates with social anhedonia and social judgment, two aspects of atypical social functioning in autism. Contrary to our hypotheses, MD was similarly present in both ASD and control groups. Anhedonia and social judgment differed between the ASD and control groups but did not correlate with MD. These results extend previous findings by suggesting that basic mechanisms of social influence are preserved in autism. The finding of intact MD in ASD stands against the intuitive idea that atypical interests stem from reduced social influence and indirectly favors the possibility that special interests might be selected for their intrinsic properties. En ligne : http://dx.doi.org/10.1186/s13229-016-0107-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Mimetic desire in autism spectrum disorder [Texte imprimé et/ou numérique] / Baudouin FORGEOT D'ARC, Auteur ; F. VINCKIER, Auteur ; M. LEBRETON, Auteur ; I. SOULIERES, Auteur ; Laurent MOTTRON, Auteur ; M. PESSIGLIONE, Auteur . - 45p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 45p. Mots-clés : Adolescent  Adult  Anhedonia  Autism Spectrum Disorder/physiopathology/psychology  Case-Control Studies  Female  Humans  Imitative Behavior/physiology  Judgment  Male  Motivation/physiology  Psychological Tests  Social Perception  Autism  Brain valuation system  Mimetic desire  Mirror neuron system  Restricted interests  Social cognition  Social influence  Social motivation Index. décimale : PER Périodiques Résumé : Mimetic desire (MD), the spontaneous propensity to pursue goals that others pursue, is a case of social influence that is believed to shape preferences. Autism spectrum disorder (ASD) is defined by both atypical interests and altered social interaction. We investigated whether MD is lower in adults with ASD compared to typically developed adults and whether MD correlates with social anhedonia and social judgment, two aspects of atypical social functioning in autism. Contrary to our hypotheses, MD was similarly present in both ASD and control groups. Anhedonia and social judgment differed between the ASD and control groups but did not correlate with MD. These results extend previous findings by suggesting that basic mechanisms of social influence are preserved in autism. The finding of intact MD in ASD stands against the intuitive idea that atypical interests stem from reduced social influence and indirectly favors the possibility that special interests might be selected for their intrinsic properties. En ligne : http://dx.doi.org/10.1186/s13229-016-0107-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Basic and complex emotion recognition in children with autism: cross-cultural findings / S. FRIDENSON-HAYO in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 52p. Titre : Basic and complex emotion recognition in children with autism: cross-cultural findings Type de document : Texte imprimé et/ou numérique Auteurs : S. FRIDENSON-HAYO, Auteur ; Steve BERGGREN, Auteur ; A. LASSALLE, Auteur ; S. TAL, Auteur ; D. PIGAT, Auteur ; Sven BÖLTE, Auteur ; Simon BARON-COHEN, Auteur ; O. GOLAN, Auteur Article en page(s) : 52p. Langues : Anglais (eng) Mots-clés : Acoustic Stimulation  Auditory Perception  Autism Spectrum Disorder/physiopathology/psychology  Case-Control Studies  Child  Child, Preschool  Cross-Cultural Comparison  Emotions  Facial Expression  Female  Humans  Israel  Male  Photic Stimulation  Psychological Tests  Sweden  United Kingdom  Video Recording  Visual Perception  Autism spectrum condition  Basic emotions  Complex emotions  Cross-cultural research  Emotion recognition Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with autism spectrum conditions (ASC) have emotion recognition deficits when tested in different expression modalities (face, voice, body). However, these findings usually focus on basic emotions, using one or two expression modalities. In addition, cultural similarities and differences in emotion recognition patterns in children with ASC have not been explored before. The current study examined the similarities and differences in the recognition of basic and complex emotions by children with ASC and typically developing (TD) controls across three cultures: Israel, Britain, and Sweden. METHODS: Fifty-five children with high-functioning ASC, aged 5-9, were compared to 58 TD children. On each site, groups were matched on age, sex, and IQ. Children were tested using four tasks, examining recognition of basic and complex emotions from voice recordings, videos of facial and bodily expressions, and emotional video scenarios including all modalities in context. RESULTS: Compared to their TD peers, children with ASC showed emotion recognition deficits in both basic and complex emotions on all three modalities and their integration in context. Complex emotions were harder to recognize, compared to basic emotions for the entire sample. Cross-cultural agreement was found for all major findings, with minor deviations on the face and body tasks. CONCLUSIONS: Our findings highlight the multimodal nature of ER deficits in ASC, which exist for basic as well as complex emotions and are relatively stable cross-culturally. Cross-cultural research has the potential to reveal both autism-specific universal deficits and the role that specific cultures play in the way empathy operates in different countries. En ligne : http://dx.doi.org/10.1186/s13229-016-0113-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Basic and complex emotion recognition in children with autism: cross-cultural findings [Texte imprimé et/ou numérique] / S. FRIDENSON-HAYO, Auteur ; Steve BERGGREN, Auteur ; A. LASSALLE, Auteur ; S. TAL, Auteur ; D. PIGAT, Auteur ; Sven BÖLTE, Auteur ; Simon BARON-COHEN, Auteur ; O. GOLAN, Auteur . - 52p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 52p. Mots-clés : Acoustic Stimulation  Auditory Perception  Autism Spectrum Disorder/physiopathology/psychology  Case-Control Studies  Child  Child, Preschool  Cross-Cultural Comparison  Emotions  Facial Expression  Female  Humans  Israel  Male  Photic Stimulation  Psychological Tests  Sweden  United Kingdom  Video Recording  Visual Perception  Autism spectrum condition  Basic emotions  Complex emotions  Cross-cultural research  Emotion recognition Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with autism spectrum conditions (ASC) have emotion recognition deficits when tested in different expression modalities (face, voice, body). However, these findings usually focus on basic emotions, using one or two expression modalities. In addition, cultural similarities and differences in emotion recognition patterns in children with ASC have not been explored before. The current study examined the similarities and differences in the recognition of basic and complex emotions by children with ASC and typically developing (TD) controls across three cultures: Israel, Britain, and Sweden. METHODS: Fifty-five children with high-functioning ASC, aged 5-9, were compared to 58 TD children. On each site, groups were matched on age, sex, and IQ. Children were tested using four tasks, examining recognition of basic and complex emotions from voice recordings, videos of facial and bodily expressions, and emotional video scenarios including all modalities in context. RESULTS: Compared to their TD peers, children with ASC showed emotion recognition deficits in both basic and complex emotions on all three modalities and their integration in context. Complex emotions were harder to recognize, compared to basic emotions for the entire sample. Cross-cultural agreement was found for all major findings, with minor deviations on the face and body tasks. CONCLUSIONS: Our findings highlight the multimodal nature of ER deficits in ASC, which exist for basic as well as complex emotions and are relatively stable cross-culturally. Cross-cultural research has the potential to reveal both autism-specific universal deficits and the role that specific cultures play in the way empathy operates in different countries. En ligne : http://dx.doi.org/10.1186/s13229-016-0113-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Gazefinder as a clinical supplementary tool for discriminating between autism spectrum disorder and typical development in male adolescents and adults / T. FUJIOKA in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 19p. Titre : Gazefinder as a clinical supplementary tool for discriminating between autism spectrum disorder and typical development in male adolescents and adults Type de document : Texte imprimé et/ou numérique Auteurs : T. FUJIOKA, Auteur ; K. INOHARA, Auteur ; Y. OKAMOTO, Auteur ; Y. MASUYA, Auteur ; M. ISHITOBI, Auteur ; Daisuke N. SAITO, Auteur ; M. JUNG, Auteur ; Sumiyoshi ARAI, Auteur ; Y. MATSUMURA, Auteur ; T. X. FUJISAWA, Auteur ; K. NARITA, Auteur ; K. SUZUKI, Auteur ; K. J. TSUCHIYA, Auteur ; N. MORI, Auteur ; T. KATAYAMA, Auteur ; M. SATO, Auteur ; T. MUNESUE, Auteur ; H. OKAZAWA, Auteur ; A. TOMODA, Auteur ; Y. WADA, Auteur ; H. KOSAKA, Auteur Article en page(s) : 19p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Area Under Curve  Autism Spectrum Disorder/diagnosis/physiopathology  Case-Control Studies  Discriminant Analysis  Fixation, Ocular/physiology  Humans  Male  Ocular Physiological Phenomena  Photic Stimulation  Psychometrics  ROC Curve  Social Behavior  Time Factors  Autism spectrum disorder  Biological motion  Eye-tracking  Face  Fixation  Gaze abnormality  Geometry Index. décimale : PER Périodiques Résumé : BACKGROUND: Gaze abnormality is a diagnostic criterion for autism spectrum disorder (ASD). However, few easy-to-use clinical tools exist to evaluate the unique eye-gaze patterns of ASD. Recently, we developed Gazefinder, an all-in-one eye-tracking system for early detection of ASD in toddlers. Because abnormal gaze patterns have been documented in various ASD age groups, we predicted that Gazefinder might also detect gaze abnormality in adolescents and adults. In this study, we tested whether Gazefinder could identify unique gaze patterns in adolescents and adults with ASD. METHODS: We measured the percentage of eye fixation time allocated to particular objects depicted in movies (i.e., eyes and mouth in human face movies, upright and inverted biological motion in movies that presented these stimuli simultaneously, and people and geometry in movies that presented these stimuli simultaneously) by male adolescents and adults with ASD (N = 26) and age-matched males with typical development (TD; N = 35). We compared these percentages between the two groups (ASD and TD) and with scores on the social responsiveness scale (SRS). Further, we conducted discriminant analyses to determine if fixation times allocated to particular objects could be used to discriminate between individuals with and without ASD. RESULTS: Compared with the TD group, the ASD group showed significantly less fixation time at locations of salient social information (i.e., eyes in the movie of human faces without lip movement and people in the movie of people and geometry), while there were no significant groupwise differences in the responses to movies of human faces with lip movement or biological motion. In a within-group correlation analysis, a few of the fixation-time items correlated with SRS, although most of them did not. No items significantly correlated with SRS in both ASD and TD groups. The percentage fixation times to eyes and people, which exhibited large effect sizes for the group difference, could differentiate ASD and TD with a sensitivity of 81.0% and a specificity of 80.0%. CONCLUSIONS: These findings suggest that Gazefinder is potentially a valuable and easy-to-use tool for objectively measuring unique gaze patterns and discriminating between ASD and TD in male adolescents and adults. En ligne : http://dx.doi.org/10.1186/s13229-016-0083-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Gazefinder as a clinical supplementary tool for discriminating between autism spectrum disorder and typical development in male adolescents and adults [Texte imprimé et/ou numérique] / T. FUJIOKA, Auteur ; K. INOHARA, Auteur ; Y. OKAMOTO, Auteur ; Y. MASUYA, Auteur ; M. ISHITOBI, Auteur ; Daisuke N. SAITO, Auteur ; M. JUNG, Auteur ; Sumiyoshi ARAI, Auteur ; Y. MATSUMURA, Auteur ; T. X. FUJISAWA, Auteur ; K. NARITA, Auteur ; K. SUZUKI, Auteur ; K. J. TSUCHIYA, Auteur ; N. MORI, Auteur ; T. KATAYAMA, Auteur ; M. SATO, Auteur ; T. MUNESUE, Auteur ; H. OKAZAWA, Auteur ; A. TOMODA, Auteur ; Y. WADA, Auteur ; H. KOSAKA, Auteur . - 19p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 19p. Mots-clés : Adolescent  Adult  Area Under Curve  Autism Spectrum Disorder/diagnosis/physiopathology  Case-Control Studies  Discriminant Analysis  Fixation, Ocular/physiology  Humans  Male  Ocular Physiological Phenomena  Photic Stimulation  Psychometrics  ROC Curve  Social Behavior  Time Factors  Autism spectrum disorder  Biological motion  Eye-tracking  Face  Fixation  Gaze abnormality  Geometry Index. décimale : PER Périodiques Résumé : BACKGROUND: Gaze abnormality is a diagnostic criterion for autism spectrum disorder (ASD). However, few easy-to-use clinical tools exist to evaluate the unique eye-gaze patterns of ASD. Recently, we developed Gazefinder, an all-in-one eye-tracking system for early detection of ASD in toddlers. Because abnormal gaze patterns have been documented in various ASD age groups, we predicted that Gazefinder might also detect gaze abnormality in adolescents and adults. In this study, we tested whether Gazefinder could identify unique gaze patterns in adolescents and adults with ASD. METHODS: We measured the percentage of eye fixation time allocated to particular objects depicted in movies (i.e., eyes and mouth in human face movies, upright and inverted biological motion in movies that presented these stimuli simultaneously, and people and geometry in movies that presented these stimuli simultaneously) by male adolescents and adults with ASD (N = 26) and age-matched males with typical development (TD; N = 35). We compared these percentages between the two groups (ASD and TD) and with scores on the social responsiveness scale (SRS). Further, we conducted discriminant analyses to determine if fixation times allocated to particular objects could be used to discriminate between individuals with and without ASD. RESULTS: Compared with the TD group, the ASD group showed significantly less fixation time at locations of salient social information (i.e., eyes in the movie of human faces without lip movement and people in the movie of people and geometry), while there were no significant groupwise differences in the responses to movies of human faces with lip movement or biological motion. In a within-group correlation analysis, a few of the fixation-time items correlated with SRS, although most of them did not. No items significantly correlated with SRS in both ASD and TD groups. The percentage fixation times to eyes and people, which exhibited large effect sizes for the group difference, could differentiate ASD and TD with a sensitivity of 81.0% and a specificity of 80.0%. CONCLUSIONS: These findings suggest that Gazefinder is potentially a valuable and easy-to-use tool for objectively measuring unique gaze patterns and discriminating between ASD and TD in male adolescents and adults. En ligne : http://dx.doi.org/10.1186/s13229-016-0083-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism / F. GEVI in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 47p. Titre : Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism Type de document : Texte imprimé et/ou numérique Auteurs : F. GEVI, Auteur ; L. ZOLLA, Auteur ; S. GABRIELE, Auteur ; A. M. PERSICO, Auteur Article en page(s) : 47p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/complications/diagnosis/urine  Biomarkers/urine  Case-Control Studies  Child  Child, Preschool  Chromatography, High Pressure Liquid  Coenzyme A/urine  Dysbiosis/complications/diagnosis/urine  Female  Humans  Hydrophobic and Hydrophilic Interactions  Indoleacetic Acids/urine  Italy  Kynurenic Acid/urine  Male  Melatonin/urine  Metabolomics/methods  Pantothenic Acid/urine  Purines/urine  Pyrimidines/urine  Quinolinic Acid/urine  Riboflavin/urine  Tryptophan/urine  Vitamin B 6/urine  Xanthurenates/urine  Autism  Autism spectrum disorder  Kynurenine  Melatonin  Metabolomics  Purinergic signaling  Quinolinic acid  Serotonin  Tryptophan Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides a sensitive tool to identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines and plasma of ASD and control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences in technology, ethnicity, age range, and definition of "control" status. METHODS: ASD-specific urinary metabolomic patterns were explored at an early age in 30 ASD children and 30 matched controls (age range 2-7, M:F = 22:8) using hydrophilic interaction chromatography (HILIC)-UHPLC and mass spectrometry, a highly sensitive, accurate, and unbiased approach. Metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathway. RESULTS: Urinary metabolites displaying the largest differences between young ASD and control children belonged to the tryptophan and purine metabolic pathways. Also, vitamin B6, riboflavin, phenylalanine-tyrosine-tryptophan biosynthesis, pantothenate and CoA, and pyrimidine metabolism differed significantly. ASD children preferentially transform tryptophan into xanthurenic acid and quinolinic acid (two catabolites of the kynurenine pathway), at the expense of kynurenic acid and especially of melatonin. Also, the gut microbiome contributes to altered tryptophan metabolism, yielding increased levels of indolyl 3-acetic acid and indolyl lactate. CONCLUSIONS: The metabolic pathways most distinctive of young Italian autistic children largely overlap with those found in rodent models of ASD following maternal immune activation or genetic manipulations. These results are consistent with the proposal of a purine-driven cell danger response, accompanied by overproduction of epileptogenic and excitotoxic quinolinic acid, large reductions in melatonin synthesis, and gut dysbiosis. These metabolic abnormalities could underlie several comorbidities frequently associated to ASD, such as seizures, sleep disorders, and gastrointestinal symptoms, and could contribute to autism severity. Their diagnostic sensitivity, disease-specificity, and interethnic variability will merit further investigation. En ligne : http://dx.doi.org/10.1186/s13229-016-0109-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism [Texte imprimé et/ou numérique] / F. GEVI, Auteur ; L. ZOLLA, Auteur ; S. GABRIELE, Auteur ; A. M. PERSICO, Auteur . - 47p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 47p. Mots-clés : Autism Spectrum Disorder/complications/diagnosis/urine  Biomarkers/urine  Case-Control Studies  Child  Child, Preschool  Chromatography, High Pressure Liquid  Coenzyme A/urine  Dysbiosis/complications/diagnosis/urine  Female  Humans  Hydrophobic and Hydrophilic Interactions  Indoleacetic Acids/urine  Italy  Kynurenic Acid/urine  Male  Melatonin/urine  Metabolomics/methods  Pantothenic Acid/urine  Purines/urine  Pyrimidines/urine  Quinolinic Acid/urine  Riboflavin/urine  Tryptophan/urine  Vitamin B 6/urine  Xanthurenates/urine  Autism  Autism spectrum disorder  Kynurenine  Melatonin  Metabolomics  Purinergic signaling  Quinolinic acid  Serotonin  Tryptophan Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is still diagnosed through behavioral observation, due to a lack of laboratory biomarkers, which could greatly aid clinicians in providing earlier and more reliable diagnoses. Metabolomics on human biofluids provides a sensitive tool to identify metabolite profiles potentially usable as biomarkers for ASD. Initial metabolomic studies, analyzing urines and plasma of ASD and control individuals, suggested that autistic patients may share some metabolic abnormalities, despite several inconsistencies stemming from differences in technology, ethnicity, age range, and definition of "control" status. METHODS: ASD-specific urinary metabolomic patterns were explored at an early age in 30 ASD children and 30 matched controls (age range 2-7, M:F = 22:8) using hydrophilic interaction chromatography (HILIC)-UHPLC and mass spectrometry, a highly sensitive, accurate, and unbiased approach. Metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathway. RESULTS: Urinary metabolites displaying the largest differences between young ASD and control children belonged to the tryptophan and purine metabolic pathways. Also, vitamin B6, riboflavin, phenylalanine-tyrosine-tryptophan biosynthesis, pantothenate and CoA, and pyrimidine metabolism differed significantly. ASD children preferentially transform tryptophan into xanthurenic acid and quinolinic acid (two catabolites of the kynurenine pathway), at the expense of kynurenic acid and especially of melatonin. Also, the gut microbiome contributes to altered tryptophan metabolism, yielding increased levels of indolyl 3-acetic acid and indolyl lactate. CONCLUSIONS: The metabolic pathways most distinctive of young Italian autistic children largely overlap with those found in rodent models of ASD following maternal immune activation or genetic manipulations. These results are consistent with the proposal of a purine-driven cell danger response, accompanied by overproduction of epileptogenic and excitotoxic quinolinic acid, large reductions in melatonin synthesis, and gut dysbiosis. These metabolic abnormalities could underlie several comorbidities frequently associated to ASD, such as seizures, sleep disorders, and gastrointestinal symptoms, and could contribute to autism severity. Their diagnostic sensitivity, disease-specificity, and interethnic variability will merit further investigation. En ligne : http://dx.doi.org/10.1186/s13229-016-0109-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Parent-reported and clinician-observed autism spectrum disorder (ASD) symptoms in children with attention deficit/hyperactivity disorder (ADHD): implications for practice under DSM-5 / R. GRZADZINSKI in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 7p. Titre : Parent-reported and clinician-observed autism spectrum disorder (ASD) symptoms in children with attention deficit/hyperactivity disorder (ADHD): implications for practice under DSM-5 Type de document : Texte imprimé et/ou numérique Auteurs : R. GRZADZINSKI, Auteur ; C. DICK, Auteur ; C. LORD, Auteur ; Somer L. BISHOP, Auteur Article en page(s) : 7p. Langues : Anglais (eng) Mots-clés : Adolescent  Age of Onset  Attention Deficit Disorder with Hyperactivity/diagnosis  Autism Spectrum Disorder/diagnosis  Child  Child, Preschool  Diagnosis, Differential  Diagnostic and Statistical Manual of Mental Disorders  Facial Expression  Female  Fixation, Ocular  Humans  Interview, Psychological  Male  Observer Variation  Parents/psychology  Psychiatry  Psychological Tests  Psychology  Severity of Illness Index  Social Behavior  Symptom Assessment  Attention Deficit/Hyperactivity Disorder (ADHD)  Autism  Autism Diagnostic Interview-Revised (ADI-R)  Autism Diagnostic Observation Schedule (ADOS)  Autism Spectrum Disorder (ASD)  Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with attention deficit/hyperactivity disorder (ADHD) often present with social difficulties, though the extent to which these clearly overlap with symptoms of autism spectrum disorder (ASD) is not well understood. METHODS: We explored parent-reported and directly-observed ASD symptoms on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) in children referred to ASD-specialty clinics who received diagnoses of either ADHD (n = 48) or ASD (n = 164). RESULTS: Of the ADHD sample, 21 % met ASD cut-offs on the ADOS and 30 % met ASD cut-offs on all domains of the ADI-R. Four social communication ADOS items (Quality of Social Overtures, Unusual Eye Contact, Facial Expressions Directed to Examiner, and Amount of Reciprocal Social Communication) adequately differentiated the groups while none of the items on the ADI-R met the criteria for adequate discrimination. CONCLUSIONS: Results of this work highlight the challenges that clinicians and researchers face when distinguishing ASD from other disorders in verbally fluent, school-age children. En ligne : http://dx.doi.org/10.1186/s13229-016-0072-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Parent-reported and clinician-observed autism spectrum disorder (ASD) symptoms in children with attention deficit/hyperactivity disorder (ADHD): implications for practice under DSM-5 [Texte imprimé et/ou numérique] / R. GRZADZINSKI, Auteur ; C. DICK, Auteur ; C. LORD, Auteur ; Somer L. BISHOP, Auteur . - 7p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 7p. Mots-clés : Adolescent  Age of Onset  Attention Deficit Disorder with Hyperactivity/diagnosis  Autism Spectrum Disorder/diagnosis  Child  Child, Preschool  Diagnosis, Differential  Diagnostic and Statistical Manual of Mental Disorders  Facial Expression  Female  Fixation, Ocular  Humans  Interview, Psychological  Male  Observer Variation  Parents/psychology  Psychiatry  Psychological Tests  Psychology  Severity of Illness Index  Social Behavior  Symptom Assessment  Attention Deficit/Hyperactivity Disorder (ADHD)  Autism  Autism Diagnostic Interview-Revised (ADI-R)  Autism Diagnostic Observation Schedule (ADOS)  Autism Spectrum Disorder (ASD)  Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with attention deficit/hyperactivity disorder (ADHD) often present with social difficulties, though the extent to which these clearly overlap with symptoms of autism spectrum disorder (ASD) is not well understood. METHODS: We explored parent-reported and directly-observed ASD symptoms on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) in children referred to ASD-specialty clinics who received diagnoses of either ADHD (n = 48) or ASD (n = 164). RESULTS: Of the ADHD sample, 21 % met ASD cut-offs on the ADOS and 30 % met ASD cut-offs on all domains of the ADI-R. Four social communication ADOS items (Quality of Social Overtures, Unusual Eye Contact, Facial Expressions Directed to Examiner, and Amount of Reciprocal Social Communication) adequately differentiated the groups while none of the items on the ADI-R met the criteria for adequate discrimination. CONCLUSIONS: Results of this work highlight the challenges that clinicians and researchers face when distinguishing ASD from other disorders in verbally fluent, school-age children. En ligne : http://dx.doi.org/10.1186/s13229-016-0072-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Erratum to: Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits / X. HE in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 14p. Titre : Erratum to: Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits Type de document : Texte imprimé et/ou numérique Auteurs : X. HE, Auteur ; S. THACKER, Auteur ; T. ROMIGH, Auteur ; Q. YU, Auteur ; T. W. FRAZIER, Auteur ; C. ENG, Auteur Article en page(s) : 14p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-015-0056-6.]