Dépouillements

Using infrared eye-tracking to explore ordinal numerical processing in toddlers with Fragile X Syndrome / E. R. OWEN in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.1 Titre : Using infrared eye-tracking to explore ordinal numerical processing in toddlers with Fragile X Syndrome Type de document : Texte imprimé et/ou numérique Auteurs : E. R. OWEN, Auteur ; H. A. BAUMGARTNER, Auteur ; S. M. RIVERA, Auteur Article en page(s) : p.1 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and non-idiopathic autism. Individuals with FXS present with a behavioral phenotype of specific and selective deficits in an array of cognitive skills. Disruption of number processing and arithmetic abilities in higher-functioning adults and female adolescents with FXS has been well established. Still, both numerical skills and developmentally antecedent cognitive processes have just begun to be investigated in toddlers with FXS. The goal of the current study was to assess how very young children with FXS respond to ordinal relationships among numerical magnitudes. METHODS: Infrared eye-tracking was used to explore infants' novelty recognition during passive viewing of ordinal numerical sequences; t-tests were used to analyze group differences in looking time. RESULTS: Ordinal recognition of numerical magnitudes is significantly impaired in young toddlers with FXS. CONCLUSIONS: This study is the first to experimentally evaluate early number sense and ordinal recognition in toddlers with FXS, and our findings reveal that ordinal recognition of numerical magnitudes is significantly impaired in young toddlers with FXS, suggesting that later arithmetic impairments associated with FXS may have their origins in a developmental impairment of this more basic aspect of numerical cognition. En ligne : http://dx.doi.org/10.1186/1866-1955-5-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=344 [article] Using infrared eye-tracking to explore ordinal numerical processing in toddlers with Fragile X Syndrome [Texte imprimé et/ou numérique] / E. R. OWEN, Auteur ; H. A. BAUMGARTNER, Auteur ; S. M. RIVERA, Auteur . - p.1. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and non-idiopathic autism. Individuals with FXS present with a behavioral phenotype of specific and selective deficits in an array of cognitive skills. Disruption of number processing and arithmetic abilities in higher-functioning adults and female adolescents with FXS has been well established. Still, both numerical skills and developmentally antecedent cognitive processes have just begun to be investigated in toddlers with FXS. The goal of the current study was to assess how very young children with FXS respond to ordinal relationships among numerical magnitudes. METHODS: Infrared eye-tracking was used to explore infants' novelty recognition during passive viewing of ordinal numerical sequences; t-tests were used to analyze group differences in looking time. RESULTS: Ordinal recognition of numerical magnitudes is significantly impaired in young toddlers with FXS. CONCLUSIONS: This study is the first to experimentally evaluate early number sense and ordinal recognition in toddlers with FXS, and our findings reveal that ordinal recognition of numerical magnitudes is significantly impaired in young toddlers with FXS, suggesting that later arithmetic impairments associated with FXS may have their origins in a developmental impairment of this more basic aspect of numerical cognition. En ligne : http://dx.doi.org/10.1186/1866-1955-5-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=344

The regulatory function of social referencing in preschoolers with Down syndrome or Williams syndrome / A. J. THURMAN in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.2 Titre : The regulatory function of social referencing in preschoolers with Down syndrome or Williams syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. J. THURMAN, Auteur ; C. B. MERVIS, Auteur Article en page(s) : p.2 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : UNLABELLED: BACKGROUND: An important developmental task is to learn to recognize another person as a source of information and to utilize this information as a method of learning about the surrounding world. This socially guided form of learning, referred to as social referencing, is critical for the development of children's understanding of other people, themselves and their surrounding world. In the present project, the regulatory function of social referencing was examined in two genetic disorders that are characterized by differing patterns of socio-cognitive development: Down syndrome (DS) and Williams syndrome (WS). METHODS: Participants were 20 children with DS and 20 children with WS aged 42 to 71 months, matched on chronological age and gender. Each child participated in four studies: one study in which we examined performance in a social referencing paradigm and three studies in which we considered performance on tasks designed to tap each of three component abilities (initiating eye contact, gaze following and emotional responsivity) important for success in social referencing. RESULTS: The majority of children in both groups demonstrated positive behavioral responses regarding the stimulus in the Social Referencing task when the adult communicated a joyful message but did not regulate their own behavior in accordance with the adult's expression of fear. Between-group differences were observed in both conditions, with most differences indicating more advanced socio-communicative competence for children with DS than for children with WS even though the overall intellectual abilities and receptive language abilities of the children with WS were significantly higher than were those of the children with DS. The results of follow-up studies indicated that children with DS were more likely to initiate eye contact (unsolicited) and to follow another person's gaze in triadic situations than were children with WS. Neither group regulated their behavior in response to expressions of fear. CONCLUSIONS: These findings provide new insight into the development of the social cognitive phenotypes associated with DS and WS. These social cognitive differences found during the preschool years likely contribute to the differing phenotypes observed later in life between individuals with DS and individuals with WS. En ligne : http://dx.doi.org/10.1186/1866-1955-5-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] The regulatory function of social referencing in preschoolers with Down syndrome or Williams syndrome [Texte imprimé et/ou numérique] / A. J. THURMAN, Auteur ; C. B. MERVIS, Auteur . - p.2. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.2 Index. décimale : PER Périodiques Résumé : UNLABELLED: BACKGROUND: An important developmental task is to learn to recognize another person as a source of information and to utilize this information as a method of learning about the surrounding world. This socially guided form of learning, referred to as social referencing, is critical for the development of children's understanding of other people, themselves and their surrounding world. In the present project, the regulatory function of social referencing was examined in two genetic disorders that are characterized by differing patterns of socio-cognitive development: Down syndrome (DS) and Williams syndrome (WS). METHODS: Participants were 20 children with DS and 20 children with WS aged 42 to 71 months, matched on chronological age and gender. Each child participated in four studies: one study in which we examined performance in a social referencing paradigm and three studies in which we considered performance on tasks designed to tap each of three component abilities (initiating eye contact, gaze following and emotional responsivity) important for success in social referencing. RESULTS: The majority of children in both groups demonstrated positive behavioral responses regarding the stimulus in the Social Referencing task when the adult communicated a joyful message but did not regulate their own behavior in accordance with the adult's expression of fear. Between-group differences were observed in both conditions, with most differences indicating more advanced socio-communicative competence for children with DS than for children with WS even though the overall intellectual abilities and receptive language abilities of the children with WS were significantly higher than were those of the children with DS. The results of follow-up studies indicated that children with DS were more likely to initiate eye contact (unsolicited) and to follow another person's gaze in triadic situations than were children with WS. Neither group regulated their behavior in response to expressions of fear. CONCLUSIONS: These findings provide new insight into the development of the social cognitive phenotypes associated with DS and WS. These social cognitive differences found during the preschool years likely contribute to the differing phenotypes observed later in life between individuals with DS and individuals with WS. En ligne : http://dx.doi.org/10.1186/1866-1955-5-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Gyrification, cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities / I. R. VIOLANTE in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.3 Titre : Gyrification, cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities Type de document : Texte imprimé et/ou numérique Auteurs : I. R. VIOLANTE, Auteur ; M. J. RIBEIRO, Auteur ; E. D. SILVA, Auteur ; Miguel CASTELO-BRANCO, Auteur Article en page(s) : p.3 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification. METHODS: We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1. RESULTS: Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions. CONCLUSIONS: The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype. En ligne : http://dx.doi.org/10.1186/1866-1955-5-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Gyrification, cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities [Texte imprimé et/ou numérique] / I. R. VIOLANTE, Auteur ; M. J. RIBEIRO, Auteur ; E. D. SILVA, Auteur ; Miguel CASTELO-BRANCO, Auteur . - p.3. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification. METHODS: We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1. RESULTS: Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions. CONCLUSIONS: The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype. En ligne : http://dx.doi.org/10.1186/1866-1955-5-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins / J. LI in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.4 Titre : Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins Type de document : Texte imprimé et/ou numérique Auteurs : J. LI, Auteur ; G. ZHAO, Auteur ; X. GAO, Auteur Article en page(s) : p.4 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs) in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd), which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX), Williams syndrome (WS), Rett syndrome and Rubinstein-Taybi syndrome (RTS). A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-5-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins [Texte imprimé et/ou numérique] / J. LI, Auteur ; G. ZHAO, Auteur ; X. GAO, Auteur . - p.4. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.4 Index. décimale : PER Périodiques Résumé : Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs) in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd), which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX), Williams syndrome (WS), Rett syndrome and Rubinstein-Taybi syndrome (RTS). A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-5-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure / M. L. KLEIBER in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.6 Titre : Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure Type de document : Texte imprimé et/ou numérique Auteurs : M. L. KLEIBER, Auteur ; K. MANTHA, Auteur ; R. L. STRINGER, Auteur ; S. M. SINGH, Auteur Article en page(s) : p.6 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Maternal alcohol consumption is known to adversely affect fetal neurodevelopment. While it is known that alcohol dose and timing play a role in the cognitive and behavioral changes associated with prenatal alcohol exposure, it is unclear what developmental processes are disrupted that may lead to these phenotypes. METHODS: Mice (n=6 per treatment per developmental time) were exposed to two acute doses of alcohol (5 g/kg) at neurodevelopmental times representing the human first, second, or third trimester equivalent. Mice were reared to adulthood and changes to their adult brain transcriptome were assessed using expression arrays. These were then categorized based on Gene Ontology annotations, canonical pathway associations, and relationships to interacting molecules. RESULTS: The results suggest that ethanol disrupts biological processes that are actively occurring at the time of exposure. These include cell proliferation during trimester one, cell migration and differentiation during trimester two, and cellular communication and neurotransmission during trimester three. Further, although ethanol altered a distinct set of genes depending on developmental timing, many of these show interrelatedness and can be associated with one another via 'hub' molecules and pathways such as those related to huntingtin and brain-derived neurotrophic factor. CONCLUSIONS: These changes to brain gene expression represent a 'molecular footprint' of neurodevelopmental alcohol exposure that is long-lasting and correlates with active processes disrupted at the time of exposure. This study provides further support that there is no neurodevelopmental time when alcohol cannot adversely affect the developing brain. En ligne : http://dx.doi.org/10.1186/1866-1955-5-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure [Texte imprimé et/ou numérique] / M. L. KLEIBER, Auteur ; K. MANTHA, Auteur ; R. L. STRINGER, Auteur ; S. M. SINGH, Auteur . - p.6. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.6 Index. décimale : PER Périodiques Résumé : BACKGROUND: Maternal alcohol consumption is known to adversely affect fetal neurodevelopment. While it is known that alcohol dose and timing play a role in the cognitive and behavioral changes associated with prenatal alcohol exposure, it is unclear what developmental processes are disrupted that may lead to these phenotypes. METHODS: Mice (n=6 per treatment per developmental time) were exposed to two acute doses of alcohol (5 g/kg) at neurodevelopmental times representing the human first, second, or third trimester equivalent. Mice were reared to adulthood and changes to their adult brain transcriptome were assessed using expression arrays. These were then categorized based on Gene Ontology annotations, canonical pathway associations, and relationships to interacting molecules. RESULTS: The results suggest that ethanol disrupts biological processes that are actively occurring at the time of exposure. These include cell proliferation during trimester one, cell migration and differentiation during trimester two, and cellular communication and neurotransmission during trimester three. Further, although ethanol altered a distinct set of genes depending on developmental timing, many of these show interrelatedness and can be associated with one another via 'hub' molecules and pathways such as those related to huntingtin and brain-derived neurotrophic factor. CONCLUSIONS: These changes to brain gene expression represent a 'molecular footprint' of neurodevelopmental alcohol exposure that is long-lasting and correlates with active processes disrupted at the time of exposure. This study provides further support that there is no neurodevelopmental time when alcohol cannot adversely affect the developing brain. En ligne : http://dx.doi.org/10.1186/1866-1955-5-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Social and emotional processing in Prader-Willi syndrome: genetic subtype differences / A. P. KEY in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.7 Titre : Social and emotional processing in Prader-Willi syndrome: genetic subtype differences Type de document : Texte imprimé et/ou numérique Auteurs : A. P. KEY, Auteur ; D. JONES, Auteur ; E. M. DYKENS, Auteur Article en page(s) : p.7 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: People with Prader-Willi syndrome (PWS) demonstrate social dysfunction and increased risk of autism spectrum disorder, especially those with the maternal uniparental disomy (mUPD) versus paternal deletion genetic subtype. This study compared the neural processing of social (faces) and nonsocial stimuli, varying in emotional valence, across genetic subtypes in 24 adolescents and adults with PWS. METHODS: Upright and inverted faces, and nonsocial objects with positive and negative emotional valence were presented to participants with PWS in an oddball paradigm with smiling faces serving as targets. Behavioral and event-related potential (ERP) data were recorded. RESULTS: There were no genetic subtype group differences in accuracy, and all participants performed above chance level. ERP responses revealed genetic subtype differences in face versus object processing. In those with deletions, the face-specific posterior N170 response varied in size for face stimuli versus inverted faces versus nonsocial objects. Persons with mUPD generated N170 of smaller amplitude and showed no stimulus differentiation. Brain responses to emotional content did not vary by subtype. All participants elicited larger posterior and anterior late positive potential responses to positive objects than to negative objects. Emotion-related differences in response to faces were limited to inverted faces only in the form of larger anterior late positive potential amplitudes to negative emotions over the right hemisphere. Detection of the target smiling faces was evident in the increased amplitude of the frontal and central P3 responses but only for inverted smiling faces. CONCLUSION: Persons with the mUPD subtype of PWS may show atypical face versus object processes, yet both subtypes demonstrated potentially altered processing, attention to and/or recognition of faces and their expressions. En ligne : http://dx.doi.org/10.1186/1866-1955-5-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Social and emotional processing in Prader-Willi syndrome: genetic subtype differences [Texte imprimé et/ou numérique] / A. P. KEY, Auteur ; D. JONES, Auteur ; E. M. DYKENS, Auteur . - p.7. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.7 Index. décimale : PER Périodiques Résumé : BACKGROUND: People with Prader-Willi syndrome (PWS) demonstrate social dysfunction and increased risk of autism spectrum disorder, especially those with the maternal uniparental disomy (mUPD) versus paternal deletion genetic subtype. This study compared the neural processing of social (faces) and nonsocial stimuli, varying in emotional valence, across genetic subtypes in 24 adolescents and adults with PWS. METHODS: Upright and inverted faces, and nonsocial objects with positive and negative emotional valence were presented to participants with PWS in an oddball paradigm with smiling faces serving as targets. Behavioral and event-related potential (ERP) data were recorded. RESULTS: There were no genetic subtype group differences in accuracy, and all participants performed above chance level. ERP responses revealed genetic subtype differences in face versus object processing. In those with deletions, the face-specific posterior N170 response varied in size for face stimuli versus inverted faces versus nonsocial objects. Persons with mUPD generated N170 of smaller amplitude and showed no stimulus differentiation. Brain responses to emotional content did not vary by subtype. All participants elicited larger posterior and anterior late positive potential responses to positive objects than to negative objects. Emotion-related differences in response to faces were limited to inverted faces only in the form of larger anterior late positive potential amplitudes to negative emotions over the right hemisphere. Detection of the target smiling faces was evident in the increased amplitude of the frontal and central P3 responses but only for inverted smiling faces. CONCLUSION: Persons with the mUPD subtype of PWS may show atypical face versus object processes, yet both subtypes demonstrated potentially altered processing, attention to and/or recognition of faces and their expressions. En ligne : http://dx.doi.org/10.1186/1866-1955-5-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

A quantitative homogeneous assay for fragile X mental retardation 1 protein / G. SCHUTZIUS in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.8 Titre : A quantitative homogeneous assay for fragile X mental retardation 1 protein Type de document : Texte imprimé et/ou numérique Auteurs : G. SCHUTZIUS, Auteur ; D. BLECKMANN, Auteur ; S. KAPPS-FOUTHIER, Auteur ; F. DI GIORGIO, Auteur ; B. GERHARTZ, Auteur ; A. WEISS, Auteur Article en page(s) : p.8 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Hypermethylation of the fragile X mental retardation 1 gene FMR1 results in decreased expression of FMR1 protein FMRP, which is the underlying cause of Fragile X syndrome - an incurable neurological disorder characterized by mental retardation, anxiety, epileptic episodes and autism. Disease-modifying therapies for Fragile X syndrome are thus aimed at treatments that increase the FMRP expression levels in the brain. We describe the development and characterization of two assays for simple and quantitative detection of FMRP protein. METHOD: Antibodies coupled to fluorophores that can be employed for time-resolved Forster's resonance energy transfer were used for the development of homogeneous, one-step immunodetection. Purified recombinant human FMRP and patient cells were used as control samples for assay development. RESULTS: The assays require small sample amounts, display high stability and reproducibility and can be used to quantify endogenous FMRP in human fibroblasts and peripheral blood mononuclear cells. Application of the assays to FXS patient cells showed that the methods can be used both for the characterization of clinical FXS patient samples as well as primary readouts in drug-discovery screens aimed at increasing endogenous FMRP levels in human cells. CONCLUSION: This study provides novel quantitative detection methods for FMRP in FXS patient cells. Importantly, due to the simplicity of the assay protocol, the method is suited to be used in screening applications to identify compounds or genetic interventions that result in increased FMRP levels in human cells. En ligne : http://dx.doi.org/10.1186/1866-1955-5-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] A quantitative homogeneous assay for fragile X mental retardation 1 protein [Texte imprimé et/ou numérique] / G. SCHUTZIUS, Auteur ; D. BLECKMANN, Auteur ; S. KAPPS-FOUTHIER, Auteur ; F. DI GIORGIO, Auteur ; B. GERHARTZ, Auteur ; A. WEISS, Auteur . - p.8. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.8 Index. décimale : PER Périodiques Résumé : BACKGROUND: Hypermethylation of the fragile X mental retardation 1 gene FMR1 results in decreased expression of FMR1 protein FMRP, which is the underlying cause of Fragile X syndrome - an incurable neurological disorder characterized by mental retardation, anxiety, epileptic episodes and autism. Disease-modifying therapies for Fragile X syndrome are thus aimed at treatments that increase the FMRP expression levels in the brain. We describe the development and characterization of two assays for simple and quantitative detection of FMRP protein. METHOD: Antibodies coupled to fluorophores that can be employed for time-resolved Forster's resonance energy transfer were used for the development of homogeneous, one-step immunodetection. Purified recombinant human FMRP and patient cells were used as control samples for assay development. RESULTS: The assays require small sample amounts, display high stability and reproducibility and can be used to quantify endogenous FMRP in human fibroblasts and peripheral blood mononuclear cells. Application of the assays to FXS patient cells showed that the methods can be used both for the characterization of clinical FXS patient samples as well as primary readouts in drug-discovery screens aimed at increasing endogenous FMRP levels in human cells. CONCLUSION: This study provides novel quantitative detection methods for FMRP in FXS patient cells. Importantly, due to the simplicity of the assay protocol, the method is suited to be used in screening applications to identify compounds or genetic interventions that result in increased FMRP levels in human cells. En ligne : http://dx.doi.org/10.1186/1866-1955-5-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

A pilot open-label trial of minocycline in patients with autism and regressive features / Carlos A. PARDO in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.9 Titre : A pilot open-label trial of minocycline in patients with autism and regressive features Type de document : Texte imprimé et/ou numérique Auteurs : Carlos A. PARDO, Auteur ; A. BUCKLEY, Auteur ; A. THURM, Auteur ; L. C. LEE, Auteur ; A. AZHAGIRI, Auteur ; D. M. NEVILLE, Auteur ; Susan E. SWEDO, Auteur Article en page(s) : p.9 Langues : Anglais (eng) Mots-clés : Autism  Bdnf  Chemokines  Clinical trial  Cytokines  Metalloproteinases  Microglia  Minocycline  Neuroinflammation  Neurotrophins Index. décimale : PER Périodiques Résumé : BACKGROUND: Minocycline is a tetracycline derivative that readily crosses the blood brain barrier and appears to have beneficial effects on neuroinflammation, microglial activation and neuroprotection in a variety of neurological disorders. Both microglial activation and neuroinflammation have been reported to be associated with autism. The study was designed to evaluate the effects of minocycline treatment on markers of neuroinflammation and autism symptomatology in children with autism and a history of developmental regression. METHODS: Eleven children were enrolled in an open-label trial of six months of minocycline (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the end of minocycline treatment and were analyzed for markers of neuroinflammation. RESULTS: Clinical improvements were negligible. The laboratory assays demonstrated significant changes in the expression profile of the truncated form of brain derived neurotrophic factor (BDNF) (P = 0.042) and hepatic growth factor (HGF) (P = 0.028) in CSF. In serum, the ratio of the truncated BDNF form and alpha-2 macroglobulin (alpha-2 M), was also significantly lower (P = 0.028) while the mature BDNF/alpha-2 M ratio revealed no difference following treatment. Only the chemokine CXCL8 (IL-8) was significantly different (P = 0.047) in serum while no significant changes were observed in CSF or serum in chemokines such as CCL2 (MCP-1) or cytokines such as TNF-alpha, CD40L, IL-6, IFN-gamma and IL-1beta when pre- and post-treatment levels of these proteins were compared. No significant pre- and post-treatment changes were seen in the profiles of plasma metalloproteinases, putative targets of the effects of minocycline. CONCLUSIONS: Changes in the pre- and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) in serum, suggest that minocycline may have effects in the CNS by modulating the production of neurotrophic growth factors. However, in this small group of children, no clinical improvements were observed during or after the six months of minocycline administration. TRIAL REGISTRATION: NCT00409747. En ligne : http://dx.doi.org/10.1186/1866-1955-5-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] A pilot open-label trial of minocycline in patients with autism and regressive features [Texte imprimé et/ou numérique] / Carlos A. PARDO, Auteur ; A. BUCKLEY, Auteur ; A. THURM, Auteur ; L. C. LEE, Auteur ; A. AZHAGIRI, Auteur ; D. M. NEVILLE, Auteur ; Susan E. SWEDO, Auteur . - p.9. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.9 Mots-clés : Autism  Bdnf  Chemokines  Clinical trial  Cytokines  Metalloproteinases  Microglia  Minocycline  Neuroinflammation  Neurotrophins Index. décimale : PER Périodiques Résumé : BACKGROUND: Minocycline is a tetracycline derivative that readily crosses the blood brain barrier and appears to have beneficial effects on neuroinflammation, microglial activation and neuroprotection in a variety of neurological disorders. Both microglial activation and neuroinflammation have been reported to be associated with autism. The study was designed to evaluate the effects of minocycline treatment on markers of neuroinflammation and autism symptomatology in children with autism and a history of developmental regression. METHODS: Eleven children were enrolled in an open-label trial of six months of minocycline (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the end of minocycline treatment and were analyzed for markers of neuroinflammation. RESULTS: Clinical improvements were negligible. The laboratory assays demonstrated significant changes in the expression profile of the truncated form of brain derived neurotrophic factor (BDNF) (P = 0.042) and hepatic growth factor (HGF) (P = 0.028) in CSF. In serum, the ratio of the truncated BDNF form and alpha-2 macroglobulin (alpha-2 M), was also significantly lower (P = 0.028) while the mature BDNF/alpha-2 M ratio revealed no difference following treatment. Only the chemokine CXCL8 (IL-8) was significantly different (P = 0.047) in serum while no significant changes were observed in CSF or serum in chemokines such as CCL2 (MCP-1) or cytokines such as TNF-alpha, CD40L, IL-6, IFN-gamma and IL-1beta when pre- and post-treatment levels of these proteins were compared. No significant pre- and post-treatment changes were seen in the profiles of plasma metalloproteinases, putative targets of the effects of minocycline. CONCLUSIONS: Changes in the pre- and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) in serum, suggest that minocycline may have effects in the CNS by modulating the production of neurotrophic growth factors. However, in this small group of children, no clinical improvements were observed during or after the six months of minocycline administration. TRIAL REGISTRATION: NCT00409747. En ligne : http://dx.doi.org/10.1186/1866-1955-5-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Developmental patterns of DR6 in normal human hippocampus and in Down syndrome / A. IYER in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.10 Titre : Developmental patterns of DR6 in normal human hippocampus and in Down syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. IYER, Auteur ; J. VAN SCHEPPINGEN, Auteur ; J. ANINK, Auteur ; I. MILENKOVIC, Auteur ; G. G. KOVACS, Auteur ; E. ARONICA, Auteur Article en page(s) : p.10 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Death receptor 6 (DR6) is highly expressed in the human brain: it has been shown to induce axon pruning and neuron death via distinct caspases and to mediate axonal degeneration through binding