. En ligne : http://dx.doi.org/10.1186/s13229-016-0075-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Erratum to: Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits [Texte imprimé et/ou numérique] / X. HE, Auteur ; S. THACKER, Auteur ; T. ROMIGH, Auteur ; Q. YU, Auteur ; T. W. FRAZIER, Auteur ; C. ENG, Auteur . - 14p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 14p. Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-015-0056-6.]. En ligne : http://dx.doi.org/10.1186/s13229-016-0075-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Assessment of olfactory detection thresholds in children with autism spectrum disorders using a pulse ejection system / H. KUMAZAKI in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 6p. Titre : Assessment of olfactory detection thresholds in children with autism spectrum disorders using a pulse ejection system Type de document : Texte imprimé et/ou numérique Auteurs : H. KUMAZAKI, Auteur ; T. MURAMATSU, Auteur ; T. X. FUJISAWA, Auteur ; M. MIYAO, Auteur ; E. MATSUURA, Auteur ; K. OKADA, Auteur ; H. KOSAKA, Auteur ; A. TOMODA, Auteur ; M. MIMURA, Auteur Article en page(s) : 6p. Langues : Anglais (eng) Mots-clés : Adolescent  Aerosols  Autism Spectrum Disorder/physiopathology/psychology  Caproates  Case-Control Studies  Child  Diagnostic Equipment  Equipment Design  Female  Humans  Hypesthesia/etiology/physiopathology/psychology  Male  Odorants  Olfactory Perception/physiology  Pentanols  Pulsatile Flow  Sensory Thresholds/physiology  Autism spectrum disorder  Laboratory-based studies  Olfaction  Olfactory detection threshold  Pulse ejection system Index. décimale : PER Périodiques Résumé : BACKGROUND: Atypical responsiveness to olfactory stimuli has been reported as the strongest predictor of social impairment in children with autism spectrum disorders (ASD). However, previous laboratory-based sensory psychophysical studies that have aimed to investigate olfactory sensitivity in children with ASD have produced inconsistent results. The methodology of these studies is limited by several factors, and more sophisticated approaches are required to produce consistent results. METHODS: We measured olfactory detection thresholds in children with ASD and typical development (TD) using a pulse ejection system-a newly developed methodology designed to resolve problems encountered in previous studies. The two odorants used as stimuli were isoamyl acetate and allyl caproate. RESULTS: Forty-three participants took part in this study: 23 (6 females, 17 males) children with ASD and 20 with TD (6 females, 14 males). Olfactory detection thresholds of children with ASD were significantly higher than those of TD children with both isoamyl acetate (2.85 +/- 0.28 vs 1.57 +/- 0.15; p < 0.001) and allyl caproate ( 3.30 +/- 0.23 vs 1.17 +/- 0.08; p < 0.001). CONCLUSIONS: We found impaired olfactory detection thresholds in children with ASD. Our results contribute to a better understanding of the olfactory abnormalities that children with ASD experience. Considering the role and effect that odors play in our daily lives, insensitivity to some odorants might have a tremendous impact on children with ASD. Future studies of olfactory processing in ASD may reveal important links between brain function, clinically relevant behavior, and treatment. En ligne : http://dx.doi.org/10.1186/s13229-016-0071-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Assessment of olfactory detection thresholds in children with autism spectrum disorders using a pulse ejection system [Texte imprimé et/ou numérique] / H. KUMAZAKI, Auteur ; T. MURAMATSU, Auteur ; T. X. FUJISAWA, Auteur ; M. MIYAO, Auteur ; E. MATSUURA, Auteur ; K. OKADA, Auteur ; H. KOSAKA, Auteur ; A. TOMODA, Auteur ; M. MIMURA, Auteur . - 6p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 6p. Mots-clés : Adolescent  Aerosols  Autism Spectrum Disorder/physiopathology/psychology  Caproates  Case-Control Studies  Child  Diagnostic Equipment  Equipment Design  Female  Humans  Hypesthesia/etiology/physiopathology/psychology  Male  Odorants  Olfactory Perception/physiology  Pentanols  Pulsatile Flow  Sensory Thresholds/physiology  Autism spectrum disorder  Laboratory-based studies  Olfaction  Olfactory detection threshold  Pulse ejection system Index. décimale : PER Périodiques Résumé : BACKGROUND: Atypical responsiveness to olfactory stimuli has been reported as the strongest predictor of social impairment in children with autism spectrum disorders (ASD). However, previous laboratory-based sensory psychophysical studies that have aimed to investigate olfactory sensitivity in children with ASD have produced inconsistent results. The methodology of these studies is limited by several factors, and more sophisticated approaches are required to produce consistent results. METHODS: We measured olfactory detection thresholds in children with ASD and typical development (TD) using a pulse ejection system-a newly developed methodology designed to resolve problems encountered in previous studies. The two odorants used as stimuli were isoamyl acetate and allyl caproate. RESULTS: Forty-three participants took part in this study: 23 (6 females, 17 males) children with ASD and 20 with TD (6 females, 14 males). Olfactory detection thresholds of children with ASD were significantly higher than those of TD children with both isoamyl acetate (2.85 +/- 0.28 vs 1.57 +/- 0.15; p < 0.001) and allyl caproate ( 3.30 +/- 0.23 vs 1.17 +/- 0.08; p < 0.001). CONCLUSIONS: We found impaired olfactory detection thresholds in children with ASD. Our results contribute to a better understanding of the olfactory abnormalities that children with ASD experience. Considering the role and effect that odors play in our daily lives, insensitivity to some odorants might have a tremendous impact on children with ASD. Future studies of olfactory processing in ASD may reveal important links between brain function, clinically relevant behavior, and treatment. En ligne : http://dx.doi.org/10.1186/s13229-016-0071-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

No relationship between early postnatal testosterone concentrations and autistic traits in 18 to 30-month-old children / Karson T. F. KUNG in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 15p. Titre : No relationship between early postnatal testosterone concentrations and autistic traits in 18 to 30-month-old children Type de document : Texte imprimé et/ou numérique Auteurs : Karson T. F. KUNG, Auteur ; M. CONSTANTINESCU, Auteur ; W. V. BROWNE, Auteur ; R. M. NOORDERHAVEN, Auteur ; M. HINES, Auteur Article en page(s) : 15p. Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder/metabolism/psychology  Birth Weight  Child Development  Child, Preschool  Female  Humans  Infant  Male  Maternal Age  Parents/education  Paternal Age  Risk Factors  Saliva/chemistry  Siblings  Surveys and Questionnaires  Symptom Assessment  Testosterone/analysis  Autism  Gender differences  Postnatal development  Sex differences  Testosterone Index. décimale : PER Périodiques Résumé : BACKGROUND: Some previous research has suggested that testosterone prenatally contributes to gender differences in autistic traits, but little is known about the role of testosterone during early postnatal development (mini-puberty). Two prior studies found no sex difference in testosterone postnatally in saliva samples and detected little to no relationship between testosterone postnatally and autistic traits in toddlers. These findings may reflect late measurements of testosterone at 3 to 4 months of age, after the peak of mini-puberty at 1 to 3 months of age. The present study examined the relationship between testosterone at 1 to 3 months of age and autistic traits at 18 to 30 months of age. FINDINGS: Testosterone was measured in saliva samples collected from children at 1 to 3 months of age. When the children (40 boys, 47 girls) reached 18 to 30 months of age, parents completed the Quantitative Checklist for Autism in Toddlers (Q-CHAT). Boys had higher concentrations of testosterone postnatally and higher Q-CHAT scores than girls. However, testosterone did not correlate with Q-CHAT scores in boys, girls, or the entire sample. CONCLUSIONS: The current results suggest that testosterone during the early postnatal period does not contribute to later autistic traits. Given our relatively small samples and therefore limited power, however, further research could usefully examine if testosterone in saliva samples collected during the peak of mini-puberty in larger groups predicts autistic traits or other traits that show gender differences. En ligne : http://dx.doi.org/10.1186/s13229-016-0078-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] No relationship between early postnatal testosterone concentrations and autistic traits in 18 to 30-month-old children [Texte imprimé et/ou numérique] / Karson T. F. KUNG, Auteur ; M. CONSTANTINESCU, Auteur ; W. V. BROWNE, Auteur ; R. M. NOORDERHAVEN, Auteur ; M. HINES, Auteur . - 15p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 15p. Mots-clés : Adult  Autism Spectrum Disorder/metabolism/psychology  Birth Weight  Child Development  Child, Preschool  Female  Humans  Infant  Male  Maternal Age  Parents/education  Paternal Age  Risk Factors  Saliva/chemistry  Siblings  Surveys and Questionnaires  Symptom Assessment  Testosterone/analysis  Autism  Gender differences  Postnatal development  Sex differences  Testosterone Index. décimale : PER Périodiques Résumé : BACKGROUND: Some previous research has suggested that testosterone prenatally contributes to gender differences in autistic traits, but little is known about the role of testosterone during early postnatal development (mini-puberty). Two prior studies found no sex difference in testosterone postnatally in saliva samples and detected little to no relationship between testosterone postnatally and autistic traits in toddlers. These findings may reflect late measurements of testosterone at 3 to 4 months of age, after the peak of mini-puberty at 1 to 3 months of age. The present study examined the relationship between testosterone at 1 to 3 months of age and autistic traits at 18 to 30 months of age. FINDINGS: Testosterone was measured in saliva samples collected from children at 1 to 3 months of age. When the children (40 boys, 47 girls) reached 18 to 30 months of age, parents completed the Quantitative Checklist for Autism in Toddlers (Q-CHAT). Boys had higher concentrations of testosterone postnatally and higher Q-CHAT scores than girls. However, testosterone did not correlate with Q-CHAT scores in boys, girls, or the entire sample. CONCLUSIONS: The current results suggest that testosterone during the early postnatal period does not contribute to later autistic traits. Given our relatively small samples and therefore limited power, however, further research could usefully examine if testosterone in saliva samples collected during the peak of mini-puberty in larger groups predicts autistic traits or other traits that show gender differences. En ligne : http://dx.doi.org/10.1186/s13229-016-0078-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

A systematic variant annotation approach for ranking genes associated with autism spectrum disorders / E. LARSEN in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 44p. Titre : A systematic variant annotation approach for ranking genes associated with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : E. LARSEN, Auteur ; I. MENASHE, Auteur ; M. N. ZIATS, Auteur ; W. PEREANU, Auteur ; A. PACKER, Auteur ; Sharmila BANERJEE-BASU, Auteur Article en page(s) : 44p. Langues : Anglais (eng) Mots-clés : Algorithms  Autism Spectrum Disorder/genetics/physiopathology  DNA-Binding Proteins/genetics  Databases, Genetic  Datasets as Topic  Gene Expression  Genetic Predisposition to Disease  Genetic Variation  Homeodomain Proteins/genetics  Humans  Molecular Sequence Annotation  Nerve Tissue Proteins/genetics  Research Design  Transcription Factors/genetics  Autistic disorder  Autosomal recessive  Common variants  Genetic variation  Rare variants Index. décimale : PER Périodiques Résumé : BACKGROUND: The search for genetic factors underlying autism spectrum disorders (ASD) has led to the identification of hundreds of genes containing thousands of variants that differ in mode of inheritance, effect size, frequency, and function. A major challenge involves assessing the collective evidence in an unbiased, systematic manner for their functional relevance. METHODS: Here, we describe a scoring algorithm for prioritization of candidate genes based on the cumulative strength of evidence for each ASD-associated variant cataloged in AutDB (also known as SFARI Gene). We retrieved data from 889 publications to generate a dataset of 2187 rare and 711 common variants distributed across 461 genes implicated in ASD. Each individual variant was manually annotated with multiple attributes extracted from the original report, followed by score assignment using a set of standardized parameters yielding a single score for each gene. RESULTS: There was a wide variation in scores; SHANK3, CHD8, and ADNP had distinctly higher scores than all other genes in the dataset. Our gene scores were significantly correlated with other recently published rankings of ASD genes (RSpearman = 0.40-0.63; p< 0.0001), providing support for our scoring algorithm. CONCLUSIONS: This new resource, which is freely available, for the first time aggregates on one-platform variants identified from various study types (simplex, multiplex, multigenerational, and consanguineous families), from both common and rare variants, and also incorporates their putative functional consequences to arrive at a genetically and biologically driven ranking scheme. This work represents a major step in moving from simply cataloging autism variants to using data-driven approaches to gain insight into their significance. En ligne : http://dx.doi.org/10.1186/s13229-016-0103-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] A systematic variant annotation approach for ranking genes associated with autism spectrum disorders [Texte imprimé et/ou numérique] / E. LARSEN, Auteur ; I. MENASHE, Auteur ; M. N. ZIATS, Auteur ; W. PEREANU, Auteur ; A. PACKER, Auteur ; Sharmila BANERJEE-BASU, Auteur . - 44p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 44p. Mots-clés : Algorithms  Autism Spectrum Disorder/genetics/physiopathology  DNA-Binding Proteins/genetics  Databases, Genetic  Datasets as Topic  Gene Expression  Genetic Predisposition to Disease  Genetic Variation  Homeodomain Proteins/genetics  Humans  Molecular Sequence Annotation  Nerve Tissue Proteins/genetics  Research Design  Transcription Factors/genetics  Autistic disorder  Autosomal recessive  Common variants  Genetic variation  Rare variants Index. décimale : PER Périodiques Résumé : BACKGROUND: The search for genetic factors underlying autism spectrum disorders (ASD) has led to the identification of hundreds of genes containing thousands of variants that differ in mode of inheritance, effect size, frequency, and function. A major challenge involves assessing the collective evidence in an unbiased, systematic manner for their functional relevance. METHODS: Here, we describe a scoring algorithm for prioritization of candidate genes based on the cumulative strength of evidence for each ASD-associated variant cataloged in AutDB (also known as SFARI Gene). We retrieved data from 889 publications to generate a dataset of 2187 rare and 711 common variants distributed across 461 genes implicated in ASD. Each individual variant was manually annotated with multiple attributes extracted from the original report, followed by score assignment using a set of standardized parameters yielding a single score for each gene. RESULTS: There was a wide variation in scores; SHANK3, CHD8, and ADNP had distinctly higher scores than all other genes in the dataset. Our gene scores were significantly correlated with other recently published rankings of ASD genes (RSpearman = 0.40-0.63; p< 0.0001), providing support for our scoring algorithm. CONCLUSIONS: This new resource, which is freely available, for the first time aggregates on one-platform variants identified from various study types (simplex, multiplex, multigenerational, and consanguineous families), from both common and rare variants, and also incorporates their putative functional consequences to arrive at a genetically and biologically driven ranking scheme. This work represents a major step in moving from simply cataloging autism variants to using data-driven approaches to gain insight into their significance. En ligne : http://dx.doi.org/10.1186/s13229-016-0103-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Deletion and duplication of 16p11.2 are associated with opposing effects on visual evoked potential amplitude / J. J. LEBLANC in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 30p. Titre : Deletion and duplication of 16p11.2 are associated with opposing effects on visual evoked potential amplitude Type de document : Texte imprimé et/ou numérique Auteurs : J. J. LEBLANC, Auteur ; C. A. NELSON, Auteur Article en page(s) : 30p. Langues : Anglais (eng) Mots-clés : Adolescent  Child  Child, Preschool  Chromosomes, Human, Pair 16/genetics  DNA Copy Number Variations  Developmental Disabilities/diagnosis/physiopathology  Electroencephalography  Evoked Potentials, Visual/physiology  Female  Gene Deletion  Gene Duplication  Humans  Male  Visual Cortex/diagnostic imaging  16p11.2 copy number variation  Visual cortex  Visual evoked potential Index. décimale : PER Périodiques Résumé : BACKGROUND: Duplication and deletion of the chromosomal region 16p11.2 cause a broad range of impairments, including intellectual disability, language disorders, and sensory symptoms. However, it is unclear how changes in 16p11.2 dosage affect cortical circuitry during development. The aim of this study was to investigate whether the visual evoked potential (VEP) could be used as a noninvasive quantitative measure of cortical processing in children with 16p11.2 copy number variation. METHODS: Pattern-reversal VEPs were successfully recorded in 19 deletion carriers, 9 duplication carriers, and 13 typically developing children between the ages of 3 and 14 years. The stimulus was a black and white checkerboard (60') that reversed contrast at 2 Hz. VEP responses were extracted from continuous EEG recorded using a high-density elasticized electrode net. RESULTS: Quantitative analysis of the VEP waveform revealed that, relative to controls, deletion carriers displayed increased amplitude and duplication carriers displayed diminished amplitude. Latencies of the VEP waveform components were unaffected by 16p11.2 status. P1 amplitude did not correlate with age, IQ, or head circumference. CONCLUSIONS: The results of this study suggest that recording VEP is a useful method to assay cortical processing in children with 16p11.2 copy number variation. There is a gene dosage-dependent effect on P1 amplitude that merits further investigation. The VEP is directly translatable to animal models, offering a promising way to probe the neurobiological mechanisms underlying cortical dysfunction in this developmental disorder. En ligne : http://dx.doi.org/10.1186/s13229-016-0095-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Deletion and duplication of 16p11.2 are associated with opposing effects on visual evoked potential amplitude [Texte imprimé et/ou numérique] / J. J. LEBLANC, Auteur ; C. A. NELSON, Auteur . - 30p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 30p. Mots-clés : Adolescent  Child  Child, Preschool  Chromosomes, Human, Pair 16/genetics  DNA Copy Number Variations  Developmental Disabilities/diagnosis/physiopathology  Electroencephalography  Evoked Potentials, Visual/physiology  Female  Gene Deletion  Gene Duplication  Humans  Male  Visual Cortex/diagnostic imaging  16p11.2 copy number variation  Visual cortex  Visual evoked potential Index. décimale : PER Périodiques Résumé : BACKGROUND: Duplication and deletion of the chromosomal region 16p11.2 cause a broad range of impairments, including intellectual disability, language disorders, and sensory symptoms. However, it is unclear how changes in 16p11.2 dosage affect cortical circuitry during development. The aim of this study was to investigate whether the visual evoked potential (VEP) could be used as a noninvasive quantitative measure of cortical processing in children with 16p11.2 copy number variation. METHODS: Pattern-reversal VEPs were successfully recorded in 19 deletion carriers, 9 duplication carriers, and 13 typically developing children between the ages of 3 and 14 years. The stimulus was a black and white checkerboard (60') that reversed contrast at 2 Hz. VEP responses were extracted from continuous EEG recorded using a high-density elasticized electrode net. RESULTS: Quantitative analysis of the VEP waveform revealed that, relative to controls, deletion carriers displayed increased amplitude and duplication carriers displayed diminished amplitude. Latencies of the VEP waveform components were unaffected by 16p11.2 status. P1 amplitude did not correlate with age, IQ, or head circumference. CONCLUSIONS: The results of this study suggest that recording VEP is a useful method to assay cortical processing in children with 16p11.2 copy number variation. There is a gene dosage-dependent effect on P1 amplitude that merits further investigation. The VEP is directly translatable to animal models, offering a promising way to probe the neurobiological mechanisms underlying cortical dysfunction in this developmental disorder. En ligne : http://dx.doi.org/10.1186/s13229-016-0095-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Commentary: sex difference differences? A reply to Constantino / D. S. MESSINGER in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 31p. Titre : Commentary: sex difference differences? A reply to Constantino Type de document : Texte imprimé et/ou numérique Auteurs : D. S. MESSINGER, Auteur ; Gregory S. YOUNG, Auteur ; S. J. WEBB, Auteur ; S. OZONOFF, Auteur ; Susan E. BRYSON, Auteur ; Alice S. CARTER, Auteur ; Leslie J. CARVER, Auteur ; Tony CHARMAN, Auteur ; Katarzyna CHAWARSKA, Auteur ; S. CURTIN, Auteur ; K. DOBKINS, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; T. HUTMAN, Auteur ; J. M. IVERSON, Auteur ; R. LANDA, Auteur ; C. A. NELSON, Auteur ; W. L. STONE, Auteur ; Helen TAGER-FLUSBERG, Auteur ; Lonnie ZWAIGENBAUM, Auteur Article en page(s) : 31p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Female protective effect  High-risk siblings  Sex differences Index. décimale : PER Périodiques Résumé : Messinger et al. found a 3.18 odds ratio of male to female ASD recurrence in 1241 prospectively followed high-risk (HR) siblings. Among high-risk siblings (with and without ASD), as well as among 583 low-risk controls, girls exhibited higher performance on the Mullen Scales of Early Learning, as well as lower restricted and repetitive behavior severity scores on the Autism Diagnostic Observation Schedule (ADOS) than boys. That is, female-favoring sex differences in developmental performance and autism traits were evident among low-risk and non-ASD high-risk children, as well as those with ASD. Constantino (Mol Autism) suggests that sex differences in categorical ASD outcomes in Messinger et al. should be understood as a female protective effect. We are receptive to Constantino's (Mol Autism) suggestion, and propose that quantitative sex differences in autism-related features are keys to understanding this female protective effect. En ligne : http://dx.doi.org/10.1186/s13229-016-0093-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Commentary: sex difference differences? A reply to Constantino [Texte imprimé et/ou numérique] / D. S. MESSINGER, Auteur ; Gregory S. YOUNG, Auteur ; S. J. WEBB, Auteur ; S. OZONOFF, Auteur ; Susan E. BRYSON, Auteur ; Alice S. CARTER, Auteur ; Leslie J. CARVER, Auteur ; Tony CHARMAN, Auteur ; Katarzyna CHAWARSKA, Auteur ; S. CURTIN, Auteur ; K. DOBKINS, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; T. HUTMAN, Auteur ; J. M. IVERSON, Auteur ; R. LANDA, Auteur ; C. A. NELSON, Auteur ; W. L. STONE, Auteur ; Helen TAGER-FLUSBERG, Auteur ; Lonnie ZWAIGENBAUM, Auteur . - 31p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 31p. Mots-clés : Autism spectrum disorder  Female protective effect  High-risk siblings  Sex differences Index. décimale : PER Périodiques Résumé : Messinger et al. found a 3.18 odds ratio of male to female ASD recurrence in 1241 prospectively followed high-risk (HR) siblings. Among high-risk siblings (with and without ASD), as well as among 583 low-risk controls, girls exhibited higher performance on the Mullen Scales of Early Learning, as well as lower restricted and repetitive behavior severity scores on the Autism Diagnostic Observation Schedule (ADOS) than boys. That is, female-favoring sex differences in developmental performance and autism traits were evident among low-risk and non-ASD high-risk children, as well as those with ASD. Constantino (Mol Autism) suggests that sex differences in categorical ASD outcomes in Messinger et al. should be understood as a female protective effect. We are receptive to Constantino's (Mol Autism) suggestion, and propose that quantitative sex differences in autism-related features are keys to understanding this female protective effect. En ligne : http://dx.doi.org/10.1186/s13229-016-0093-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders / N. F. MINSHAWI in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 2p. Titre : A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : N. F. MINSHAWI, Auteur ; L. K. WINK, Auteur ; R. SHAFFER, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; H. LIU, Auteur ; S. HURWITZ, Auteur ; C. J. MCDOUGLE, Auteur ; N. B. SWIEZY, Auteur ; C. A. ERICKSON, Auteur Article en page(s) : 2p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/drug therapy/psychology/therapy  Behavior Therapy  Child  Child, Preschool  Cycloserine/adverse effects/therapeutic use  Double-Blind Method  Excitatory Amino Acid Agonists/adverse effects/therapeutic use  Female  Humans  Interpersonal Relations  Learning/drug effects  Male  Parents/psychology  Severity of Illness Index  Social Skills  Treatment Failure  Autism spectrum disorders  Social deficits  Social skills training  d-cycloserine Index. décimale : PER Périodiques Résumé : BACKGROUND: Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. METHODS: A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio. RESULTS: No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. CONCLUSIONS: The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. TRIAL REGISTRATION: ClinicalTrials.govNCT01086475. En ligne : http://dx.doi.org/10.1186/s13229-015-0062-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders [Texte imprimé et/ou numérique] / N. F. MINSHAWI, Auteur ; L. K. WINK, Auteur ; R. SHAFFER, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; H. LIU, Auteur ; S. HURWITZ, Auteur ; C. J. MCDOUGLE, Auteur ; N. B. SWIEZY, Auteur ; C. A. ERICKSON, Auteur . - 2p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 2p. Mots-clés : Autism Spectrum Disorder/drug therapy/psychology/therapy  Behavior Therapy  Child  Child, Preschool  Cycloserine/adverse effects/therapeutic use  Double-Blind Method  Excitatory Amino Acid Agonists/adverse effects/therapeutic use  Female  Humans  Interpersonal Relations  Learning/drug effects  Male  Parents/psychology  Severity of Illness Index  Social Skills  Treatment Failure  Autism spectrum disorders  Social deficits  Social skills training  d-cycloserine Index. décimale : PER Périodiques Résumé : BACKGROUND: Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. METHODS: A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio. RESULTS: No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. CONCLUSIONS: The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. TRIAL REGISTRATION: ClinicalTrials.govNCT01086475. En ligne : http://dx.doi.org/10.1186/s13229-015-0062-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder / C. NEWELL in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 37p. Titre : Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : C. NEWELL, Auteur ; M. R. BOMHOF, Auteur ; R. A. REIMER, Auteur ; D. S. HITTEL, Auteur ; J. M. RHO, Auteur ; J. SHEARER, Auteur Article en page(s) : 37p. Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/microbiology  Bacteria/isolation & purification  Behavior, Animal  Cecum/microbiology  Diet, Ketogenic  Disease Models, Animal  Feces/microbiology  Gastrointestinal Microbiome  Male  Mice  Mice, Inbred C57BL  Social Behavior  Autism spectrum disorder  BTBR mouse  Gut microbiome  Ketogenic diet Index. décimale : PER Périodiques Résumé : BACKGROUND: Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile. FINDINGS: Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals. CONCLUSIONS: Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model. En ligne : http://dx.doi.org/10.1186/s13229-016-0099-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder [Texte imprimé et/ou numérique] / C. NEWELL, Auteur ; M. R. BOMHOF, Auteur ; R. A. REIMER, Auteur ; D. S. HITTEL, Auteur ; J. M. RHO, Auteur ; J. SHEARER, Auteur . - 37p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 37p. Mots-clés : Animals  Autism Spectrum Disorder/microbiology  Bacteria/isolation & purification  Behavior, Animal  Cecum/microbiology  Diet, Ketogenic  Disease Models, Animal  Feces/microbiology  Gastrointestinal Microbiome  Male  Mice  Mice, Inbred C57BL  Social Behavior  Autism spectrum disorder  BTBR mouse  Gut microbiome  Ketogenic diet Index. décimale : PER Périodiques Résumé : BACKGROUND: Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile. FINDINGS: Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals. CONCLUSIONS: Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model. En ligne : http://dx.doi.org/10.1186/s13229-016-0099-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology / L. S. NGUYEN in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 1p. Titre : Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology Type de document : Texte imprimé et/ou numérique Auteurs : L. S. NGUYEN, Auteur ; M. LEPLEUX, Auteur ; M. MAKHLOUF, Auteur ; C. MARTIN, Auteur ; J. FREGEAC, Auteur ; K. SIQUIER-PERNET, Auteur ; A. PHILIPPE, Auteur ; F. FERON, Auteur ; B. GEPNER, Auteur ; C. ROUGEULLE, Auteur ; Y. HUMEAU, Auteur ; L. COLLEAUX, Auteur Article en page(s) : 1p. Langues : Anglais (eng) Mots-clés : 3' Untranslated Regions/genetics  Adult  Adult Stem Cells/metabolism  Animals  Astrocytes/metabolism  Autism Spectrum Disorder/genetics/pathology/physiopathology  Cells, Cultured  Female  Fibroblasts/metabolism  Genetic Vectors/genetics  Hippocampus/cytology/embryology  Humans  Lentivirus/genetics  Male  Mice  MicroRNAs/genetics/physiology  Neurons/metabolism/ultrastructure  Olfactory Mucosa/pathology  Organ Specificity  Real-Time Polymerase Chain Reaction  Transcriptome  Young Adult  Astrocyte  Autism spectrum disorders  MicroRNA  Neuron  Olfactory mucosa stem cells Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders caused by the interaction between genetic vulnerability and environmental factors. MicroRNAs (miRNAs) are key posttranscriptional regulators involved in multiple aspects of brain development and function. Previous studies have investigated miRNAs expression in ASD using non-neural cells like lymphoblastoid cell lines (LCL) or postmortem tissues. However, the relevance of LCLs is questionable in the context of a neurodevelopmental disorder, and the impact of the cause of death and/or post-death handling of tissue likely contributes to the variations observed between studies on brain samples. METHODS: miRNA profiling using TLDA high-throughput real-time qPCR was performed on miRNAs extracted from olfactory mucosal stem cells (OMSCs) biopsied from eight patients and six controls. This tissue is considered as a closer tissue to neural stem cells that could be sampled in living patients and was never investigated for such a purpose before. Real-time PCR was used to validate a set of differentially expressed miRNAs, and bioinformatics analysis determined common pathways and gene targets. Luciferase assays and real-time PCR analysis were used to evaluate the effect of miRNAs misregulation on the expression and translation of several autism-related transcripts. Viral vector-mediated expression was used to evaluate the impact of miRNAs deregulation on neuronal or glial cells functions. RESULTS: We identified a signature of four miRNAs (miR-146a, miR-221, miR-654-5p, and miR-656) commonly deregulated in ASD. This signature is conserved in primary skin fibroblasts and may allow discriminating between ASD and intellectual disability samples. Putative target genes of the differentially expressed miRNAs were enriched for pathways previously associated to ASD, and altered levels of neuronal transcripts targeted by miR-146a, miR-221, and miR-656 were observed in patients' cells. In the mouse brain, miR-146a, and miR-221 display strong neuronal expression in regions important for high cognitive functions, and we demonstrated that reproducing abnormal miR-146a expression in mouse primary cell cultures leads to impaired neuronal dendritic arborization and increased astrocyte glutamate uptake capacities. CONCLUSIONS: While independent replication experiments are needed to clarify whether these four miRNAS could serve as early biomarkers of ASD, these findings may have important diagnostic implications. They also provide mechanistic connection between miRNA dysregulation and ASD pathophysiology and may open up new opportunities for therapeutic. En ligne : http://dx.doi.org/10.1186/s13229-015-0064-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology [Texte imprimé et/ou numérique] / L. S. NGUYEN, Auteur ; M. LEPLEUX, Auteur ; M. MAKHLOUF, Auteur ; C. MARTIN, Auteur ; J. FREGEAC, Auteur ; K. SIQUIER-PERNET, Auteur ; A. PHILIPPE, Auteur ; F. FERON, Auteur ; B. GEPNER, Auteur ; C. ROUGEULLE, Auteur ; Y. HUMEAU, Auteur ; L. COLLEAUX, Auteur . - 1p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 1p. Mots-clés : 3' Untranslated Regions/genetics  Adult  Adult Stem Cells/metabolism  Animals  Astrocytes/metabolism  Autism Spectrum Disorder/genetics/pathology/physiopathology  Cells, Cultured  Female  Fibroblasts/metabolism  Genetic Vectors/genetics  Hippocampus/cytology/embryology  Humans  Lentivirus/genetics  Male  Mice  MicroRNAs/genetics/physiology  Neurons/metabolism/ultrastructure  Olfactory Mucosa/pathology  Organ Specificity  Real-Time Polymerase Chain Reaction  Transcriptome  Young Adult  Astrocyte  Autism spectrum disorders  MicroRNA  Neuron  Olfactory mucosa stem cells Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders caused by the interaction between genetic vulnerability and environmental factors. MicroRNAs (miRNAs) are key posttranscriptional regulators involved in multiple aspects of brain development and function. Previous studies have investigated miRNAs expression in ASD using non-neural cells like lymphoblastoid cell lines (LCL) or postmortem tissues. However, the relevance of LCLs is questionable in the context of a neurodevelopmental disorder, and the impact of the cause of death and/or post-death handling of tissue likely contributes to the variations observed between studies on brain samples. METHODS: miRNA profiling using TLDA high-throughput real-time qPCR was performed on miRNAs extracted from olfactory mucosal stem cells (OMSCs) biopsied from eight patients and six controls. This tissue is considered as a closer tissue to neural stem cells that could be sampled in living patients and was never investigated for such a purpose before. Real-time PCR was used to validate a set of differentially expressed miRNAs, and bioinformatics analysis determined common pathways and gene targets. Luciferase assays and real-time PCR analysis were used to evaluate the effect of miRNAs misregulation on the expression and translation of several autism-related transcripts. Viral vector-mediated expression was used to evaluate the impact of miRNAs deregulation on neuronal or glial cells functions. RESULTS: We identified a signature of four miRNAs (miR-146a, miR-221, miR-654-5p, and miR-656) commonly deregulated in ASD. This signature is conserved in primary skin fibroblasts and may allow discriminating between ASD and intellectual disability samples. Putative target genes of the differentially expressed miRNAs were enriched for pathways previously associated to ASD, and altered levels of neuronal transcripts targeted by miR-146a, miR-221, and miR-656 were observed in patients' cells. In the mouse brain, miR-146a, and miR-221 display strong neuronal expression in regions important for high cognitive functions, and we demonstrated that reproducing abnormal miR-146a expression in mouse primary cell cultures leads to impaired neuronal dendritic arborization and increased astrocyte glutamate uptake capacities. CONCLUSIONS: While independent replication experiments are needed to clarify whether these four miRNAS could serve as early biomarkers of ASD, these findings may have important diagnostic implications. They also provide mechanistic connection between miRNA dysregulation and ASD pathophysiology and may open up new opportunities for therapeutic. En ligne : http://dx.doi.org/10.1186/s13229-015-0064-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Name recognition in autism: EEG evidence of altered patterns of brain activity and connectivity / A. NOWICKA in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 38p. Titre : Name recognition in autism: EEG evidence of altered patterns of brain activity and connectivity Type de document : Texte imprimé et/ou numérique Auteurs : A. NOWICKA, Auteur ; H. B. CYGAN, Auteur ; P. TACIKOWSKI, Auteur ; P. OSTASZEWSKI, Auteur ; R. KUS, Auteur Article en page(s) : 38p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autistic Disorder/physiopathology  Brain/physiology  Electroencephalography  Evoked Potentials  Humans  Male  Names  Recognition (Psychology)  Young Adult  Autism spectrum disorder  Coherence  Directed transfer function  Erp  Event-related desynchronization and synchronization Index. décimale : PER Périodiques Résumé : BACKGROUND: Impaired orienting to social stimuli is one of the core early symptoms of autism spectrum disorder (ASD). However, in contrast to faces, name processing has rarely been studied in individuals with ASD. Here, we investigated brain activity and functional connectivity associated with recognition of names in the high-functioning ASD group and in the control group. METHODS: EEG was recorded in 15 young males with ASD and 15 matched one-to-one control individuals. EEG data were analyzed with the event-related potential (ERP), event-related desynchronization and event-related synchronization (ERD/S), as well as coherence and direct transfer function (DTF) methods. Four categories of names were presented visually: one's own, close-other's, famous, and unknown. RESULTS: Differences between the ASD and control groups were found for ERP, coherence, and DTF. In individuals with ASD, P300 (a positive ERP component) to own-name and to a close-other's name were similar whereas in control participants, P300 to own-name was enhanced when compared to all other names. Analysis of coherence and DTF revealed disruption of fronto-posterior task-related connectivity in individuals with ASD within the beta range frequencies. Moreover, DTF indicated the directionality of those impaired connections-they were going from parieto-occipital to frontal regions. DTF also showed inter-group differences in short-range connectivity: weaker connections within the frontal region and stronger connections within the occipital region in the ASD group in comparison to the control group. CONCLUSIONS: Our findings suggest a lack of the self-preference effect and impaired functioning of the attentional network during recognition of visually presented names in individuals with ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0102-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Name recognition in autism: EEG evidence of altered patterns of brain activity and connectivity [Texte imprimé et/ou numérique] / A. NOWICKA, Auteur ; H. B. CYGAN, Auteur ; P. TACIKOWSKI, Auteur ; P. OSTASZEWSKI, Auteur ; R. KUS, Auteur . - 38p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 38p. Mots-clés : Adolescent  Adult  Autistic Disorder/physiopathology  Brain/physiology  Electroencephalography  Evoked Potentials  Humans  Male  Names  Recognition (Psychology)  Young Adult  Autism spectrum disorder  Coherence  Directed transfer function  Erp  Event-related desynchronization and synchronization Index. décimale : PER Périodiques Résumé : BACKGROUND: Impaired orienting to social stimuli is one of the core early symptoms of autism spectrum disorder (ASD). However, in contrast to faces, name processing has rarely been studied in individuals with ASD. Here, we investigated brain activity and functional connectivity associated with recognition of names in the high-functioning ASD group and in the control group. METHODS: EEG was recorded in 15 young males with ASD and 15 matched one-to-one control individuals. EEG data were analyzed with the event-related potential (ERP), event-related desynchronization and event-related synchronization (ERD/S), as well as coherence and direct transfer function (DTF) methods. Four categories of names were presented visually: one's own, close-other's, famous, and unknown. RESULTS: Differences between the ASD and control groups were found for ERP, coherence, and DTF. In individuals with ASD, P300 (a positive ERP component) to own-name and to a close-other's name were similar whereas in control participants, P300 to own-name was enhanced when compared to all other names. Analysis of coherence and DTF revealed disruption of fronto-posterior task-related connectivity in individuals with ASD within the beta range frequencies. Moreover, DTF indicated the directionality of those impaired connections-they were going from parieto-occipital to frontal regions. DTF also showed inter-group differences in short-range connectivity: weaker connections within the frontal region and stronger connections within the occipital region in the ASD group in comparison to the control group. CONCLUSIONS: Our findings suggest a lack of the self-preference effect and impaired functioning of the attentional network during recognition of visually presented names in individuals with ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0102-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Others' emotions teach, but not in autism: an eye-tracking pupillometry study / H. J. NUSKE in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 36p. Titre : Others' emotions teach, but not in autism: an eye-tracking pupillometry study Type de document : Texte imprimé et/ou numérique Auteurs : H. J. NUSKE, Auteur ; G. VIVANTI, Auteur ; Cheryl DISSANAYAKE, Auteur Article en page(s) : 36p. Langues : Anglais (eng) Mots-clés : Attention  Autistic Disorder/physiopathology  Child, Preschool  Emotions/physiology  Facial Expression  Female  Humans  Male  Pupil/physiology  Autism  Autonomic nervous system  Emotion  Eye-tracking pupillometry  Social learning  Social-emotional calibration Index. décimale : PER Périodiques Résumé : BACKGROUND: Much research has investigated deficit in emotional reactivity to others in people with autism, but scant attention has been paid to how this deficit affects their own reactions to features of their environment (objects, events, practices, etc.). The present study presents a preliminary analysis on whether calibrating one's own emotional reactions to others' emotional reactions about features of the world, a process we term social-emotional calibration, is disrupted in autism. METHODS: To examine this process, we used a novel eye-tracking pupillometry paradigm in which we showed 20 preschoolers with autism and 20 matched typically developing preschoolers' videos of an actor opening a box and reacting to the occluded object inside, with fear or happiness. We expected preschoolers to come to perceive the box as containing a positive or threatening stimulus through emotionally calibrating to the actor's emotional expressions. Children's mean pupil diameter (indicating emotional reactivity) was measured whilst viewing an up-close, visually identical image of the box before and then after the scene, and this difference was taken as an index of social-emotional