to N-terminal beta amyloid precursor protein (N-APP). METHODS: We investigated the expression of DR6 during prenatal and postnatal development in human hippocampus and temporal cortex by immunocytochemistry and Western blot analysis (118 normal human brain specimens; 9 to 41 gestational weeks; 1 day to 7 months postnatally; 3 to 91 years). To investigate the role of N-APP/DR6/caspase 6 pathway in the development of hippocampal Alzheimer's disease (AD)-associated pathology, we examined DR6 immunoreactivity (IR) in the developing hippocampus from patients with Down syndrome (DS; 48 brain specimens; 14 to 41 gestational weeks; 7 days to 8 months postnatally; 15 to 64 years) and in adults with DS and AD. RESULTS: DR6 was highly expressed in human adult hippocampus and temporal cortex: we observed consistent similar temporal and spatial expression in both control and DS brain. Western blot analysis of total homogenates of temporal cortex and hippocampus showed developmental regulation of DR6. In the hippocampus, DR6 IR was first apparent in the stratum lacunosum-moleculare at 16 weeks of gestation, followed by stratum oriens, radiatum, pyramidale (CA1 to CA4) and molecular layer of the dentate gyrus between 21 and 23 gestational weeks, reaching a pattern similar to adult hippocampus around birth. Increased DR6 expression in dystrophic neurites was detected focally in a 15-year-old DS patient. Abnormal DR6 expression pattern, with increased expression within dystrophic neurites in and around amyloid plaques was observed in adult DS patients with widespread AD-associated neurodegeneration and was similar to the pattern observed in AD hippocampus. Double-labeling experiments demonstrated the colocalization, in dystrophic neurites, of DR6 with APP. We also observed colocalization with hyper-phosphorylated Tau and with caspase 6 (increased in hippocampus with AD pathology) in plaque-associated dystrophic neurites and within the white matter. CONCLUSIONS: These findings demonstrate a developmental regulation of DR6 in human hippocampus and suggest an abnormal activation of the N-APP/DR6/caspase 6 pathway, which can contribute to initiation or progression of hippocampal AD-associated pathology. En ligne : http://dx.doi.org/10.1186/1866-1955-5-10 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Developmental patterns of DR6 in normal human hippocampus and in Down syndrome [Texte imprimé et/ou numérique] / A. IYER, Auteur ; J. VAN SCHEPPINGEN, Auteur ; J. ANINK, Auteur ; I. MILENKOVIC, Auteur ; G. G. KOVACS, Auteur ; E. ARONICA, Auteur . - p.10. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.10 Index. décimale : PER Périodiques Résumé : BACKGROUND: Death receptor 6 (DR6) is highly expressed in the human brain: it has been shown to induce axon pruning and neuron death via distinct caspases and to mediate axonal degeneration through binding to N-terminal beta amyloid precursor protein (N-APP). METHODS: We investigated the expression of DR6 during prenatal and postnatal development in human hippocampus and temporal cortex by immunocytochemistry and Western blot analysis (118 normal human brain specimens; 9 to 41 gestational weeks; 1 day to 7 months postnatally; 3 to 91 years). To investigate the role of N-APP/DR6/caspase 6 pathway in the development of hippocampal Alzheimer's disease (AD)-associated pathology, we examined DR6 immunoreactivity (IR) in the developing hippocampus from patients with Down syndrome (DS; 48 brain specimens; 14 to 41 gestational weeks; 7 days to 8 months postnatally; 15 to 64 years) and in adults with DS and AD. RESULTS: DR6 was highly expressed in human adult hippocampus and temporal cortex: we observed consistent similar temporal and spatial expression in both control and DS brain. Western blot analysis of total homogenates of temporal cortex and hippocampus showed developmental regulation of DR6. In the hippocampus, DR6 IR was first apparent in the stratum lacunosum-moleculare at 16 weeks of gestation, followed by stratum oriens, radiatum, pyramidale (CA1 to CA4) and molecular layer of the dentate gyrus between 21 and 23 gestational weeks, reaching a pattern similar to adult hippocampus around birth. Increased DR6 expression in dystrophic neurites was detected focally in a 15-year-old DS patient. Abnormal DR6 expression pattern, with increased expression within dystrophic neurites in and around amyloid plaques was observed in adult DS patients with widespread AD-associated neurodegeneration and was similar to the pattern observed in AD hippocampus. Double-labeling experiments demonstrated the colocalization, in dystrophic neurites, of DR6 with APP. We also observed colocalization with hyper-phosphorylated Tau and with caspase 6 (increased in hippocampus with AD pathology) in plaque-associated dystrophic neurites and within the white matter. CONCLUSIONS: These findings demonstrate a developmental regulation of DR6 in human hippocampus and suggest an abnormal activation of the N-APP/DR6/caspase 6 pathway, which can contribute to initiation or progression of hippocampal AD-associated pathology. En ligne : http://dx.doi.org/10.1186/1866-1955-5-10 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Autism and the broad autism phenotype: familial patterns and intergenerational transmission / Noah J. SASSON in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.11 Titre : Autism and the broad autism phenotype: familial patterns and intergenerational transmission Type de document : Texte imprimé et/ou numérique Auteurs : Noah J. SASSON, Auteur ; K. S. LAM, Auteur ; M. PARLIER, Auteur ; Julie L. DANIELS, Auteur ; J. PIVEN, Auteur Article en page(s) : p.11 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Features of the Broad Autism Phenotype (BAP) are disproportionately prevalent in parents of a child with autism, highlighting familial patterns indicative of heritability. It is unclear, however, whether the presence of BAP features in both parents confers an increased liability for autism. The current study explores whether the presence of BAP features in two biological parents occurs more frequently in parents of a child with autism relative to comparison parents, whether parental pairs of a child with autism more commonly consist of one or two parents with BAP features, and whether these features are associated with severity of autism behaviors in probands. METHOD: Seven hundred eleven parents of a child with an autism spectrum disorder and 981 comparison parents completed the Broad Autism Phenotype Questionnaire. Parents of a child with autism also completed the Social Communication Questionnaire. RESULTS: Although parental pairs of a child with autism were more likely than comparison parental pairs to have both parents characterized by the presence of the BAP, they more commonly consisted of a single parent with BAP features. The presence of the BAP in parents was associated with the severity of autism behaviors in probands, with the lowest severity occurring for children of parental pairs in which neither parent exhibited a BAP feature. Severity did not differ between children of two affected parents and those of just one. CONCLUSIONS: Collectively, these findings indicate that parental pairs of children with autism frequently consist of a single parent with BAP characteristics and suggest that future studies searching for implicated genes may benefit from a more narrow focus that identifies the transmitting parent. The evidence of intergenerational transmission reported here also provides further confirmation of the high heritability of autism that is unaccounted for by the contribution of de novo mutations currently emphasized in the field of autism genetics. En ligne : http://dx.doi.org/10.1186/1866-1955-5-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Autism and the broad autism phenotype: familial patterns and intergenerational transmission [Texte imprimé et/ou numérique] / Noah J. SASSON, Auteur ; K. S. LAM, Auteur ; M. PARLIER, Auteur ; Julie L. DANIELS, Auteur ; J. PIVEN, Auteur . - p.11. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.11 Index. décimale : PER Périodiques Résumé : BACKGROUND: Features of the Broad Autism Phenotype (BAP) are disproportionately prevalent in parents of a child with autism, highlighting familial patterns indicative of heritability. It is unclear, however, whether the presence of BAP features in both parents confers an increased liability for autism. The current study explores whether the presence of BAP features in two biological parents occurs more frequently in parents of a child with autism relative to comparison parents, whether parental pairs of a child with autism more commonly consist of one or two parents with BAP features, and whether these features are associated with severity of autism behaviors in probands. METHOD: Seven hundred eleven parents of a child with an autism spectrum disorder and 981 comparison parents completed the Broad Autism Phenotype Questionnaire. Parents of a child with autism also completed the Social Communication Questionnaire. RESULTS: Although parental pairs of a child with autism were more likely than comparison parental pairs to have both parents characterized by the presence of the BAP, they more commonly consisted of a single parent with BAP features. The presence of the BAP in parents was associated with the severity of autism behaviors in probands, with the lowest severity occurring for children of parental pairs in which neither parent exhibited a BAP feature. Severity did not differ between children of two affected parents and those of just one. CONCLUSIONS: Collectively, these findings indicate that parental pairs of children with autism frequently consist of a single parent with BAP characteristics and suggest that future studies searching for implicated genes may benefit from a more narrow focus that identifies the transmitting parent. The evidence of intergenerational transmission reported here also provides further confirmation of the high heritability of autism that is unaccounted for by the contribution of de novo mutations currently emphasized in the field of autism genetics. En ligne : http://dx.doi.org/10.1186/1866-1955-5-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome / J. J. WOLFF in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.12 Titre : Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. J. WOLFF, Auteur ; Heather C. HAZLETT, Auteur ; A. A. LIGHTBODY, Auteur ; A. L. REISS, Auteur ; J. PIVEN, Auteur Article en page(s) : p.12 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Following from previous work suggesting that neurobehavioral features distinguish fragile X and idiopathic variants of autism, we investigated the relationships between four forms of repetitive behavior (stereotypy, self-injury, compulsivity, ritual behavior) and caudate nuclei volume in two groups: boys with fragile X syndrome, a subset of whom met criteria for autism, and a comparison group of boys with idiopathic autism. METHODS: Bilateral caudate nuclei volumes were measured in boys aged 3 to 6 years with fragile X syndrome (n = 41), the subset of boys with fragile X syndrome and autism (n = 16), and boys with idiopathic autism (n = 30). Repetitive behaviors were measured using the Repetitive Behavior Scales-Revised. RESULTS: For boys with idiopathic autism, left caudate volume was modestly associated with self-injury, while both compulsive and ritual behaviors showed significant positive correlations with bilateral caudate nuclei volumes, replicating previous results. For boys with fragile X syndrome, there was no such association between caudate volume and compulsive behaviors. However, we did identify significant positive correlations between self-injury total scores and number of self-injury topographies with bilateral caudate nuclei volumes. CONCLUSIONS: These findings suggest a specific role for the caudate nucleus in the early pathogenesis of self-injurious behavior associated with both idiopathic autism and fragile X syndrome. Results further indicate that the caudate may be differentially associated with compulsive behavior, highlighting the utility of isolating discrete brain-behavior associations within and between subtypes of autism spectrum disorder. En ligne : http://dx.doi.org/10.1186/1866-1955-5-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome [Texte imprimé et/ou numérique] / J. J. WOLFF, Auteur ; Heather C. HAZLETT, Auteur ; A. A. LIGHTBODY, Auteur ; A. L. REISS, Auteur ; J. PIVEN, Auteur . - p.12. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.12 Index. décimale : PER Périodiques Résumé : BACKGROUND: Following from previous work suggesting that neurobehavioral features distinguish fragile X and idiopathic variants of autism, we investigated the relationships between four forms of repetitive behavior (stereotypy, self-injury, compulsivity, ritual behavior) and caudate nuclei volume in two groups: boys with fragile X syndrome, a subset of whom met criteria for autism, and a comparison group of boys with idiopathic autism. METHODS: Bilateral caudate nuclei volumes were measured in boys aged 3 to 6 years with fragile X syndrome (n = 41), the subset of boys with fragile X syndrome and autism (n = 16), and boys with idiopathic autism (n = 30). Repetitive behaviors were measured using the Repetitive Behavior Scales-Revised. RESULTS: For boys with idiopathic autism, left caudate volume was modestly associated with self-injury, while both compulsive and ritual behaviors showed significant positive correlations with bilateral caudate nuclei volumes, replicating previous results. For boys with fragile X syndrome, there was no such association between caudate volume and compulsive behaviors. However, we did identify significant positive correlations between self-injury total scores and number of self-injury topographies with bilateral caudate nuclei volumes. CONCLUSIONS: These findings suggest a specific role for the caudate nucleus in the early pathogenesis of self-injurious behavior associated with both idiopathic autism and fragile X syndrome. Results further indicate that the caudate may be differentially associated with compulsive behavior, highlighting the utility of isolating discrete brain-behavior associations within and between subtypes of autism spectrum disorder. En ligne : http://dx.doi.org/10.1186/1866-1955-5-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Spontaneous and cued gaze-following in autism and Williams syndrome / D. M. RIBY in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.13 Titre : Spontaneous and cued gaze-following in autism and Williams syndrome Type de document : Texte imprimé et/ou numérique Auteurs : D. M. RIBY, Auteur ; P. J. HANCOCK, Auteur ; N. JONES, Auteur ; M. HANLEY, Auteur Article en page(s) : p.13 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: From a young age the typical development of social functioning relies upon the allocation of attention to socially relevant information, which in turn allows experience at processing such information and thus enhances social cognition. As such, research has attempted to identify the developmental processes that are derailed in some neuro-developmental disorders that impact upon social functioning. Williams syndrome (WS) and autism are disorders of development that are characterized by atypical yet divergent social phenotypes and atypicalities of attention to people. METHODS: We used eye tracking to explore how individuals with WS and autism attended to, and subsequently interpreted, an actor's eye gaze cue within a social scene. Images were presented for 3 seconds, initially with an instruction simply to look at the picture. The images were then shown again, with the participant asked to identify the object being looked at. Allocation of eye gaze in each condition was analyzed by analysis of variance and accuracy of identification was compared with t tests. RESULTS: Participants with WS allocated more gaze time to face and eyes than their matched controls, both with and without being asked to identify the item being looked at; while participants with autism spent less time on face and eyes in both conditions. When cued to follow gaze, participants with WS increased gaze to the correct targets; those with autism looked more at the face and eyes but did not increase gaze to the correct targets, while continuing to look much more than their controls at implausible targets. Both groups identified fewer objects than their controls. CONCLUSIONS: The atypicalities found are likely to be entwined with the deficits shown in interpreting social cognitive cues from the images. WS and autism are characterized by atypicalities of social attention that impact upon socio-cognitive expertise, but, importantly, the type of atypicality is syndrome specific. En ligne : http://dx.doi.org/10.1186/1866-1955-5-13 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Spontaneous and cued gaze-following in autism and Williams syndrome [Texte imprimé et/ou numérique] / D. M. RIBY, Auteur ; P. J. HANCOCK, Auteur ; N. JONES, Auteur ; M. HANLEY, Auteur . - p.13. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.13 Index. décimale : PER Périodiques Résumé : BACKGROUND: From a young age the typical development of social functioning relies upon the allocation of attention to socially relevant information, which in turn allows experience at processing such information and thus enhances social cognition. As such, research has attempted to identify the developmental processes that are derailed in some neuro-developmental disorders that impact upon social functioning. Williams syndrome (WS) and autism are disorders of development that are characterized by atypical yet divergent social phenotypes and atypicalities of attention to people. METHODS: We used eye tracking to explore how individuals with WS and autism attended to, and subsequently interpreted, an actor's eye gaze cue within a social scene. Images were presented for 3 seconds, initially with an instruction simply to look at the picture. The images were then shown again, with the participant asked to identify the object being looked at. Allocation of eye gaze in each condition was analyzed by analysis of variance and accuracy of identification was compared with t tests. RESULTS: Participants with WS allocated more gaze time to face and eyes than their matched controls, both with and without being asked to identify the item being looked at; while participants with autism spent less time on face and eyes in both conditions. When cued to follow gaze, participants with WS increased gaze to the correct targets; those with autism looked more at the face and eyes but did not increase gaze to the correct targets, while continuing to look much more than their controls at implausible targets. Both groups identified fewer objects than their controls. CONCLUSIONS: The atypicalities found are likely to be entwined with the deficits shown in interpreting social cognitive cues from the images. WS and autism are characterized by atypicalities of social attention that impact upon socio-cognitive expertise, but, importantly, the type of atypicality is syndrome specific. En ligne : http://dx.doi.org/10.1186/1866-1955-5-13 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates / E. M. BARENDSE in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.14 Titre : Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates Type de document : Texte imprimé et/ou numérique Auteurs : E. M. BARENDSE, Auteur ; M. P. HENDRIKS, Auteur ; J. F. JANSEN, Auteur ; W. H. BACKES, Auteur ; P. A. HOFMAN, Auteur ; G. THOONEN, Auteur ; R. P. KESSELS, Auteur ; A. P. ALDENKAMP, Auteur Article en page(s) : p.14 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum. En ligne : http://dx.doi.org/10.1186/1866-1955-5-14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates [Texte imprimé et/ou numérique] / E. M. BARENDSE, Auteur ; M. P. HENDRIKS, Auteur ; J. F. JANSEN, Auteur ; W. H. BACKES, Auteur ; P. A. HOFMAN, Auteur ; G. THOONEN, Auteur ; R. P. KESSELS, Auteur ; A. P. ALDENKAMP, Auteur . - p.14. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.14 Index. décimale : PER Périodiques Résumé : Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum. En ligne : http://dx.doi.org/10.1186/1866-1955-5-14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Comparative DNA methylation among females with neurodevelopmental disorders and seizures identifies TAC1 as a MeCP2 target gene / Kimberly A. ALDINGER in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.15 Titre : Comparative DNA methylation among females with neurodevelopmental disorders and seizures identifies TAC1 as a MeCP2 target gene Type de document : Texte imprimé et/ou numérique Auteurs : Kimberly A. ALDINGER, Auteur ; J. T. PLUMMER, Auteur ; P. LEVITT, Auteur Article en page(s) : p.15 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Several proteins involved in epigenetic regulation cause syndromic neurodevelopmental disorders when human genes are mutated. More general involvement of epigenetic mechanisms in neurodevelopmental phenotypes is unclear. METHODS: In an attempt to determine whether DNA methylation differentiates clinical subgroups, profiling was performed on bisulfite converted DNA from lymphoblastoid cell lines (LCLs) in discovery (n = 20) and replication (n = 40) cohorts of females with Rett syndrome (RTT; n = 18), autism (AUT; n = 17), seizure disorder (SEZ; n = 6), and controls (CTL; n = 19) using Illumina HumanMethylation27 arrays. TAC1 CpGs were validated using a Sequenom EpiTYPER assay and expression was measured in LCLs and postmortem brain. Chromatin immunoprecipitation was performed in HEK cells. Cells were treated with valproic acid and MeCP2 binding was assessed. RESULTS: Two female-only cohorts were analyzed. DNA methylation profiling in a discovery cohort identified 40 CpGs that exhibited statistically significant differential methylation (>/=15%) between clinical groups (P <0.01). Hierarchical clustering and principal components analysis suggested neurodevelopmental groups were distinct from CTL, but not from each other. In a larger and more heterogeneous replication cohort, these 40 CpG sites suggested no clear difference between clinical groups. Pooled analysis of DNA methylation across all 60 samples suggested only four differentially methylated CpG sites (P <0.0005), including TAC1. TAC1 promoter CpG hypermethylation was validated in AUT and SEZ (P <0.005). Analyzed for the first time in postmortem brain, TAC1 expression was reduced in cingulate cortex in RTT and AUT+SEZ (P = 0.003). However, no significant difference in TAC1 promoter CpG methylation was detected in RTT and AUT+SEZ brains. Additional molecular analyses revealed that MeCP2 binds directly to the TAC1 promoter and is sensitive to antiepileptic drug treatment. CONCLUSION: These data suggest that DNA methylation is not widely altered in RTT, consistent with subtle changes in gene expression previously observed. However, TAC1 may be an important target for further functional analyses in RTT. Studies of larger sample cohorts using primary cells that also consider shared clinical features and drug treatments may be required to address apparent subtle disruptions of DNA methylation in neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-5-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Comparative DNA methylation among females with neurodevelopmental disorders and seizures identifies TAC1 as a MeCP2 target gene [Texte imprimé et/ou numérique] / Kimberly A. ALDINGER, Auteur ; J. T. PLUMMER, Auteur ; P. LEVITT, Auteur . - p.15. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.15 Index. décimale : PER Périodiques Résumé : BACKGROUND: Several proteins involved in epigenetic regulation cause syndromic neurodevelopmental disorders when human genes are mutated. More general involvement of epigenetic mechanisms in neurodevelopmental phenotypes is unclear. METHODS: In an attempt to determine whether DNA methylation differentiates clinical subgroups, profiling was performed on bisulfite converted DNA from lymphoblastoid cell lines (LCLs) in discovery (n = 20) and replication (n = 40) cohorts of females with Rett syndrome (RTT; n = 18), autism (AUT; n = 17), seizure disorder (SEZ; n = 6), and controls (CTL; n = 19) using Illumina HumanMethylation27 arrays. TAC1 CpGs were validated using a Sequenom EpiTYPER assay and expression was measured in LCLs and postmortem brain. Chromatin immunoprecipitation was performed in HEK cells. Cells were treated with valproic acid and MeCP2 binding was assessed. RESULTS: Two female-only cohorts were analyzed. DNA methylation profiling in a discovery cohort identified 40 CpGs that exhibited statistically significant differential methylation (>/=15%) between clinical groups (P <0.01). Hierarchical clustering and principal components analysis suggested neurodevelopmental groups were distinct from CTL, but not from each other. In a larger and more heterogeneous replication cohort, these 40 CpG sites suggested no clear difference between clinical groups. Pooled analysis of DNA methylation across all 60 samples suggested only four differentially methylated CpG sites (P <0.0005), including TAC1. TAC1 promoter CpG hypermethylation was validated in AUT and SEZ (P <0.005). Analyzed for the first time in postmortem brain, TAC1 expression was reduced in cingulate cortex in RTT and AUT+SEZ (P = 0.003). However, no significant difference in TAC1 promoter CpG methylation was detected in RTT and AUT+SEZ brains. Additional molecular analyses revealed that MeCP2 binds directly to the TAC1 promoter and is sensitive to antiepileptic drug treatment. CONCLUSION: These data suggest that DNA methylation is not widely altered in RTT, consistent with subtle changes in gene expression previously observed. However, TAC1 may be an important target for further functional analyses in RTT. Studies of larger sample cohorts using primary cells that also consider shared clinical features and drug treatments may be required to address apparent subtle disruptions of DNA methylation in neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-5-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Organization of brain networks governed by long-range connections index autistic traits in the general population / P. BARTTFELD in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.16 Titre : Organization of brain networks governed by long-range connections index autistic traits in the general population Type de document : Texte imprimé et/ou numérique Auteurs : P. BARTTFELD, Auteur ; L. AMORUSO, Auteur ; J. AIS, Auteur ; S. CUKIER, Auteur ; L. BAVASSI, Auteur ; A. TOMIO, Auteur ; F. MANES, Auteur ; A. IBANEZ, Auteur ; M. SIGMAN, Auteur Article en page(s) : p.16 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: The dimensional approach to autism spectrum disorder (ASD) considers ASD as the extreme of a dimension traversing through the entire population. We explored the potential utility of electroencephalography (EEG) functional connectivity as a biomarker. We hypothesized that individual differences in autistic traits of typical subjects would involve a long-range connectivity diminution within the delta band. METHODS: Resting-state EEG functional connectivity was measured for 74 neurotypical subjects. All participants also provided a questionnaire (Social Responsiveness Scale, SRS) that was completed by an informant who knows the participant in social settings. We conducted multivariate regression between the SRS score and functional connectivity in all EEG frequency bands. We explored modulations of network graph metrics characterizing the optimality of a network using the SRS score. RESULTS: Our results show a decay in functional connectivity mainly within the delta and theta bands (the lower part of the EEG spectrum) associated with an increasing number of autistic traits. When inspecting the impact of autistic traits on the global organization of the functional network, we found that the optimal properties of the network are inversely related to the number of autistic traits, suggesting that the autistic dimension, throughout the entire population, modulates the efficiency of functional brain networks. CONCLUSIONS: EEG functional connectivity at low frequencies and its associated network properties may be associated with some autistic traits in the general population. En ligne : http://dx.doi.org/10.1186/1866-1955-5-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Organization of brain networks governed by long-range connections index autistic traits in the general population [Texte imprimé et/ou numérique] / P. BARTTFELD, Auteur ; L. AMORUSO, Auteur ; J. AIS, Auteur ; S. CUKIER, Auteur ; L. BAVASSI, Auteur ; A. TOMIO, Auteur ; F. MANES, Auteur ; A. IBANEZ, Auteur ; M. SIGMAN, Auteur . - p.16. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.16 Index. décimale : PER Périodiques Résumé : BACKGROUND: The dimensional approach to autism spectrum disorder (ASD) considers ASD as the extreme of a dimension traversing through the entire population. We explored the potential utility of electroencephalography (EEG) functional connectivity as a biomarker. We hypothesized that individual differences in autistic traits of typical subjects would involve a long-range connectivity diminution within the delta band. METHODS: Resting-state EEG functional connectivity was measured for 74 neurotypical subjects. All participants also provided a questionnaire (Social Responsiveness Scale, SRS) that was completed by an informant who knows the participant in social settings. We conducted multivariate regression between the SRS score and functional connectivity in all EEG frequency bands. We explored modulations of network graph metrics characterizing the optimality of a network using the SRS score. RESULTS: Our results show a decay in functional connectivity mainly within the delta and theta bands (the lower part of the EEG spectrum) associated with an increasing number of autistic traits. When inspecting the impact of autistic traits on the global organization of the functional network, we found that the optimal properties of the network are inversely related to the number of autistic traits, suggesting that the autistic dimension, throughout the entire population, modulates the efficiency of functional brain networks. CONCLUSIONS: EEG functional connectivity at low frequencies and its associated network properties may be associated with some autistic traits in the general population. En ligne : http://dx.doi.org/10.1186/1866-1955-5-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