calibration and compared between groups. RESULTS: Whilst the typically developing preschoolers responded more emotionally to the box after, compared to before the scene (as indexed by an increase in pupil size), those with autism did not, suggesting their reaction to the object was not affected by the actor's emotional expressions. The groups did not differ in looking duration to the emotional expressions; thus, the pupil dilation findings cannot be explained by differences in visual attention. More social-emotional calibration on the happy condition was associated with less severe autism symptoms. CONCLUSIONS: Through the measurement of physiological reactivity, findings suggest social-emotional calibration is diminished in children with autism, with calibration to others' positive emotions as particularly important. This study highlights a possible mechanism by which individuals with autism develop idiosyncratic reactions to features of their environment, which is likely to impact their active and harmonious participation on social and cultural practices from infancy, throughout the lifespan. More research is needed to examine the mediators and developmental sequence of this tendency to emotionally calibrate to others' feelings about the world. En ligne : http://dx.doi.org/10.1186/s13229-016-0098-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Others' emotions teach, but not in autism: an eye-tracking pupillometry study [Texte imprimé et/ou numérique] / H. J. NUSKE, Auteur ; G. VIVANTI, Auteur ; Cheryl DISSANAYAKE, Auteur . - 36p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 36p. Mots-clés : Attention  Autistic Disorder/physiopathology  Child, Preschool  Emotions/physiology  Facial Expression  Female  Humans  Male  Pupil/physiology  Autism  Autonomic nervous system  Emotion  Eye-tracking pupillometry  Social learning  Social-emotional calibration Index. décimale : PER Périodiques Résumé : BACKGROUND: Much research has investigated deficit in emotional reactivity to others in people with autism, but scant attention has been paid to how this deficit affects their own reactions to features of their environment (objects, events, practices, etc.). The present study presents a preliminary analysis on whether calibrating one's own emotional reactions to others' emotional reactions about features of the world, a process we term social-emotional calibration, is disrupted in autism. METHODS: To examine this process, we used a novel eye-tracking pupillometry paradigm in which we showed 20 preschoolers with autism and 20 matched typically developing preschoolers' videos of an actor opening a box and reacting to the occluded object inside, with fear or happiness. We expected preschoolers to come to perceive the box as containing a positive or threatening stimulus through emotionally calibrating to the actor's emotional expressions. Children's mean pupil diameter (indicating emotional reactivity) was measured whilst viewing an up-close, visually identical image of the box before and then after the scene, and this difference was taken as an index of social-emotional calibration and compared between groups. RESULTS: Whilst the typically developing preschoolers responded more emotionally to the box after, compared to before the scene (as indexed by an increase in pupil size), those with autism did not, suggesting their reaction to the object was not affected by the actor's emotional expressions. The groups did not differ in looking duration to the emotional expressions; thus, the pupil dilation findings cannot be explained by differences in visual attention. More social-emotional calibration on the happy condition was associated with less severe autism symptoms. CONCLUSIONS: Through the measurement of physiological reactivity, findings suggest social-emotional calibration is diminished in children with autism, with calibration to others' positive emotions as particularly important. This study highlights a possible mechanism by which individuals with autism develop idiosyncratic reactions to features of their environment, which is likely to impact their active and harmonious participation on social and cultural practices from infancy, throughout the lifespan. More research is needed to examine the mediators and developmental sequence of this tendency to emotionally calibrate to others' feelings about the world. En ligne : http://dx.doi.org/10.1186/s13229-016-0098-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families / J. PAGE in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 39p. Titre : Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families Type de document : Texte imprimé et/ou numérique Auteurs : J. PAGE, Auteur ; John N. CONSTANTINO, Auteur ; K. ZAMBRANA, Auteur ; E. MARTIN, Auteur ; I. TUNC, Auteur ; Y. ZHANG, Auteur ; Anna ABBACCHI, Auteur ; D. MESSINGER, Auteur Article en page(s) : 39p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/genetics  Child  Child, Preschool  Female  Genetic Predisposition to Disease  Hispanic Americans/genetics  Humans  Male  Parents  Phenotype  Siblings  Ancestry  Assortative mating  Hispanic  Measurement  Social Responsiveness Scale Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent studies have indicated that quantitative autistic traits (QATs) of parents reflect inherited liabilities that may index background genetic risk for clinical autism spectrum disorder (ASD) in their offspring. Moreover, preferential mating for QATs has been observed as a potential factor in concentrating autistic liabilities in some families across generations. Heretofore, intergenerational studies of QATs have focused almost exclusively on Caucasian populations-the present study explored these phenomena in a well-characterized Hispanic population. METHODS: The present study examined QAT scores in siblings and parents of 83 Hispanic probands meeting research diagnostic criteria for ASD, and 64 non-ASD controls, using the Social Responsiveness Scale-2 (SRS-2). Ancestry of the probands was characterized by genotype, using information from 541,929 single nucleotide polymorphic markers. RESULTS: In families of Hispanic children with an ASD diagnosis, the pattern of quantitative trait correlations observed between ASD-affected children and their first-degree relatives (ICCs on the order of 0.20), between unaffected first-degree relatives in ASD-affected families (sibling/mother ICC = 0.36; sibling/father ICC = 0.53), and between spouses (mother/father ICC = 0.48) were in keeping with the influence of transmitted background genetic risk and strong preferential mating for variation in quantitative autistic trait burden. Results from analysis of ancestry-informative genetic markers among probands in this sample were consistent with that from other Hispanic populations. CONCLUSIONS: Quantitative autistic traits represent measurable indices of inherited liability to ASD in Hispanic families. The accumulation of autistic traits occurs within generations, between spouses, and across generations, among Hispanic families affected by ASD. The occurrence of preferential mating for QATs-the magnitude of which may vary across cultures-constitutes a mechanism by which background genetic liability for ASD can accumulate in a given family in successive generations. En ligne : http://dx.doi.org/10.1186/s13229-016-0100-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families [Texte imprimé et/ou numérique] / J. PAGE, Auteur ; John N. CONSTANTINO, Auteur ; K. ZAMBRANA, Auteur ; E. MARTIN, Auteur ; I. TUNC, Auteur ; Y. ZHANG, Auteur ; Anna ABBACCHI, Auteur ; D. MESSINGER, Auteur . - 39p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 39p. Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/genetics  Child  Child, Preschool  Female  Genetic Predisposition to Disease  Hispanic Americans/genetics  Humans  Male  Parents  Phenotype  Siblings  Ancestry  Assortative mating  Hispanic  Measurement  Social Responsiveness Scale Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent studies have indicated that quantitative autistic traits (QATs) of parents reflect inherited liabilities that may index background genetic risk for clinical autism spectrum disorder (ASD) in their offspring. Moreover, preferential mating for QATs has been observed as a potential factor in concentrating autistic liabilities in some families across generations. Heretofore, intergenerational studies of QATs have focused almost exclusively on Caucasian populations-the present study explored these phenomena in a well-characterized Hispanic population. METHODS: The present study examined QAT scores in siblings and parents of 83 Hispanic probands meeting research diagnostic criteria for ASD, and 64 non-ASD controls, using the Social Responsiveness Scale-2 (SRS-2). Ancestry of the probands was characterized by genotype, using information from 541,929 single nucleotide polymorphic markers. RESULTS: In families of Hispanic children with an ASD diagnosis, the pattern of quantitative trait correlations observed between ASD-affected children and their first-degree relatives (ICCs on the order of 0.20), between unaffected first-degree relatives in ASD-affected families (sibling/mother ICC = 0.36; sibling/father ICC = 0.53), and between spouses (mother/father ICC = 0.48) were in keeping with the influence of transmitted background genetic risk and strong preferential mating for variation in quantitative autistic trait burden. Results from analysis of ancestry-informative genetic markers among probands in this sample were consistent with that from other Hispanic populations. CONCLUSIONS: Quantitative autistic traits represent measurable indices of inherited liability to ASD in Hispanic families. The accumulation of autistic traits occurs within generations, between spouses, and across generations, among Hispanic families affected by ASD. The occurrence of preferential mating for QATs-the magnitude of which may vary across cultures-constitutes a mechanism by which background genetic liability for ASD can accumulate in a given family in successive generations. En ligne : http://dx.doi.org/10.1186/s13229-016-0100-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Intact priors for gaze direction in adults with high-functioning autism spectrum conditions / P. J. PELL in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 25p. Titre : Intact priors for gaze direction in adults with high-functioning autism spectrum conditions Type de document : Texte imprimé et/ou numérique Auteurs : P. J. PELL, Auteur ; I. MARESCHAL, Auteur ; Andrew J. CALDER, Auteur ; Elisabeth A. H. VON DEM HAGEN, Auteur ; C. W. CLIFFORD, Auteur ; Simon BARON-COHEN, Auteur ; M. P. EWBANK, Auteur Article en page(s) : 25p. Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder/physiopathology  Bayes Theorem  Female  Fixation, Ocular/physiology  Humans  Male  Pattern Recognition, Visual  Photic Stimulation  Visual Perception  Young Adult  Autism  Autistic traits  Bayesian priors  Gaze perception  Uncertainty Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism Spectrum Conditions (ASC) are associated with a range of perceptual atypicalities, including abnormalities in gaze processing. Pellicano and Burr (Trends Cogn Sci 16(10):504-10, 2012) have argued that these atypicalities might be explained within a Bayesian framework, in which perception represents the combination of sensory information with prior knowledge. They propose that the Bayesian priors of individuals with ASC might be attenuated, such that their perception is less reliant on prior knowledge than neurotypical individuals. An important tenet of Bayesian decision theory is that increased uncertainty about incoming sensory information will lead to a greater influence of the prior on perception. Consistent with this, Mareschal et al. (Curr Biol 23(8):717-21, 2013) showed that when noise is added to the eyes of a face (increasing uncertainty about gaze direction), gaze is more likely to be perceived as direct. METHODS: We adopted the same paradigm as Mareschal et al. to determine whether the influence of a prior on gaze perception is reduced in neurotypical participants with high numbers of autistic traits (experiment 1) and in individuals with a clinical diagnosis of ASC (experiment 2). Participants were presented with synthetic faces and asked to make a judgement about the relative gaze directions of the faces. Uncertainty about gaze direction was manipulated by adding noise to the eyes of a face. RESULTS: Consistent with previous work, in both experiment 1 and experiment 2, participants showed a bias towards perceiving gaze as direct under conditions of uncertainty. However, there was no evidence that the magnitude of this bias was reduced either in the ASC group or in neurotypical controls with a high number of autistic traits. CONCLUSIONS: Our findings challenge the attenuated priors theory of perception in ASC (Trends Cogn Sci 16(10):504-10, 2012) and related proposals (Trends Cogn Sci 17(1):1, 2013, Front Hum Neurosci 8:302, 2014), and suggest priors for gaze direction are intact in high-functioning ASC. En ligne : http://dx.doi.org/10.1186/s13229-016-0085-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Intact priors for gaze direction in adults with high-functioning autism spectrum conditions [Texte imprimé et/ou numérique] / P. J. PELL, Auteur ; I. MARESCHAL, Auteur ; Andrew J. CALDER, Auteur ; Elisabeth A. H. VON DEM HAGEN, Auteur ; C. W. CLIFFORD, Auteur ; Simon BARON-COHEN, Auteur ; M. P. EWBANK, Auteur . - 25p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 25p. Mots-clés : Adult  Autism Spectrum Disorder/physiopathology  Bayes Theorem  Female  Fixation, Ocular/physiology  Humans  Male  Pattern Recognition, Visual  Photic Stimulation  Visual Perception  Young Adult  Autism  Autistic traits  Bayesian priors  Gaze perception  Uncertainty Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism Spectrum Conditions (ASC) are associated with a range of perceptual atypicalities, including abnormalities in gaze processing. Pellicano and Burr (Trends Cogn Sci 16(10):504-10, 2012) have argued that these atypicalities might be explained within a Bayesian framework, in which perception represents the combination of sensory information with prior knowledge. They propose that the Bayesian priors of individuals with ASC might be attenuated, such that their perception is less reliant on prior knowledge than neurotypical individuals. An important tenet of Bayesian decision theory is that increased uncertainty about incoming sensory information will lead to a greater influence of the prior on perception. Consistent with this, Mareschal et al. (Curr Biol 23(8):717-21, 2013) showed that when noise is added to the eyes of a face (increasing uncertainty about gaze direction), gaze is more likely to be perceived as direct. METHODS: We adopted the same paradigm as Mareschal et al. to determine whether the influence of a prior on gaze perception is reduced in neurotypical participants with high numbers of autistic traits (experiment 1) and in individuals with a clinical diagnosis of ASC (experiment 2). Participants were presented with synthetic faces and asked to make a judgement about the relative gaze directions of the faces. Uncertainty about gaze direction was manipulated by adding noise to the eyes of a face. RESULTS: Consistent with previous work, in both experiment 1 and experiment 2, participants showed a bias towards perceiving gaze as direct under conditions of uncertainty. However, there was no evidence that the magnitude of this bias was reduced either in the ASC group or in neurotypical controls with a high number of autistic traits. CONCLUSIONS: Our findings challenge the attenuated priors theory of perception in ASC (Trends Cogn Sci 16(10):504-10, 2012) and related proposals (Trends Cogn Sci 17(1):1, 2013, Front Hum Neurosci 8:302, 2014), and suggest priors for gaze direction are intact in high-functioning ASC. En ligne : http://dx.doi.org/10.1186/s13229-016-0085-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Increased expression of the PI3K catalytic subunit p110delta underlies elevated S6 phosphorylation and protein synthesis in an individual with autism from a multiplex family / A. C. POOPAL in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 3p. Titre : Increased expression of the PI3K catalytic subunit p110delta underlies elevated S6 phosphorylation and protein synthesis in an individual with autism from a multiplex family Type de document : Texte imprimé et/ou numérique Auteurs : A. C. POOPAL, Auteur ; L. M. SCHROEDER, Auteur ; P. S. HORN, Auteur ; Gary J. BASSELL, Auteur ; C. GROSS, Auteur Article en page(s) : 3p. Langues : Anglais (eng) Mots-clés : Adenine/analogs & derivatives/pharmacology  Autistic Disorder/enzymology/genetics/pathology  Biomarkers  Cell Line  Class I Phosphatidylinositol 3-Kinases/antagonists &  inhibitors/biosynthesis/genetics/physiology  Diseases in Twins  Enzyme-Linked Immunosorbent Assay  Family Health  Female  Humans  Lymphocytes/enzymology  Male  Molecular Targeted Therapy  Nerve Tissue Proteins/genetics/metabolism  Phosphorylation  Protein Processing, Post-Translational  Quinazolines/pharmacology  Ribosomal Protein S6 Kinases/metabolism  Signal Transduction/genetics  TOR Serine-Threonine Kinases/physiology  Autism  Biomarker  Ic87114  PI3K/mTOR signaling  S6 phosphorylation  p110delta Index. décimale : PER Périodiques Résumé : BACKGROUND: Dysfunctions in the PI3K/mTOR pathway have gained a lot of attention in autism research. This was initially based on the discovery of several monogenic autism spectrum disorders with mutations or defects in PI3K/mTOR signaling components. Recent genetic studies corroborate that defective PI3K/mTOR signaling might be a shared pathomechanism in autism disorders of so far unknown etiology, but functional molecular analyses in human cells are rare. The goals of this study were to perform a functional screen of cell lines from patients with idiopathic autism for defects in PI3K/mTOR signaling, to test if further functional analyses are suitable to detect underlying molecular mechanisms, and to evaluate this approach as a biomarker tool to identify therapeutic targets. METHODS: We performed phospho-S6- and S6-specific ELISA experiments on 21 lymphoblastoid cell lines from the AGRE collection and on 37 lymphoblastoid cell lines from the Simons Simplex Collection and their healthy siblings. Cell lines from one individual with increased S6 phosphorylation and his multiplex family were analyzed in further detail to identify upstream defects in PI3K signaling associated with autism diagnosis. RESULTS: We detected significantly increased S6 phosphorylation in 3 of the 21 lymphoblastoid cell lines from AGRE compared to a healthy control and in 1 of the 37 lymphoblastoid cell lines from the Simons Simplex Collection compared to the healthy sibling. Further analysis of cells from one individual with elevated S6 phosphorylation showed increased expression of the PI3K catalytic subunit p110delta, which was also observed in lymphoblastoid cells from other autistic siblings but not unaffected members in his multiplex family. The p110delta-selective inhibitor IC87114 reduced elevated S6 phosphorylation and protein synthesis in this cell line. CONCLUSIONS: Our results suggest that functional analysis of PI3K/mTOR signaling is a biomarker tool to identify disease-associated molecular defects that could serve as therapeutic targets in autism. Using this approach, we discovered impaired signaling and protein synthesis through the PI3K catalytic subunit p110delta as an underlying molecular defect and potential treatment target in select autism spectrum disorders. Increased p110delta activity was recently associated with schizophrenia, and our results suggest that p110delta may also be implicated in autism. En ligne : http://dx.doi.org/10.1186/s13229-015-0066-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Increased expression of the PI3K catalytic subunit p110delta underlies elevated S6 phosphorylation and protein synthesis in an individual with autism from a multiplex family [Texte imprimé et/ou numérique] / A. C. POOPAL, Auteur ; L. M. SCHROEDER, Auteur ; P. S. HORN, Auteur ; Gary J. BASSELL, Auteur ; C. GROSS, Auteur . - 3p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 3p. Mots-clés : Adenine/analogs & derivatives/pharmacology  Autistic Disorder/enzymology/genetics/pathology  Biomarkers  Cell Line  Class I Phosphatidylinositol 3-Kinases/antagonists &  inhibitors/biosynthesis/genetics/physiology  Diseases in Twins  Enzyme-Linked Immunosorbent Assay  Family Health  Female  Humans  Lymphocytes/enzymology  Male  Molecular Targeted Therapy  Nerve Tissue Proteins/genetics/metabolism  Phosphorylation  Protein Processing, Post-Translational  Quinazolines/pharmacology  Ribosomal Protein S6 Kinases/metabolism  Signal Transduction/genetics  TOR Serine-Threonine Kinases/physiology  Autism  Biomarker  Ic87114  PI3K/mTOR signaling  S6 phosphorylation  p110delta Index. décimale : PER Périodiques Résumé : BACKGROUND: Dysfunctions in the PI3K/mTOR pathway have gained a lot of attention in autism research. This was initially based on the discovery of several monogenic autism spectrum disorders with mutations or defects in PI3K/mTOR signaling components. Recent genetic studies corroborate that defective PI3K/mTOR signaling might be a shared pathomechanism in autism disorders of so far unknown etiology, but functional molecular analyses in human cells are rare. The goals of this study were to perform a functional screen of cell lines from patients with idiopathic autism for defects in PI3K/mTOR signaling, to test if further functional analyses are suitable to detect underlying molecular mechanisms, and to evaluate this approach as a biomarker tool to identify therapeutic targets. METHODS: We performed phospho-S6- and S6-specific ELISA experiments on 21 lymphoblastoid cell lines from the AGRE collection and on 37 lymphoblastoid cell lines from the Simons Simplex Collection and their healthy siblings. Cell lines from one individual with increased S6 phosphorylation and his multiplex family were analyzed in further detail to identify upstream defects in PI3K signaling associated with autism diagnosis. RESULTS: We detected significantly increased S6 phosphorylation in 3 of the 21 lymphoblastoid cell lines from AGRE compared to a healthy control and in 1 of the 37 lymphoblastoid cell lines from the Simons Simplex Collection compared to the healthy sibling. Further analysis of cells from one individual with elevated S6 phosphorylation showed increased expression of the PI3K catalytic subunit p110delta, which was also observed in lymphoblastoid cells from other autistic siblings but not unaffected members in his multiplex family. The p110delta-selective inhibitor IC87114 reduced elevated S6 phosphorylation and protein synthesis in this cell line. CONCLUSIONS: Our results suggest that functional analysis of PI3K/mTOR signaling is a biomarker tool to identify disease-associated molecular defects that could serve as therapeutic targets in autism. Using this approach, we discovered impaired signaling and protein synthesis through the PI3K catalytic subunit p110delta as an underlying molecular defect and potential treatment target in select autism spectrum disorders. Increased p110delta activity was recently associated with schizophrenia, and our results suggest that p110delta may also be implicated in autism. En ligne : http://dx.doi.org/10.1186/s13229-015-0066-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study / A. RAUSCH in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 13p. Titre : Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study Type de document : Texte imprimé et/ou numérique Auteurs : A. RAUSCH, Auteur ; W. ZHANG, Auteur ; K. V. HAAK, Auteur ; M. MENNES, Auteur ; E. J. HERMANS, Auteur ; E. VAN OORT, Auteur ; G. VAN WINGEN, Auteur ; Christian F. BECKMANN, Auteur ; Jan K. BUITELAAR, Auteur ; W. B. GROEN, Auteur Article en page(s) : 13p. Langues : Anglais (eng) Mots-clés : Adolescent  Afferent Pathways/pathology/physiopathology  Amygdala/pathology/physiopathology  Autism Spectrum Disorder/pathology/physiopathology  Basolateral Nuclear Complex/pathology/physiopathology  Central Amygdaloid Nucleus/pathology/physiopathology  Connectome  Efferent Pathways/pathology/physiopathology  Emotions  Female  Humans  Image Processing, Computer-Assisted  Magnetic Resonance Imaging  Male  Models, Neurological  Models, Psychological  Neocortex/pathology/physiopathology  Nerve Net/pathology/physiopathology  Signal-To-Noise Ratio  Social Perception  Surveys and Questionnaires  Temporal Lobe/pathology/physiopathology  Young Adult  Amygdala  Autism spectrum disorder  Centromedial  Connectivity  Input-output  Laterobasal  Nuclei  Superficial Index. décimale : PER Périodiques Résumé : BACKGROUND: Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygdaloid social-perceptual input nuclei and emotion-regulation output nuclei in ASD versus controls. METHODS: We collected resting state functional magnetic resonance imaging (fMRI) data, tailored to provide optimal sensitivity in the amygdala as well as the neocortex, in 20 adolescents and young adults with ASD and 25 matched controls. We performed a regular correlation analysis between the entire amygdala (EA) and the whole brain and used a partial correlation analysis to investigate whole-brain functional connectivity uniquely related to each of the amygdaloid subregions. RESULTS: Between-group comparison of regular EA correlations showed significantly reduced connectivity in visuospatial and superior parietal areas in ASD compared to controls. Partial correlation analysis revealed that this effect was driven by the left superficial and right laterobasal input subregions, but not the centromedial output nuclei. CONCLUSIONS: These results indicate reduced connectivity of specifically the amygdaloid sensory input channels in ASD, suggesting that abnormal amygdalo-cortical connectivity can be traced down to the socio-perceptual pathways. En ligne : http://dx.doi.org/10.1186/s13229-015-0060-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study [Texte imprimé et/ou numérique] / A. RAUSCH, Auteur ; W. ZHANG, Auteur ; K. V. HAAK, Auteur ; M. MENNES, Auteur ; E. J. HERMANS, Auteur ; E. VAN OORT, Auteur ; G. VAN WINGEN, Auteur ; Christian F. BECKMANN, Auteur ; Jan K. BUITELAAR, Auteur ; W. B. GROEN, Auteur . - 13p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 13p. Mots-clés : Adolescent  Afferent Pathways/pathology/physiopathology  Amygdala/pathology/physiopathology  Autism Spectrum Disorder/pathology/physiopathology  Basolateral Nuclear Complex/pathology/physiopathology  Central Amygdaloid Nucleus/pathology/physiopathology  Connectome  Efferent Pathways/pathology/physiopathology  Emotions  Female  Humans  Image Processing, Computer-Assisted  Magnetic Resonance Imaging  Male  Models, Neurological  Models, Psychological  Neocortex/pathology/physiopathology  Nerve Net/pathology/physiopathology  Signal-To-Noise Ratio  Social Perception  Surveys and Questionnaires  Temporal Lobe/pathology/physiopathology  Young Adult  Amygdala  Autism spectrum disorder  Centromedial  Connectivity  Input-output  Laterobasal  Nuclei  Superficial Index. décimale : PER Périodiques Résumé : BACKGROUND: Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygdaloid social-perceptual input nuclei and emotion-regulation output nuclei in ASD versus controls. METHODS: We collected resting state functional magnetic resonance imaging (fMRI) data, tailored to provide optimal sensitivity in the amygdala as well as the neocortex, in 20 adolescents and young adults with ASD and 25 matched controls. We performed a regular correlation analysis between the entire amygdala (EA) and the whole brain and used a partial correlation analysis to investigate whole-brain functional connectivity uniquely related to each of the amygdaloid subregions. RESULTS: Between-group comparison of regular EA correlations showed significantly reduced connectivity in visuospatial and superior parietal areas in ASD compared to controls. Partial correlation analysis revealed that this effect was driven by the left superficial and right laterobasal input subregions, but not the centromedial output nuclei. CONCLUSIONS: These results indicate reduced connectivity of specifically the amygdaloid sensory input channels in ASD, suggesting that abnormal amygdalo-cortical connectivity can be traced down to the socio-perceptual pathways. En ligne : http://dx.doi.org/10.1186/s13229-015-0060-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study / A. RETICO in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 5p. Titre : The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study Type de document : Texte imprimé et/ou numérique Auteurs : A. RETICO, Auteur ; A. GIULIANO, Auteur ; Raffaella TANCREDI, Auteur ; A. COSENZA, Auteur ; Fabio APICELLA, Auteur ; A. NARZISI, Auteur ; L. BIAGI, Auteur ; M. TOSETTI, Auteur ; F. MURATORI, Auteur ; Sara CALDERONI, Auteur Article en page(s) : 5p. Langues : Anglais (eng) Mots-clés : Area Under Curve  Autism Spectrum Disorder/pathology  Cerebrospinal Fluid  Child  Child, Preschool  Female  Gray Matter/pathology  Humans  Infant  Intelligence  Magnetic Resonance Imaging  Male  Neuroimaging  Organ Size  Phenotype  Research Design  Severity of Illness Index  Sex Characteristics  Support Vector Machine  White Matter/pathology  Autism spectrum disorders  Gender differences  Structural MRI  Young children Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic, hormonal, and environmental factors contribute since infancy to sexual dimorphism in regional brain structures of subjects with typical development. However, the neuroanatomical differences between male and female children with autism spectrum disorders (ASD) are an intriguing and still poorly investigated issue. This study aims to evaluate whether the brain of young children with ASD exhibits sex-related structural differences and if a correlation exists between clinical ASD features and neuroanatomical underpinnings. METHODS: A total of 152 structural MRI scans were analysed. Specifically, 76 young children with ASD (38 males and 38 females; 2-7 years of age; mean = 53 months, standard deviation = 17 months) were evaluated employing a support vector machine (SVM)-based analysis of the grey matter (GM). Group comparisons consisted of 76 age-, gender- and non-verbal-intelligence quotient-matched children with typical development or idiopathic developmental delay without autism. RESULTS: For both genders combined, SVM showed a significantly increased GM volume in young children with ASD with respect to control subjects, predominantly in the bilateral superior frontal gyrus (Brodmann area -BA- 10), bilateral precuneus (BA 31), bilateral superior temporal gyrus (BA 20/22), whereas less GM in patients with ASD was found in right inferior temporal gyrus (BA 37). For the within gender comparisons (i.e., females with ASD vs. controls and males with ASD vs. controls), two overlapping regions in bilateral precuneus (BA 31) and left superior frontal gyrus (BA 9/10) were detected. Sex-by-group analyses revealed in males with ASD compared to matched controls two male-specific regions of increased GM volume (left middle occipital gyrus-BA 19-and right superior temporal gyrus-BA 22). Comparisons in females with and without ASD demonstrated increased GM volumes predominantly in the bilateral frontal regions. Additional regions of significantly increased GM volume in the right anterior cingulate cortex (BA 32) and right cerebellum were typical only of females with ASD. CONCLUSIONS: Despite the specific behavioural correlates of sex-dimorphism in ASD, brain morphology as yet remains unclear and requires future dedicated investigations. This study provides evidence of structural brain gender differences in young children with ASD that possibly contribute to the different phenotypic disease manifestations in males and females. En ligne : http://dx.doi.org/10.1186/s13229-015-0067-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study [Texte imprimé et/ou numérique] / A. RETICO, Auteur ; A. GIULIANO, Auteur ; Raffaella TANCREDI, Auteur ; A. COSENZA, Auteur ; Fabio APICELLA, Auteur ; A. NARZISI, Auteur ; L. BIAGI, Auteur ; M. TOSETTI, Auteur ; F. MURATORI, Auteur ; Sara CALDERONI, Auteur . - 5p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 5p. Mots-clés : Area Under Curve  Autism Spectrum Disorder/pathology  Cerebrospinal Fluid  Child  Child, Preschool  Female  Gray Matter/pathology  Humans  Infant  Intelligence  Magnetic Resonance Imaging  Male  Neuroimaging  Organ Size  Phenotype  Research Design  Severity of Illness Index  Sex Characteristics  Support Vector Machine  White Matter/pathology  Autism spectrum disorders  Gender differences  Structural MRI  Young children Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic, hormonal, and environmental factors contribute since infancy to sexual dimorphism in regional brain structures of subjects with typical development. However, the neuroanatomical differences between male and female children with autism spectrum disorders (ASD) are an intriguing and still poorly investigated issue. This study aims to evaluate whether the brain of young children with ASD exhibits sex-related structural differences and if a correlation exists between clinical ASD features and neuroanatomical underpinnings. METHODS: A total of 152 structural MRI scans were analysed. Specifically, 76 young children with ASD (38 males and 38 females; 2-7 years of age; mean = 53 months, standard deviation = 17 months) were evaluated employing a support vector machine (SVM)-based analysis of the grey matter (GM). Group comparisons consisted of 76 age-, gender- and non-verbal-intelligence quotient-matched children with typical development or idiopathic developmental delay without autism. RESULTS: For both genders combined, SVM showed a significantly increased GM volume in young children with ASD with respect to control subjects, predominantly in the bilateral superior frontal gyrus (Brodmann area -BA- 10), bilateral precuneus (BA 31), bilateral superior temporal gyrus (BA 20/22), whereas less GM in patients with ASD was found in right inferior temporal gyrus (BA 37). For the within gender comparisons (i.e., females with ASD vs. controls and males with ASD vs. controls), two overlapping regions in bilateral precuneus (BA 31) and left superior frontal gyrus (BA 9/10) were detected. Sex-by-group analyses revealed in males with ASD compared to matched controls two male-specific regions of increased GM volume (left middle occipital gyrus-BA 19-and right superior temporal gyrus-BA 22). Comparisons in females with and without ASD demonstrated increased GM volumes predominantly in the bilateral frontal regions. Additional regions of significantly increased GM volume in the right anterior cingulate cortex (BA 32) and right cerebellum were typical only of females with ASD. CONCLUSIONS: Despite the specific behavioural correlates of sex-dimorphism in ASD, brain morphology as yet remains unclear and requires future dedicated investigations. This study provides evidence of structural brain gender differences in young children with ASD that possibly contribute to the different phenotypic disease manifestations in males and females. En ligne : http://dx.doi.org/10.1186/s13229-015-0067-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Bengali translation and characterisation of four cognitive and trait measures for autism spectrum conditions in India / A. RUDRA in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 50p. Titre : Bengali translation and characterisation of four cognitive and trait measures for autism spectrum conditions in India Type de document : Texte imprimé et/ou numérique Auteurs : A. RUDRA, Auteur ; J. R. RAM, Auteur ; T. LOUCAS, Auteur ; Matthew K. BELMONTE, Auteur ; Bhismadev CHAKRABARTI, Auteur Article en page(s) : 50p. Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder/physiopathology/psychology  Case-Control Studies  Child  Cognition/physiology  Cross-Cultural Comparison  Empathy  Facial Expression  Female  Humans  India  Intelligence Tests/standards  Language  Male  Regression Analysis  Social Skills  Surveys and Questionnaires  Theory of Mind  Translations  Assessment  Autism  Behaviour  Bengali  Central coherence  Perceptual construal  Theory of mind  Translation  Validity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism is characterised by atypical social-communicative behaviour and restricted range of interests and repetitive behaviours. These features exist in a continuum in the general population. Behavioural measures validated across cultures and languages are required to quantify the dimensional traits of autism in these social and non-social domains. Bengali is the seventh most spoken language in the world. However, there is a serious dearth of data on standard measures of autism-related social and visual cognition in Bengali. METHODS: Bengali translations of two measures related to social-communicative functioning (the Children's Reading the Mind in the Eyes Test (RMET) and a facial emotion recognition test with stimuli taken from the Karolinska Directed Emotional Faces database), one measure of visual perceptual disembedding (the Embedded Figures Test), and a questionnaire measure (the Children's Empathy Quotient) were tested in 25 children with autism spectrum conditions (ASC) and 26 control children (mean age = 10.7 years) in Kolkata, India. Group differences were analysed by t test and multiple regression (after accounting for potential effects of gender, IQ, and age). RESULTS: Behavioural and trait measures were associated with group differences in the expected directions: ASC children scored lower on the Children's Empathy Quotient and the RMET, as well as on facial emotion recognition, but were faster and more accurate on the Embedded Figures Test. Distributional properties of these measures within groups are similar to those reported in Western countries. CONCLUSIONS: These results provide an empirical demonstration of cross-cultural generalisability and applicability of these standard behavioural and trait measures related to autism, in a major world language. En ligne : http://dx.doi.org/10.1186/s13229-016-0111-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Bengali translation and characterisation of four cognitive and trait measures for autism spectrum conditions in India [Texte imprimé et/ou numérique] / A. RUDRA, Auteur ; J. R. RAM, Auteur ; T. LOUCAS, Auteur ; Matthew K. BELMONTE, Auteur ; Bhismadev CHAKRABARTI, Auteur . - 50p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 50p. Mots-clés : Adolescent  Autism Spectrum Disorder/physiopathology/psychology  Case-Control Studies  Child  Cognition/physiology  Cross-Cultural Comparison  Empathy  Facial Expression  Female  Humans  India  Intelligence Tests/standards  Language  Male  Regression Analysis  Social Skills  Surveys and Questionnaires  Theory of Mind  Translations  Assessment  Autism  Behaviour  Bengali  Central coherence  Perceptual construal  Theory of mind  Translation  Validity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism is characterised by atypical social-communicative behaviour and restricted range of interests and repetitive behaviours. These features exist in a continuum in the general population. Behavioural measures validated across cultures and languages are required to quantify the dimensional traits of autism in these social and non-social domains. Bengali is the seventh most spoken language in the world. However, there is a serious dearth of data on standard measures of autism-related social and visual cognition in Bengali. METHODS: Bengali translations of two measures related to social-communicative functioning (the Children's Reading the Mind in the Eyes Test (RMET) and a facial emotion recognition test with stimuli taken from the Karolinska Directed Emotional Faces database), one measure of visual perceptual disembedding (the Embedded Figures Test), and a questionnaire measure (the Children's Empathy Quotient) were tested in 25 children with autism spectrum conditions (ASC) and 26 control children (mean age = 10.7 years) in Kolkata, India. Group differences were analysed by t test and multiple regression (after accounting for potential effects of gender, IQ, and age). RESULTS: Behavioural and trait measures were associated with group differences in the expected directions: ASC children scored lower on the Children's Empathy Quotient and the RMET, as well as on facial emotion recognition, but were faster and more accurate on the Embedded Figures Test. Distributional properties of these measures within groups are similar to those reported in Western countries. CONCLUSIONS: These results provide an empirical demonstration of cross-cultural generalisability and applicability of these standard behavioural and trait measures related to autism, in a major world language. En ligne : http://dx.doi.org/10.1186/s13229-016-0111-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

An investigation of the 'female camouflage effect' in autism using a computerized ADOS-2 and a test of sex/gender differences / A. RYNKIEWICZ in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 10p. Titre : An investigation of the 'female camouflage effect' in autism using a computerized ADOS-2 and a test of sex/gender differences Type de document : Texte imprimé et/ou numérique Auteurs : A. RYNKIEWICZ, Auteur ; B. SCHULLER, Auteur ; E. MARCHI, Auteur ; S. PIANA, Auteur ; A. CAMURRI, Auteur ; A. LASSALLE, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 10p. Langues : Anglais (eng) Mots-clés : Asperger Syndrome/diagnosis/psychology  Autistic Disorder/diagnosis/psychology  Child  Child, Preschool  Communication Disorders/diagnosis/etiology  Culture  Diagnosis, Computer-Assisted/methods  Diagnostic Errors  Emotions  Facial Expression  Female  Fixation, Ocular  Gestures  Humans  Male  Parents  Poland  Psychomotor Performance  Severity of Illness Index  Sex Characteristics  Sex Factors  Social Behavior  Software  Stereotyped Behavior  Surveys and Questionnaires  Ados-2  Computer application  Diagnosis  Females with autism Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum conditions (autism) are diagnosed more frequently in boys than in girls. Females with autism may have been under-identified due to not only a male-biased understanding of autism but also females' camouflaging. The study describes a new technique that allows automated coding of non-verbal mode of communication (gestures) and offers the possibility of objective, evaluation of gestures, independent of human judgment. The EyesWeb software platform and the Kinect sensor during two demonstration activities of ADOS-2 (Autism Diagnostic Observation Schedule, Second Edition) were used. METHODS: The study group consisted of 33 high-functioning Polish girls and boys with formal diagnosis of autism or Asperger syndrome aged 5-10, with fluent speech, IQ average and above and their parents (girls with autism, n = 16; boys with autism, n = 17). All children were assessed during two demonstration activities of Module 3 of ADOS-2, administered in Polish, and coded using Polish codes. Children were also assessed with Polish versions of the Eyes and Faces Tests. Parents provided information on the author-reviewed Polish research translation of SCQ (Social Communication Questionnaire, Current and Lifetime) and Polish version of AQ Child (Autism Spectrum Quotient, Child). RESULTS: Girls with autism tended to use gestures more vividly as compared to boys with autism during two demonstration activities of ADOS-2. Girls with autism made significantly more mistakes than boys with autism on the Faces Test. All children with autism had high scores in AQ Child, which confirmed the presence of autistic traits in this group. The current communication skills of boys with autism reported by parents in SCQ were significantly better than those of girls with autism. However, both girls with autism and boys with autism improved in the social and communication abilities over the lifetime. The number of stereotypic behaviours in boys significantly decreased over life whereas it remained at a comparable level in girls with autism. CONCLUSIONS: High-functioning females with autism might present better on non-verbal (gestures) mode of communication than boys with autism. It may camouflage other diagnostic features. It poses risk of under-diagnosis or not receiving the appropriate diagnosis for this population. Further research is required to examine this phenomenon so appropriate gender revisions to the diagnostic assessments might be implemented. En ligne : http://dx.doi.org/10.1186/s13229-016-0073-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] An investigation of the 'female camouflage effect' in autism using a computerized ADOS-2 and a test of sex/gender differences [Texte imprimé et/ou numérique] / A. RYNKIEWICZ, Auteur ; B. SCHULLER, Auteur ; E. MARCHI, Auteur ; S. PIANA, Auteur ; A. CAMURRI, Auteur ; A. LASSALLE, Auteur ; Simon BARON-COHEN, Auteur . - 10p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 10p. Mots-clés : Asperger Syndrome/diagnosis/psychology  Autistic Disorder/diagnosis/psychology  Child  Child, Preschool  Communication Disorders/diagnosis/etiology  Culture  Diagnosis, Computer-Assisted/methods  Diagnostic Errors  Emotions  Facial Expression  Female  Fixation, Ocular  Gestures  Humans  Male  Parents  Poland  Psychomotor Performance  Severity of Illness Index  Sex Characteristics  Sex Factors  Social Behavior  Software  Stereotyped Behavior  Surveys and Questionnaires  Ados-2  Computer application  Diagnosis  Females with autism Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum conditions (autism) are diagnosed more frequently in boys than in girls. Females with autism may have been under-identified due to not only a male-biased understanding of autism but also females' camouflaging. The study describes a new technique that allows automated coding of non-verbal mode of communication (gestures) and offers the possibility of objective, evaluation of gestures, independent of human judgment. The EyesWeb software platform and the Kinect sensor during two demonstration activities of ADOS-2 (Autism Diagnostic Observation Schedule, Second Edition) were used. METHODS: The study group consisted of 33 high-functioning Polish girls and boys with formal diagnosis of autism or Asperger syndrome aged 5-10, with fluent speech, IQ average and above and their parents (girls with autism, n = 16; boys with autism, n = 17). All children were assessed during two demonstration activities of Module 3 of ADOS-2, administered in Polish, and coded using Polish codes. Children were also assessed with Polish versions of the Eyes and Faces Tests. Parents provided information on the author-reviewed Polish research translation of SCQ (Social Communication Questionnaire, Current and Lifetime) and Polish version of AQ Child (Autism Spectrum Quotient, Child). RESULTS: Girls with autism tended to use gestures more vividly as compared to boys with autism during two demonstration activities of ADOS-2. Girls with autism made significantly more mistakes than boys with autism on the Faces Test. All children with autism had high scores in AQ Child, which confirmed the presence of autistic traits in this group. The current communication skills of boys with autism reported by parents in SCQ were significantly better than those of girls with autism. However, both girls with autism and boys with autism improved in the social and communication abilities over the lifetime. The number of stereotypic behaviours in boys significantly decreased