The effect of chronic prenatal hypoxia on the development of mature neurons in the cerebellum / K. SO in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.17 Titre : The effect of chronic prenatal hypoxia on the development of mature neurons in the cerebellum Type de document : Texte imprimé et/ou numérique Auteurs : K. SO, Auteur ; Y. CHUNG, Auteur ; H. LEE, Auteur ; E. KIM, Auteur ; Y. JEON, Auteur Article en page(s) : p.17 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Adverse intrauterine circumstances can result in abnormal brain development, and can contribute to many neurological disorders such as cerebral palsy and cognitive and behavioral deficits. These neurological problems are caused by conditions that cause chronic placental insufficiency (CPI), such as hypoxia and acidemia. Hypoxia has been implicated in structural alterations of the cerebellum during development; however, the changes to the cerebellar external granular layer (EGL) induced by chronic prenatal hypoxia are not well understood. We therefore investigated the effect of chronic prenatal hypoxia on the development of mature neurons in the EGL using the guinea pig CPI model. METHODS: Unilateral uterine artery ligation was performed at 30 to 32 days of gestation (dg) - with term defined as approximately 67 dg. At 50 dg, 60 dg, and one week after birth, fetuses and newborns were sacrificed and assigned to either the growth-restricted (GR) or control (no ligation) group. After fixation, dissection, and sectioning of cerebellar tissue from these animals, immunohistochemistry was performed with antibodies raised to hypoxia-induced factor 1alpha (Hif1alpha), Pax6, NeuroD, and NeuN. RESULTS: The induction of hypoxia was confirmed by the presence of Hif1alpha immunoreactivity in the EGL of the GR (but not control) fetuses. The only other cellular immunoreactivity found in any of the tissues was to the NeuN antibody, which is a marker of mature neurons. The proportion of NeuN-immunoreactive (NeuN-IR) cells to the total number of cells in the EGL did not differ between the GR and control groups at 50 and 60 dg. The density of NeuN-IR cells was greater in GR fetuses than in controls at 60 dg (P < 0.05) but not at 50 dg. At one week after birth, the EGL was just one cell thick, and only a few NeuN-IR cells could be observed in both groups. TUNEL assays performed to enable the evaluation of apoptosis in the cerebellar EGL revealed that cell death was not affected by hypoxia at 50 dg, 60 dg, and one week after birth. CONCLUSION: These findings indicate that chronic prenatal hypoxia affects the process of neuronal production late in fetal life, but that this effect does not persist postnatally. En ligne : http://dx.doi.org/10.1186/1866-1955-5-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] The effect of chronic prenatal hypoxia on the development of mature neurons in the cerebellum [Texte imprimé et/ou numérique] / K. SO, Auteur ; Y. CHUNG, Auteur ; H. LEE, Auteur ; E. KIM, Auteur ; Y. JEON, Auteur . - p.17. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.17 Index. décimale : PER Périodiques Résumé : BACKGROUND: Adverse intrauterine circumstances can result in abnormal brain development, and can contribute to many neurological disorders such as cerebral palsy and cognitive and behavioral deficits. These neurological problems are caused by conditions that cause chronic placental insufficiency (CPI), such as hypoxia and acidemia. Hypoxia has been implicated in structural alterations of the cerebellum during development; however, the changes to the cerebellar external granular layer (EGL) induced by chronic prenatal hypoxia are not well understood. We therefore investigated the effect of chronic prenatal hypoxia on the development of mature neurons in the EGL using the guinea pig CPI model. METHODS: Unilateral uterine artery ligation was performed at 30 to 32 days of gestation (dg) - with term defined as approximately 67 dg. At 50 dg, 60 dg, and one week after birth, fetuses and newborns were sacrificed and assigned to either the growth-restricted (GR) or control (no ligation) group. After fixation, dissection, and sectioning of cerebellar tissue from these animals, immunohistochemistry was performed with antibodies raised to hypoxia-induced factor 1alpha (Hif1alpha), Pax6, NeuroD, and NeuN. RESULTS: The induction of hypoxia was confirmed by the presence of Hif1alpha immunoreactivity in the EGL of the GR (but not control) fetuses. The only other cellular immunoreactivity found in any of the tissues was to the NeuN antibody, which is a marker of mature neurons. The proportion of NeuN-immunoreactive (NeuN-IR) cells to the total number of cells in the EGL did not differ between the GR and control groups at 50 and 60 dg. The density of NeuN-IR cells was greater in GR fetuses than in controls at 60 dg (P < 0.05) but not at 50 dg. At one week after birth, the EGL was just one cell thick, and only a few NeuN-IR cells could be observed in both groups. TUNEL assays performed to enable the evaluation of apoptosis in the cerebellar EGL revealed that cell death was not affected by hypoxia at 50 dg, 60 dg, and one week after birth. CONCLUSION: These findings indicate that chronic prenatal hypoxia affects the process of neuronal production late in fetal life, but that this effect does not persist postnatally. En ligne : http://dx.doi.org/10.1186/1866-1955-5-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Behavioral profile of adults with Prader-Willi syndrome: correlations with individual and environmental variables / J. JAUREGI in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.18 Titre : Behavioral profile of adults with Prader-Willi syndrome: correlations with individual and environmental variables Type de document : Texte imprimé et/ou numérique Auteurs : J. JAUREGI, Auteur ; V. LAURIER, Auteur ; P. COPET, Auteur ; M. TAUBER, Auteur ; D. THUILLEAUX, Auteur Article en page(s) : p.18 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Maladaptive behavior has been reported as a phenotypical feature in Prader-Willi syndrome (PWS). It severely limits social adaptation and the quality of life of children and adults with the syndrome. Different factors have been linked with the intensity and form of these behavioral disturbances but there is no consensus about the cause. Consequently, there is still controversy regarding management strategies and there is a need for new data. METHODS: The behavior of 100 adults with PWS attending a dedicated center was assessed using the Developmental Behavior Checklist for Adults (DBC-A) and the PWS-specific Hyperphagia Questionnaire. The DBC-A was completed separately by trained caregivers at the center and relatives or caregivers in a natural setting. Genotype, gender, age, degree of obesity and cognitive impairment were analyzed as variables with a hypothetical influence on behavioral features. RESULTS: Patients showed a relatively high rate of behavioral disturbances other than hyperphagia. Disruptive and social relating were the highest scoring DBC-A subscales whereas anxiety/antisocial and self-absorbed were the lowest. When hospital caregiver and natural caregiver scores were compared, scores for the latter were higher for all subscales except for disruptive and anxiety/antisocial. These effects of institutional management were underlined. In the DBC-A, 22 items have descriptive indications of PWS behavior and were used for further comparisons and correlation analysis. In contrast to previous reports, rates of disturbed behavior were lower in patients with a deletion genotype. However, the behavioral profile was similar for both genotypes. No differences were found in any measurement when comparing type I and type II deletions. The other analyzed variables showed little relevance. CONCLUSIONS: Significant rates of behavioral disorders were highlighted and their typology described in a large cohort of adults with PWS. The deletion genotype was related to a lower severity of symptoms. Some major behavioral problems, such as hyperphagia, may be well controlled if living circumstances are adapted to the specific requirements of individuals with PWS. En ligne : http://dx.doi.org/10.1186/1866-1955-5-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Behavioral profile of adults with Prader-Willi syndrome: correlations with individual and environmental variables [Texte imprimé et/ou numérique] / J. JAUREGI, Auteur ; V. LAURIER, Auteur ; P. COPET, Auteur ; M. TAUBER, Auteur ; D. THUILLEAUX, Auteur . - p.18. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.18 Index. décimale : PER Périodiques Résumé : BACKGROUND: Maladaptive behavior has been reported as a phenotypical feature in Prader-Willi syndrome (PWS). It severely limits social adaptation and the quality of life of children and adults with the syndrome. Different factors have been linked with the intensity and form of these behavioral disturbances but there is no consensus about the cause. Consequently, there is still controversy regarding management strategies and there is a need for new data. METHODS: The behavior of 100 adults with PWS attending a dedicated center was assessed using the Developmental Behavior Checklist for Adults (DBC-A) and the PWS-specific Hyperphagia Questionnaire. The DBC-A was completed separately by trained caregivers at the center and relatives or caregivers in a natural setting. Genotype, gender, age, degree of obesity and cognitive impairment were analyzed as variables with a hypothetical influence on behavioral features. RESULTS: Patients showed a relatively high rate of behavioral disturbances other than hyperphagia. Disruptive and social relating were the highest scoring DBC-A subscales whereas anxiety/antisocial and self-absorbed were the lowest. When hospital caregiver and natural caregiver scores were compared, scores for the latter were higher for all subscales except for disruptive and anxiety/antisocial. These effects of institutional management were underlined. In the DBC-A, 22 items have descriptive indications of PWS behavior and were used for further comparisons and correlation analysis. In contrast to previous reports, rates of disturbed behavior were lower in patients with a deletion genotype. However, the behavioral profile was similar for both genotypes. No differences were found in any measurement when comparing type I and type II deletions. The other analyzed variables showed little relevance. CONCLUSIONS: Significant rates of behavioral disorders were highlighted and their typology described in a large cohort of adults with PWS. The deletion genotype was related to a lower severity of symptoms. Some major behavioral problems, such as hyperphagia, may be well controlled if living circumstances are adapted to the specific requirements of individuals with PWS. En ligne : http://dx.doi.org/10.1186/1866-1955-5-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Dementia in Down's syndrome: an MRI comparison with Alzheimer's disease in the general population / D. MULLINS in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.19 Titre : Dementia in Down's syndrome: an MRI comparison with Alzheimer's disease in the general population Type de document : Texte imprimé et/ou numérique Auteurs : D. MULLINS, Auteur ; Eileen DALY, Auteur ; A. SIMMONS, Auteur ; F. BEACHER, Auteur ; C. M. FOY, Auteur ; S. LOVESTONE, Auteur ; B. HALLAHAN, Auteur ; K. C. MURPHY, Auteur ; D. G. MURPHY, Auteur Article en page(s) : p.19 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Down's syndrome (DS) is the most common genetic cause of intellectual disability. People with DS are at an increased risk of Alzheimer's disease (AD) compared to the general population. Neuroimaging studies of AD have focused on medial temporal structures; however, to our knowledge, no in vivo case-control study exists comparing the anatomy of dementia in DS to people with AD in the general population. We therefore compared the in vivo brain anatomy of people with DS and dementia (DS+) to those with AD in the general population. METHOD: Using MRI in 192 adults, we compared the volume of whole brain matter, lateral ventricles, temporal lobes and hippocampus in DS subjects with and without dementia (DS+, DS-), to each other and to three non-DS groups. These included one group of individuals with AD and two groups of controls (each age-matched for their respective DS and general population AD cohorts). RESULTS: AD and DS+ subjects showed significant reductions in the volume of the whole brain, hippocampus and temporal lobes and a significant elevation in the volume of the lateral ventricle, compared to their non-demented counterparts. People with DS+ had a smaller reduction in temporal lobe volume compared to individuals with AD. CONCLUSIONS: DS+ and AD subjects have a significant reduction in volume of the same brain regions. We found preliminary evidence that DS individuals may be more sensitive to tissue loss than others and have less 'cognitive reserve'. En ligne : http://dx.doi.org/10.1186/1866-1955-5-19 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Dementia in Down's syndrome: an MRI comparison with Alzheimer's disease in the general population [Texte imprimé et/ou numérique] / D. MULLINS, Auteur ; Eileen DALY, Auteur ; A. SIMMONS, Auteur ; F. BEACHER, Auteur ; C. M. FOY, Auteur ; S. LOVESTONE, Auteur ; B. HALLAHAN, Auteur ; K. C. MURPHY, Auteur ; D. G. MURPHY, Auteur . - p.19. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.19 Index. décimale : PER Périodiques Résumé : BACKGROUND: Down's syndrome (DS) is the most common genetic cause of intellectual disability. People with DS are at an increased risk of Alzheimer's disease (AD) compared to the general population. Neuroimaging studies of AD have focused on medial temporal structures; however, to our knowledge, no in vivo case-control study exists comparing the anatomy of dementia in DS to people with AD in the general population. We therefore compared the in vivo brain anatomy of people with DS and dementia (DS+) to those with AD in the general population. METHOD: Using MRI in 192 adults, we compared the volume of whole brain matter, lateral ventricles, temporal lobes and hippocampus in DS subjects with and without dementia (DS+, DS-), to each other and to three non-DS groups. These included one group of individuals with AD and two groups of controls (each age-matched for their respective DS and general population AD cohorts). RESULTS: AD and DS+ subjects showed significant reductions in the volume of the whole brain, hippocampus and temporal lobes and a significant elevation in the volume of the lateral ventricle, compared to their non-demented counterparts. People with DS+ had a smaller reduction in temporal lobe volume compared to individuals with AD. CONCLUSIONS: DS+ and AD subjects have a significant reduction in volume of the same brain regions. We found preliminary evidence that DS individuals may be more sensitive to tissue loss than others and have less 'cognitive reserve'. En ligne : http://dx.doi.org/10.1186/1866-1955-5-19 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study / Jennifer L. BRUNO in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.20 Titre : Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study Type de document : Texte imprimé et/ou numérique Auteurs : Jennifer L. BRUNO, Auteur ; E. W. SHELLY, Auteur ; E. M. QUINTIN, Auteur ; M. ROSTAMI, Auteur ; S. PATNAIK, Auteur ; D. SPIELMAN, Auteur ; D. MAYER, Auteur ; M. GU, Auteur ; A. A. LIGHTBODY, Auteur ; A. L. REISS, Auteur Article en page(s) : p.20 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: The profile of cognitive and behavioral variation observed in individuals with fragile X syndrome (FXS), the most common known cause of inherited intellectual impairment, suggests aberrant functioning of specific brain systems. Research investigating animal models of FXS, characterized by limited or lack of fragile X mental retardation protein, (FMRP), has linked brain dysfunction to deficits in the cholinergic and glutamatergic systems. Thus, we sought to examine in vivo levels of neurometabolites related to cholinergic and glutamatergic functioning in males and females with FXS. METHODS: The study participants included 18 adolescents and young adults with FXS, and a comparison group of 18 individuals without FXS matched for age, sex and general intellectual functioning. Proton magnetic resonance spectroscopy (MRS) was used to assess neurometabolite levels in the caudate nucleus, a region known to be greatly enlarged and involved in abnormal brain circuitry in individuals with FXS. A general linear model framework was used to compare group differences in metabolite concentration. RESULTS: We observed a decrease in choline (P = 0.027) and in glutamate + glutamine (P = 0.032) in the caudate nucleus of individuals with FXS, relative to individuals in the comparison group. CONCLUSIONS: This study provides evidence of metabolite differences in the caudate nucleus, a brain region of potential importance to our understanding of the neural deficits underlying FXS. These metabolic differences may be related to aberrant receptor signaling seen in animal models. Furthermore, identification of the specific neurometabolites involved in FXS dysfunction could provide critical biomarkers for the design and efficacy tracking of disease-specific pharmacological treatments. En ligne : http://dx.doi.org/10.1186/1866-1955-5-20 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study [Texte imprimé et/ou numérique] / Jennifer L. BRUNO, Auteur ; E. W. SHELLY, Auteur ; E. M. QUINTIN, Auteur ; M. ROSTAMI, Auteur ; S. PATNAIK, Auteur ; D. SPIELMAN, Auteur ; D. MAYER, Auteur ; M. GU, Auteur ; A. A. LIGHTBODY, Auteur ; A. L. REISS, Auteur . - p.20. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.20 Index. décimale : PER Périodiques Résumé : BACKGROUND: The profile of cognitive and behavioral variation observed in individuals with fragile X syndrome (FXS), the most common known cause of inherited intellectual impairment, suggests aberrant functioning of specific brain systems. Research investigating animal models of FXS, characterized by limited or lack of fragile X mental retardation protein, (FMRP), has linked brain dysfunction to deficits in the cholinergic and glutamatergic systems. Thus, we sought to examine in vivo levels of neurometabolites related to cholinergic and glutamatergic functioning in males and females with FXS. METHODS: The study participants included 18 adolescents and young adults with FXS, and a comparison group of 18 individuals without FXS matched for age, sex and general intellectual functioning. Proton magnetic resonance spectroscopy (MRS) was used to assess neurometabolite levels in the caudate nucleus, a region known to be greatly enlarged and involved in abnormal brain circuitry in individuals with FXS. A general linear model framework was used to compare group differences in metabolite concentration. RESULTS: We observed a decrease in choline (P = 0.027) and in glutamate + glutamine (P = 0.032) in the caudate nucleus of individuals with FXS, relative to individuals in the comparison group. CONCLUSIONS: This study provides evidence of metabolite differences in the caudate nucleus, a brain region of potential importance to our understanding of the neural deficits underlying FXS. These metabolic differences may be related to aberrant receptor signaling seen in animal models. Furthermore, identification of the specific neurometabolites involved in FXS dysfunction could provide critical biomarkers for the design and efficacy tracking of disease-specific pharmacological treatments. En ligne : http://dx.doi.org/10.1186/1866-1955-5-20 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Intracranial arachnoid cysts: impairment of higher cognitive functions and postoperative improvement / B. Gjerde P in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.21 Titre : Intracranial arachnoid cysts: impairment of higher cognitive functions and postoperative improvement Type de document : Texte imprimé et/ou numérique Auteurs : B. Gjerde P, Auteur ; M. SCHMID, Auteur ; A. HAMMAR, Auteur ; K. WESTER, Auteur Article en page(s) : p.21 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Intracranial arachnoid cysts have been shown to yield cognitive impairment over a range of basic mental functions, and these functions normalize after surgical cyst decompression. We wanted to investigate whether such cysts may also impair executive cognitive functions, and whether surgical cyst decompression leads to an improvement. METHODS: This study included 22 patients with arachnoid cysts and 13 control patients scheduled for low back surgery. All subjects were tested with Delis-Kaplan Executive Function System (D-KEFS) tests, assessing executive function 1 day before surgery and a minimum of 3 months after surgery. The data were analyzed according to scaled score computations based on raw scores provided by D-KEFS, adjusted for age, gender, and educational norms. RESULTS: Preoperatively, the patients with cysts group performed worse than the control group in verbal knowledge, mental flexibility, inhibitory capacity, problem solving, and planning skills. Postoperatively, the patients with cysts group significantly improved performance and were no longer different from the control group in the following subtests: inhibition, inhibition/switching, letter fluency, category switching, and total switching accuracy. The patients with cysts group also significantly improved performance in color naming, category fluency, and in the Tower test, but nevertheless remained impaired at follow-up compared with the control group. The control group did not show a similar improvement, except for the Tower test. Cyst size or postoperative volume reduction did not correlate with cognitive performance or postoperative improvement. Patients with left-sided temporal cysts performed poorer than patients with right-sided cysts on a complex verbal task demanding mental flexibility. CONCLUSIONS: Arachnoid cysts seem to impair not only basic cognition, but also executive functions. Most of this impairment appears to be reversible after surgical cyst decompression. These results may have implications for future preoperative considerations for patients with intracranial arachnoid cysts. En ligne : http://dx.doi.org/10.1186/1866-1955-5-21 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Intracranial arachnoid cysts: impairment of higher cognitive functions and postoperative improvement [Texte imprimé et/ou numérique] / B. Gjerde P, Auteur ; M. SCHMID, Auteur ; A. HAMMAR, Auteur ; K. WESTER, Auteur . - p.21. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.21 Index. décimale : PER Périodiques Résumé : BACKGROUND: Intracranial arachnoid cysts have been shown to yield cognitive impairment over a range of basic mental functions, and these functions normalize after surgical cyst decompression. We wanted to investigate whether such cysts may also impair executive cognitive functions, and whether surgical cyst decompression leads to an improvement. METHODS: This study included 22 patients with arachnoid cysts and 13 control patients scheduled for low back surgery. All subjects were tested with Delis-Kaplan Executive Function System (D-KEFS) tests, assessing executive function 1 day before surgery and a minimum of 3 months after surgery. The data were analyzed according to scaled score computations based on raw scores provided by D-KEFS, adjusted for age, gender, and educational norms. RESULTS: Preoperatively, the patients with cysts group performed worse than the control group in verbal knowledge, mental flexibility, inhibitory capacity, problem solving, and planning skills. Postoperatively, the patients with cysts group significantly improved performance and were no longer different from the control group in the following subtests: inhibition, inhibition/switching, letter fluency, category switching, and total switching accuracy. The patients with cysts group also significantly improved performance in color naming, category fluency, and in the Tower test, but nevertheless remained impaired at follow-up compared with the control group. The control group did not show a similar improvement, except for the Tower test. Cyst size or postoperative volume reduction did not correlate with cognitive performance or postoperative improvement. Patients with left-sided temporal cysts performed poorer than patients with right-sided cysts on a complex verbal task demanding mental flexibility. CONCLUSIONS: Arachnoid cysts seem to impair not only basic cognition, but also executive functions. Most of this impairment appears to be reversible after surgical cyst decompression. These results may have implications for future preoperative considerations for patients with intracranial arachnoid cysts. En ligne : http://dx.doi.org/10.1186/1866-1955-5-21 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Developmental maturation of astrocytes and pathogenesis of neurodevelopmental disorders / Y. YANG in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.22 Titre : Developmental maturation of astrocytes and pathogenesis of neurodevelopmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : Y. YANG, Auteur ; H. HIGASHIMORI, Auteur ; L. MOREL, Auteur Article en page(s) : p.22 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Recent studies have implicated potentially significant roles for astrocytes in the pathogenesis of neurodevelopmental disorders. Astrocytes undergo a dramatic maturation process following early differentiation from which typical morphology and important functions are acquired. Despite significant progress in understanding their early differentiation, very little is known about how astrocytes become functionally mature. In addition, whether functional maturation of astrocytes is disrupted in neurodevelopmental disorders and the consequences of this disruption remains essentially unknown. In this review, we discuss our perspectives about how astrocyte developmental maturation is regulated, and how disruption of the astrocyte functional maturation process, especially alterations in their ability to regulate glutamate homeostasis, may alter synaptic physiology and contribute to the pathogenesis of neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-5-22 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Developmental maturation of astrocytes and pathogenesis of neurodevelopmental disorders [Texte imprimé et/ou numérique] / Y. YANG, Auteur ; H. HIGASHIMORI, Auteur ; L. MOREL, Auteur . - p.22. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.22 Index. décimale : PER Périodiques Résumé : Recent studies have implicated potentially significant roles for astrocytes in the pathogenesis of neurodevelopmental disorders. Astrocytes undergo a dramatic maturation process following early differentiation from which typical morphology and important functions are acquired. Despite significant progress in understanding their early differentiation, very little is known about how astrocytes become functionally mature. In addition, whether functional maturation of astrocytes is disrupted in neurodevelopmental disorders and the consequences of this disruption remains essentially unknown. In this review, we discuss our perspectives about how astrocyte developmental maturation is regulated, and how disruption of the astrocyte functional maturation process, especially alterations in their ability to regulate glutamate homeostasis, may alter synaptic physiology and contribute to the pathogenesis of neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-5-22 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Methotrexate treatment of FraX fibroblasts results in FMR1 transcription but not in detectable FMR1 protein levels / C. BRENDEL in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.23 Titre : Methotrexate treatment of FraX fibroblasts results in FMR1 transcription but not in detectable FMR1 protein levels Type de document : Texte imprimé et/ou numérique Auteurs : C. BRENDEL, Auteur ; B. MIELKE, Auteur ; M. HILLEBRAND, Auteur ; J. GARTNER, Auteur ; P. HUPPKE, Auteur Article en page(s) : p.23 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome is caused by the loss of FMRP expression due to methylation of the FMR1 promoter. Treatment of fragile X syndrome patients' lymphoblastoid cells with 5-azadeoxycytidine results in demethylation of the promoter and reactivation of the gene. The aim of the study was to analyze if methotrexate, an agent which also reduces DNA methylation but with less toxicity than 5-azadeoxycytidine, has therapeutic potential in fragile X syndrome. METHODS: Fibroblasts of fragile X syndrome patients were treated with methotrexate in concentrations ranging from 1 to 4 mug/ml for up to 14 days. FMR1 and FMRP expression were analyzed by quantitative PCR and western blotting. RESULTS: FMR1 mRNA was detected and levels correlated positively with methotrexate concentrations and time of treatment, but western blotting did not show detectable FMRP levels. CONCLUSIONS: We show that it is possible to reactivate FMR1 transcription in fibroblasts of fragile X syndrome patients by treatment with methotrexate. However, we were not able to show FMRP expression, possibly due to the reduced translation efficacy caused by the triplet repeat extension. Unless FMR1 reactivation is more effective in vivo our results indicate that methotrexate has no role in the treatment of fragile X syndrome. En ligne : http://dx.doi.org/10.1186/1866-1955-5-23 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Methotrexate treatment of FraX fibroblasts results in FMR1 transcription but not in detectable FMR1 protein levels [Texte imprimé et/ou numérique] / C. BRENDEL, Auteur ; B. MIELKE, Auteur ; M. HILLEBRAND, Auteur ; J. GARTNER, Auteur ; P. HUPPKE, Auteur . - p.23. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.23 Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome is caused by the loss of FMRP expression due to methylation of the FMR1 promoter. Treatment of fragile X syndrome patients' lymphoblastoid cells with 5-azadeoxycytidine results in demethylation of the promoter and reactivation of the gene. The aim of the study was to analyze if methotrexate, an agent which also reduces DNA methylation but with less toxicity than 5-azadeoxycytidine, has therapeutic potential in fragile X syndrome. METHODS: Fibroblasts of fragile X syndrome patients were treated with methotrexate in concentrations ranging from 1 to 4 mug/ml for up to 14 days. FMR1 and FMRP expression were analyzed by quantitative PCR and western blotting. RESULTS: FMR1 mRNA was detected and levels correlated positively with methotrexate concentrations and time of treatment, but western blotting did not show detectable FMRP levels. CONCLUSIONS: We show that it is possible to reactivate FMR1 transcription in fibroblasts of fragile X syndrome patients by treatment with methotrexate. However, we were not able to show FMRP expression, possibly due to the reduced translation efficacy caused by the triplet repeat extension. Unless FMR1 reactivation is more effective in vivo our results indicate that methotrexate has no role in the treatment of fragile X syndrome. En ligne : http://dx.doi.org/10.1186/1866-1955-5-23 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Resting state EEG abnormalities in autism spectrum disorders / J. WANG in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.24 Titre : Resting state EEG abnormalities in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : J. WANG, Auteur ; J. BARSTEIN, Auteur ; L. E. ETHRIDGE, Auteur ; M. W. MOSCONI, Auteur ; Y. TAKARAE, Auteur ; J. A. SWEENEY, Auteur Article en page(s) : p.24 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are a group of complex and heterogeneous developmental disorders involving multiple neural system dysfunctions. In an effort to understand neurophysiological substrates, identify etiopathophysiologically distinct subgroups of patients, and track outcomes of novel treatments with translational biomarkers, EEG (electroencephalography) studies offer a promising research strategy in ASD. Resting-state EEG studies of ASD suggest a U-shaped profile of electrophysiological power alterations, with excessive power in low-frequency and high-frequency bands, abnormal functional connectivity, and enhanced power in the left hemisphere of the brain. In this review, we provide a summary of recent findings, discuss limitations in available research that may contribute to inconsistencies in the literature, and offer suggestions for future research in this area for advancing the understanding of ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-24 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Resting state EEG abnormalities in autism spectrum disorders [Texte imprimé et/ou numérique] / J. WANG, Auteur ; J. BARSTEIN, Auteur ; L. E. ETHRIDGE, Auteur ; M. W. MOSCONI, Auteur ; Y. TAKARAE, Auteur ; J. A. SWEENEY, Auteur . - p.24. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.24 Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are a group of complex and heterogeneous developmental disorders involving multiple neural system dysfunctions. In an effort to understand neurophysiological substrates, identify etiopathophysiologically distinct subgroups of patients, and track outcomes of novel treatments with translational biomarkers, EEG (electroencephalography) studies offer a promising research strategy in ASD. Resting-state EEG studies of ASD suggest a U-shaped profile of electrophysiological power alterations, with excessive power in low-frequency and high-frequency bands, abnormal functional connectivity, and enhanced power in the left hemisphere of the brain. In this review, we provide a summary of recent findings, discuss limitations in available research that may contribute to inconsistencies in the literature, and offer suggestions for future research in this area for advancing the understanding of ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-24 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

The broad autism phenotype predicts child functioning in autism spectrum disorders / C. R. MAXWELL in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.25 Titre : The broad autism phenotype predicts child functioning in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : C. R. MAXWELL, Auteur ; Julia PARISH-MORRIS, Auteur ; O. HSIN, Auteur ; J. C. BUSH, Auteur ; Robert T. SCHULTZ, Auteur Article en page(s) : p.25 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Broad autism phenotype (BAP) is a milder expression of the social and communication impairments seen in autism spectrum disorders (ASD). While prior studies characterized the BAP in unaffected family members of probands with ASD, the relationship between parental BAP traits and proband symptomatology remains poorly understood. This study utilizes the Broad Autism Phenotype Questionnaire (BAPQ) in parents and the Social Responsiveness Scale (SRS) in children to examine this connection. We hypothesized that in families affected by ASD, elevated maternal and paternal BAPQ scores would correlate with greater autism symptomatology in diagnosed children. In an extension of prior research, we also explored this relationship in families with typically developing children (TDC). METHODS: Two hundred and forty-five children with ASD, 129 TDC and all parents were recruited as part of a larger study investigating relationships between genes, brain and behavior. The Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS) and expert clinical judgment confirmed ASD diagnoses in children. SRS was collected for all children. Parents completed a self-report BAPQ and an informant report BAPQ for their spouse; an average of self-report and informant report for each parent was used in all analyses. RESULTS: Mothers and fathers of children with ASD had significantly higher rates of BAP traits as compared to parents of TDC. Maternal and paternal BAPQ total scores were not correlated with child IQ in either group. In the ASD group, 10% of mothers and 21% of fathers scored above the established BAP threshold compared to 4% of TDC parents. Crude regression analyses showed that maternal and paternal BAPQ total scores accounted for significant variance in child SRS scores in both ASD (17.1%) and TDC (19.8%) families. CONCLUSIONS: Our results suggest that broad autism symptomatology in parents is moderately associated with their child's autism symptomatology. This result extended to TDC families, suggesting that the BAPQ and SRS capture subtle, subclinical social variation in both children and adults. These findings could help define multi-generational social impairments in future phenotypic and genetic studies. En ligne : http://dx.doi.org/10.1186/1866-1955-5-25 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] The broad autism phenotype predicts child functioning in autism spectrum disorders [Texte imprimé et/ou numérique] / C. R. MAXWELL, Auteur ; Julia PARISH-MORRIS, Auteur ; O. HSIN, Auteur ; J. C. BUSH, Auteur ; Robert T. SCHULTZ, Auteur . - p.25. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.25 Index. décimale : PER Périodiques Résumé : BACKGROUND: Broad autism phenotype (BAP) is a milder expression of the social and communication impairments seen in autism spectrum disorders (ASD). While prior studies characterized the BAP in unaffected family members of probands with ASD, the relationship between parental BAP traits and proband symptomatology remains poorly understood. This study utilizes the Broad Autism Phenotype Questionnaire (BAPQ) in parents and the Social Responsiveness Scale (SRS) in children to examine this connection. We hypothesized that in families affected by ASD, elevated maternal and paternal BAPQ scores would correlate with greater autism symptomatology in diagnosed children. In an extension of prior research, we also explored this relationship in families with typically developing children (TDC). METHODS: Two hundred and forty-five children with ASD, 129 TDC and all parents were recruited as part of a larger study investigating relationships between genes, brain and behavior. The Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS) and expert clinical judgment confirmed ASD diagnoses in children. SRS was collected for all children. Parents completed a self-report BAPQ and an informant report BAPQ for their spouse; an average of self-report and informant report for each parent was used in all analyses. RESULTS: Mothers and fathers of children with ASD had significantly higher rates of BAP traits as compared to parents of TDC. Maternal and paternal BAPQ total scores were not correlated with child IQ in either group. In the ASD group, 10% of mothers and 21% of fathers scored above the established BAP threshold compared to 4% of TDC parents. Crude regression analyses showed that maternal and paternal BAPQ total scores accounted for significant variance in child SRS scores in both ASD (17.1%) and TDC (19.8%) families. CONCLUSIONS: Our results suggest that broad autism symptomatology in parents is moderately associated with their child's autism symptomatology. This result extended to TDC families, suggesting that the BAPQ and SRS capture subtle, subclinical social variation in both children and adults. These findings could help define multi-generational social impairments in future phenotypic and genetic studies. En ligne : http://dx.doi.org/10.1186/1866-1955-5-25 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Sensory and motor secondary symptoms as indicators of brain vulnerability / N. LEVIT-BINNUN in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.26 Titre : Sensory and motor secondary symptoms as indicators of brain vulnerability Type de document : Texte imprimé et/ou numérique Auteurs : N. LEVIT-BINNUN, Auteur ; M. DAVIDOVITCH, Auteur ; Y. GOLLAND, Auteur Article en page(s) : p.26 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : In addition to the primary symptoms that distinguish one disorder from the next, clinicians have identified, yet largely overlooked, another set of symptoms that appear across many disorders, termed secondary symptoms. In the emerging era of systems neuroscience, which highlights that many disorders share common deficits in global network features, the nonspecific nature of secondary symptoms should attract attention. Herein we provide a scholarly review of the literature on a subset of secondary symptoms--sensory and motor. We demonstrate that their pattern of appearance--across a wide range of psychopathologies, much before the full-blown disorder appears, and in healthy individuals who display a variety of negative symptoms--resembles the pattern of appearance of network abnormalities. We propose that sensory and motor secondary symptoms can be important indicators of underlying network aberrations and thus of vulnerable brain states putting individuals at risk for psychopathology following extreme circumstances. En ligne : http://dx.doi.org/10.1186/1866-1955-5-26 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Sensory and motor secondary symptoms as indicators of brain vulnerability [Texte imprimé et/ou numérique] / N. LEVIT-BINNUN, Auteur ; M. DAVIDOVITCH, Auteur ; Y. GOLLAND, Auteur . - p.26. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.26 Index. décimale : PER Périodiques Résumé : In addition to the primary symptoms that distinguish one disorder from the next, clinicians have identified, yet largely overlooked, another set of symptoms that appear across many disorders, termed secondary symptoms. In the emerging era of systems neuroscience, which highlights that many disorders share common deficits in global network features, the nonspecific nature of secondary symptoms should attract attention. Herein we provide a scholarly review of the literature on a subset of secondary symptoms--sensory and motor. We demonstrate that their pattern of appearance--across a wide range of psychopathologies, much before the full-blown disorder appears, and in healthy individuals who display a variety of negative symptoms--resembles the pattern of appearance of network abnormalities. We propose that sensory and motor secondary symptoms can be important indicators of underlying network aberrations and thus of vulnerable brain states putting individuals at risk for psychopathology following extreme circumstances. En ligne : http://dx.doi.org/10.1186/1866-1955-5-26 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Prevalence of selected clinical problems in older adults with autism and intellectual disability / D. KATS in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.27 Titre : Prevalence of selected clinical problems in older adults with autism and intellectual disability Type de document : Texte imprimé et/ou numérique Auteurs : D. KATS, Auteur ; L. PAYNE, Auteur ; M. PARLIER, Auteur ; J. PIVEN, Auteur Article en page(s) : p.27 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Originally described as a disorder of childhood, evidence now demonstrates the lifelong nature of autism spectrum disorder (ASD). Despite the increase of the population over age 65, older adults with ASD remain a scarcely explored subpopulation. This study set out to investigate the prevalence of clinically relevant behaviors and medical problems in a sample of US adults aged 30 to 59 with ASD and intellectual disability (ID), in comparison to those with ID only. METHODS: A cross-sectional study, with both an exploratory and replication analysis, was conducted using National Core Indicators (NCI) multi-state surveys from 2009 to 2010 and 2010 to 2011. There were 4,989 and 4,261 adults aged 30-59 with ID examined from the 2009 to 2010 and 2010 to 2011 samples, respectively. The two consecutive annual samples consisted of 438 (9%) and 298 (7%) individuals with ASD and ID. Variables were chosen from the NCI data as outcomes, including medication use for behavior problems, severe or aggressive behavior problems and selected medical conditions. RESULTS: No age-associated disparities were observed between adults with ASD and ID versus adults with ID only in either sample. For the 2009 to 2010 sample, the prevalence of support needed to manage self-injurious, disruptive and destructive behavior in subjects with ASD and ID ranged from 40 to 60%. Similarly, the prevalence estimates of self-injurious, disruptive and destructive behavior were each almost double in adults with ASD and ID relative to those with ID only. These results were replicated in the 2010 to 2011 sample. CONCLUSIONS: The findings of this study highlight the urgent need for research on the nature and treatment of severe behavior problems in the rapidly increasing population of older adults with ASD. They also suggest the importance of developing policies that expand our capacity to care for these individuals. En ligne : http://dx.doi.org/10.1186/1866-1955-5-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Prevalence of selected clinical problems in older adults with autism and intellectual disability [Texte imprimé et/ou numérique] / D. KATS, Auteur ; L. PAYNE, Auteur ; M. PARLIER, Auteur ; J. PIVEN, Auteur . - p.27. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.27 Index. décimale : PER Périodiques Résumé : BACKGROUND: Originally described as a disorder of childhood, evidence now demonstrates the lifelong nature of autism spectrum disorder (ASD). Despite the increase of the population over age 65, older adults with ASD remain a scarcely explored subpopulation. This study set out to investigate the prevalence of clinically relevant behaviors and medical problems in a sample of US adults aged 30 to 59 with ASD and intellectual disability (ID), in comparison to those with ID only. METHODS: A cross-sectional study, with both an exploratory and replication analysis, was conducted using National Core Indicators (NCI) multi-state surveys from 2009 to 2010 and 2010 to 2011. There were 4,989 and 4,261 adults aged 30-59 with ID examined from the 2009 to 2010 and 2010 to 2011 samples, respectively. The two consecutive annual samples consisted of 438 (9%) and 298 (7%) individuals with ASD and ID. Variables were chosen from the NCI data as outcomes, including medication use for behavior problems, severe or aggressive behavior problems and selected medical conditions. RESULTS: No age-associated disparities were observed between adults with ASD and ID versus adults with ID only in either sample. For the 2009 to 2010 sample, the prevalence of support needed to manage self-injurious, disruptive and destructive behavior in subjects with ASD and ID ranged from 40 to 60%. Similarly, the prevalence estimates of self-injurious, disruptive and destructive behavior were each almost double in adults with ASD and ID relative to those with ID only. These results were replicated in the 2010 to 2011 sample. CONCLUSIONS: The findings of this study highlight the urgent need for research on the nature and treatment of severe behavior problems in the rapidly increasing population of older adults with ASD. They also suggest the importance of developing policies that expand our capacity to care for these individuals. En ligne : http://dx.doi.org/10.1186/1866-1955-5-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Eye tracking in early autism research / T. FALCK-YTTER in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.28 Titre : Eye tracking in early autism research Type de document : Texte imprimé et/ou numérique Auteurs : T. FALCK-YTTER, Auteur ; Sven BÖLTE, Auteur ; G. GREDEBACK, Auteur Article en page(s) : p.28 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Eye tracking has the potential to characterize autism at a unique intermediate level, with links 'down' to underlying neurocognitive networks, as well as 'up' to everyday function and dysfunction. Because it is non-invasive and does not require advanced motor responses or language, eye tracking is particularly important for the study of young children and infants. In this article, we review eye tracking studies of young children with autism spectrum disorder (ASD) and children at risk for ASD. Reduced looking time at people and faces, as well as problems with disengagement of attention, appear to be among the earliest signs of ASD, emerging during the first year of life. In toddlers with ASD, altered looking patterns across facial parts such as the eyes and mouth have been found, together with limited orienting to biological motion. We provide a detailed discussion of these and other key findings and highlight methodological opportunities and challenges for eye tracking research of young children with ASD. We conclude that eye tracking can reveal important features of the complex picture of autism. En ligne : http://dx.doi.org/10.1186/1866-1955-5-28 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Eye tracking in early autism research [Texte imprimé et/ou numérique] / T. FALCK-YTTER, Auteur ; Sven BÖLTE, Auteur ; G. GREDEBACK, Auteur . - p.28. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.28 Index. décimale : PER Périodiques Résumé : Eye tracking has the potential to characterize autism at a unique intermediate level, with links 'down' to underlying neurocognitive networks, as well as 'up' to everyday function and dysfunction. Because it is non-invasive and does not require advanced motor responses or language, eye tracking is particularly important for the study of young children and infants. In this article, we review eye tracking studies of young children with autism spectrum disorder (ASD) and children at risk for ASD. Reduced looking time at people and faces, as well as problems with disengagement of attention, appear to be among the earliest signs of ASD, emerging during the first year of life. In toddlers with ASD, altered looking patterns across facial parts such as the eyes and mouth have been found, together with limited orienting to biological motion. We provide a detailed discussion of these and other key findings and highlight methodological opportunities and challenges for eye tracking research of young children with ASD. We conclude that eye tracking can reveal important features of the complex picture of autism. En ligne : http://dx.doi.org/10.1186/1866-1955-5-28 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech / E. A. WORTHEY in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.29 Titre : Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech Type de document : Texte imprimé et/ou numérique Auteurs : E. A. WORTHEY, Auteur ; G. RACA, Auteur ; J. J. LAFFIN, Auteur ; B. M. WILK, Auteur ; J. M. HARRIS, Auteur ; K. J. JAKIELSKI, Auteur ; D. P. DIMMOCK, Auteur ; E. A. STRAND, Auteur ; L. D. SHRIBERG, Auteur Article en page(s) : p.29 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CAS. METHODS: As part of a larger study of children and youth with motor speech sound disorders, 32 participants were classified as positive for CAS on the basis of a behavioral classification marker using auditory-perceptual and acoustic methods that quantify the competence, precision and stability of a speaker's speech, prosody and voice. WES of 10 randomly selected participants was completed using the Illumina Genome Analyzer IIx Sequencing System. Image analysis, base calling, demultiplexing, read mapping, and variant calling were performed using Illumina software. Software developed in-house was used for variant annotation, prioritization and interpretation to identify those variants likely to be deleterious to neurodevelopmental substrates of speech-language development. RESULTS: Among potentially deleterious variants, clinically reportable findings of interest occurred on a total of five chromosomes (Chr3, Chr6, Chr7, Chr9 and Chr17), which included six genes either strongly associated with CAS (FOXP1 and CNTNAP2) or associated with disorders with phenotypes overlapping CAS (ATP13A4, CNTNAP1, KIAA0319 and SETX). A total of 8 (80%) of the 10 participants had clinically reportable variants in one or two of the six genes, with variants in ATP13A4, KIAA0319 and CNTNAP2 being the most prevalent. CONCLUSIONS: Similar to the results reported in emerging WES studies of other complex neurodevelopmental disorders, our findings from this first WES study of CAS are interpreted as support for heterogeneous genetic origins of this pediatric motor speech disorder with multiple genes, pathways and complex interactions. We also submit that our findings illustrate the potential use of WES for both gene identification and case-by-case clinical diagnostics in pediatric motor speech disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-5-29 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech [Texte imprimé et/ou numérique] / E. A. WORTHEY, Auteur ; G. RACA, Auteur ; J. J. LAFFIN, Auteur ; B. M. WILK, Auteur ; J. M. HARRIS, Auteur ; K. J. JAKIELSKI, Auteur ; D. P. DIMMOCK, Auteur ; E. A. STRAND, Auteur ; L. D. SHRIBERG, Auteur . - p.29. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.29 Index. décimale : PER Périodiques Résumé : BACKGROUND: Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CAS. METHODS: As part of a larger study of children and youth with motor speech sound disorders, 32 participants were classified as positive for CAS on the basis of a behavioral classification marker using auditory-perceptual and acoustic methods that quantify the competence, precision and stability of a speaker's speech, prosody and voice. WES of 10 randomly selected participants was completed using the Illumina Genome Analyzer IIx Sequencing System. Image analysis, base calling, demultiplexing, read mapping, and variant calling were performed using Illumina software. Software developed in-house was used for variant annotation, prioritization and interpretation to identify those variants likely to be deleterious to neurodevelopmental substrates of speech-language development. RESULTS: Among potentially deleterious variants, clinically reportable findings of interest occurred on a total of five chromosomes (Chr3, Chr6, Chr7, Chr9 and Chr17), which included six genes either strongly associated with CAS (FOXP1 and CNTNAP2) or associated with disorders with phenotypes overlapping CAS (ATP13A4, CNTNAP1, KIAA0319 and SETX). A total of 8 (80%) of the 10 participants had clinically reportable variants in one or two of the six genes, with variants in ATP13A4, KIAA0319 and CNTNAP2 being the most prevalent. CONCLUSIONS: Similar to the results reported in emerging WES studies of other complex neurodevelopmental disorders, our findings from this first WES study of CAS are interpreted as support for heterogeneous genetic origins of this pediatric motor speech disorder with multiple genes, pathways and complex interactions. We also submit that our findings illustrate the potential use of WES for both gene identification and case-by-case clinical diagnostics in pediatric motor speech disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-5-29 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

A molecular genetic study of autism and related phenotypes in extended pedigrees / J. PIVEN in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.30 Titre : A molecular genetic study of autism and related phenotypes in extended pedigrees Type de document : Texte imprimé et/ou numérique Auteurs : J. PIVEN, Auteur ; V. J. VIELAND, Auteur ; M. PARLIER, Auteur ; A. THOMPSON, Auteur ; I. O'CONNER, Auteur ; M. WOODBURY-SMITH, Auteur ; Y. HUANG, Auteur ; K. A. WALTERS, Auteur ; B. FERNANDEZ, Auteur ; P. SZATMARI, Auteur Article en page(s) : p.30 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. METHODS: We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. RESULTS: Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior', showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. CONCLUSIONS: These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-30 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] A molecular genetic study of autism and related phenotypes in extended pedigrees [Texte imprimé et/ou numérique] / J. PIVEN, Auteur ; V. J. VIELAND, Auteur ; M. PARLIER, Auteur ; A. THOMPSON, Auteur ; I. O'CONNER, Auteur ; M. WOODBURY-SMITH, Auteur ; Y. HUANG, Auteur ; K. A. WALTERS, Auteur ; B. FERNANDEZ, Auteur ; P. SZATMARI, Auteur . - p.30. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.30 Index. décimale : PER Périodiques Résumé : BACKGROUND: Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. METHODS: We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. RESULTS: Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior', showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. CONCLUSIONS: These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-30 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Divergent structural brain abnormalities between different genetic subtypes of children with Prader-Willi syndrome / A. LUKOSHE in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.31 Titre : Divergent structural brain abnormalities between different genetic subtypes of children with Prader-Willi syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. LUKOSHE, Auteur ; T. WHITE, Auteur ; M. N. SCHMIDT, Auteur ; A. VAN DER LUGT, Auteur ; A. C. HOKKEN-KOELEGA, Auteur Article en page(s) : p.31 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses. METHODS: High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite. RESULTS: Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD. CONCLUSIONS: Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-31 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Divergent structural brain abnormalities between different genetic subtypes of children with Prader-Willi syndrome [Texte imprimé et/ou numérique] / A. LUKOSHE, Auteur ; T. WHITE, Auteur ; M. N. SCHMIDT, Auteur ; A. VAN DER LUGT, Auteur ; A. C. HOKKEN-KOELEGA, Auteur . - p.31. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.31 Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses. METHODS: High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite. RESULTS: Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD. CONCLUSIONS: Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-31 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Examining associations between anxiety and cortisol in high functioning male children with autism / D. M. SIMON in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.32 Titre : Examining associations between anxiety and cortisol in high functioning male children with autism Type de document : Texte imprimé et/ou numérique Auteurs : D. M. SIMON, Auteur ; B. A. CORBETT, Auteur Article en page(s) : p.32 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is characterized by deficits in communication and social ability, as well as restricted interests and repetitive behavior. Anxiety is a persistent anticipation or apprehension about one or more situations to which a person is exposed, and affects many people, including children with ASD. Stress, by contrast, is a response to situations that are threatening, uncontrollable, or unexpected. Indices of anxiety are often measured through informants, with parents and teachers serving as the primary sources of reported anxiety in children. However, self-report measures exist, allowing current (state) and persistent (trait) anxiety to be assessed. The current study was designed to evaluate whether children with autism could identify their own levels of anxiety and the degree to which these levels were associated with symptom profile and physiological arousal. METHODS: Self-reported state and trait anxiety were collected during exposure to different stress paradigms for 40 children (21 typically developing, 19 with autistic disorder) and compared to parent reported social ability (Social Responsiveness Scale) and stress responsivity (cortisol). RESULTS: Significant differences were found between typically developing and children with autism for both state and trait anxiety across all conditions. Associations were identified between severity of parent-reported social impairment and both types of self-report anxiety. No relationship was found between stress (salivary cortisol) and anxiety in children with autism. CONCLUSIONS: Children with autism are able to consistently report their persistent level of anxiety symptoms in stressful situations of benign character. Therefore, the inclusion of such measures may be useful in identifying and tracking symptoms in children with autism under appropriate circumstances. En ligne : http://dx.doi.org/10.1186/1866-1955-5-32 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Examining associations between anxiety and cortisol in high functioning male children with autism [Texte imprimé et/ou numérique] / D. M. SIMON, Auteur ; B. A. CORBETT, Auteur . - p.32. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.32 Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is characterized by deficits in communication and social ability, as well as restricted interests and repetitive behavior. Anxiety is a persistent anticipation or apprehension about one or more situations to which a person is exposed, and affects many people, including children with ASD. Stress, by contrast, is a response to situations that are threatening, uncontrollable, or unexpected. Indices of anxiety are often measured through informants, with parents and teachers serving as the primary sources of reported anxiety in children. However, self-report measures exist, allowing current (state) and persistent (trait) anxiety to be assessed. The current study was designed to evaluate whether children with autism could identify their own levels of anxiety and the degree to which these levels were associated with symptom profile and physiological arousal. METHODS: Self-reported state and trait anxiety were collected during exposure to different stress paradigms for 40 children (21 typically developing, 19 with autistic disorder) and compared to parent reported social ability (Social Responsiveness Scale) and stress responsivity (cortisol). RESULTS: Significant differences were found between typically developing and children with autism for both state and trait anxiety across all conditions. Associations were identified between severity of parent-reported social impairment and both types of self-report anxiety. No relationship was found between stress (salivary cortisol) and anxiety in children with autism. CONCLUSIONS: Children with autism are able to consistently report their persistent level of anxiety symptoms in stressful situations of benign character. Therefore, the inclusion of such measures may be useful in identifying and tracking symptoms in children with autism under appropriate circumstances. En ligne : http://dx.doi.org/10.1186/1866-1955-5-32 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345