over life whereas it remained at a comparable level in girls with autism. CONCLUSIONS: High-functioning females with autism might present better on non-verbal (gestures) mode of communication than boys with autism. It may camouflage other diagnostic features. It poses risk of under-diagnosis or not receiving the appropriate diagnosis for this population. Further research is required to examine this phenomenon so appropriate gender revisions to the diagnostic assessments might be implemented. En ligne : http://dx.doi.org/10.1186/s13229-016-0073-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Placental methylome analysis from a prospective autism study / D. I. SCHROEDER in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 51p. Titre : Placental methylome analysis from a prospective autism study Type de document : Texte imprimé et/ou numérique Auteurs : D. I. SCHROEDER, Auteur ; Rebecca J. SCHMIDT, Auteur ; F. K. CRARY-DOOLEY, Auteur ; Cheryl K. WALKER, Auteur ; S. OZONOFF, Auteur ; Daniel J. TANCREDI, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; J. M. LASALLE, Auteur Article en page(s) : 51p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis/genetics  Biomarkers/metabolism  Child, Preschool  DNA Methylation  Early Diagnosis  Enhancer Elements, Genetic  Epigenesis, Genetic  Female  Genome, Human  Genome-Wide Association Study  High-Throughput Nucleotide Sequencing  Humans  Infant, Newborn  Intercellular Signaling Peptides and Proteins/genetics/metabolism  Male  Membrane Proteins/genetics/metabolism  Placenta/metabolism  Pregnancy  Biomarkers  DNA methylation  Epigenetics  Genomics  Methylome  Placenta Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders that are behaviorally diagnosed in early childhood. Most ASD cases likely arise from a complex mixture of genetic and environmental factors, an interface where the epigenetic marks of DNA methylation may be useful as risk biomarkers. The placenta is a potentially useful surrogate tissue characterized by a methylation pattern of partially methylated domains (PMDs) and highly methylated domains (HMDs) reflective of methylation patterns observed in the early embryo. METHODS: In this study, we investigated human term placentas from the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) prospective study by whole genome bisulfite sequencing. We also examined the utility of PMD/HMDs in detecting methylation differences consistent with ASD diagnosis at age three. RESULTS: We found that while human placental methylomes have highly reproducible PMD and HMD locations, there is a greater variation between individuals in methylation levels over PMDs than HMDs due to both sampling and individual variability. In a comparison of methylation differences in placental samples from 24 ASD and 23 typically developing (TD) children, a HMD containing a putative fetal brain enhancer near DLL1 was found to reach genome-wide significance and was validated for significantly higher methylation in ASD by pyrosequencing. CONCLUSIONS: These results suggest that the placenta could be an informative surrogate tissue for predictive ASD biomarkers in high-risk families. En ligne : http://dx.doi.org/10.1186/s13229-016-0114-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Placental methylome analysis from a prospective autism study [Texte imprimé et/ou numérique] / D. I. SCHROEDER, Auteur ; Rebecca J. SCHMIDT, Auteur ; F. K. CRARY-DOOLEY, Auteur ; Cheryl K. WALKER, Auteur ; S. OZONOFF, Auteur ; Daniel J. TANCREDI, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; J. M. LASALLE, Auteur . - 51p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 51p. Mots-clés : Autism Spectrum Disorder/diagnosis/genetics  Biomarkers/metabolism  Child, Preschool  DNA Methylation  Early Diagnosis  Enhancer Elements, Genetic  Epigenesis, Genetic  Female  Genome, Human  Genome-Wide Association Study  High-Throughput Nucleotide Sequencing  Humans  Infant, Newborn  Intercellular Signaling Peptides and Proteins/genetics/metabolism  Male  Membrane Proteins/genetics/metabolism  Placenta/metabolism  Pregnancy  Biomarkers  DNA methylation  Epigenetics  Genomics  Methylome  Placenta Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders that are behaviorally diagnosed in early childhood. Most ASD cases likely arise from a complex mixture of genetic and environmental factors, an interface where the epigenetic marks of DNA methylation may be useful as risk biomarkers. The placenta is a potentially useful surrogate tissue characterized by a methylation pattern of partially methylated domains (PMDs) and highly methylated domains (HMDs) reflective of methylation patterns observed in the early embryo. METHODS: In this study, we investigated human term placentas from the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) prospective study by whole genome bisulfite sequencing. We also examined the utility of PMD/HMDs in detecting methylation differences consistent with ASD diagnosis at age three. RESULTS: We found that while human placental methylomes have highly reproducible PMD and HMD locations, there is a greater variation between individuals in methylation levels over PMDs than HMDs due to both sampling and individual variability. In a comparison of methylation differences in placental samples from 24 ASD and 23 typically developing (TD) children, a HMD containing a putative fetal brain enhancer near DLL1 was found to reach genome-wide significance and was validated for significantly higher methylation in ASD by pyrosequencing. CONCLUSIONS: These results suggest that the placenta could be an informative surrogate tissue for predictive ASD biomarkers in high-risk families. En ligne : http://dx.doi.org/10.1186/s13229-016-0114-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Emotional decision-making in autism spectrum disorder: the roles of interoception and alexithymia / P. SHAH in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 43p. Titre : Emotional decision-making in autism spectrum disorder: the roles of interoception and alexithymia Type de document : Texte imprimé et/ou numérique Auteurs : P. SHAH, Auteur ; Caroline CATMUR, Auteur ; Geoffrey BIRD, Auteur Article en page(s) : 43p. Langues : Anglais (eng) Mots-clés : Adult  Affective Symptoms/physiopathology/psychology  Autism Spectrum Disorder/physiopathology/psychology  Case-Control Studies  Decision Making  Female  Frustration  Happiness  Humans  Intelligence Tests  Interoception/physiology  Male  Alexithymia  Autism  Decision-making  Emotion  Framing effect  Insula  Interoception  Replication Index. décimale : PER Périodiques Résumé : The way choices are framed influences decision-making. These "framing effects" emerge through the integration of emotional responses into decision-making under uncertainty. It was previously reported that susceptibility to the framing effect was reduced in individuals with autism spectrum disorder (ASD) due to a reduced tendency to incorporate emotional information into the decision-making process. However, recent research indicates that, where observed, emotional processing impairments in ASD may be due to co-occurring alexithymia. Alexithymia is thought to arise due to impaired interoception (the ability to perceive the internal state of one's body), raising the possibility that emotional signals are not perceived and thus not integrated into decision-making in those with alexithymia and that therefore reduced framing effects in ASD are a product of co-occurring alexithymia rather than ASD per se. Accordingly, the present study compared framing effects in autistic individuals with neurotypical controls matched for alexithymia. Results showed a marked deviation between groups. The framing effect was, in line with previous data, significantly smaller in autistic individuals, and there was no relationship between alexithymia or interoception and decision-making in the ASD group. In the neurotypical group, however, the size of the framing effect was associated with alexithymia and interoception, even after controlling for autistic traits. These results demonstrate that although framing effects are associated with interoception and alexithymia in the neurotypical population, emotional and interoceptive signals have less impact upon the decision-making process in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0104-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Emotional decision-making in autism spectrum disorder: the roles of interoception and alexithymia [Texte imprimé et/ou numérique] / P. SHAH, Auteur ; Caroline CATMUR, Auteur ; Geoffrey BIRD, Auteur . - 43p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 43p. Mots-clés : Adult  Affective Symptoms/physiopathology/psychology  Autism Spectrum Disorder/physiopathology/psychology  Case-Control Studies  Decision Making  Female  Frustration  Happiness  Humans  Intelligence Tests  Interoception/physiology  Male  Alexithymia  Autism  Decision-making  Emotion  Framing effect  Insula  Interoception  Replication Index. décimale : PER Périodiques Résumé : The way choices are framed influences decision-making. These "framing effects" emerge through the integration of emotional responses into decision-making under uncertainty. It was previously reported that susceptibility to the framing effect was reduced in individuals with autism spectrum disorder (ASD) due to a reduced tendency to incorporate emotional information into the decision-making process. However, recent research indicates that, where observed, emotional processing impairments in ASD may be due to co-occurring alexithymia. Alexithymia is thought to arise due to impaired interoception (the ability to perceive the internal state of one's body), raising the possibility that emotional signals are not perceived and thus not integrated into decision-making in those with alexithymia and that therefore reduced framing effects in ASD are a product of co-occurring alexithymia rather than ASD per se. Accordingly, the present study compared framing effects in autistic individuals with neurotypical controls matched for alexithymia. Results showed a marked deviation between groups. The framing effect was, in line with previous data, significantly smaller in autistic individuals, and there was no relationship between alexithymia or interoception and decision-making in the ASD group. In the neurotypical group, however, the size of the framing effect was associated with alexithymia and interoception, even after controlling for autistic traits. These results demonstrate that although framing effects are associated with interoception and alexithymia in the neurotypical population, emotional and interoceptive signals have less impact upon the decision-making process in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0104-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Altered gaze following during live interaction in infants at risk for autism: an eye tracking study / E. THORUP in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 12p. Titre : Altered gaze following during live interaction in infants at risk for autism: an eye tracking study Type de document : Texte imprimé et/ou numérique Auteurs : E. THORUP, Auteur ; P. NYSTROM, Auteur ; G. GREDEBACK, Auteur ; Sven BÖLTE, Auteur ; T. FALCK-YTTER, Auteur Article en page(s) : 12p. Langues : Anglais (eng) Mots-clés : Attention/physiology  Autism Spectrum Disorder/diagnosis/epidemiology/physiopathology  Cues  Early Diagnosis  Eye Movements  Family Health  Female  Fixation, Ocular/physiology  Head Movements  Humans  Imitative Behavior/physiology  Infant  Male  Pursuit, Smooth/physiology  Risk  Single-Blind Method  Social Behavior  Social Perception  Autism  Communication  Early development  Gaze following  Joint attention  Neurodevelopmental disorders  Social cognition  Younger siblings Index. décimale : PER Périodiques Résumé : BACKGROUND: The ability to follow gaze is an important prerequisite for joint attention, which is often compromised in children with autism spectrum disorder (ASD). The direction of both the head and eyes provides cues to other people's attention direction, but previous studies have not separated these factors and their relation to ASD susceptibility. Development of gaze following typically occurs before ASD diagnosis is possible, and studies of high-risk populations are therefore important. METHODS: Eye tracking was used to assess gaze following during interaction in a group of 10-month-old infants at high familial risk for ASD (high-risk group) as well as a group of infants with no family history of ASD (low-risk group). The infants watched an experimenter gaze at objects in the periphery. Performance was compared across two conditions: one in which the experimenter moved both the eyes and head toward the objects (Eyes and Head condition) and one that involved movement of the eyes only (Eyes Only condition). RESULTS: A group by condition interaction effect was found. Specifically, whereas gaze following accuracy was comparable across the two conditions in the low-risk group, infants in the high-risk group were more likely to follow gaze in the Eyes and Head condition than in the Eyes Only condition. CONCLUSIONS: In an ecologically valid social situation, responses to basic non-verbal orienting cues were found to be altered in infants at risk for ASD. The results indicate that infants at risk for ASD may rely disproportionally on information from the head when following gaze and point to the importance of separating information from the eyes and the head when studying social perception in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0069-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Altered gaze following during live interaction in infants at risk for autism: an eye tracking study [Texte imprimé et/ou numérique] / E. THORUP, Auteur ; P. NYSTROM, Auteur ; G. GREDEBACK, Auteur ; Sven BÖLTE, Auteur ; T. FALCK-YTTER, Auteur . - 12p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 12p. Mots-clés : Attention/physiology  Autism Spectrum Disorder/diagnosis/epidemiology/physiopathology  Cues  Early Diagnosis  Eye Movements  Family Health  Female  Fixation, Ocular/physiology  Head Movements  Humans  Imitative Behavior/physiology  Infant  Male  Pursuit, Smooth/physiology  Risk  Single-Blind Method  Social Behavior  Social Perception  Autism  Communication  Early development  Gaze following  Joint attention  Neurodevelopmental disorders  Social cognition  Younger siblings Index. décimale : PER Périodiques Résumé : BACKGROUND: The ability to follow gaze is an important prerequisite for joint attention, which is often compromised in children with autism spectrum disorder (ASD). The direction of both the head and eyes provides cues to other people's attention direction, but previous studies have not separated these factors and their relation to ASD susceptibility. Development of gaze following typically occurs before ASD diagnosis is possible, and studies of high-risk populations are therefore important. METHODS: Eye tracking was used to assess gaze following during interaction in a group of 10-month-old infants at high familial risk for ASD (high-risk group) as well as a group of infants with no family history of ASD (low-risk group). The infants watched an experimenter gaze at objects in the periphery. Performance was compared across two conditions: one in which the experimenter moved both the eyes and head toward the objects (Eyes and Head condition) and one that involved movement of the eyes only (Eyes Only condition). RESULTS: A group by condition interaction effect was found. Specifically, whereas gaze following accuracy was comparable across the two conditions in the low-risk group, infants in the high-risk group were more likely to follow gaze in the Eyes and Head condition than in the Eyes Only condition. CONCLUSIONS: In an ecologically valid social situation, responses to basic non-verbal orienting cues were found to be altered in infants at risk for ASD. The results indicate that infants at risk for ASD may rely disproportionally on information from the head when following gaze and point to the importance of separating information from the eyes and the head when studying social perception in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0069-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Alexithymia, but not autism spectrum disorder, may be related to the production of emotional facial expressions / D. A. TREVISAN in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 46p. Titre : Alexithymia, but not autism spectrum disorder, may be related to the production of emotional facial expressions Type de document : Texte imprimé et/ou numérique Auteurs : D. A. TREVISAN, Auteur ; M. BOWERING, Auteur ; Elina BIRMINGHAM, Auteur Article en page(s) : 46p. Langues : Anglais (eng) Mots-clés : Adolescent  Affective Symptoms/physiopathology/psychology  Autism Spectrum Disorder/classification/physiopathology/psychology  Case-Control Studies  Child  Facial Expression  Female  Humans  Male  Pattern Recognition, Automated/statistics & numerical data  Social Perception  Software  Alexithymia  Autism  Facial expressions Index. décimale : PER Périodiques Résumé : BACKGROUND: A prominent diagnostic criterion of autism spectrum disorder (ASD) relates to the abnormal or diminished use of facial expressions. Yet little is known about the mechanisms that contribute to this feature of ASD. METHODS: We showed children with and without ASD emotionally charged video clips in order to parse out individual differences in spontaneous production of facial expressions using automated facial expression analysis software. RESULTS: Using hierarchical multiple regression, we sought to determine whether alexithymia (characterized by difficulties interpreting one's own feeling states) contributes to diminished facial expression production. Across groups, alexithymic traits-but not ASD traits, IQ, or sex-were associated with quantity of facial expression production. CONCLUSIONS: These results accord with a growing body of research suggesting that many emotion processing abnormalities observed in ASD may be explained by co-occurring alexithymia. Developmental and clinical considerations are discussed, and it is argued that alexithymia is an important but too often ignored trait associated with ASD that may have implications for subtyping individuals on the autism spectrum. En ligne : http://dx.doi.org/10.1186/s13229-016-0108-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Alexithymia, but not autism spectrum disorder, may be related to the production of emotional facial expressions [Texte imprimé et/ou numérique] / D. A. TREVISAN, Auteur ; M. BOWERING, Auteur ; Elina BIRMINGHAM, Auteur . - 46p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 46p. Mots-clés : Adolescent  Affective Symptoms/physiopathology/psychology  Autism Spectrum Disorder/classification/physiopathology/psychology  Case-Control Studies  Child  Facial Expression  Female  Humans  Male  Pattern Recognition, Automated/statistics & numerical data  Social Perception  Software  Alexithymia  Autism  Facial expressions Index. décimale : PER Périodiques Résumé : BACKGROUND: A prominent diagnostic criterion of autism spectrum disorder (ASD) relates to the abnormal or diminished use of facial expressions. Yet little is known about the mechanisms that contribute to this feature of ASD. METHODS: We showed children with and without ASD emotionally charged video clips in order to parse out individual differences in spontaneous production of facial expressions using automated facial expression analysis software. RESULTS: Using hierarchical multiple regression, we sought to determine whether alexithymia (characterized by difficulties interpreting one's own feeling states) contributes to diminished facial expression production. Across groups, alexithymic traits-but not ASD traits, IQ, or sex-were associated with quantity of facial expression production. CONCLUSIONS: These results accord with a growing body of research suggesting that many emotion processing abnormalities observed in ASD may be explained by co-occurring alexithymia. Developmental and clinical considerations are discussed, and it is argued that alexithymia is an important but too often ignored trait associated with ASD that may have implications for subtyping individuals on the autism spectrum. En ligne : http://dx.doi.org/10.1186/s13229-016-0108-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Short report: relationship between restricted and repetitive behaviours in children with autism spectrum disorder and their parents / M. ULJAREVIC in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 29p. Titre : Short report: relationship between restricted and repetitive behaviours in children with autism spectrum disorder and their parents Type de document : Texte imprimé et/ou numérique Auteurs : M. ULJAREVIC, Auteur ; D. W. EVANS, Auteur ; Gail A. ALVARES, Auteur ; Andrew J. O. WHITEHOUSE, Auteur Article en page(s) : 29p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/diagnosis/physiopathology  Child  Child Behavior/physiology  Child, Preschool  Female  Humans  Male  Middle Aged  Parents/psychology  Phenotype  Stereotyped Behavior  Autism  Broader Autism Phenotype  Parents  Repetitive behaviours Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviours (RRBs) constitute a core symptom domain of autism spectrum disorder (ASD). However, the nature of RRBs in the context of the Broader Autism Phenotype (BAP) is not well understood. In particular, the relationship between RRBs in ASD probands and their parents remains largely unexplored. The current study explored the link between parental RRBs, measured via Interest in Patterns and Resistance to Changes subscales of the Autism Quotient and their children's RRBs, measured via Autism Diagnostic Observation Schedule RRB standardized domain score. FINDINGS: Having both parents within the top 20% of their RRB scores was associated with an increase of RRB scores for their children; however, no parent-of-origin effects were identified. Although the trend was observed for both Interest in Patterns and Resistance to Changes subscale, it was only statistically significant for Interest in Patterns. CONCLUSIONS: This paper provides significant contribution to our understanding of association between RRBs in parents and their children with ASD. Future work should also address the BAP in distinct genetic subtypes (whole chromosome aneuploidies, single gene mutations, copy number variations) of neurodevelopmental and neuropsychiatric disorders that involve RRBs. En ligne : http://dx.doi.org/10.1186/s13229-016-0091-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Short report: relationship between restricted and repetitive behaviours in children with autism spectrum disorder and their parents [Texte imprimé et/ou numérique] / M. ULJAREVIC, Auteur ; D. W. EVANS, Auteur ; Gail A. ALVARES, Auteur ; Andrew J. O. WHITEHOUSE, Auteur . - 29p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 29p. Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/diagnosis/physiopathology  Child  Child Behavior/physiology  Child, Preschool  Female  Humans  Male  Middle Aged  Parents/psychology  Phenotype  Stereotyped Behavior  Autism  Broader Autism Phenotype  Parents  Repetitive behaviours Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviours (RRBs) constitute a core symptom domain of autism spectrum disorder (ASD). However, the nature of RRBs in the context of the Broader Autism Phenotype (BAP) is not well understood. In particular, the relationship between RRBs in ASD probands and their parents remains largely unexplored. The current study explored the link between parental RRBs, measured via Interest in Patterns and Resistance to Changes subscales of the Autism Quotient and their children's RRBs, measured via Autism Diagnostic Observation Schedule RRB standardized domain score. FINDINGS: Having both parents within the top 20% of their RRB scores was associated with an increase of RRB scores for their children; however, no parent-of-origin effects were identified. Although the trend was observed for both Interest in Patterns and Resistance to Changes subscale, it was only statistically significant for Interest in Patterns. CONCLUSIONS: This paper provides significant contribution to our understanding of association between RRBs in parents and their children with ASD. Future work should also address the BAP in distinct genetic subtypes (whole chromosome aneuploidies, single gene mutations, copy number variations) of neurodevelopmental and neuropsychiatric disorders that involve RRBs. En ligne : http://dx.doi.org/10.1186/s13229-016-0091-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Social affiliation motives modulate spontaneous learning in Williams syndrome but not in autism / G. VIVANTI in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 40p. Titre : Social affiliation motives modulate spontaneous learning in Williams syndrome but not in autism Type de document : Texte imprimé et/ou numérique Auteurs : G. VIVANTI, Auteur ; D. R. HOCKING, Auteur ; P. FANNING, Auteur ; Cheryl DISSANAYAKE, Auteur Article en page(s) : 40p. Langues : Anglais (eng) Mots-clés : Attention  Autistic Disorder/psychology  Child, Preschool  Female  Humans  Learning  Male  Williams Syndrome/psychology  Autism  Imitation  Social cognition  Social learning  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with autism spectrum disorder (ASD) and those with Williams syndrome (WS) have difficulties with learning, though the nature of these remains unclear. METHODS: In this study, we used novel eye-tracking and behavioral paradigms to measure how 36 preschoolers with ASD and 21 age- and IQ-matched peers with WS attend to and learn novel behaviors (1) from the outcomes of their own actions (non-social learning), (2) through imitation of others' actions (social learning), and across situations in which imitative learning served either an instrumental function or fulfilled social affiliation motives. RESULTS: The two groups demonstrated similar abilities to learn from the consequences of their own actions and to imitate new actions that were instrumental to the achievement of a tangible goal. Children with WS, unlike those with ASD, increased their attention and imitative learning performance when the model acted in a socially engaging manner. CONCLUSIONS: Learning abnormalities in ASD appear to be linked to the social rather than instrumental dimensions of learning. En ligne : http://dx.doi.org/10.1186/s13229-016-0101-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Social affiliation motives modulate spontaneous learning in Williams syndrome but not in autism [Texte imprimé et/ou numérique] / G. VIVANTI, Auteur ; D. R. HOCKING, Auteur ; P. FANNING, Auteur ; Cheryl DISSANAYAKE, Auteur . - 40p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 40p. Mots-clés : Attention  Autistic Disorder/psychology  Child, Preschool  Female  Humans  Learning  Male  Williams Syndrome/psychology  Autism  Imitation  Social cognition  Social learning  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with autism spectrum disorder (ASD) and those with Williams syndrome (WS) have difficulties with learning, though the nature of these remains unclear. METHODS: In this study, we used novel eye-tracking and behavioral paradigms to measure how 36 preschoolers with ASD and 21 age- and IQ-matched peers with WS attend to and learn novel behaviors (1) from the outcomes of their own actions (non-social learning), (2) through imitation of others' actions (social learning), and across situations in which imitative learning served either an instrumental function or fulfilled social affiliation motives. RESULTS: The two groups demonstrated similar abilities to learn from the consequences of their own actions and to imitate new actions that were instrumental to the achievement of a tangible goal. Children with WS, unlike those with ASD, increased their attention and imitative learning performance when the model acted in a socially engaging manner. CONCLUSIONS: Learning abnormalities in ASD appear to be linked to the social rather than instrumental dimensions of learning. En ligne : http://dx.doi.org/10.1186/s13229-016-0101-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Erratum to: 22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening / T. L. WENGER in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 34p. Titre : Erratum to: 22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening Type de document : Texte imprimé et/ou numérique Auteurs : T. L. WENGER, Auteur ; J. S. MILLER, Auteur ; L. M. DEPOLO, Auteur ; A. B. DE MARCHENA, Auteur ; Caitlin C. CLEMENTS, Auteur ; B. S. EMANUEL, Auteur ; E. H. ZACKAI, Auteur ; D. M. MCDONALD-MCGINN, Auteur ; Robert T. SCHULTZ, Auteur Article en page(s) : 34p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-016-0097-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Erratum to: 22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening [Texte imprimé et/ou numérique] / T. L. WENGER, Auteur ; J. S. MILLER, Auteur ; L. M. DEPOLO, Auteur ; A. B. DE MARCHENA, Auteur ; Caitlin C. CLEMENTS, Auteur ; B. S. EMANUEL, Auteur ; E. H. ZACKAI, Auteur ; D. M. MCDONALD-MCGINN, Auteur ; Robert T. SCHULTZ, Auteur . - 34p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 34p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-016-0097-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening / T. L. WENGER in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 27p. Titre : 22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening Type de document : Texte imprimé et/ou numérique Auteurs : T. L. WENGER, Auteur ; J. S. MILLER, Auteur ; L. M. DEPOLO, Auteur ; A. B. DE MARCHENA, Auteur ; Caitlin C. CLEMENTS, Auteur ; B. S. EMANUEL, Auteur ; E. H. ZACKAI, Auteur ; D. M. MCDONALD-MCGINN, Auteur ; Robert T. SCHULTZ, Auteur Article en page(s) : 27p. Langues : Anglais (eng) Mots-clés : Abnormalities, Multiple/diagnosis  Adolescent  Adult  Analysis of Variance  Autism Spectrum Disorder/complications/diagnosis/epidemiology  Child  Child, Preschool  Chromosome Duplication  Chromosomes, Human, Pair 22  DiGeorge Syndrome/complications/diagnosis  Female  Genetic Testing  Humans  Male  Middle Aged  Social Behavior  Surveys and Questionnaires  Young Adult  22q11.2 deletion syndrome  22q11.2 duplication syndrome  Autism spectrum disorder  Developmental delay  Medical characterization  Medical screening  Neuropsychiatric functioning  Syndromic autism  Typically developing controls Index. décimale : PER Périodiques Résumé : BACKGROUND: Widespread use of microarray technology has led to increasing identification of 22q11.2 duplication syndrome (22q11.2DupS), the reciprocal syndrome of the well-characterized 22q11.2 deletion syndrome (22q11.2DS). Individuals with 22q11.2DS have elevated rates of community diagnoses of autism spectrum disorder (ASD), schizophrenia, and a range of medical problems and birth defects that necessitate extensive medical screening. Case reports of 22q11.2DupS include patients with ASD, fewer medical problems, and no schizophrenia; however, no prospective cohort study has been reported. The goals of the study were to (1) characterize the neuropsychiatric functioning of a cohort of individuals with 22q11.2DupS in comparison to large samples of typically developing controls (TDCs), ASD and 22q11.2DS; (2) estimate the prevalence of ASD in 22q11.2DupS; (3) determine whether the indications that prompted the genetic testing in 22q11.2DupS differ from 22q11.2DS and (4) determine whether comprehensive medical screening should be recommended for those diagnosed with 22q11.2DupS. METHODS: Medical characterization was done by parental questionnaire and medical chart review of individuals with 22q11.2DupS (n = 37) and 22q11.2DS (n = 101). Neuropsychiatric characterization of children with 22.11.2DupS, 22q11.2DS, TDCs, and ASD was done by parent-report questionnaires; in addition, the ASD and 22q11.2DupS groups received the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. RESULTS: Individuals with 22q11.2DupS, 22q11.2DS, and ASD had significantly impaired social interaction and adaptive behavior skills compared to TDCs. Overall, 38% of children aged 2-18 with 22q11.2DupS had community diagnoses of ASD, but fewer (14-25%) met on the basis of best clinical judgment that included ADI-R and ADOS data. Indications for genetic testing were significantly different for 22q11.2DupS and 22q11.2DS, with the deletions more commonly tested because of birth defects or medical problems, and the duplications because of developmental delay. However, when the screening protocol for 22q11.2DS was applied to the 22q11.2DupS sample, several medical problems were identified that would pose significant risk if left undetected. CONCLUSIONS: 22q11.2DupS has a high rate of ASD at 14-25%, among the highest of any genetic disorder. Prospective medical screening should be done for all patients with 22q11.2DupS, including those diagnosed due to developmental delays and ASD alone. En ligne : http://dx.doi.org/10.1186/s13229-016-0090-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] 22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening [Texte imprimé et/ou numérique] / T. L. WENGER, Auteur ; J. S. MILLER, Auteur ; L. M. DEPOLO, Auteur ; A. B. DE MARCHENA, Auteur ; Caitlin C. CLEMENTS, Auteur ; B. S. EMANUEL, Auteur ; E. H. ZACKAI, Auteur ; D. M. MCDONALD-MCGINN, Auteur ; Robert T. SCHULTZ, Auteur . - 27p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 27p. Mots-clés : Abnormalities, Multiple/diagnosis  Adolescent  Adult  Analysis of Variance  Autism Spectrum Disorder/complications/diagnosis/epidemiology  Child  Child, Preschool  Chromosome Duplication  Chromosomes, Human, Pair 22  DiGeorge Syndrome/complications/diagnosis  Female  Genetic Testing  Humans  Male  Middle Aged  Social Behavior  Surveys and Questionnaires  Young Adult  22q11.2 deletion syndrome  22q11.2 duplication syndrome  Autism spectrum disorder  Developmental delay  Medical characterization  Medical screening  Neuropsychiatric functioning  Syndromic autism  Typically developing controls Index. décimale : PER Périodiques Résumé : BACKGROUND: Widespread use of microarray technology has led to increasing identification of 22q11.2 duplication syndrome (22q11.2DupS), the reciprocal syndrome of the well-characterized 22q11.2 deletion syndrome (22q11.2DS). Individuals with 22q11.2DS have elevated rates of community diagnoses of autism spectrum disorder (ASD), schizophrenia, and a range of medical problems and birth defects that necessitate extensive medical screening. Case reports of 22q11.2DupS include patients with ASD, fewer medical problems, and no schizophrenia; however, no prospective cohort study has been reported. The goals of the study were to (1) characterize the neuropsychiatric functioning of a cohort of individuals with 22q11.2DupS in comparison to large samples of typically developing controls (TDCs), ASD and 22q11.2DS; (2) estimate the prevalence of ASD in 22q11.2DupS; (3) determine whether the indications that prompted the genetic testing in 22q11.2DupS differ from 22q11.2DS and (4) determine whether comprehensive medical screening should be recommended for those diagnosed with 22q11.2DupS. METHODS: Medical characterization was done by parental questionnaire and medical chart review of individuals with 22q11.2DupS (n = 37) and 22q11.2DS (n = 101). Neuropsychiatric characterization of children with 22.11.2DupS, 22q11.2DS, TDCs, and ASD was done by parent-report questionnaires; in addition, the ASD and 22q11.2DupS groups received the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. RESULTS: Individuals with 22q11.2DupS, 22q11.2DS, and ASD had significantly impaired social interaction and adaptive behavior skills compared to TDCs. Overall, 38% of children aged 2-18 with 22q11.2DupS had community diagnoses of ASD, but fewer (14-25%) met on the basis of best clinical judgment that included ADI-R and ADOS data. Indications for genetic testing were significantly different for 22q11.2DupS and 22q11.2DS, with the deletions more commonly tested because of birth defects or medical problems, and the duplications because of developmental delay. However, when the screening protocol for 22q11.2DS was applied to the 22q11.2DupS sample, several medical problems were identified that would pose significant risk if left undetected. CONCLUSIONS: 22q11.2DupS has a high rate of ASD at 14-25%, among the highest of any genetic disorder. Prospective medical screening should be done for all patients with 22q11.2DupS, including those diagnosed due to developmental delays and ASD alone. En ligne : http://dx.doi.org/10.1186/s13229-016-0090-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Olfactory processing in adults with autism spectrum disorders / B. WICKER in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 4p. Titre : Olfactory processing in adults with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : B. WICKER, Auteur ; E. MONFARDINI, Auteur ; J. P. ROYET, Auteur Article en page(s) : 4p. Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder/physiopathology/psychology  Differential Threshold/physiology  Emotions/physiology  Female  Humans  Hyperesthesia/etiology/physiopathology/psychology  Hypesthesia/etiology/physiopathology/psychology  Male  Odorants  Olfactory Pathways/physiopathology  Olfactory Perception/physiology  Pleasure  Recognition (Psychology)/physiology  Sensory Thresholds  Young Adult  Autism spectrum disorders  Hyperresponsiveness  Identification  Intensity  Olfaction  Pleasantness  Suprathreshold detection Index. décimale : PER Périodiques Résumé : BACKGROUND: As evidenced in the DSM-V, autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyper- or hypo-reactivity), but very few studies have evaluated olfactory abilities in individuals with ASD. METHODS: Fifteen adults with ASD and 15 typically developing participants underwent olfactory tests focused on superficial (suprathreshold detection task), perceptual (intensity and pleasantness judgment tasks), and semantic (identification task) odor processing. RESULTS: In terms of suprathreshold detection performance, decreased discrimination scores and increased bias scores were observed in the ASD group. Furthermore, the participants with ASD exhibited increased intensity judgment scores and impaired scores for pleasantness judgments of unpleasant odorants. Decreased identification performance was also observed in the participants with ASD compared with the typically developing participants. This decrease was partly attributed to a higher number of near misses (a category close to veridical labels) among the participants with ASD than was observed among the typically developing participants. CONCLUSIONS: The changes in discrimination and bias scores were the result of a high number of false alarms among the participants with ASD, which suggests the adoption of a liberal attitude in their responses. Atypical intensity and pleasantness ratings were associated with hyperresponsiveness and flattened emotional reactions, respectively, which are typical of participants with ASD. The high number of near misses as non-veridical labels suggested that categorical processing is functional in individuals with ASD and could be explained by attention-deficit/hyperactivity disorder. These findings are discussed in terms of dysfunction of the olfactory system. En ligne : http://dx.doi.org/10.1186/s13229-016-0070-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Olfactory processing in adults with autism spectrum disorders [Texte imprimé et/ou numérique] / B. WICKER, Auteur ; E. MONFARDINI, Auteur ; J. P. ROYET, Auteur . - 4p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 4p. Mots-clés : Adult  Autism Spectrum Disorder/physiopathology/psychology  Differential Threshold/physiology  Emotions/physiology  Female  Humans  Hyperesthesia/etiology/physiopathology/psychology  Hypesthesia/etiology/physiopathology/psychology  Male  Odorants  Olfactory Pathways/physiopathology  Olfactory Perception/physiology  Pleasure  Recognition (Psychology)/physiology  Sensory Thresholds  Young Adult  Autism spectrum disorders  Hyperresponsiveness  Identification  Intensity  Olfaction  Pleasantness  Suprathreshold detection Index. décimale : PER Périodiques Résumé : BACKGROUND: As evidenced in the DSM-V, autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyper- or hypo-reactivity), but very few studies have evaluated olfactory abilities in individuals with ASD. METHODS: Fifteen adults with ASD and 15 typically developing participants underwent olfactory tests focused on superficial (suprathreshold detection task), perceptual (intensity and pleasantness judgment tasks), and semantic (identification task) odor processing. RESULTS: In terms of suprathreshold detection performance, decreased discrimination scores and increased bias scores were observed in the ASD group. Furthermore, the participants with ASD exhibited increased intensity judgment scores and impaired scores for pleasantness judgments of unpleasant odorants. Decreased identification performance was also observed in the participants with ASD compared with the typically developing participants. This decrease was partly attributed to a higher number of near misses (a category close to veridical labels) among the participants with ASD than was observed among the typically developing participants. CONCLUSIONS: The changes in discrimination and bias scores were the result of a high number of false alarms among the participants with ASD, which suggests the adoption of a liberal attitude in their responses. Atypical intensity and pleasantness ratings were associated with hyperresponsiveness and flattened emotional reactions, respectively, which are typical of participants with ASD. The high number of near misses as non-veridical labels suggested that categorical processing is functional in individuals with ASD and could be explained by attention-deficit/hyperactivity disorder. These findings are discussed in terms of dysfunction of the olfactory system. En ligne : http://dx.doi.org/10.1186/s13229-016-0070-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder / L. K. WINK in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 26p. Titre : A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : L. K. WINK, Auteur ; R. ADAMS, Auteur ; Z. WANG, Auteur ; J. E. KLAUNIG, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; C. J. MCDOUGLE, Auteur ; C. A. ERICKSON, Auteur Article en page(s) : 26p. Langues : Anglais (eng) Mots-clés : Acetylcysteine/pharmacology/therapeutic use  Administration, Oral  Autism Spectrum Disorder/drug therapy  Child  Child, Preschool  Comet Assay  DNA Damage/drug effects  Double-Blind Method  Drug Administration Schedule  Female  Follow-Up Studies  Free Radical Scavengers/pharmacology/therapeutic use  Glutathione/blood  Homocysteine/blood  Humans  Male  Oxidation-Reduction  Oxidative Stress/drug effects  Pilot Projects  Placebo Effect  Social Behavior  Autism  Autism spectrum disorder  N-acetylcysteine  Oxidative stress  Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments. The goal of this study was to evaluate efficacy, safety, and tolerability of oral N-acetylcysteine (NAC), an antioxidant whose function overlaps with proposed mechanisms of ASD pathophysiology, targeting core social impairment in youth with ASD. METHODS: This study was a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD. Study participants were medically healthy youth age 4 to 12 years with ASD, weighing >/=15 kg, and judged to be moderately ill based on the Clinical Global Impressions Severity scale. The participants were randomized via computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The primary outcome measure of efficacy was the Clinical Global Impressions Improvement (CGI-I) scale anchored to core social impairment. To investigate the impact of NAC on oxidative stress markers in peripheral blood, venous blood samples were collected at screen and week 12. RESULTS: Thirty-one patients were enrolled (NAC = 16, placebo = 15). Three participants were lost to follow-up, and three left the trial due to adverse effects. The average daily dose of NAC at week 12 was 56.2 mg/kg (SD = 9.7) with dose ranging from 33.6 to 64.3 mg/kg. The frequency of adverse events was so low that comparisons between groups could not be conducted. At week 12, there was no statistically significant difference between the NAC and placebo groups on the CGI-I (p > 0.69) but the glutathione (GSH) level in blood was significantly higher in the NAC group (p < 0.05). The oxidative glutathione disulfide (GSSG) level increased in the NAC group, however only at a trend level of significance (p = 0.09). There was no significant difference between the NAC and placebo groups in the GSH/GSSG ratio, DNA strand break and oxidative damage, and blood homocysteine levels at week 12 (ps > 0.16). CONCLUSIONS: The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD. TRIAL REGISTRATION: Clinicaltrials.gov NCT00453180. En ligne : http://dx.doi.org/10.1186/s13229-016-0088-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder [Texte imprimé et/ou numérique] / L. K. WINK, Auteur ; R. ADAMS, Auteur ; Z. WANG, Auteur ; J. E. KLAUNIG, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; C. J. MCDOUGLE, Auteur ; C. A. ERICKSON, Auteur . - 26p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 26p. Mots-clés : Acetylcysteine/pharmacology/therapeutic use  Administration, Oral  Autism Spectrum Disorder/drug therapy  Child  Child, Preschool  Comet Assay  DNA Damage/drug effects  Double-Blind Method  Drug Administration Schedule  Female  Follow-Up Studies  Free Radical Scavengers/pharmacology/therapeutic use  Glutathione/blood  Homocysteine/blood  Humans  Male  Oxidation-Reduction  Oxidative Stress/drug effects  Pilot Projects  Placebo Effect  Social Behavior  Autism  Autism spectrum disorder  N-acetylcysteine  Oxidative stress  Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments. The goal of this study was to evaluate efficacy, safety, and tolerability of oral N-acetylcysteine (NAC), an antioxidant whose function overlaps with proposed mechanisms of ASD pathophysiology, targeting core social impairment in youth with ASD. METHODS: This study was a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD. Study participants were medically healthy youth age 4 to 12 years with ASD, weighing >/=15 kg, and judged to be moderately ill based on the Clinical Global Impressions Severity scale. The participants were randomized via computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The primary outcome measure of efficacy was the Clinical Global Impressions Improvement (CGI-I) scale anchored to core social impairment. To investigate the impact of NAC on oxidative stress markers in peripheral blood, venous blood samples were collected at screen and week 12. RESULTS: Thirty-one patients were enrolled (NAC = 16, placebo = 15). Three participants were lost to follow-up, and three left the trial due to adverse effects. The average daily dose of NAC at week 12 was 56.2 mg/kg (SD = 9.7) with dose ranging from 33.6 to 64.3 mg/kg. The frequency of adverse events was so low that comparisons between groups could not be conducted. At week 12, there was no statistically significant difference between the NAC and placebo groups on the CGI-I (p > 0.69) but the glutathione (GSH) level in blood was significantly higher in the NAC group (p < 0.05). The oxidative glutathione disulfide (GSSG) level increased in the NAC group, however only at a trend level of significance (p = 0.09). There was no significant difference between the NAC and placebo groups in the GSH/GSSG ratio, DNA strand break and oxidative damage, and blood homocysteine levels at week 12 (ps > 0.16). CONCLUSIONS: The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD. TRIAL REGISTRATION: Clinicaltrials.gov NCT00453180. En ligne : http://dx.doi.org/10.1186/s13229-016-0088-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation / T. YAMADA in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 41p. Titre : Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation Type de document : Texte imprimé et/ou numérique Auteurs : T. YAMADA, Auteur ; T. ITAHASHI, Auteur ; M. NAKAMURA, Auteur ; H. WATANABE, Auteur ; M. KURODA, Auteur ; H. OHTA, Auteur ; C. KANAI, Auteur ; N. KATO, Auteur ; R. I. HASHIMOTO, Auteur Article en page(s) : 41p. Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder/diagnostic imaging/pathology/physiopathology  Brain Mapping/methods  Case-Control Studies  Cerebral Cortex/diagnostic imaging/pathology/physiopathology  Cluster Analysis  Functional Laterality  Humans  Image Interpretation, Computer-Assisted  Magnetic Resonance Imaging  Male  Middle Aged  Nerve Net/diagnostic imaging/pathology/physiopathology  Neural Pathways/diagnostic imaging/pathology/physiopathology  Autism spectrum disorder  Connectivity-based functional parcellation  Insula  Resting-state functional magnetic resonance imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: The insular cortex comprises multiple functionally differentiated sub-regions, each of which has different patterns of connectivity with other brain regions. Such diverse connectivity patterns are thought to underlie a wide range of insular functions, including cognitive, affective, and sensorimotor processing, many of which are abnormal in autism spectrum disorder (ASD). Although past neuroimaging studies of ASD have shown structural and functional abnormalities in the insula, possible alterations in the sub-regional organization of the insula and the functional characteristics of each sub-region have not been examined in the ASD brain. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with ASD and 38 matched typically developed (TD) controls. A data-driven clustering analysis was applied to rs-fMRI data of voxels in the left and right insula to automatically group voxels with similar intrinsic connectivity pattern into a cluster. After determining the optimal number of clusters based on information theoretic measures of variation of information and mutual information, functional parcellation patterns in both the left and the right insula were compared between the TD and ASD groups. Furthermore, functional profiles of each sub-region were meta-analytically decoded using Neurosynth and were compared between the groups. RESULTS: We observed notable alterations in the anterior sector of the left insula and the middle ventral sub-region of the right insula in the ASD brain. Meta-analytic decoding revealed that whereas the anterior sector of the left insula contained two functionally differentiated sub-regions for cognitive, sensorimotor, and emotional/affective functions in TD brain, only a single functional cluster for cognitive and sensorimotor functions was identified in the anterior sector in the ASD brain. In the right insula, the middle ventral sub-region, which is primarily specialized for sensory- and auditory-related functions, showed a significant volumetric increase in the ASD brain compared with the TD brain. CONCLUSIONS: The results indicate an altered organization of sub-regions in specific parts of the left and right insula of the ASD brain. The alterations in the left and right insula may constitute neural substrates underlying abnormalities in emotional/affective and sensory functions in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0106-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation [Texte imprimé et/ou numérique] / T. YAMADA, Auteur ; T. ITAHASHI, Auteur ; M. NAKAMURA, Auteur ; H. WATANABE, Auteur ; M. KURODA, Auteur ; H. OHTA, Auteur ; C. KANAI, Auteur ; N. KATO, Auteur ; R. I. HASHIMOTO, Auteur . - 41p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 41p. Mots-clés : Adult  Autism Spectrum Disorder/diagnostic imaging/pathology/physiopathology  Brain Mapping/methods  Case-Control Studies  Cerebral Cortex/diagnostic imaging/pathology/physiopathology  Cluster Analysis  Functional Laterality  Humans  Image Interpretation, Computer-Assisted  Magnetic Resonance Imaging  Male  Middle Aged  Nerve Net/diagnostic imaging/pathology/physiopathology  Neural Pathways/diagnostic imaging/pathology/physiopathology  Autism spectrum disorder  Connectivity-based functional parcellation  Insula  Resting-state functional magnetic resonance imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: The insular cortex comprises multiple functionally differentiated sub-regions, each of which has different patterns of connectivity with other brain regions. Such diverse connectivity patterns are thought to underlie a wide range of insular functions, including cognitive, affective, and sensorimotor processing, many of which are abnormal in autism spectrum disorder (ASD). Although past neuroimaging studies of ASD have shown structural and functional abnormalities in the insula, possible alterations in the sub-regional organization of the insula and the functional characteristics of each sub-region have not been examined in the ASD brain. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 36 adult males with ASD and 38 matched typically developed (TD) controls. A data-driven clustering analysis was applied to rs-fMRI data of voxels in the left and right insula to automatically group voxels with similar intrinsic connectivity pattern into a cluster. After determining the optimal number of clusters based on information theoretic measures of variation of information and mutual information, functional parcellation patterns in both the left and the right insula were compared between the TD and ASD groups. Furthermore, functional profiles of each sub-region were meta-analytically decoded using Neurosynth and were compared between the groups. RESULTS: We observed notable alterations in the anterior sector of the left insula and the middle ventral sub-region of the right insula in the ASD brain. Meta-analytic decoding revealed that whereas the anterior sector of the left insula contained two functionally differentiated sub-regions for cognitive, sensorimotor, and emotional/affective functions in TD brain, only a single functional cluster for cognitive and sensorimotor functions was identified in the anterior sector in the ASD brain. In the right insula, the middle ventral sub-region, which is primarily specialized for sensory- and auditory-related functions, showed a significant volumetric increase in the ASD brain compared with the TD brain. CONCLUSIONS: The results indicate an altered organization of sub-regions in specific parts of the left and right insula of the ASD brain. The alterations in the left and right insula may constitute neural substrates underlying abnormalities in emotional/affective and sensory functions in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0106-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Cortical morphological markers in children with autism: a structural magnetic resonance imaging study of thickness, area, volume, and gyrification / D. Y. YANG in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 11p. Titre : Cortical morphological markers in children with autism: a structural magnetic resonance imaging study of thickness, area, volume, and gyrification Type de document : Texte imprimé et/ou numérique Auteurs : D. Y. YANG, Auteur ; D. BEAM, Auteur ; Kevin A. PELPHREY, Auteur ; Sebiha M. ABDULLAHI, Auteur ; R. J. JOU, Auteur Article en page(s) : 11p. Langues : Anglais (eng) Mots-clés : Age Factors  Cerebral Cortex/pathology  Child  Child Development Disorders, Pervasive/pathology  Child, Preschool  Gray Matter/pathology  Humans  Image Processing, Computer-Assisted  Magnetic Resonance Imaging  Male  Neuroimaging  Organ Size  White Matter/pathology  Autism spectrum disorder  Brain development  Brain structure  Neuroanatomy  Surface-based morphometry Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with autism spectrum disorder (ASD) have been characterized by altered cerebral cortical structures; however, the field has yet to identify consistent markers and prior studies have included mostly adolescents and adults. While there are multiple cortical morphological measures, including cortical thickness, surface area, cortical volume, and cortical gyrification, few single studies have examined all these measures. The current study analyzed all of the four measures and focused on pre-adolescent children with ASD. METHODS: We employed the FreeSurfer pipeline to examine surface-based morphometry in 60 high-functioning boys with ASD (mean age = 8.35 years, range = 4-12 years) and 41 gender-, age-, and IQ-matched typically developing (TD) peers (mean age = 8.83 years), while testing for age-by-diagnosis interaction and between-group differences. RESULTS: During childhood and in specific regions, ASD participants exhibited a lack of normative age-related cortical thinning and volumetric reduction and an abnormal age-related increase in gyrification. Regarding surface area, ASD and TD exhibited statistically comparable age-related development during childhood. Across childhood, ASD relative to TD participants tended to have higher mean levels of gyrification in specific regions. Within ASD, those with higher Social Responsiveness Scale total raw scores tended to have greater age-related increase in gyrification in specific regions during childhood. CONCLUSIONS: ASD is characterized by cortical neuroanatomical abnormalities that are age-, measure-, statistical model-, and region-dependent. The current study is the first to examine the development of all four cortical measures in one of the largest pre-adolescent samples. Strikingly, Neurosynth-based quantitative reverse inference of the surviving clusters suggests that many of the regions identified above are related to social perception, language, self-referential, and action observation networks-those frequently found to be functionally altered in individuals with ASD. The comprehensive, multilevel analyses across a wide range of cortical measures help fill a knowledge gap and present a complex but rich picture of neuroanatomical developmental differences in children with ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0076-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Cortical morphological markers in children with autism: a structural magnetic resonance imaging study of thickness, area, volume, and gyrification [Texte imprimé et/ou numérique] / D. Y. YANG, Auteur ; D. BEAM, Auteur ; Kevin A. PELPHREY, Auteur ; Sebiha M. ABDULLAHI, Auteur ; R. J. JOU, Auteur . - 11p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 11p. Mots-clés : Age Factors  Cerebral Cortex/pathology  Child  Child Development Disorders, Pervasive/pathology  Child, Preschool  Gray Matter/pathology  Humans  Image Processing, Computer-Assisted  Magnetic Resonance Imaging  Male  Neuroimaging  Organ Size  White Matter/pathology  Autism spectrum disorder  Brain development  Brain structure  Neuroanatomy  Surface-based morphometry Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with autism spectrum disorder (ASD) have been characterized by altered cerebral cortical structures; however, the field has yet to identify consistent markers and prior studies have included mostly adolescents and adults. While there are multiple cortical morphological measures, including cortical thickness, surface area, cortical volume, and cortical gyrification, few single studies have examined all these measures. The current study analyzed all of the four measures and focused on pre-adolescent children with ASD. METHODS: We employed the FreeSurfer pipeline to examine surface-based morphometry in 60 high-functioning boys with ASD (mean age = 8.35 years, range = 4-12 years) and 41 gender-, age-, and IQ-matched typically developing (TD) peers (mean age = 8.83 years), while testing for age-by-diagnosis interaction and between-group differences. RESULTS: During childhood and in specific regions, ASD participants exhibited a lack of normative age-related cortical thinning and volumetric reduction and an abnormal age-related increase in gyrification. Regarding surface area, ASD and TD exhibited statistically comparable age-related development during childhood. Across childhood, ASD relative to TD participants tended to have higher mean levels of gyrification in specific regions. Within ASD, those with higher Social Responsiveness Scale total raw scores tended to have greater age-related increase in gyrification in specific regions during childhood. CONCLUSIONS: ASD is characterized by cortical neuroanatomical abnormalities that are age-, measure-, statistical model-, and region-dependent. The current study is the first to examine the development of all four cortical measures in one of the largest pre-adolescent samples. Strikingly, Neurosynth-based quantitative reverse inference of the surviving clusters suggests that many of the regions identified above are related to social perception, language, self-referential, and action observation networks-those frequently found to be functionally altered in individuals with ASD. The comprehensive, multilevel analyses across a wide range of cortical measures help fill a knowledge gap and present a complex but rich picture of neuroanatomical developmental differences in children with ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0076-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder / C. L. YIN in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 23p. Titre : Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : C. L. YIN, Auteur ; H. I. CHEN, Auteur ; L. H. LI, Auteur ; Yi-Ling CHIEN, Auteur ; H. M. LIAO, Auteur ; Miao-Churn CHOU, Auteur ; W. J. CHOU, Auteur ; W. C. TSAI, Auteur ; Yen-Nan CHIU, Auteur ; Y. Y. WU, Auteur ; C. Z. LO, Auteur ; J. Y. WU, Auteur ; Y. T. CHEN, Auteur ; S. S. GAU, Auteur Article en page(s) : 23p. Langues : Anglais (eng) Mots-clés : Adolescent  Asian Continental Ancestry Group/genetics  Autism Spectrum Disorder/etiology/genetics  Child  China  Cohort Studies  DNA Copy Number Variations  Down-Regulation  Exons  Female  Genome-Wide Association Study  Genotype  Humans  Male  Odds Ratio  Pedigree  Phenotype  Polymorphism, Single Nucleotide  Ubiquitin-Protein Ligases/genetics  Autism spectrum disorder (ASD)  Copy number variations (CNVs)  Family study  Gene expression  Park2 Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. METHODS: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). RESULTS: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. CONCLUSIONS: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. TRIAL REGISTRATION: ClinicalTrials.gov NCT00494754. En ligne : http://dx.doi.org/10.1186/s13229-016-0087-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder [Texte imprimé et/ou numérique] / C. L. YIN, Auteur ; H. I. CHEN, Auteur ; L. H. LI, Auteur ; Yi-Ling CHIEN, Auteur ; H. M. LIAO, Auteur ; Miao-Churn CHOU, Auteur ; W. J. CHOU, Auteur ; W. C. TSAI, Auteur ; Yen-Nan CHIU, Auteur ; Y. Y. WU, Auteur ; C. Z. LO, Auteur ; J. Y. WU, Auteur ; Y. T. CHEN, Auteur ; S. S. GAU, Auteur . - 23p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 23p. Mots-clés : Adolescent  Asian Continental Ancestry Group/genetics  Autism Spectrum Disorder/etiology/genetics  Child  China  Cohort Studies  DNA Copy Number Variations  Down-Regulation  Exons  Female  Genome-Wide Association Study  Genotype  Humans  Male  Odds Ratio  Pedigree  Phenotype  Polymorphism, Single Nucleotide  Ubiquitin-Protein Ligases/genetics  Autism spectrum disorder (ASD)  Copy number variations (CNVs)  Family study  Gene expression  Park2 Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. METHODS: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). RESULTS: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. CONCLUSIONS: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. TRIAL REGISTRATION: ClinicalTrials.gov NCT00494754. En ligne : http://dx.doi.org/10.1186/s13229-016-0087-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition / A. M. YOUNG in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 9p. Titre : From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition Type de document : Texte imprimé et/ou numérique Auteurs : A. M. YOUNG, Auteur ; Bhismadev CHAKRABARTI, Auteur ; D. ROBERTS, Auteur ; Meng-Chuan LAI, Auteur ; J. SUCKLING, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 9p. Langues : Anglais (eng) Mots-clés : Amniotic Fluid/chemistry  Animals  Antigens, Surface/immunology  Autism Spectrum Disorder/genetics/immunology/pathology  Autoantibodies/analysis  Body Fluids/chemistry  Brain/embryology/immunology/pathology  Brain Chemistry  Chemokines/analysis  Cytokines/analysis  Female  Glutamic Acid/metabolism  HLA Antigens/immunology  Haplorhini  Humans  Immunity, Maternally-Acquired  Inflammation  Inflammation Mediators/analysis  Lipopolysaccharides/blood  Maternal-Fetal Exchange  Mice  Nerve Tissue Proteins/immunology  Neuroglia/physiology  Neuroimaging  Pregnancy  Pregnancy Complications, Infectious/blood  Prenatal Exposure Delayed Effects  Signal Transduction  Autism  Brain  NF-kappaB Index. décimale : PER Périodiques Résumé : Growing evidence points toward a critical role for early (prenatal) atypical neurodevelopmental processes in the aetiology of autism spectrum condition (ASC). One such process that could impact early neural development is inflammation. We review the evidence for atypical expression of molecular markers in the amniotic fluid, serum, cerebrospinal fluid (CSF), and the brain parenchyma that suggest a role for inflammation in the emergence of ASC. This is complemented with a number of neuroimaging and neuropathological studies describing microglial activation. Implications for treatment are discussed. En ligne : http://dx.doi.org/10.1186/s13229-016-0068-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition [Texte imprimé et/ou numérique] / A. M. YOUNG, Auteur ; Bhismadev CHAKRABARTI, Auteur ; D. ROBERTS, Auteur ; Meng-Chuan LAI, Auteur ; J. SUCKLING, Auteur ; Simon BARON-COHEN, Auteur . - 9p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 9p. Mots-clés : Amniotic Fluid/chemistry  Animals  Antigens, Surface/immunology  Autism Spectrum Disorder/genetics/immunology/pathology  Autoantibodies/analysis  Body Fluids/chemistry  Brain/embryology/immunology/pathology  Brain Chemistry  Chemokines/analysis  Cytokines/analysis  Female  Glutamic Acid/metabolism  HLA Antigens/immunology  Haplorhini  Humans  Immunity, Maternally-Acquired  Inflammation  Inflammation Mediators/analysis  Lipopolysaccharides/blood  Maternal-Fetal Exchange  Mice  Nerve Tissue Proteins/immunology  Neuroglia/physiology  Neuroimaging  Pregnancy  Pregnancy Complications, Infectious/blood  Prenatal Exposure Delayed Effects  Signal Transduction  Autism  Brain  NF-kappaB Index. décimale : PER Périodiques Résumé : Growing evidence points toward a critical role for early (prenatal) atypical neurodevelopmental processes in the aetiology of autism spectrum condition (ASC). One such process that could impact early neural development is inflammation. We review the evidence for atypical expression of molecular markers in the amniotic fluid, serum, cerebrospinal fluid (CSF), and the brain parenchyma that suggest a role for inflammation in the emergence of ASC. This is complemented with a number of neuroimaging and neuropathological studies describing microglial activation. Implications for treatment are discussed. En ligne : http://dx.doi.org/10.1186/s13229-016-0068-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons / Y. ZHOU in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 42p. Titre : CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons Type de document : Texte imprimé et/ou numérique Auteurs : Y. ZHOU, Auteur ; D. KUMARI, Auteur ; N. SCIASCIA, Auteur ; K. USDIN, Auteur Article en page(s) : 42p. Langues : Anglais (eng) Mots-clés : 5' Untranslated Regions  Alleles  Cell Differentiation  Cell Line  DNA Methylation  Embryonic Stem Cells/metabolism/pathology  Fragile X Mental Retardation Protein/genetics/metabolism  Fragile X Syndrome/genetics/metabolism/pathology  Gene Silencing  Humans  Induced Pluripotent Stem Cells/metabolism/pathology  Male  Neurons/metabolism/pathology  Primary Cell Culture  Time Factors  Trinucleotide Repeat Expansion  Fragile X syndrome  Repeat contractions  Repeat expansion mutation  Repeat-mediated gene silencing  Stem cells Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5' untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. METHODS: We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons. We used a PCR assay optimized for the amplification of large CGG repeats for sizing, and a quantitative methylation-specific PCR for the analysis of FMR1 promoter methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were determined by western blotting and immunofluorescence. Chromatin immunoprecipitation was used to study the association of repressive histone marks with the FMR1 gene in FXS ESCs. RESULTS: We show here that while FMR1 gene silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles contract and when the repeat number drops below ~400, DNA methylation erodes, even when the repeat number remains >200. The resultant active alleles do not show the large step-wise expansions seen in stem cells from other repeat expansion diseases. Furthermore, there may be selection against large active alleles and these alleles do not expand further or become silenced on neuronal differentiation. CONCLUSIONS: Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats. En ligne : http://dx.doi.org/10.1186/s13229-016-0105-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons [Texte imprimé et/ou numérique] / Y. ZHOU, Auteur ; D. KUMARI, Auteur ; N. SCIASCIA, Auteur ; K. USDIN, Auteur . - 42p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 42p. Mots-clés : 5' Untranslated Regions  Alleles  Cell Differentiation  Cell Line  DNA Methylation  Embryonic Stem Cells/metabolism/pathology  Fragile X Mental Retardation Protein/genetics/metabolism  Fragile X Syndrome/genetics/metabolism/pathology  Gene Silencing  Humans  Induced Pluripotent Stem Cells/metabolism/pathology  Male  Neurons/metabolism/pathology  Primary Cell Culture  Time Factors  Trinucleotide Repeat Expansion  Fragile X syndrome  Repeat contractions  Repeat expansion mutation  Repeat-mediated gene silencing  Stem cells Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5' untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. METHODS: We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons. We used a PCR assay optimized for the amplification of large CGG repeats for sizing, and a quantitative methylation-specific PCR for the analysis of FMR1 promoter methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were determined by western blotting and immunofluorescence. Chromatin immunoprecipitation was used to study the association of repressive histone marks with the FMR1 gene in FXS ESCs. RESULTS: We show here that while FMR1 gene silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles contract and when the repeat number drops below ~400, DNA methylation erodes, even when the repeat number remains >200. The resultant active alleles do not show the large step-wise expansions seen in stem cells from other repeat expansion diseases. Furthermore, there may be selection against large active alleles and these alleles do not expand further or become silenced on neuronal differentiation. CONCLUSIONS: Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats. En ligne : http://dx.doi.org/10.1186/s13229-016-0105-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329