Dépouillements

Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study / Donald B. Jr BAILEY in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.1 Titre : Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study Type de document : Texte imprimé et/ou numérique Auteurs : Donald B. Jr BAILEY, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Anne C. WHEELER, Auteur ; M. RASPA, Auteur ; F. MERRIEN, Auteur ; J. RICART, Auteur ; B. KOUMARAS, Auteur ; G. ROSENKRANZ, Auteur ; M. TOMLINSON, Auteur ; F. VON RAISON, Auteur ; G. APOSTOL, Auteur Article en page(s) : p.1 Langues : Anglais (eng) Mots-clés : Afq056  Cgi-i  Clinical Global Impression-Improvement  Fragile X syndrome  Mavoglurant Index. décimale : PER Périodiques Résumé : BACKGROUND: A phase II randomized, placebo-controlled, double-blind study and subsequent open-label extension study evaluated the efficacy, safety, and tolerability of mavoglurant (AFQ056), a selective metabotropic glutamate receptor subtype-5 antagonist, in treating behavioral symptoms in adolescent patients with fragile X syndrome (FXS). A novel method was applied to analyze changes in symptom domains in patients with FXS using the narratives associated with the clinician-rated Clinical Global Impression-Improvement (CGI-I) scale. METHODS: In the core study, patients were randomized to receive mavoglurant (25, 50, or 100 mg BID) or placebo over 12 weeks. In the extension, patients received 100 mg BID mavoglurant (or the highest tolerated dose) for up to 32 months. Global improvement, as a measure of treatment response, was assessed using the CGI-I scale. Investigators assigning CGI-I scores of 1 (very much improved), 2 (much improved), 6 (much worse), or 7 (very much worse) were provided a standard narrative template to collect further information about the changes observed in patients. Investigator feedback was coded and clustered into categories of improvement or worsening to identify potential areas of improvement with mavoglurant. Treatment effect in each category was characterized using the Cochran-Mantel-Haenszel test. RESULTS: A total of 134 and 103 patients had reached 2 weeks or more of core and extension study treatment, respectively, by the pre-assigned cutoff date for investigator feedback. In the core study, 34 CGI-I scores of 1 or 2 were reported in 28 patients; one patient scored 6. Analysis of the CGI-I narratives did not indicate greater treatment response in patients receiving mavoglurant compared with placebo in any specific improvement domain. There were 54 CGI-I scores of 1 or 2 in 47 patients in the extension study. The most frequently reported categories of improvement were behavior and mood (79.3 and 76.6 % in core and extension studies, respectively), engagement (75.9 and 78.7 %), and communication (69.0 and 61.7 %). CONCLUSIONS: A method was established to capture and categorize FXS symptoms using CGI-I narratives. Although this method did not show benefit of drug over placebo, narratives from investigators were mostly based on parental report and thus do not represent a completely objective alternative assessment. TRIAL REGISTRATION: The studies described are registered at ClinicalTrials.gov with clinical trial identifier numbers NCT01357239 and NCT01433354. En ligne : http://dx.doi.org/10.1186/s11689-015-9134-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study [Texte imprimé et/ou numérique] / Donald B. Jr BAILEY, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Anne C. WHEELER, Auteur ; M. RASPA, Auteur ; F. MERRIEN, Auteur ; J. RICART, Auteur ; B. KOUMARAS, Auteur ; G. ROSENKRANZ, Auteur ; M. TOMLINSON, Auteur ; F. VON RAISON, Auteur ; G. APOSTOL, Auteur . - p.1. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.1 Mots-clés : Afq056  Cgi-i  Clinical Global Impression-Improvement  Fragile X syndrome  Mavoglurant Index. décimale : PER Périodiques Résumé : BACKGROUND: A phase II randomized, placebo-controlled, double-blind study and subsequent open-label extension study evaluated the efficacy, safety, and tolerability of mavoglurant (AFQ056), a selective metabotropic glutamate receptor subtype-5 antagonist, in treating behavioral symptoms in adolescent patients with fragile X syndrome (FXS). A novel method was applied to analyze changes in symptom domains in patients with FXS using the narratives associated with the clinician-rated Clinical Global Impression-Improvement (CGI-I) scale. METHODS: In the core study, patients were randomized to receive mavoglurant (25, 50, or 100 mg BID) or placebo over 12 weeks. In the extension, patients received 100 mg BID mavoglurant (or the highest tolerated dose) for up to 32 months. Global improvement, as a measure of treatment response, was assessed using the CGI-I scale. Investigators assigning CGI-I scores of 1 (very much improved), 2 (much improved), 6 (much worse), or 7 (very much worse) were provided a standard narrative template to collect further information about the changes observed in patients. Investigator feedback was coded and clustered into categories of improvement or worsening to identify potential areas of improvement with mavoglurant. Treatment effect in each category was characterized using the Cochran-Mantel-Haenszel test. RESULTS: A total of 134 and 103 patients had reached 2 weeks or more of core and extension study treatment, respectively, by the pre-assigned cutoff date for investigator feedback. In the core study, 34 CGI-I scores of 1 or 2 were reported in 28 patients; one patient scored 6. Analysis of the CGI-I narratives did not indicate greater treatment response in patients receiving mavoglurant compared with placebo in any specific improvement domain. There were 54 CGI-I scores of 1 or 2 in 47 patients in the extension study. The most frequently reported categories of improvement were behavior and mood (79.3 and 76.6 % in core and extension studies, respectively), engagement (75.9 and 78.7 %), and communication (69.0 and 61.7 %). CONCLUSIONS: A method was established to capture and categorize FXS symptoms using CGI-I narratives. Although this method did not show benefit of drug over placebo, narratives from investigators were mostly based on parental report and thus do not represent a completely objective alternative assessment. TRIAL REGISTRATION: The studies described are registered at ClinicalTrials.gov with clinical trial identifier numbers NCT01357239 and NCT01433354. En ligne : http://dx.doi.org/10.1186/s11689-015-9134-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Atypical functional connectivity in resting-state networks of individuals with 22q11.2 deletion syndrome: associations with neurocognitive and psychiatric functioning / L. M. MATTIACCIO in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.2 Titre : Atypical functional connectivity in resting-state networks of individuals with 22q11.2 deletion syndrome: associations with neurocognitive and psychiatric functioning Type de document : Texte imprimé et/ou numérique Auteurs : L. M. MATTIACCIO, Auteur ; I. L. COMAN, Auteur ; M. J. SCHREINER, Auteur ; Kevin M. ANTSHEL, Auteur ; W. P. FREMONT, Auteur ; Carrie E. BEARDEN, Auteur ; W. R. KATES, Auteur Article en page(s) : p.2 Langues : Anglais (eng) Mots-clés : 22q11.2 deletion syndrome  Ica  Resting-state fMRI  Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated with deficits in neuropsychological functioning and psychiatric disorders. This deletion confers a high risk for the development of psychosis, as approximately 30-45 % of individuals develop psychosis in adulthood. Previous reports of resting-state functional magnetic resonance imaging (rs-fMRI) functional connectivity patterns in 22q11DS have demonstrated that atypical connectivity is associated with both the emergence and severity of psychotic symptoms. However, due to sample overlap and large age ranges of samples spanning multiple critical periods of brain maturation, more independent studies with samples within the window of time when psychotic symptoms have been shown to emerge (ages 17-26) are needed. Resting-state networks (RSNs) in 22q11DS during this stage of brain development may thus provide insight into the dynamic changes in functional integration that influence the incidence of prodromal symptoms and neurocognitive deficits characteristic of this syndrome. METHODS: Independent component analysis (ICA) was performed to identify RSNs in a combined sample of 55 individuals with 22q11DS (27 males; age range 17-26) and 29 controls (17 males; age range 17-23, consisting of 8 siblings without the deletion and 21 typically developed individuals) from two research sites. We conducted a full factorial analysis to determine group differences between 22q11DS and controls. A Poisson regression analysis was conducted in the 22q11DS group to determine relationships of rs-fMRI network connectivity with psychiatric symptoms based on factors of the 18-item Brief Psychiatric Rating Scale. Nonparametric Spearman correlations were performed to test associations between within-network functional connectivity (FC) and performance on measures of verbal memory (California Verbal Learning Test) and executive function (Behavior Rating Inventory of Executive Function Adult version) in 22q11DS. RESULTS: Between-group network connectivity analyses revealed significant differences in 9 RSNs. Decreased network FC in 22q11DS was observed in the following networks: high-level visual processing network (HLVPN), low-level visual processing network (LLVPN), visual/precuneus network, left frontal-parietal network (LFPN), right frontal-parietal network (RFPN), and self-referential network (SRN). In contrast, greater network FC in 22q11DS was observed in subclusters of the LLVPN, visual/precuneus network, limbic network (LN), default mode network (DMN), and visuospatial processing network (VSPN). Increased functional connectivity of the right cuneus (visual/precuneus network) and right superior parietal lobule (DMN) in 22q11DS was positively associated with both thought disturbance and disorganization factors of the Brief Psychiatric Rating Scale (BPRS). Decreased functional connectivity in the left posterior cingulate (LLVPN) was associated with higher thought disturbance scores in 22q11DS. No associations with our neurocognitive measures passed correction for multiple comparisons (Bonferroni-corrected p En ligne : http://dx.doi.org/10.1186/s11689-016-9135-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Atypical functional connectivity in resting-state networks of individuals with 22q11.2 deletion syndrome: associations with neurocognitive and psychiatric functioning [Texte imprimé et/ou numérique] / L. M. MATTIACCIO, Auteur ; I. L. COMAN, Auteur ; M. J. SCHREINER, Auteur ; Kevin M. ANTSHEL, Auteur ; W. P. FREMONT, Auteur ; Carrie E. BEARDEN, Auteur ; W. R. KATES, Auteur . - p.2. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.2 Mots-clés : 22q11.2 deletion syndrome  Ica  Resting-state fMRI  Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated with deficits in neuropsychological functioning and psychiatric disorders. This deletion confers a high risk for the development of psychosis, as approximately 30-45 % of individuals develop psychosis in adulthood. Previous reports of resting-state functional magnetic resonance imaging (rs-fMRI) functional connectivity patterns in 22q11DS have demonstrated that atypical connectivity is associated with both the emergence and severity of psychotic symptoms. However, due to sample overlap and large age ranges of samples spanning multiple critical periods of brain maturation, more independent studies with samples within the window of time when psychotic symptoms have been shown to emerge (ages 17-26) are needed. Resting-state networks (RSNs) in 22q11DS during this stage of brain development may thus provide insight into the dynamic changes in functional integration that influence the incidence of prodromal symptoms and neurocognitive deficits characteristic of this syndrome. METHODS: Independent component analysis (ICA) was performed to identify RSNs in a combined sample of 55 individuals with 22q11DS (27 males; age range 17-26) and 29 controls (17 males; age range 17-23, consisting of 8 siblings without the deletion and 21 typically developed individuals) from two research sites. We conducted a full factorial analysis to determine group differences between 22q11DS and controls. A Poisson regression analysis was conducted in the 22q11DS group to determine relationships of rs-fMRI network connectivity with psychiatric symptoms based on factors of the 18-item Brief Psychiatric Rating Scale. Nonparametric Spearman correlations were performed to test associations between within-network functional connectivity (FC) and performance on measures of verbal memory (California Verbal Learning Test) and executive function (Behavior Rating Inventory of Executive Function Adult version) in 22q11DS. RESULTS: Between-group network connectivity analyses revealed significant differences in 9 RSNs. Decreased network FC in 22q11DS was observed in the following networks: high-level visual processing network (HLVPN), low-level visual processing network (LLVPN), visual/precuneus network, left frontal-parietal network (LFPN), right frontal-parietal network (RFPN), and self-referential network (SRN). In contrast, greater network FC in 22q11DS was observed in subclusters of the LLVPN, visual/precuneus network, limbic network (LN), default mode network (DMN), and visuospatial processing network (VSPN). Increased functional connectivity of the right cuneus (visual/precuneus network) and right superior parietal lobule (DMN) in 22q11DS was positively associated with both thought disturbance and disorganization factors of the Brief Psychiatric Rating Scale (BPRS). Decreased functional connectivity in the left posterior cingulate (LLVPN) was associated with higher thought disturbance scores in 22q11DS. No associations with our neurocognitive measures passed correction for multiple comparisons (Bonferroni-corrected p En ligne : http://dx.doi.org/10.1186/s11689-016-9135-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Genomic sequencing of a dyslexia susceptibility haplotype encompassing ROBO1 / S. MASSINEN in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.4 Titre : Genomic sequencing of a dyslexia susceptibility haplotype encompassing ROBO1 Type de document : Texte imprimé et/ou numérique Auteurs : S. MASSINEN, Auteur ; J. WANG, Auteur ; K. LAIVUORI, Auteur ; A. BIEDER, Auteur ; I. TAPIA PAEZ, Auteur ; H. JIAO, Auteur ; J. KERE, Auteur Article en page(s) : p.4 Langues : Anglais (eng) Mots-clés : Dyslexia  Robo1  Whole genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: The DYX5 locus for developmental dyslexia was mapped to chromosome 3 by linkage study of a large Finnish family, and later, roundabout guidance receptor 1 (ROBO1) was implicated as a candidate gene at DYX5 with suppressed expression from the segregating rare haplotype. A functional magnetoencephalographic study of several family members revealed abnormal auditory processing of interaural interaction, supporting a defect in midline crossing of auditory pathways. In the current study, we have characterized genetic variation in the broad ROBO1 gene region in the DYX5-linked family, aiming to identify variants that would increase our understanding of the altered expression of ROBO1. METHODS: We have used a whole genome sequencing strategy on a pooled sample of 19 individuals in combination with two individually sequenced genomes. The discovered genetic variants were annotated and filtered. Subsequently, the most interesting variants were functionally tested using relevant methods, including electrophoretic mobility shift assay (EMSA), luciferase assay, and gene knockdown by lentiviral small hairpin RNA (shRNA) in lymphoblasts. RESULTS: We found one novel intronic single nucleotide variant (SNV) and three novel intergenic SNVs in the broad region of ROBO1 that were specific to the dyslexia susceptibility haplotype. Functional testing by EMSA did not support the binding of transcription factors to three of the SNVs, but one of the SNVs was bound by the LIM homeobox 2 (LHX2) protein, with increased binding affinity for the non-reference allele. Knockdown of LHX2 in lymphoblast cell lines extracted from subjects from the DYX5-linked family showed decreasing expression of ROBO1, supporting the idea that LHX2 regulates ROBO1 also in human. CONCLUSIONS: The discovered variants may explain the segregation of dyslexia in this family, but the effect appears subtle in the experimental settings. Their impact on the developing human brain remains suggestive based on the association and subtle experimental support. En ligne : http://dx.doi.org/10.1186/s11689-016-9136-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Genomic sequencing of a dyslexia susceptibility haplotype encompassing ROBO1 [Texte imprimé et/ou numérique] / S. MASSINEN, Auteur ; J. WANG, Auteur ; K. LAIVUORI, Auteur ; A. BIEDER, Auteur ; I. TAPIA PAEZ, Auteur ; H. JIAO, Auteur ; J. KERE, Auteur . - p.4. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.4 Mots-clés : Dyslexia  Robo1  Whole genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: The DYX5 locus for developmental dyslexia was mapped to chromosome 3 by linkage study of a large Finnish family, and later, roundabout guidance receptor 1 (ROBO1) was implicated as a candidate gene at DYX5 with suppressed expression from the segregating rare haplotype. A functional magnetoencephalographic study of several family members revealed abnormal auditory processing of interaural interaction, supporting a defect in midline crossing of auditory pathways. In the current study, we have characterized genetic variation in the broad ROBO1 gene region in the DYX5-linked family, aiming to identify variants that would increase our understanding of the altered expression of ROBO1. METHODS: We have used a whole genome sequencing strategy on a pooled sample of 19 individuals in combination with two individually sequenced genomes. The discovered genetic variants were annotated and filtered. Subsequently, the most interesting variants were functionally tested using relevant methods, including electrophoretic mobility shift assay (EMSA), luciferase assay, and gene knockdown by lentiviral small hairpin RNA (shRNA) in lymphoblasts. RESULTS: We found one novel intronic single nucleotide variant (SNV) and three novel intergenic SNVs in the broad region of ROBO1 that were specific to the dyslexia susceptibility haplotype. Functional testing by EMSA did not support the binding of transcription factors to three of the SNVs, but one of the SNVs was bound by the LIM homeobox 2 (LHX2) protein, with increased binding affinity for the non-reference allele. Knockdown of LHX2 in lymphoblast cell lines extracted from subjects from the DYX5-linked family showed decreasing expression of ROBO1, supporting the idea that LHX2 regulates ROBO1 also in human. CONCLUSIONS: The discovered variants may explain the segregation of dyslexia in this family, but the effect appears subtle in the experimental settings. Their impact on the developing human brain remains suggestive based on the association and subtle experimental support. En ligne : http://dx.doi.org/10.1186/s11689-016-9136-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome / A. Ting WANG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.5 Titre : Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. Ting WANG, Auteur ; T. LIM, Auteur ; J. JAMISON, Auteur ; L. BUSH, Auteur ; L. V. SOORYA, Auteur ; Teresa TAVASSOLI, Auteur ; P. M. SIPER, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur Article en page(s) : p.5 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS), a neurodevelopmental disorder caused by deletion or mutation in the SHANK3 gene, is one of the more common single-locus causes of autism spectrum disorder (ASD). PMS is characterized by global developmental delay, hypotonia, delayed or absent speech, increased risk of seizures, and minor dysmorphic features. Impairments in language and communication are one of the most consistent characteristics of PMS. Although there is considerable overlap in the social communicative deficits associated with PMS and ASD, there is a dearth of data on underlying abnormalities at the level of neural systems in PMS. No controlled neuroimaging studies of PMS have been reported to date. The goal of this study was to examine the neural circuitry supporting the perception of auditory communicative signals in children with PMS as compared to idiopathic ASD (iASD). METHODS: Eleven children with PMS and nine comparison children with iASD were scanned using functional magnetic resonance imaging (fMRI) under light sedation. The fMRI paradigm was a previously validated passive auditory task, which presented communicative (e.g., speech, sounds of agreement, disgust) and non-communicative vocalizations (e.g., sneezing, coughing, yawning). RESULTS: Previous research has shown that the superior temporal gyrus (STG) responds selectively to communicative vocal signals in typically developing children and adults. Here, selective activity for communicative relative to non-communicative vocalizations was detected in the right STG in the PMS group, but not in the iASD group. The PMS group also showed preferential activity for communicative vocalizations in a range of other brain regions associated with social cognition, such as the medial prefrontal cortex (MPFC), insula, and inferior frontal gyrus. Interestingly, better orienting toward social sounds was positively correlated with selective activity in the STG and other "social brain" regions, including the MPFC, in the PMS group. Finally, selective MPFC activity for communicative sounds was associated with receptive language level in the PMS group and expressive language in the iASD group. CONCLUSIONS: Despite shared behavioral features, children with PMS differed from children with iASD in their neural response to communicative vocal sounds and showed relative strengths in this area. Furthermore, the relationship between clinical characteristics and neural selectivity also differed between the two groups, suggesting that shared ASD features may partially reflect different neurofunctional abnormalities due to differing etiologies. En ligne : http://dx.doi.org/10.1186/s11689-016-9138-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / A. Ting WANG, Auteur ; T. LIM, Auteur ; J. JAMISON, Auteur ; L. BUSH, Auteur ; L. V. SOORYA, Auteur ; Teresa TAVASSOLI, Auteur ; P. M. SIPER, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur . - p.5. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.5 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS), a neurodevelopmental disorder caused by deletion or mutation in the SHANK3 gene, is one of the more common single-locus causes of autism spectrum disorder (ASD). PMS is characterized by global developmental delay, hypotonia, delayed or absent speech, increased risk of seizures, and minor dysmorphic features. Impairments in language and communication are one of the most consistent characteristics of PMS. Although there is considerable overlap in the social communicative deficits associated with PMS and ASD, there is a dearth of data on underlying abnormalities at the level of neural systems in PMS. No controlled neuroimaging studies of PMS have been reported to date. The goal of this study was to examine the neural circuitry supporting the perception of auditory communicative signals in children with PMS as compared to idiopathic ASD (iASD). METHODS: Eleven children with PMS and nine comparison children with iASD were scanned using functional magnetic resonance imaging (fMRI) under light sedation. The fMRI paradigm was a previously validated passive auditory task, which presented communicative (e.g., speech, sounds of agreement, disgust) and non-communicative vocalizations (e.g., sneezing, coughing, yawning). RESULTS: Previous research has shown that the superior temporal gyrus (STG) responds selectively to communicative vocal signals in typically developing children and adults. Here, selective activity for communicative relative to non-communicative vocalizations was detected in the right STG in the PMS group, but not in the iASD group. The PMS group also showed preferential activity for communicative vocalizations in a range of other brain regions associated with social cognition, such as the medial prefrontal cortex (MPFC), insula, and inferior frontal gyrus. Interestingly, better orienting toward social sounds was positively correlated with selective activity in the STG and other "social brain" regions, including the MPFC, in the PMS group. Finally, selective MPFC activity for communicative sounds was associated with receptive language level in the PMS group and expressive language in the iASD group. CONCLUSIONS: Despite shared behavioral features, children with PMS differed from children with iASD in their neural response to communicative vocal sounds and showed relative strengths in this area. Furthermore, the relationship between clinical characteristics and neural selectivity also differed between the two groups, suggesting that shared ASD features may partially reflect different neurofunctional abnormalities due to differing etiologies. En ligne : http://dx.doi.org/10.1186/s11689-016-9138-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Limited impact of Cntn4 mutation on autism-related traits in developing and adult C57BL/6J mice / R. T. MOLENHUIS in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.6 Titre : Limited impact of Cntn4 mutation on autism-related traits in developing and adult C57BL/6J mice Type de document : Texte imprimé et/ou numérique Auteurs : R. T. MOLENHUIS, Auteur ; Hilgo BRUINING, Auteur ; E. REMMELINK, Auteur ; L. DE VISSER, Auteur ; M. LOOS, Auteur ; J. P. H. BURBACH, Auteur ; M. J. KAS, Auteur Article en page(s) : p.6 Langues : Anglais (eng) Mots-clés : 3p deletion syndrome  Autism spectrum disorder  Behavior  Cntn4  Developmental trajectories  Hyperreactivity  Mouse model  Negative findings  Reversal learning  Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 (Cntn4) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages. METHODS: C57BL/6J mice with heterozygous and homozygous disruption of Cntn4 were studied through an extensive, partially longitudinal, test battery at various developmental stages, including various paradigms testing social and restricted repetitive behaviors. RESULTS: Developmental neurological and cognitive screenings revealed no significant differences between genotypes, and ASD-related behavioral domains were also unchanged in Cntn4-deficient versus wild-type mice. The impact of Cntn4-deficiency was found to be limited to increased startle responsiveness following auditory stimuli of different high amplitudes in heterozygous and homozygous Cntn4-deficient mice and enhanced acquisition in a spatial learning task in homozygous mice. CONCLUSIONS: Disruption of Cntn4 in the C57BL/6J background does not affect specific autism-related phenotypes in developing or adult mice but causes subtle non-disorder specific changes in sensory behavioral responses and cognitive performance. En ligne : http://dx.doi.org/10.1186/s11689-016-9140-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Limited impact of Cntn4 mutation on autism-related traits in developing and adult C57BL/6J mice [Texte imprimé et/ou numérique] / R. T. MOLENHUIS, Auteur ; Hilgo BRUINING, Auteur ; E. REMMELINK, Auteur ; L. DE VISSER, Auteur ; M. LOOS, Auteur ; J. P. H. BURBACH, Auteur ; M. J. KAS, Auteur . - p.6. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.6 Mots-clés : 3p deletion syndrome  Autism spectrum disorder  Behavior  Cntn4  Developmental trajectories  Hyperreactivity  Mouse model  Negative findings  Reversal learning  Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 (Cntn4) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages. METHODS: C57BL/6J mice with heterozygous and homozygous disruption of Cntn4 were studied through an extensive, partially longitudinal, test battery at various developmental stages, including various paradigms testing social and restricted repetitive behaviors. RESULTS: Developmental neurological and cognitive screenings revealed no significant differences between genotypes, and ASD-related behavioral domains were also unchanged in Cntn4-deficient versus wild-type mice. The impact of Cntn4-deficiency was found to be limited to increased startle responsiveness following auditory stimuli of different high amplitudes in heterozygous and homozygous Cntn4-deficient mice and enhanced acquisition in a spatial learning task in homozygous mice. CONCLUSIONS: Disruption of Cntn4 in the C57BL/6J background does not affect specific autism-related phenotypes in developing or adult mice but causes subtle non-disorder specific changes in sensory behavioral responses and cognitive performance. En ligne : http://dx.doi.org/10.1186/s11689-016-9140-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Reduced engagement with social stimuli in 6-month-old infants with later autism spectrum disorder: a longitudinal prospective study of infants at high familial risk / E. J. JONES in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.7 Titre : Reduced engagement with social stimuli in 6-month-old infants with later autism spectrum disorder: a longitudinal prospective study of infants at high familial risk Type de document : Texte imprimé et/ou numérique Auteurs : E. J. JONES, Auteur ; K. VENEMA, Auteur ; R. EARL, Auteur ; R. LOWY, Auteur ; K. BARNES, Auteur ; A. ESTES, Auteur ; G. DAWSON, Auteur ; S. J. WEBB, Auteur Article en page(s) : p.7 Langues : Anglais (eng) Mots-clés : Asd  Event-related potential  Habituation  Social attention  Social information processing Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1 % of the population and close to 20 % of prospectively studied infants with an older sibling with ASD. Although significant progress has been made in characterizing the emergence of behavioral symptoms of ASD, far less is known about the underlying disruptions to early learning. Recent models suggest that core aspects of the causal path to ASD may only be apparent in early infancy. Here, we investigated social attention in 6- and 12-month-old infants who did and did not meet criteria for ASD at 24 months using both cognitive and electrophysiological methods. We hypothesized that a reduction in attention engagement to faces would be associated with later ASD. METHODS: In a prospective longitudinal design, we used measures of both visual attention (habituation) and brain function (event-related potentials to faces and objects) at 6 and 12 months and investigated the relationship to ASD outcome at 24 months. RESULTS: High-risk infants who met criteria for ASD at 24 months showed shorter epochs of visual attention, faster but less prolonged neural activation to faces, and delayed sensitization responses (increases in looking) to faces at 6 months; these differences were less apparent at 12 months. These findings are consistent with disrupted engagement of sustained attention to social stimuli. CONCLUSIONS: These findings suggest that there may be fundamental early disruptions to attention engagement that may have cascading consequences for later social functioning. En ligne : http://dx.doi.org/10.1186/s11689-016-9139-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Reduced engagement with social stimuli in 6-month-old infants with later autism spectrum disorder: a longitudinal prospective study of infants at high familial risk [Texte imprimé et/ou numérique] / E. J. JONES, Auteur ; K. VENEMA, Auteur ; R. EARL, Auteur ; R. LOWY, Auteur ; K. BARNES, Auteur ; A. ESTES, Auteur ; G. DAWSON, Auteur ; S. J. WEBB, Auteur . - p.7. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.7 Mots-clés : Asd  Event-related potential  Habituation  Social attention  Social information processing Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1 % of the population and close to 20 % of prospectively studied infants with an older sibling with ASD. Although significant progress has been made in characterizing the emergence of behavioral symptoms of ASD, far less is known about the underlying disruptions to early learning. Recent models suggest that core aspects of the causal path to ASD may only be apparent in early infancy. Here, we investigated social attention in 6- and 12-month-old infants who did and did not meet criteria for ASD at 24 months using both cognitive and electrophysiological methods. We hypothesized that a reduction in attention engagement to faces would be associated with later ASD. METHODS: In a prospective longitudinal design, we used measures of both visual attention (habituation) and brain function (event-related potentials to faces and objects) at 6 and 12 months and investigated the relationship to ASD outcome at 24 months. RESULTS: High-risk infants who met criteria for ASD at 24 months showed shorter epochs of visual attention, faster but less prolonged neural activation to faces, and delayed sensitization responses (increases in looking) to faces at 6 months; these differences were less apparent at 12 months. These findings are consistent with disrupted engagement of sustained attention to social stimuli. CONCLUSIONS: These findings suggest that there may be fundamental early disruptions to attention engagement that may have cascading consequences for later social functioning. En ligne : http://dx.doi.org/10.1186/s11689-016-9139-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Erratum to: Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome / A. Ting WANG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.8 Titre : Erratum to: Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. Ting WANG, Auteur ; T. LIM, Auteur ; J. JAMISON, Auteur ; L. BUSH, Auteur ; L. V. SOORYA, Auteur ; Teresa TAVASSOLI, Auteur ; P. M. SIPER, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur Article en page(s) : p.8 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s11689-016-9138-9.]. En ligne : http://dx.doi.org/10.1186/s11689-016-9143-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Erratum to: Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / A. Ting WANG, Auteur ; T. LIM, Auteur ; J. JAMISON, Auteur ; L. BUSH, Auteur ; L. V. SOORYA, Auteur ; Teresa TAVASSOLI, Auteur ; P. M. SIPER, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur . - p.8. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.8 Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s11689-016-9138-9.]. En ligne : http://dx.doi.org/10.1186/s11689-016-9143-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Specific pattern of maturation and differentiation in the formation of cortical tubers in tuberous sclerosis omplex (TSC): evidence from layer-specific marker expression / A. MUHLEBNER in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.9 Titre : Specific pattern of maturation and differentiation in the formation of cortical tubers in tuberous sclerosis omplex (TSC): evidence from layer-specific marker expression Type de document : Texte imprimé et/ou numérique Auteurs : A. MUHLEBNER, Auteur ; A. M. IYER, Auteur ; J. VAN SCHEPPINGEN, Auteur ; J. ANINK, Auteur ; F. E. JANSEN, Auteur ; T. J. VEERSEMA, Auteur ; K. P. BRAUN, Auteur ; W. G. SPLIET, Auteur ; W. VAN HECKE, Auteur ; F. SOYLEMEZOGLU, Auteur ; M. FEUCHT, Auteur ; P. KRSEK, Auteur ; J. ZAMECNIK, Auteur ; C. G. BIEN, Auteur ; T. POLSTER, Auteur ; R. CORAS, Auteur ; I. BLUMCKE, Auteur ; E. ARONICA, Auteur Article en page(s) : p.9 Langues : Anglais (eng) Mots-clés : Cortical layer markers  Epilepsy  Neuropathology  Neurosurgery  Tuberous sclerosis complex Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem disorder that results from mutations in the TSC1 or TSC2 genes, leading to constitutive activation of the mammalian target of rapamycin (mTOR) signaling pathway. Cortical tubers represent typical lesions of the central nervous system (CNS) in TSC. The pattern of cortical layering disruption observed in brain tissue of TSC patients is not yet fully understood, and little is known about the origin and phenotype of individual abnormal cell types recognized in tubers. METHODS: In the present study, we aimed to characterize dysmorphic neurons (DNs) and giant cells (GCs) of cortical tubers using neocortical layer-specific markers (NeuN, SMI32, Tbr1, Satb2, Cux2, ER81, and RORbeta) and to compare the features with the histo-morphologically similar focal cortical dysplasia (FCD) type IIb. We studied a cohort of nine surgically resected cortical tubers, five FCD type IIb, and four control samples using immunohistochemistry and in situ hybridization. RESULTS: Cortical tuber displayed a prominent cell loss in all cortical layers. Moreover, we observed altered proportions of layer-specific markers within the dysplastic region. DNs, in both tubers and FCD type IIb, were found positive for different cortical layer markers, regardless of their laminar location, and their immunophenotype resembles that of cortical projection neurons. CONCLUSIONS: These findings demonstrate that, similar to FCD type IIb, cortical layering is markedly disturbed in cortical tubers of TSC patients. Distribution of these disturbances is comparable in all tubers and suggests a dysmaturation affecting early and late migratory patterns, with a more severe impairment of the late stage of maturation. En ligne : http://dx.doi.org/10.1186/s11689-016-9142-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Specific pattern of maturation and differentiation in the formation of cortical tubers in tuberous sclerosis omplex (TSC): evidence from layer-specific marker expression [Texte imprimé et/ou numérique] / A. MUHLEBNER, Auteur ; A. M. IYER, Auteur ; J. VAN SCHEPPINGEN, Auteur ; J. ANINK, Auteur ; F. E. JANSEN, Auteur ; T. J. VEERSEMA, Auteur ; K. P. BRAUN, Auteur ; W. G. SPLIET, Auteur ; W. VAN HECKE, Auteur ; F. SOYLEMEZOGLU, Auteur ; M. FEUCHT, Auteur ; P. KRSEK, Auteur ; J. ZAMECNIK, Auteur ; C. G. BIEN, Auteur ; T. POLSTER, Auteur ; R. CORAS, Auteur ; I. BLUMCKE, Auteur ; E. ARONICA, Auteur . - p.9. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.9 Mots-clés : Cortical layer markers  Epilepsy  Neuropathology  Neurosurgery  Tuberous sclerosis complex Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem disorder that results from mutations in the TSC1 or TSC2 genes, leading to constitutive activation of the mammalian target of rapamycin (mTOR) signaling pathway. Cortical tubers represent typical lesions of the central nervous system (CNS) in TSC. The pattern of cortical layering disruption observed in brain tissue of TSC patients is not yet fully understood, and little is known about the origin and phenotype of individual abnormal cell types recognized in tubers. METHODS: In the present study, we aimed to characterize dysmorphic neurons (DNs) and giant cells (GCs) of cortical tubers using neocortical layer-specific markers (NeuN, SMI32, Tbr1, Satb2, Cux2, ER81, and RORbeta) and to compare the features with the histo-morphologically similar focal cortical dysplasia (FCD) type IIb. We studied a cohort of nine surgically resected cortical tubers, five FCD type IIb, and four control samples using immunohistochemistry and in situ hybridization. RESULTS: Cortical tuber displayed a prominent cell loss in all cortical layers. Moreover, we observed altered proportions of layer-specific markers within the dysplastic region. DNs, in both tubers and FCD type IIb, were found positive for different cortical layer markers, regardless of their laminar location, and their immunophenotype resembles that of cortical projection neurons. CONCLUSIONS: These findings demonstrate that, similar to FCD type IIb, cortical layering is markedly disturbed in cortical tubers of TSC patients. Distribution of these disturbances is comparable in all tubers and suggests a dysmaturation affecting early and late migratory patterns, with a more severe impairment of the late stage of maturation. En ligne : http://dx.doi.org/10.1186/s11689-016-9142-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Developmental trajectories of executive functions in 22q11.2 deletion syndrome / J. MAEDER in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.10 Titre : Developmental trajectories of executive functions in 22q11.2 deletion syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. MAEDER, Auteur ; M. SCHNEIDER, Auteur ; M. BOSTELMANN, Auteur ; M. DEBBANE, Auteur ; B. GLASER, Auteur ; S. MENGHETTI, Auteur ; M. SCHAER, Auteur ; S. ELIEZ, Auteur Article en page(s) : p.10 Langues : Anglais (eng) Mots-clés : 22q11.2 deletion syndrome  Adaptive functioning  Development  Executive functions Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder associated with a specific cognitive profile. Higher-order cognitive skills like executive functions (EF) are reported as a relative weakness in this population. The present study aimed to delineate the developmental trajectories of multiple EF domains in a longitudinal sample using a broader age range than previous studies. Given the high incidence of psychotic symptoms in 22q11.2DS, we also compared the development of EF in participants with/without comorbid psychotic symptoms. Given the importance of EF in daily life, the third aim of the study was to characterize the link between EF and adaptive functioning. METHODS: The sample consisted of 95 individuals with 22q11.2DS and 100 typically developing controls aged 6-26 years. A large proportion of the sample (55.38 %) had multiple time points available. Between-group differences in the developmental trajectories of three subdomains of EF (verbal fluency, working memory, and inhibition) were examined using mixed models regression analyses. Analyses were repeated comparing only the 22q11.2DS group based on the presence/absence of psychotic symptoms to investigate the influence of executive dysfunction on the emergence of psychotic symptoms. Hierarchical stepwise regression analyses were also conducted to investigate the predictive value of EF on adaptive functioning. RESULTS: We observed lower performance on EF domains, as well as atypical development of working memory and verbal fluency. Participants who presented with negative symptoms exhibited different developmental trajectories of inhibition and working memory. Adaptive functioning level was not significantly predicted by EF scores. CONCLUSIONS: The present study highlighted domain-specific atypical trajectories of EF in individuals with 22q11.DS and explored the link with psychotic symptoms. However, no relation between EF and adaptive functioning was observed. En ligne : http://dx.doi.org/10.1186/s11689-016-9141-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Developmental trajectories of executive functions in 22q11.2 deletion syndrome [Texte imprimé et/ou numérique] / J. MAEDER, Auteur ; M. SCHNEIDER, Auteur ; M. BOSTELMANN, Auteur ; M. DEBBANE, Auteur ; B. GLASER, Auteur ; S. MENGHETTI, Auteur ; M. SCHAER, Auteur ; S. ELIEZ, Auteur . - p.10. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.10 Mots-clés : 22q11.2 deletion syndrome  Adaptive functioning  Development  Executive functions Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder associated with a specific cognitive profile. Higher-order cognitive skills like executive functions (EF) are reported as a relative weakness in this population. The present study aimed to delineate the developmental trajectories of multiple EF domains in a longitudinal sample using a broader age range than previous studies. Given the high incidence of psychotic symptoms in 22q11.2DS, we also compared the development of EF in participants with/without comorbid psychotic symptoms. Given the importance of EF in daily life, the third aim of the study was to characterize the link between EF and adaptive functioning. METHODS: The sample consisted of 95 individuals with 22q11.2DS and 100 typically developing controls aged 6-26 years. A large proportion of the sample (55.38 %) had multiple time points available. Between-group differences in the developmental trajectories of three subdomains of EF (verbal fluency, working memory, and inhibition) were examined using mixed models regression analyses. Analyses were repeated comparing only the 22q11.2DS group based on the presence/absence of psychotic symptoms to investigate the influence of executive dysfunction on the emergence of psychotic symptoms. Hierarchical stepwise regression analyses were also conducted to investigate the predictive value of EF on adaptive functioning. RESULTS: We observed lower performance on EF domains, as well as atypical development of working memory and verbal fluency. Participants who presented with negative symptoms exhibited different developmental trajectories of inhibition and working memory. Adaptive functioning level was not significantly predicted by EF scores. CONCLUSIONS: The present study highlighted domain-specific atypical trajectories of EF in individuals with 22q11.DS and explored the link with psychotic symptoms. However, no relation between EF and adaptive functioning was observed. En ligne : http://dx.doi.org/10.1186/s11689-016-9141-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Array-based molecular karyotyping in fetuses with isolated brain malformations identifies disease-causing CNVs / M. SCHUMANN in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.11 Titre : Array-based molecular karyotyping in fetuses with isolated brain malformations identifies disease-causing CNVs Type de document : Texte imprimé et/ou numérique Auteurs : M. SCHUMANN, Auteur ; A. HOFMANN, Auteur ; S. K. KRUTZKE, Auteur ; A. C. HILGER, Auteur ; F. MARSCH, Auteur ; D. STIENEN, Auteur ; U. GEMBRUCH, Auteur ; M. LUDWIG, Auteur ; W. M. MERZ, Auteur ; H. REUTTER, Auteur Article en page(s) : p.11 Langues : Anglais (eng) Mots-clés : Array-based karyotyping  Brain malformation  Copy number variation (CNV)  De novo occurrence Index. décimale : PER Périodiques Résumé : BACKGROUND: The overall birth prevalence for congenital malformations of the central nervous system (CNS) among Europeans may be as high as 1 in 100 live births. The etiological factors remain largely unknown. The aim of this study was to detect causative copy number variations (CNVs) in fetuses of terminated pregnancies with prenatally detected isolated brain malformations. METHODS: Array-based molecular karyotyping was performed in a cohort of 35 terminated fetuses with isolated CNS malformations. Identified putative disease-causing CNVs were confirmed using quantitative polymerase chain reaction or multiplex ligation-dependent probe amplification. RESULTS: Based on their de novo occurrence and/or their established association with congenital brain malformations, we detected five disease-causing CNVs in four fetuses involving chromosomal regions 6p25.1-6p25.3 (FOXC1), 6q27, 16p12.3, Xp22.2-Xp22.32 (MID1), and Xp22.32-Xp22.33. Furthermore, we detected a probably disease-causing CNV involving chromosomal region 3p26.3 in one fetus, and in addition, we detected 12 CNVs in nine fetuses of unknown clinical significance. All CNVs except for two were absent in 1307 healthy in-house controls (frequency <0.0008). Each of the two CNVs present in in-house controls was present only once (frequency = 0.0008). Furthermore, our data suggests the involvement of CNTN6 and KLHL15 in the etiology of agenesis of the corpus callosum, the involvement of RASD1 and PTPRD in Dandy-Walker malformation, and the involvement of ERMARD in ventriculomegaly. CONCLUSIONS: Our study suggests that CNVs play an important role in the etiology of isolated brain malformations. En ligne : http://dx.doi.org/10.1186/s11689-016-9144-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Array-based molecular karyotyping in fetuses with isolated brain malformations identifies disease-causing CNVs [Texte imprimé et/ou numérique] / M. SCHUMANN, Auteur ; A. HOFMANN, Auteur ; S. K. KRUTZKE, Auteur ; A. C. HILGER, Auteur ; F. MARSCH, Auteur ; D. STIENEN, Auteur ; U. GEMBRUCH, Auteur ; M. LUDWIG, Auteur ; W. M. MERZ, Auteur ; H. REUTTER, Auteur . - p.11. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.11 Mots-clés : Array-based karyotyping  Brain malformation  Copy number variation (CNV)  De novo occurrence Index. décimale : PER Périodiques Résumé : BACKGROUND: The overall birth prevalence for congenital malformations of the central nervous system (CNS) among Europeans may be as high as 1 in 100 live births. The etiological factors remain largely unknown. The aim of this study was to detect causative copy number variations (CNVs) in fetuses of terminated pregnancies with prenatally detected isolated brain malformations. METHODS: Array-based molecular karyotyping was performed in a cohort of 35 terminated fetuses with isolated CNS malformations. Identified putative disease-causing CNVs were confirmed using quantitative polymerase chain reaction or multiplex ligation-dependent probe amplification. RESULTS: Based on their de novo occurrence and/or their established association with congenital brain malformations, we detected five disease-causing CNVs in four fetuses involving chromosomal regions 6p25.1-6p25.3 (FOXC1), 6q27, 16p12.3, Xp22.2-Xp22.32 (MID1), and Xp22.32-Xp22.33. Furthermore, we detected a probably disease-causing CNV involving chromosomal region 3p26.3 in one fetus, and in addition, we detected 12 CNVs in nine fetuses of unknown clinical significance. All CNVs except for two were absent in 1307 healthy in-house controls (frequency <0.0008). Each of the two CNVs present in in-house controls was present only once (frequency = 0.0008). Furthermore, our data suggests the involvement of CNTN6 and KLHL15 in the etiology of agenesis of the corpus callosum, the involvement of RASD1 and PTPRD in Dandy-Walker malformation, and the involvement of ERMARD in ventriculomegaly. CONCLUSIONS: Our study suggests that CNVs play an important role in the etiology of isolated brain malformations. En ligne : http://dx.doi.org/10.1186/s11689-016-9144-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update / A. THURM in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.12 Titre : Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update Type de document : Texte imprimé et/ou numérique Auteurs : A. THURM, Auteur ; E. TIERNEY, Auteur ; C. FARMER, Auteur ; P. ALBERT, Auteur ; L. JOSEPH, Auteur ; Susan E. SWEDO, Auteur ; S. BIANCONI, Auteur ; I. BUKELIS, Auteur ; C. WHEELER, Auteur ; G. SARPHARE, Auteur ; D. LANHAM, Auteur ; C. A. WASSIF, Auteur ; F. D. PORTER, Auteur Article en page(s) : p.12 Langues : Anglais (eng) Mots-clés : Autism  Developmental delay  Smith-Lemli-Opitz  Sterols Index. décimale : PER Périodiques Résumé : BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive inborn error of cholesterol metabolism syndrome with neurocognitive manifestations. SLOS is the result of mutations in the gene encoding the 7-dehydrocholesterol reductase, which results in the elevation of the cholesterol precursor 7-dehydrocholesterol (7-DHC). Previous reports indicate that intellectual disability, behavioral disturbances, and autism symptoms are frequently part of the SLOS behavioral phenotype. In the current study, we characterize the developmental history and current behavior of 33 individuals with SLOS aged 4 to 23 years and report on biomarkers 7-DHC and 8-DHC in relation to cognition and behavior. METHODS: This was an observational case series, wherein participants with SLOS underwent extensive behavioral evaluation of cognitive function, adaptive function, autism symptoms, and problem behaviors, in addition to parent report of developmental milestones. Serum and CSF were contemporaneously obtained from the majority of participants. RESULTS: Developmental milestones such as walking, talking, and toileting were uniformly delayed. Overall levels of cognitive and adaptive functioning were low; no participant received adaptive behavior scores in the average range, and the mean level of cognitive functioning in the full sample was in the moderate range of impairment. Aggressive behavior was present in nearly half of participants. Although the majority of participants had elevated scores on the gold standard autism diagnostic instruments, only about half of participants received a clinical diagnosis of autism spectrum disorder. Finally, while CSF cholesterol was not found to correlate with cognitive or adaptive functioning, both serum and CSF 7-DHC and 8-DHC (and their ratios with cholesterol) were moderately and negatively correlated with functioning in this group. CONCLUSIONS: A history of developmental delay, followed by intellectual disability, is common in individuals with SLOS. Although autism spectrum disorder appears to be a frequent diagnosis in this population, it is apparent that the low level of functioning observed in SLOS may artificially inflate scores on standard autism assessments. Our findings further support that cholesterol precursors 7-DHC and 8-DHC are important biomarkers of the level of functioning in SLOS, especially regarding cognitive abilities, and thus may be to explore as mediators within the context of treatment trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00001721, NCT00064792. En ligne : http://dx.doi.org/10.1186/s11689-016-9145-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update [Texte imprimé et/ou numérique] / A. THURM, Auteur ; E. TIERNEY, Auteur ; C. FARMER, Auteur ; P. ALBERT, Auteur ; L. JOSEPH, Auteur ; Susan E. SWEDO, Auteur ; S. BIANCONI, Auteur ; I. BUKELIS, Auteur ; C. WHEELER, Auteur ; G. SARPHARE, Auteur ; D. LANHAM, Auteur ; C. A. WASSIF, Auteur ; F. D. PORTER, Auteur . - p.12. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.12 Mots-clés : Autism  Developmental delay  Smith-Lemli-Opitz  Sterols Index. décimale : PER Périodiques Résumé : BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive inborn error of cholesterol metabolism syndrome with neurocognitive manifestations. SLOS is the result of mutations in the gene encoding the 7-dehydrocholesterol reductase, which results in the elevation of the cholesterol precursor 7-dehydrocholesterol (7-DHC). Previous reports indicate that intellectual disability, behavioral disturbances, and autism symptoms are frequently part of the SLOS behavioral phenotype. In the current study, we characterize the developmental history and current behavior of 33 individuals with SLOS aged 4 to 23 years and report on biomarkers 7-DHC and 8-DHC in relation to cognition and behavior. METHODS: This was an observational case series, wherein participants with SLOS underwent extensive behavioral evaluation of cognitive function, adaptive function, autism symptoms, and problem behaviors, in addition to parent report of developmental milestones. Serum and CSF were contemporaneously obtained from the majority of participants. RESULTS: Developmental milestones such as walking, talking, and toileting were uniformly delayed. Overall levels of cognitive and adaptive functioning were low; no participant received adaptive behavior scores in the average range, and the mean level of cognitive functioning in the full sample was in the moderate range of impairment. Aggressive behavior was present in nearly half of participants. Although the majority of participants had elevated scores on the gold standard autism diagnostic instruments, only about half of participants received a clinical diagnosis of autism spectrum disorder. Finally, while CSF cholesterol was not found to correlate with cognitive or adaptive functioning, both serum and CSF 7-DHC and 8-DHC (and their ratios with cholesterol) were moderately and negatively correlated with functioning in this group. CONCLUSIONS: A history of developmental delay, followed by intellectual disability, is common in individuals with SLOS. Although autism spectrum disorder appears to be a frequent diagnosis in this population, it is apparent that the low level of functioning observed in SLOS may artificially inflate scores on standard autism assessments. Our findings further support that cholesterol precursors 7-DHC and 8-DHC are important biomarkers of the level of functioning in SLOS, especially regarding cognitive abilities, and thus may be to explore as mediators within the context of treatment trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00001721, NCT00064792. En ligne : http://dx.doi.org/10.1186/s11689-016-9145-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

An investigation of NFXL1, a gene implicated in a study of specific language impairment / R. NUDEL in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.13 Titre : An investigation of NFXL1, a gene implicated in a study of specific language impairment Type de document : Texte imprimé et/ou numérique Auteurs : R. NUDEL, Auteur Article en page(s) : p.13 Langues : Anglais (eng) Mots-clés : Cerebellum  Language disorder  Nfxl1  Neurodevelopment  Neurogenetics  Specific language impairment  Transcription factor Index. décimale : PER Périodiques Résumé : BACKGROUND: A recent study identified NFXL1 as a candidate gene for specific language impairment. The protein encoded by this gene is predicted to be a transcription factor based on domain similarities with NFX1, a repressor of HLA class II genes, which have themselves been implicated in specific language impairment. However, there is very little literature on the function of NFXL1. METHODS: This report describes a study of NFXL1 expression in several human tissues and an investigation of differential expression in several specific brain regions through quantitative PCR as well as a study of the protein's sub-cellular localization in HEK cells and SH-SY5Y cells through immunofluorescence. RESULTS: The NFXL1 transcript was found in all investigated tissues. In the brain, a high level of NFXL1 expression was found in the cerebellum. An analysis of the sub-cellular localization of the protein showed a cytoplasmic pattern in the investigated cells. CONCLUSIONS: The NFXL1 transcript was present in samples from different tissues; in the brain, a high expression level was found in a region implicated in some language-related pathologies. NFXL1 did not show nuclear localization, suggesting that, if it regulates transcription, certain conditions may be required for it to translocate to the nucleus. En ligne : http://dx.doi.org/10.1186/s11689-016-9146-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] An investigation of NFXL1, a gene implicated in a study of specific language impairment [Texte imprimé et/ou numérique] / R. NUDEL, Auteur . - p.13. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.13 Mots-clés : Cerebellum  Language disorder  Nfxl1  Neurodevelopment  Neurogenetics  Specific language impairment  Transcription factor Index. décimale : PER Périodiques Résumé : BACKGROUND: A recent study identified NFXL1 as a candidate gene for specific language impairment. The protein encoded by this gene is predicted to be a transcription factor based on domain similarities with NFX1, a repressor of HLA class II genes, which have themselves been implicated in specific language impairment. However, there is very little literature on the function of NFXL1. METHODS: This report describes a study of NFXL1 expression in several human tissues and an investigation of differential expression in several specific brain regions through quantitative PCR as well as a study of the protein's sub-cellular localization in HEK cells and SH-SY5Y cells through immunofluorescence. RESULTS: The NFXL1 transcript was found in all investigated tissues. In the brain, a high level of NFXL1 expression was found in the cerebellum. An analysis of the sub-cellular localization of the protein showed a cytoplasmic pattern in the investigated cells. CONCLUSIONS: The NFXL1 transcript was present in samples from different tissues; in the brain, a high expression level was found in a region implicated in some language-related pathologies. NFXL1 did not show nuclear localization, suggesting that, if it regulates transcription, certain conditions may be required for it to translocate to the nucleus. En ligne : http://dx.doi.org/10.1186/s11689-016-9146-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus / D. SINCLAIR in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.14 Titre : Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus Type de document : Texte imprimé et/ou numérique Auteurs : D. SINCLAIR, Auteur ; J. CESARE, Auteur ; M. MCMULLEN, Auteur ; G. C. CARLSON, Auteur ; C. G. HAHN, Auteur ; K. E. BORGMANN-WINTER, Auteur Article en page(s) : p.14 Langues : Anglais (eng) Mots-clés : Cortex  Dtnbp1  Development  Dysbindin  GluN2B  Hippocampus  Nmda  Phosphorylation  Postsynaptic density  Sex difference Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia differentially impact males and females and are highly heritable. The ways in which sex and genetic vulnerability influence the pathogenesis of these disorders are not clearly understood. The n-methyl-d-aspartate (NMDA) receptor pathway has been implicated in schizophrenia and autism spectrum disorders and changes dramatically across postnatal development at the level of the GluN2B-GluN2A subunit "switch" (a shift from reliance on GluN2B-containing receptors to reliance on GluN2A-containing receptors). We investigated whether sex and genetic vulnerability (specifically, null mutation of DTNBP1 [dysbindin; a possible susceptibility gene for schizophrenia]) influence the developmental GluN2B-GluN2A switch. METHODS: Subcellular fractionation to enrich for postsynaptic density (PSD), together with Western blotting and kinase assay, were used to investigate the GluN2B-GluN2A switch in the cortex and hippocampus of male and female DTNBP1 null mutant mice and their wild-type littermates. Main effects of sex and DTNBP1 genotype, and interactions with age, were assessed using factorial ANOVA. RESULTS: Sex differences in the GluN2B-GluN2A switch emerged across development at the frontal cortical synapse, in parameters related to GluN2B. Males across genotypes displayed higher GluN2B:GluN2A and GluN2B:GluN1 ratios (p < 0.05 and p < 0.01, respectively), higher GluN2B phosphorylation at Y1472 (p < 0.01), and greater abundance of PLCgamma (p < 0.01) and Fyn (p = 0.055) relative to females. In contrast, effects of DTNBP1 were evident exclusively in the hippocampus. The developmental trajectory of GluN2B was disrupted in DTNBP1 null mice (genotype x age interaction p < 0.05), which also displayed an increased synaptic GluN2A:GluN1 ratio (p < 0.05) and decreased PLCgamma (p < 0.05) and Fyn (only in females; p < 0.0005) compared to wild-types. CONCLUSIONS: Sex and DTNBP1 mutation influence the GluN2B-GluN2A switch at the synapse in a brain-region-specific fashion involving pY1472-GluN2B, Fyn, and PLCgamma. This highlights the possible mechanisms through which risk factors may mediate their effects on vulnerability to disorders of NMDA receptor dysfunction. En ligne : http://dx.doi.org/10.1186/s11689-016-9148-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus [Texte imprimé et/ou numérique] / D. SINCLAIR, Auteur ; J. CESARE, Auteur ; M. MCMULLEN, Auteur ; G. C. CARLSON, Auteur ; C. G. HAHN, Auteur ; K. E. BORGMANN-WINTER, Auteur . - p.14. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.14 Mots-clés : Cortex  Dtnbp1  Development  Dysbindin  GluN2B  Hippocampus  Nmda  Phosphorylation  Postsynaptic density  Sex difference Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia differentially impact males and females and are highly heritable. The ways in which sex and genetic vulnerability influence the pathogenesis of these disorders are not clearly understood. The n-methyl-d-aspartate (NMDA) receptor pathway has been implicated in schizophrenia and autism spectrum disorders and changes dramatically across postnatal development at the level of the GluN2B-GluN2A subunit "switch" (a shift from reliance on GluN2B-containing receptors to reliance on GluN2A-containing receptors). We investigated whether sex and genetic vulnerability (specifically, null mutation of DTNBP1 [dysbindin; a possible susceptibility gene for schizophrenia]) influence the developmental GluN2B-GluN2A switch. METHODS: Subcellular fractionation to enrich for postsynaptic density (PSD), together with Western blotting and kinase assay, were used to investigate the GluN2B-GluN2A switch in the cortex and hippocampus of male and female DTNBP1 null mutant mice and their wild-type littermates. Main effects of sex and DTNBP1 genotype, and interactions with age, were assessed using factorial ANOVA. RESULTS: Sex differences in the GluN2B-GluN2A switch emerged across development at the frontal cortical synapse, in parameters related to GluN2B. Males across genotypes displayed higher GluN2B:GluN2A and GluN2B:GluN1 ratios (p < 0.05 and p < 0.01, respectively), higher GluN2B phosphorylation at Y1472 (p < 0.01), and greater abundance of PLCgamma (p < 0.01) and Fyn (p = 0.055) relative to females. In contrast, effects of DTNBP1 were evident exclusively in the hippocampus. The developmental trajectory of GluN2B was disrupted in DTNBP1 null mice (genotype x age interaction p < 0.05), which also displayed an increased synaptic GluN2A:GluN1 ratio (p < 0.05) and decreased PLCgamma (p < 0.05) and Fyn (only in females; p < 0.0005) compared to wild-types. CONCLUSIONS: Sex and DTNBP1 mutation influence the GluN2B-GluN2A switch at the synapse in a brain-region-specific fashion involving pY1472-GluN2B, Fyn, and PLCgamma. This highlights the possible mechanisms through which risk factors may mediate their effects on vulnerability to disorders of NMDA receptor dysfunction. En ligne : http://dx.doi.org/10.1186/s11689-016-9148-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

A functional neuroimaging study of fusiform response to restricted interests in children and adolescents with autism spectrum disorder / J. H. FOSS-FEIG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.15 Titre : A functional neuroimaging study of fusiform response to restricted interests in children and adolescents with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : J. H. FOSS-FEIG, Auteur ; R. W. MCGUGIN, Auteur ; I. GAUTHIER, Auteur ; L. E. MASH, Auteur ; Pamela VENTOLA, Auteur ; Carissa J. CASCIO, Auteur Article en page(s) : p.15 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Expertise  Fusiform face area  Fusiform gyrus  Restricted interests  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: While autism spectrum disorder (ASD) is characterized by both social communication deficits and restricted and repetitive patterns of behavior and interest, literature examining possible neural bases of the latter class of symptoms is limited. The fusiform face area (FFA) is a region in the ventral temporal cortex that not only shows preferential responsiveness to faces but also responds to non-face objects of visual expertise. Because restricted interests in ASD are accompanied by high levels of visual expertise, the objective of this study was to determine the extent to which this region responds to images related to restricted interests in individuals with ASD, compared to individuals without ASD who have a strong hobby or interest. METHODS: Children and adolescents with and without ASD with hobbies or interests that consumed a pre-determined minimum amount of time were identified, and the intensity, frequency, and degree of interference of these interests were quantified. Each participant underwent functional magnetic resonance imaging (fMRI) while viewing images related to their personal restricted interests (in the ASD group) or strong interest or hobby (in the comparison group). A generalized linear model was used to compare the intensity and spatial extent of fusiform gyrus response between groups, controlling for the appearance of faces in the stimuli. RESULTS: Images related to interests and expertise elicited response in FFA in both ASD and typically developing individuals, but this response was more robust in ASD. CONCLUSIONS: These findings add neurobiological support to behavioral observations that restricted interests are associated with enhanced visual expertise in ASD, above and beyond what would be expected for simply a strong interest. Further, the results suggest that brain regions associated with social functioning may not be inherently less responsive in ASD, but rather may be recruited by different environmental stimuli. This study contributes to our understanding of the neural basis of restricted interests in ASD and may provide clues toward developing novel interventions. En ligne : http://dx.doi.org/10.1186/s11689-016-9149-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] A functional neuroimaging study of fusiform response to restricted interests in children and adolescents with autism spectrum disorder [Texte imprimé et/ou numérique] / J. H. FOSS-FEIG, Auteur ; R. W. MCGUGIN, Auteur ; I. GAUTHIER, Auteur ; L. E. MASH, Auteur ; Pamela VENTOLA, Auteur ; Carissa J. CASCIO, Auteur . - p.15. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.15 Mots-clés : Autism spectrum disorder  Expertise  Fusiform face area  Fusiform gyrus  Restricted interests  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: While autism spectrum disorder (ASD) is characterized by both social communication deficits and restricted and repetitive patterns of behavior and interest, literature examining possible neural bases of the latter class of symptoms is limited. The fusiform face area (FFA) is a region in the ventral temporal cortex that not only shows preferential responsiveness to faces but also responds to non-face objects of visual expertise. Because restricted interests in ASD are accompanied by high levels of visual expertise, the objective of this study was to determine the extent to which this region responds to images related to restricted interests in individuals with ASD, compared to individuals without ASD who have a strong hobby or interest. METHODS: Children and adolescents with and without ASD with hobbies or interests that consumed a pre-determined minimum amount of time were identified, and the intensity, frequency, and degree of interference of these interests were quantified. Each participant underwent functional magnetic resonance imaging (fMRI) while viewing images related to their personal restricted interests (in the ASD group) or strong interest or hobby (in the comparison group). A generalized linear model was used to compare the intensity and spatial extent of fusiform gyrus response between groups, controlling for the appearance of faces in the stimuli. RESULTS: Images related to interests and expertise elicited response in FFA in both ASD and typically developing individuals, but this response was more robust in ASD. CONCLUSIONS: These findings add neurobiological support to behavioral observations that restricted interests are associated with enhanced visual expertise in ASD, above and beyond what would be expected for simply a strong interest. Further, the results suggest that brain regions associated with social functioning may not be inherently less responsive in ASD, but rather may be recruited by different environmental stimuli. This study contributes to our understanding of the neural basis of restricted interests in ASD and may provide clues toward developing novel interventions. En ligne : http://dx.doi.org/10.1186/s11689-016-9149-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Developmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome: a systematic and prospective study in 34 children / R. J. ZWANENBURG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.16 Titre : Developmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome: a systematic and prospective study in 34 children Type de document : Texte imprimé et/ou numérique Auteurs : R. J. ZWANENBURG, Auteur ; S. A. RUITER, Auteur ; E. R. VAN DEN HEUVEL, Auteur ; B. C. FLAPPER, Auteur ; C. M. VAN RAVENSWAAIJ-ARTS, Auteur Article en page(s) : p.16 Langues : Anglais (eng) Mots-clés : 22q13 deletion syndrome  Autism  Developmental phenotype  Intellectual disability  Neurodevelopmental disorders  Phelan-McDermid syndrome  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by global developmental delay, cognitive deficits, and behaviour in the autism spectrum. Knowledge about developmental and behavioural characteristics of this rare chromosomal disorder is still limited despite a rapid growing number of diagnoses. Our aim was to study a new and relatively large cohort to further characterize the developmental phenotype of children with PMS. METHODS: We performed a descriptive study of children with a 22q13.3 deletion including SHANK3, aged 8 to 178 months, who were systematically (n = 34) and longitudinally (n = 29) assessed with standardized instruments: Bayley Scales of Infant and Toddler Development, third edition; Wechsler Preschool and Primary Scale of Intelligence, third edition; and Vineland Screener for Social and Adaptive Behavior. RESULTS: Maximal developmental functioning ranged from 34 to 52 months depending on the developmental domain. In general, children performed poorest in the domain of language and best on the domain of motor (young children) or cognitive development (older children). At the individual level, 25 % scored better for receptive and 18 % for expressive language, whereas 22 % scored better for fine and 33 % for gross motor function. Developmental quotients were higher in younger children and decreased with age for all developmental domains, with 38 % of the children showing no improvement of cognitive developmental functioning. Almost all children (33/34) had significant deficits in adaptive behaviour. Children with very small deletions, covering only the SHANK3, ACR, and RABL2B genes, had a more favourable developmental phenotype. CONCLUSIONS: Cognitive, motor, and especially language development were significantly impaired in all children with PMS but also highly variable and unpredictable. In addition, deficits in adaptive behaviour further hampered their cognitive development. Therefore, cognitive and behavioural characteristics should be evaluated and followed in each child with PMS to adapt supportive and therapeutic strategies to individual needs. Further research evaluating the relationship between deletion characteristics and the developmental phenotype is warranted to improve counselling of parents. En ligne : http://dx.doi.org/10.1186/s11689-016-9150-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Developmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome: a systematic and prospective study in 34 children [Texte imprimé et/ou numérique] / R. J. ZWANENBURG, Auteur ; S. A. RUITER, Auteur ; E. R. VAN DEN HEUVEL, Auteur ; B. C. FLAPPER, Auteur ; C. M. VAN RAVENSWAAIJ-ARTS, Auteur . - p.16. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.16 Mots-clés : 22q13 deletion syndrome  Autism  Developmental phenotype  Intellectual disability  Neurodevelopmental disorders  Phelan-McDermid syndrome  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by global developmental delay, cognitive deficits, and behaviour in the autism spectrum. Knowledge about developmental and behavioural characteristics of this rare chromosomal disorder is still limited despite a rapid growing number of diagnoses. Our aim was to study a new and relatively large cohort to further characterize the developmental phenotype of children with PMS. METHODS: We performed a descriptive study of children with a 22q13.3 deletion including SHANK3, aged 8 to 178 months, who were systematically (n = 34) and longitudinally (n = 29) assessed with standardized instruments: Bayley Scales of Infant and Toddler Development, third edition; Wechsler Preschool and Primary Scale of Intelligence, third edition; and Vineland Screener for Social and Adaptive Behavior. RESULTS: Maximal developmental functioning ranged from 34 to 52 months depending on the developmental domain. In general, children performed poorest in the domain of language and best on the domain of motor (young children) or cognitive development (older children). At the individual level, 25 % scored better for receptive and 18 % for expressive language, whereas 22 % scored better for fine and 33 % for gross motor function. Developmental quotients were higher in younger children and decreased with age for all developmental domains, with 38 % of the children showing no improvement of cognitive developmental functioning. Almost all children (33/34) had significant deficits in adaptive behaviour. Children with very small deletions, covering only the SHANK3, ACR, and RABL2B genes, had a more favourable developmental phenotype. CONCLUSIONS: Cognitive, motor, and especially language development were significantly impaired in all children with PMS but also highly variable and unpredictable. In addition, deficits in adaptive behaviour further hampered their cognitive development. Therefore, cognitive and behavioural characteristics should be evaluated and followed in each child with PMS to adapt supportive and therapeutic strategies to individual needs. Further research evaluating the relationship between deletion characteristics and the developmental phenotype is warranted to improve counselling of parents. En ligne : http://dx.doi.org/10.1186/s11689-016-9150-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Investigating the effects of copy number variants on reading and language performance / A. GIALLUISI in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.17 Titre : Investigating the effects of copy number variants on reading and language performance Type de document : Texte imprimé et/ou numérique Auteurs : A. GIALLUISI, Auteur ; A. VISCONTI, Auteur ; E. G. WILLCUTT, Auteur ; S. D. SMITH, Auteur ; B. F. PENNINGTON, Auteur ; M. FALCHI, Auteur ; J. C. DEFRIES, Auteur ; R. K. OLSON, Auteur ; C. FRANCKS, Auteur ; S. E. FISHER, Auteur Article en page(s) : p.17 Langues : Anglais (eng) Mots-clés : Cldrc  Copy number variants  Developmental dyslexia  Family-based GWAS  Language  Meta-analysis  Reading  Reading disability Index. décimale : PER Périodiques Résumé : BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV. RESULTS: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10(-2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls. CONCLUSIONS: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language. En ligne : http://dx.doi.org/10.1186/s11689-016-9147-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Investigating the effects of copy number variants on reading and language performance [Texte imprimé et/ou numérique] / A. GIALLUISI, Auteur ; A. VISCONTI, Auteur ; E. G. WILLCUTT, Auteur ; S. D. SMITH, Auteur ; B. F. PENNINGTON, Auteur ; M. FALCHI, Auteur ; J. C. DEFRIES, Auteur ; R. K. OLSON, Auteur ; C. FRANCKS, Auteur ; S. E. FISHER, Auteur . - p.17. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.17 Mots-clés : Cldrc  Copy number variants  Developmental dyslexia  Family-based GWAS  Language  Meta-analysis  Reading  Reading disability Index. décimale : PER Périodiques Résumé : BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV. RESULTS: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10(-2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls. CONCLUSIONS: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language. En ligne : http://dx.doi.org/10.1186/s11689-016-9147-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects / C. LINTAS in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.18 Titre : Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects Type de document : Texte imprimé et/ou numérique Auteurs : C. LINTAS, Auteur ; R. SACCO, Auteur ; A. M. PERSICO, Auteur Article en page(s) : p.18 Langues : Anglais (eng) Mots-clés : Autism  DNA methylation  Epigenetics  Post-mortem brains  Reelin Index. décimale : PER Périodiques Résumé : BACKGROUND: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. METHODS: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. RESULTS: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5' region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3' promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. CONCLUSIONS: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression. En ligne : http://dx.doi.org/10.1186/s11689-016-9151-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects [Texte imprimé et/ou numérique] / C. LINTAS, Auteur ; R. SACCO, Auteur ; A. M. PERSICO, Auteur . - p.18. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.18 Mots-clés : Autism  DNA methylation  Epigenetics  Post-mortem brains  Reelin Index. décimale : PER Périodiques Résumé : BACKGROUND: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. METHODS: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. RESULTS: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5' region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3' promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. CONCLUSIONS: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression. En ligne : http://dx.doi.org/10.1186/s11689-016-9151-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome / C. DISTEFANO in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.19 Titre : Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome Type de document : Texte imprimé et/ou numérique Auteurs : C. DISTEFANO, Auteur ; A. GULSRUD, Auteur ; S. HUBERTY, Auteur ; Connie KASARI, Auteur ; E. COOK, Auteur ; L. T. REITER, Auteur ; R. THIBERT, Auteur ; S. S. JESTE, Auteur Article en page(s) : p.19 Langues : Anglais (eng) Mots-clés : Adaptive functioning  Autism spectrum disorder  Duplication 15q syndrome  Intellectual disability  Social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: One of the most common genetic variants associated with autism spectrum disorder (ASD) are duplications of chromosome 15q11.2-q13.1 (Dup15q syndrome). To identify distinctive developmental and behavioral features in Dup15q syndrome, we examined the social communication, adaptive, and cognitive skills in clinic-referred subjects and compared the characteristics of children with Dup15q syndrome to age/IQ-matched children with non-syndromic ASD. Behavior and development were also analyzed within the Dup15q group for differences related to copy number or epilepsy. METHODS: Participants included 13 children with Dup15q syndrome and 13 children with non-syndromic ASD, matched on chronological and mental age, ages 22 months-12 years. In the Dup15q group, ten participants had isodicentric and three had interstitial duplications. Four children had active epilepsy (all isodicentric). Participants were assessed for verbal and non-verbal cognition, ASD characteristics based on the Autism Diagnostic Observation Schedule (ADOS), and adaptive function based on the Vineland Adaptive Behavior Scales (VABS). Group comparisons were performed between Dup15q and ASD participants, as well as within the Dup15q group based on duplication type and epilepsy status. RESULTS: All children with Dup15q syndrome met the criteria for ASD; ASD severity scores were significantly lower than children in the non-syndromic ASD group. ADOS profiles demonstrated a relative strength in items related to social interest. Children with Dup15q syndrome also demonstrated significantly more impairment in motor and daily living skills. Within the Dup15q group, children with epilepsy demonstrated significantly lower cognitive and adaptive function than those without epilepsy. CONCLUSIONS: The relative strength observed in social interest and responsiveness in the context of impaired motor skills represents an important avenue for intervention, including aggressive treatment of epilepsy, early and consistent focus on motor skills, and intervention targeting joint attention and language within a play context, in order to build on social interest to further develop social communication abilities. Longitudinal research beginning in early development will elucidate the temporal relationships between developmental domains and neurological comorbidities in these children at high risk for neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/s11689-016-9152-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome [Texte imprimé et/ou numérique] / C. DISTEFANO, Auteur ; A. GULSRUD, Auteur ; S. HUBERTY, Auteur ; Connie KASARI, Auteur ; E. COOK, Auteur ; L. T. REITER, Auteur ; R. THIBERT, Auteur ; S. S. JESTE, Auteur . - p.19. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.19 Mots-clés : Adaptive functioning  Autism spectrum disorder  Duplication 15q syndrome  Intellectual disability  Social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: One of the most common genetic variants associated with autism spectrum disorder (ASD) are duplications of chromosome 15q11.2-q13.1 (Dup15q syndrome). To identify distinctive developmental and behavioral features in Dup15q syndrome, we examined the social communication, adaptive, and cognitive skills in clinic-referred subjects and compared the characteristics of children with Dup15q syndrome to age/IQ-matched children with non-syndromic ASD. Behavior and development were also analyzed within the Dup15q group for differences related to copy number or epilepsy. METHODS: Participants included 13 children with Dup15q syndrome and 13 children with non-syndromic ASD, matched on chronological and mental age, ages 22 months-12 years. In the Dup15q group, ten participants had isodicentric and three had interstitial duplications. Four children had active epilepsy (all isodicentric). Participants were assessed for verbal and non-verbal cognition, ASD characteristics based on the Autism Diagnostic Observation Schedule (ADOS), and adaptive function based on the Vineland Adaptive Behavior Scales (VABS). Group comparisons were performed between Dup15q and ASD participants, as well as within the Dup15q group based on duplication type and epilepsy status. RESULTS: All children with Dup15q syndrome met the criteria for ASD; ASD severity scores were significantly lower than children in the non-syndromic ASD group. ADOS profiles demonstrated a relative strength in items related to social interest. Children with Dup15q syndrome also demonstrated significantly more impairment in motor and daily living skills. Within the Dup15q group, children with epilepsy demonstrated significantly lower cognitive and adaptive function than those without epilepsy. CONCLUSIONS: The relative strength observed in social interest and responsiveness in the context of impaired motor skills represents an important avenue for intervention, including aggressive treatment of epilepsy, early and consistent focus on motor skills, and intervention targeting joint attention and language within a play context, in order to build on social interest to further develop social communication abilities. Longitudinal research beginning in early development will elucidate the temporal relationships between developmental domains and neurological comorbidities in these children at high risk for neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/s11689-016-9152-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Methods for acquiring MRI data in children with autism spectrum disorder and intellectual impairment without the use of sedation / Christine W. NORDAHL in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.20 Titre : Methods for acquiring MRI data in children with autism spectrum disorder and intellectual impairment without the use of sedation Type de document : Texte imprimé et/ou numérique Auteurs : Christine W. NORDAHL, Auteur ; M. MELLO, Auteur ; A. M. SHEN, Auteur ; M. D. SHEN, Auteur ; Laurie A. VISMARA, Auteur ; D. LI, Auteur ; K. HARRINGTON, Auteur ; C. TANASE, Auteur ; Beth GOODLIN-JONES, Auteur ; S. ROGERS, Auteur ; Leonard ABBEDUTO, Auteur ; David G. AMARAL, Auteur Article en page(s) : p.20 Langues : Anglais (eng) Mots-clés : Applied behavior analysis  Brain  Compliance  Intellectual disability  Low-functioning autism  Mri  Neurodevelopment Index. décimale : PER Périodiques Résumé : BACKGROUND: Magnetic resonance imaging (MRI) has been widely used in studies evaluating the neuropathology of autism spectrum disorder (ASD). Studies are often limited, however, to higher functioning individuals with ASD. MRI studies of individuals with ASD and comorbid intellectual disability (ID) are lacking, due in part to the challenges of acquiring images without the use of sedation. METHODS: Utilizing principles of applied behavior analysis (ABA), we developed a protocol for acquiring structural MRI scans in school-aged children with ASD and intellectual impairment. Board certified behavior analysts worked closely with each child and their parent(s), utilizing behavior change techniques such as pairing, shaping, desensitization, and positive reinforcement, through a series of mock scanner visits to prepare the child for the MRI scan. An objective, quantitative assessment of motion artifact in T1- and diffusion-weighted scans was implemented to ensure that high-quality images were acquired. RESULTS: The sample consisted of 17 children with ASD who are participants in the UC Davis Autism Phenome Project, a longitudinal MRI study aimed at evaluating brain developmental trajectories from early to middle childhood. At the time of their initial scan (2-3.5 years), all 17 children had a diagnosis of ASD and development quotient (DQ) <70. At the time of the current scan (9-13 years), 13 participants continued to have IQs in the range of ID (mean IQ = 54.1, sd = 12.1), and four participants had IQs in the normal range (mean = 102.2, sd = 7.5). The success rate in acquiring T1-weighted images that met quality assurance for acceptable motion artifact was 100 %. The success rate for acquiring high-quality diffusion-weighted images was 94 %. CONCLUSIONS: By using principles of ABA in a research MRI setting, it is feasible to acquire high-quality images in school-aged children with ASD and intellectual impairment without the use of sedation. This is especially critical to ensure that ongoing longitudinal studies of brain development can extend from infancy and early childhood into middle childhood in children with ASD at all levels of functioning, including those with comorbid ID. En ligne : http://dx.doi.org/10.1186/s11689-016-9154-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Methods for acquiring MRI data in children with autism spectrum disorder and intellectual impairment without the use of sedation [Texte imprimé et/ou numérique] / Christine W. NORDAHL, Auteur ; M. MELLO, Auteur ; A. M. SHEN, Auteur ; M. D. SHEN, Auteur ; Laurie A. VISMARA, Auteur ; D. LI, Auteur ; K. HARRINGTON, Auteur ; C. TANASE, Auteur ; Beth GOODLIN-JONES, Auteur ; S. ROGERS, Auteur ; Leonard ABBEDUTO, Auteur ; David G. AMARAL, Auteur . - p.20. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.20 Mots-clés : Applied behavior analysis  Brain  Compliance  Intellectual disability  Low-functioning autism  Mri  Neurodevelopment Index. décimale : PER Périodiques Résumé : BACKGROUND: Magnetic resonance imaging (MRI) has been widely used in studies evaluating the neuropathology of autism spectrum disorder (ASD). Studies are often limited, however, to higher functioning individuals with ASD. MRI studies of individuals with ASD and comorbid intellectual disability (ID) are lacking, due in part to the challenges of acquiring images without the use of sedation. METHODS: Utilizing principles of applied behavior analysis (ABA), we developed a protocol for acquiring structural MRI scans in school-aged children with ASD and intellectual impairment. Board certified behavior analysts worked closely with each child and their parent(s), utilizing behavior change techniques such as pairing, shaping, desensitization, and positive reinforcement, through a series of mock scanner visits to prepare the child for the MRI scan. An objective, quantitative assessment of motion artifact in T1- and diffusion-weighted scans was implemented to ensure that high-quality images were acquired. RESULTS: The sample consisted of 17 children with ASD who are participants in the UC Davis Autism Phenome Project, a longitudinal MRI study aimed at evaluating brain developmental trajectories from early to middle childhood. At the time of their initial scan (2-3.5 years), all 17 children had a diagnosis of ASD and development quotient (DQ) <70. At the time of the current scan (9-13 years), 13 participants continued to have IQs in the range of ID (mean IQ = 54.1, sd = 12.1), and four participants had IQs in the normal range (mean = 102.2, sd = 7.5). The success rate in acquiring T1-weighted images that met quality assurance for acceptable motion artifact was 100 %. The success rate for acquiring high-quality diffusion-weighted images was 94 %. CONCLUSIONS: By using principles of ABA in a research MRI setting, it is feasible to acquire high-quality images in school-aged children with ASD and intellectual impairment without the use of sedation. This is especially critical to ensure that ongoing longitudinal studies of brain development can extend from infancy and early childhood into middle childhood in children with ASD at all levels of functioning, including those with comorbid ID. En ligne : http://dx.doi.org/10.1186/s11689-016-9154-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: a prospective cohort study of risk markers / C. RICHARDS in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.21 Titre : Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: a prospective cohort study of risk markers Type de document : Texte imprimé et/ou numérique Auteurs : C. RICHARDS, Auteur ; J. MOSS, Auteur ; L. NELSON, Auteur ; C. OLIVER, Auteur Article en page(s) : p.21 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Hyperactivity  Impulsivity  Pain  Prevalence  Risk marker  Self-injury Index. décimale : PER Périodiques Résumé : BACKGROUND: There are few studies documenting the persistence of self-injury in individuals with autism spectrum disorder (ASD) and consequently limited data on behavioural and demographic characteristics associated with persistence. In this longitudinal study, we investigated self-injury in a cohort of individuals with ASD over 3 years to identify behavioural and demographic characteristics associated with persistence. METHODS: Carers of 67 individuals with ASD (Median age of individuals with ASD in years = 13.5, Interquartile Range = 10.00-17.00), completed questionnaires relating to the presence and topography of self-injury at T1 and three years later at T2. Analyses were conducted to evaluate the persistence of self-injury and to evaluate the behavioural and demographic characteristics associated with persistence of self-injury. RESULTS: At T2 self-injurious behaviour had persisted in 77.8 % of individuals. Behavioural correlates of being non-verbal, having lower ability and higher levels of overactivity, impulsivity and repetitive behaviour, were associated with self-injury at both time points. Risk markers of impulsivity (p = 0.021) and deficits in social interaction (p = 0.026) at T1 were associated with the persistence of self-injury over 3 years. CONCLUSIONS: Impulsivity and deficits in social interaction are associated with persistent self-injury in ASD and thus may act as behavioural risk markers. The identification of these risk markers evidences a role for behaviour dysregulation in the development and maintenance of self-injury. The findings have clinical implications for proactive intervention; these behavioural characteristics may be utilised to identify 'at risk' individuals for whom self-injury is likely to be persistent and therefore those individuals for whom early intervention may be most warranted. En ligne : http://dx.doi.org/10.1186/s11689-016-9153-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: a prospective cohort study of risk markers [Texte imprimé et/ou numérique] / C. RICHARDS, Auteur ; J. MOSS, Auteur ; L. NELSON, Auteur ; C. OLIVER, Auteur . - p.21. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.21 Mots-clés : Autism spectrum disorder  Hyperactivity  Impulsivity  Pain  Prevalence  Risk marker  Self-injury Index. décimale : PER Périodiques Résumé : BACKGROUND: There are few studies documenting the persistence of self-injury in individuals with autism spectrum disorder (ASD) and consequently limited data on behavioural and demographic characteristics associated with persistence. In this longitudinal study, we investigated self-injury in a cohort of individuals with ASD over 3 years to identify behavioural and demographic characteristics associated with persistence. METHODS: Carers of 67 individuals with ASD (Median age of individuals with ASD in years = 13.5, Interquartile Range = 10.00-17.00), completed questionnaires relating to the presence and topography of self-injury at T1 and three years later at T2. Analyses were conducted to evaluate the persistence of self-injury and to evaluate the behavioural and demographic characteristics associated with persistence of self-injury. RESULTS: At T2 self-injurious behaviour had persisted in 77.8 % of individuals. Behavioural correlates of being non-verbal, having lower ability and higher levels of overactivity, impulsivity and repetitive behaviour, were associated with self-injury at both time points. Risk markers of impulsivity (p = 0.021) and deficits in social interaction (p = 0.026) at T1 were associated with the persistence of self-injury over 3 years. CONCLUSIONS: Impulsivity and deficits in social interaction are associated with persistent self-injury in ASD and thus may act as behavioural risk markers. The identification of these risk markers evidences a role for behaviour dysregulation in the development and maintenance of self-injury. The findings have clinical implications for proactive intervention; these behavioural characteristics may be utilised to identify 'at risk' individuals for whom self-injury is likely to be persistent and therefore those individuals for whom early intervention may be most warranted. En ligne : http://dx.doi.org/10.1186/s11689-016-9153-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Complexities of X chromosome inactivation status in female human induced pluripotent stem cells-a brief review and scientific update for autism research / M. G. DANDULAKIS in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.22 Titre : Complexities of X chromosome inactivation status in female human induced pluripotent stem cells-a brief review and scientific update for autism research Type de document : Texte imprimé et/ou numérique Auteurs : M. G. DANDULAKIS, Auteur ; K. MEGANATHAN, Auteur ; K. L. KROLL, Auteur ; A. BONNI, Auteur ; John N. CONSTANTINO, Auteur Article en page(s) : p.22 Langues : Anglais (eng) Mots-clés : Asd  Autism  Developmental disorders  X chromosome  X-inactivation  X-linked ASD  X-reactivation  iPSC  "Female protective effect" Index. décimale : PER Périodiques Résumé : Induced pluripotent stem cells (iPSCs) allow researchers to make customized patient-derived cell lines by reprogramming noninvasively retrieved somatic cells. These cell lines have the potential to faithfully represent an individual's genetic background; therefore, in the absence of available human brain tissue from a living patient, these models have a significant advantage relative to other models of neurodevelopmental disease. When using human induced pluripotent stem cells (hiPSCs) to model X-linked developmental disorders or inherited conditions that undergo sex-specific modulation of penetrance (e.g., autism spectrum disorders), there are significant complexities in the course and status of X chromosome inactivation (XCI) that are crucial to consider in establishing the validity of cellular models. There are major gaps and inconsistencies in the existing literature regarding XCI status during the derivation and maintenance of hiPSCs and their differentiation into neurons. Here, we briefly describe the importance of the problem, review the findings and inconsistencies of the existing literature, delineate options for specifying XCI status in clonal populations, and develop recommendations for future studies. En ligne : http://dx.doi.org/10.1186/s11689-016-9155-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Complexities of X chromosome inactivation status in female human induced pluripotent stem cells-a brief review and scientific update for autism research [Texte imprimé et/ou numérique] / M. G. DANDULAKIS, Auteur ; K. MEGANATHAN, Auteur ; K. L. KROLL, Auteur ; A. BONNI, Auteur ; John N. CONSTANTINO, Auteur . - p.22. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.22 Mots-clés : Asd  Autism  Developmental disorders  X chromosome  X-inactivation  X-linked ASD  X-reactivation  iPSC  "Female protective effect" Index. décimale : PER Périodiques Résumé : Induced pluripotent stem cells (iPSCs) allow researchers to make customized patient-derived cell lines by reprogramming noninvasively retrieved somatic cells. These cell lines have the potential to faithfully represent an individual's genetic background; therefore, in the absence of available human brain tissue from a living patient, these models have a significant advantage relative to other models of neurodevelopmental disease. When using human induced pluripotent stem cells (hiPSCs) to model X-linked developmental disorders or inherited conditions that undergo sex-specific modulation of penetrance (e.g., autism spectrum disorders), there are significant complexities in the course and status of X chromosome inactivation (XCI) that are crucial to consider in establishing the validity of cellular models. There are major gaps and inconsistencies in the existing literature regarding XCI status during the derivation and maintenance of hiPSCs and their differentiation into neurons. Here, we briefly describe the importance of the problem, review the findings and inconsistencies of the existing literature, delineate options for specifying XCI status in clonal populations, and develop recommendations for future studies. En ligne : http://dx.doi.org/10.1186/s11689-016-9155-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats / Y. WU in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.23 Titre : Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats Type de document : Texte imprimé et/ou numérique Auteurs : Y. WU, Auteur ; W. ZHONG, Auteur ; N. CUI, Auteur ; C. M. JOHNSON, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur Article en page(s) : p.23 Langues : Anglais (eng) Mots-clés : Behaviors  Breathing  Locus coeruleus  Mecp2-null rat  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species. Therefore, we performed these studies to characterize phenotypes of a novel Mecp2 (-/Y) rat model and compared them with the Mecp2 (tm1.1Bird) mouse model of RTT. METHODS: RTT-like phenotypes were systematically studied and compared between Mecp2 (-/Y) rats and Mecp2 (-/Y) mice. In-cage conditions of the rats were monitored. Grip strength and spontaneous locomotion were used to evaluate the motor function. Three-chamber test was performed to show autism-type behaviors. Breathing activity was recorded with the plethysmograph. Individual neurons in the locus coeruleus (LC) were studied in the whole-cell current clamp. The lifespan of the rats was determined with their survival time. RESULTS: Mecp2 (-/Y) rats displayed growth retardation, malocclusion, and lack of movements, while hindlimb clasping was not seen. They had weaker forelimb grip strength and a lower rate of locomotion than the WT littermates. Defects in social interaction with other rats were obvious. Breathing frequency variation and apnea in the null rats were significantly higher than in the WT. LC neurons in the null rats showed excessive firing activity. A half of the null rats died in 2 months. Most of the RTT-like symptoms were comparable to those seen in Mecp2 (-/Y) mice, while some appeared more or less severe. The findings that most RTT-like symptoms exist in the rat model with moderate variations and differences from the mouse models support the usefulness of both Mecp2 (-/Y) rodent models. CONCLUSIONS: The novel Mecp2 (-/Y) rat model recapitulated numerous RTT-like symptoms as Mecp2 (-/Y) mouse models did, which makes it a valuable alternative model in the RTT studies when the body size matters. En ligne : http://dx.doi.org/10.1186/s11689-016-9156-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats [Texte imprimé et/ou numérique] / Y. WU, Auteur ; W. ZHONG, Auteur ; N. CUI, Auteur ; C. M. JOHNSON, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur . - p.23. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.23 Mots-clés : Behaviors  Breathing  Locus coeruleus  Mecp2-null rat  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species. Therefore, we performed these studies to characterize phenotypes of a novel Mecp2 (-/Y) rat model and compared them with the Mecp2 (tm1.1Bird) mouse model of RTT. METHODS: RTT-like phenotypes were systematically studied and compared between Mecp2 (-/Y) rats and Mecp2 (-/Y) mice. In-cage conditions of the rats were monitored. Grip strength and spontaneous locomotion were used to evaluate the motor function. Three-chamber test was performed to show autism-type behaviors. Breathing activity was recorded with the plethysmograph. Individual neurons in the locus coeruleus (LC) were studied in the whole-cell current clamp. The lifespan of the rats was determined with their survival time. RESULTS: Mecp2 (-/Y) rats displayed growth retardation, malocclusion, and lack of movements, while hindlimb clasping was not seen. They had weaker forelimb grip strength and a lower rate of locomotion than the WT littermates. Defects in social interaction with other rats were obvious. Breathing frequency variation and apnea in the null rats were significantly higher than in the WT. LC neurons in the null rats showed excessive firing activity. A half of the null rats died in 2 months. Most of the RTT-like symptoms were comparable to those seen in Mecp2 (-/Y) mice, while some appeared more or less severe. The findings that most RTT-like symptoms exist in the rat model with moderate variations and differences from the mouse models support the usefulness of both Mecp2 (-/Y) rodent models. CONCLUSIONS: The novel Mecp2 (-/Y) rat model recapitulated numerous RTT-like symptoms as Mecp2 (-/Y) mouse models did, which makes it a valuable alternative model in the RTT studies when the body size matters. En ligne : http://dx.doi.org/10.1186/s11689-016-9156-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes / K. A. PETTIGREW in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.24 Titre : Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes Type de document : Texte imprimé et/ou numérique Auteurs : K. A. PETTIGREW, Auteur ; E. FRINTON, Auteur ; R. NUDEL, Auteur ; M. T. M. CHAN, Auteur ; P. THOMPSON, Auteur ; M. E. HAYIOU-THOMAS, Auteur ; J. B. TALCOTT, Auteur ; J. STEIN, Auteur ; A. P. MONACO, Auteur ; C. HULME, Auteur ; M. J. SNOWLING, Auteur ; D. F. NEWBURY, Auteur ; S. PARACCHINI, Auteur Article en page(s) : p.24 Langues : Anglais (eng) Mots-clés : Candidate gene  Dyslexia  Genetic association  Language impairment  Parent-of-origin Index. décimale : PER Périodiques Résumé : BACKGROUND: Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5-10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. METHODS: We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. RESULTS: We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. CONCLUSIONS: A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits. En ligne : http://dx.doi.org/10.1186/s11689-016-9157-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes [Texte imprimé et/ou numérique] / K. A. PETTIGREW, Auteur ; E. FRINTON, Auteur ; R. NUDEL, Auteur ; M. T. M. CHAN, Auteur ; P. THOMPSON, Auteur ; M. E. HAYIOU-THOMAS, Auteur ; J. B. TALCOTT, Auteur ; J. STEIN, Auteur ; A. P. MONACO, Auteur ; C. HULME, Auteur ; M. J. SNOWLING, Auteur ; D. F. NEWBURY, Auteur ; S. PARACCHINI, Auteur . - p.24. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.24 Mots-clés : Candidate gene  Dyslexia  Genetic association  Language impairment  Parent-of-origin Index. décimale : PER Périodiques Résumé : BACKGROUND: Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5-10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. METHODS: We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. RESULTS: We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. CONCLUSIONS: A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits. En ligne : http://dx.doi.org/10.1186/s11689-016-9157-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Neural correlates of reward processing in adults with 22q11 deletion syndrome / E. D. A. VAN DUIN in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.25 Titre : Neural correlates of reward processing in adults with 22q11 deletion syndrome Type de document : Texte imprimé et/ou numérique Auteurs : E. D. A. VAN DUIN, Auteur ; L. GOOSSENS, Auteur ; D. HERNAUS, Auteur ; F. DA SILVA ALVES, Auteur ; N. SCHMITZ, Auteur ; K. SCHRUERS, Auteur ; T. VAN AMELSVOORT, Auteur Article en page(s) : p.25 Langues : Anglais (eng) Mots-clés : 22q11 deletion syndrome  Comt  Psychosis  Reward Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS. METHODS: This study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8. RESULTS: During anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found. During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate. Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate. CONCLUSIONS: This is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS engage a fronto-temporal neural network. Compared to healthy controls, people with 22q11DS primarily displayed reduced activity in medial frontal regions during reward anticipation. COMT hemizygosity affects responsivity of the reward system in this condition. Alterations in reward processing partly underlain by the dopamine system may play a role in susceptibility for psychosis in 22q11DS. En ligne : http://dx.doi.org/10.1186/s11689-016-9158-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Neural correlates of reward processing in adults with 22q11 deletion syndrome [Texte imprimé et/ou numérique] / E. D. A. VAN DUIN, Auteur ; L. GOOSSENS, Auteur ; D. HERNAUS, Auteur ; F. DA SILVA ALVES, Auteur ; N. SCHMITZ, Auteur ; K. SCHRUERS, Auteur ; T. VAN AMELSVOORT, Auteur . - p.25. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.25 Mots-clés : 22q11 deletion syndrome  Comt  Psychosis  Reward Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS. METHODS: This study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8. RESULTS: During anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found. During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate. Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate. CONCLUSIONS: This is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS engage a fronto-temporal neural network. Compared to healthy controls, people with 22q11DS primarily displayed reduced activity in medial frontal regions during reward anticipation. COMT hemizygosity affects responsivity of the reward system in this condition. Alterations in reward processing partly underlain by the dopamine system may play a role in susceptibility for psychosis in 22q11DS. En ligne : http://dx.doi.org/10.1186/s11689-016-9158-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Sex bias in autism spectrum disorder in neurofibromatosis type 1 / S. GARG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.26 Titre : Sex bias in autism spectrum disorder in neurofibromatosis type 1 Type de document : Texte imprimé et/ou numérique Auteurs : S. GARG, Auteur ; Hein HEUVELMAN, Auteur ; S. HUSON, Auteur ; H. TOBIN, Auteur ; J. GREEN, Auteur Article en page(s) : p.26 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Neurofibromatosis type 1  Sex bias  Syndromic autism Index. décimale : PER Périodiques Résumé : BACKGROUND: Despite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis type 1, a single-gene model of syndromic autism. METHODS: We analysed data from n = 194 children aged 4-16 years with neurofibromatosis type 1. Sex differences were evaluated across the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), verbal IQ, Social Responsiveness Scale (SRS) and Conners questionnaires. RESULTS: There was 2.68:1 male:female ratio in children meeting ASD criteria on the deep phenotyping measures. On symptom profile, males with neurofibromatosis type 1 (NF1) + ASD were more impaired on reciprocal social interaction and communication domains of the ADI-R but we found no differences on the restricted, repetitive behaviours (RRBs) domain of the ADI-R and no differences on the social on the ADOS. NF1 ASD males and females were comparable on verbal IQ, and the inattention/hyperactivity domains of the Conners questionnaire. CONCLUSIONS: There is a significant male bias in the prevalence of ASD in NF1. The phenotypic profile of NF1 + ASD cases includes greater social communication impairment in males. We discuss the implications of our findings and the rationale for using NF1 as a model for investigating sex bias in idiopathic ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9159-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Sex bias in autism spectrum disorder in neurofibromatosis type 1 [Texte imprimé et/ou numérique] / S. GARG, Auteur ; Hein HEUVELMAN, Auteur ; S. HUSON, Auteur ; H. TOBIN, Auteur ; J. GREEN, Auteur . - p.26. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.26 Mots-clés : Autism spectrum disorder  Neurofibromatosis type 1  Sex bias  Syndromic autism Index. décimale : PER Périodiques Résumé : BACKGROUND: Despite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis type 1, a single-gene model of syndromic autism. METHODS: We analysed data from n = 194 children aged 4-16 years with neurofibromatosis type 1. Sex differences were evaluated across the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), verbal IQ, Social Responsiveness Scale (SRS) and Conners questionnaires. RESULTS: There was 2.68:1 male:female ratio in children meeting ASD criteria on the deep phenotyping measures. On symptom profile, males with neurofibromatosis type 1 (NF1) + ASD were more impaired on reciprocal social interaction and communication domains of the ADI-R but we found no differences on the restricted, repetitive behaviours (RRBs) domain of the ADI-R and no differences on the social on the ADOS. NF1 ASD males and females were comparable on verbal IQ, and the inattention/hyperactivity domains of the Conners questionnaire. CONCLUSIONS: There is a significant male bias in the prevalence of ASD in NF1. The phenotypic profile of NF1 + ASD cases includes greater social communication impairment in males. We discuss the implications of our findings and the rationale for using NF1 as a model for investigating sex bias in idiopathic ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9159-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

A quantitative measure of restricted and repetitive behaviors for early childhood / J. J. WOLFF in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.27 Titre : A quantitative measure of restricted and repetitive behaviors for early childhood Type de document : Texte imprimé et/ou numérique Auteurs : J. J. WOLFF, Auteur ; Brian A. BOYD, Auteur ; J. T. ELISON, Auteur Article en page(s) : p.27 Langues : Anglais (eng) Mots-clés : Circumscribed interests  Measurement  Motor stereotypy  Repetitive behavior  Ritualistic behavior  Self-injurious behavior  Toddlers Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviors are characteristic phenotypic features of many neurodevelopmental, psychiatric, and neurological conditions. During early childhood, such behaviors are considered normative. More research is needed to delineate the dimensions of restricted and repetitive behavior across typical and atypical development during this period. METHODS: We developed the 34-item parent-rated Repetitive Behavior Scale for Early Childhood (RBS-EC) to capture quantitative, dimensional features across a broad range of behaviors contributing to this domain. We evaluated its psychometric properties and factor structure in a community sample of 914 toddlers. RESULTS: The RBS-EC showed excellent overall internal consistency (alpha = 0.90), strong test-retest reliability (ICC = 0.87 for topographies and 0.90 for frequency) and evidence of convergent and discriminative validity. Using a split-half approach to factor analysis, we identified that a three- or four-factor structure best fit the data and confirmatory factor analysis indicated acceptable fit for both models. The empirically derived four-factor model was consistent with our conceptual model and included repetitive motor, restricted interests and behavior, ritual and routine, and self-directed behavior. CONCLUSIONS: This initial study indicates that the RBS-EC is a reliable and valid instrument for characterizing quantitative, dimensional aspects of restricted and repetitive behaviors in young children. En ligne : http://dx.doi.org/10.1186/s11689-016-9161-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] A quantitative measure of restricted and repetitive behaviors for early childhood [Texte imprimé et/ou numérique] / J. J. WOLFF, Auteur ; Brian A. BOYD, Auteur ; J. T. ELISON, Auteur . - p.27. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.27 Mots-clés : Circumscribed interests  Measurement  Motor stereotypy  Repetitive behavior  Ritualistic behavior  Self-injurious behavior  Toddlers Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviors are characteristic phenotypic features of many neurodevelopmental, psychiatric, and neurological conditions. During early childhood, such behaviors are considered normative. More research is needed to delineate the dimensions of restricted and repetitive behavior across typical and atypical development during this period. METHODS: We developed the 34-item parent-rated Repetitive Behavior Scale for Early Childhood (RBS-EC) to capture quantitative, dimensional features across a broad range of behaviors contributing to this domain. We evaluated its psychometric properties and factor structure in a community sample of 914 toddlers. RESULTS: The RBS-EC showed excellent overall internal consistency (alpha = 0.90), strong test-retest reliability (ICC = 0.87 for topographies and 0.90 for frequency) and evidence of convergent and discriminative validity. Using a split-half approach to factor analysis, we identified that a three- or four-factor structure best fit the data and confirmatory factor analysis indicated acceptable fit for both models. The empirically derived four-factor model was consistent with our conceptual model and included repetitive motor, restricted interests and behavior, ritual and routine, and self-directed behavior. CONCLUSIONS: This initial study indicates that the RBS-EC is a reliable and valid instrument for characterizing quantitative, dimensional aspects of restricted and repetitive behaviors in young children. En ligne : http://dx.doi.org/10.1186/s11689-016-9161-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Cumulative life events, traumatic experiences, and psychiatric symptomatology in transition-aged youth with autism spectrum disorder / Julie LOUNDS TAYLOR in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.28 Titre : Cumulative life events, traumatic experiences, and psychiatric symptomatology in transition-aged youth with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Julie LOUNDS TAYLOR, Auteur ; K. O. GOTHAM, Auteur Article en page(s) : p.28 Langues : Anglais (eng) Mots-clés : Anxiety  Autism spectrum disorder  Depression  Internalizing  Life events  Trauma Index. décimale : PER Périodiques Résumé : BACKGROUND: Co-occurring mood and anxiety symptomatology is commonly observed among youth with autism spectrum disorders (ASD) during adolescence and adulthood. Yet, little is known about the factors that might predispose youth with ASD to mood and anxiety problems. In this study, we focus on the role of cumulative stressful life events and trauma in co-occurring psychopathology among youth with ASD who are preparing to exit high school. Specifically, we examined the distribution of cumulative life events and traumatic experiences and their relations with mood and anxiety symptomatology. METHODS: Participants included 36 youth with ASD, all of whom were in their last year of high school. Cumulative life events and trauma were assessed by parent report. Mood and anxiety symptomatology was determined using a variety of methods (structured interview, questionnaire, self- and informant report). Frequencies were used to examine the distributions of cumulative life events (count of total events) and trauma (coded into any trauma vs. no trauma), as well as mood and anxiety symptomatology (categorized into clinical-level, sub-threshold, or none for each). Bivariate relations between life events/trauma and mood/anxiety symptomatology were assessed using analysis of variance and chi-square. Ordinal logistic regression models were used to test whether significant bivariate relations remained after controlling for the sex of the youth with ASD and his/her IQ. RESULTS: Over 50 % of youth had experienced at least one trauma. Nearly one half had clinical-level mood or anxiety symptomatology. There was a statistically significant relation between absence/presence of trauma and mood symptomatology; nearly 90 % of the youth with clinical-level mood symptoms had at least one trauma, compared to 40 % of those with no mood symptomatology. CONCLUSIONS: Our findings suggest that contextual factors such as trauma might be important for the development of mood symptomatology in individuals with ASD. Although this idea is well-accepted in typically developing populations, contextual factors are rarely studied in investigations of psychopathology or transition outcomes in ASD. Given the high rates of psychiatric comorbidities in this population, future research should continue to identify the range of possible factors-both behavioral and contextual-that might influence the emergence of these disorders. En ligne : http://dx.doi.org/10.1186/s11689-016-9160-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Cumulative life events, traumatic experiences, and psychiatric symptomatology in transition-aged youth with autism spectrum disorder [Texte imprimé et/ou numérique] / Julie LOUNDS TAYLOR, Auteur ; K. O. GOTHAM, Auteur . - p.28. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.28 Mots-clés : Anxiety  Autism spectrum disorder  Depression  Internalizing  Life events  Trauma Index. décimale : PER Périodiques Résumé : BACKGROUND: Co-occurring mood and anxiety symptomatology is commonly observed among youth with autism spectrum disorders (ASD) during adolescence and adulthood. Yet, little is known about the factors that might predispose youth with ASD to mood and anxiety problems. In this study, we focus on the role of cumulative stressful life events and trauma in co-occurring psychopathology among youth with ASD who are preparing to exit high school. Specifically, we examined the distribution of cumulative life events and traumatic experiences and their relations with mood and anxiety symptomatology. METHODS: Participants included 36 youth with ASD, all of whom were in their last year of high school. Cumulative life events and trauma were assessed by parent report. Mood and anxiety symptomatology was determined using a variety of methods (structured interview, questionnaire, self- and informant report). Frequencies were used to examine the distributions of cumulative life events (count of total events) and trauma (coded into any trauma vs. no trauma), as well as mood and anxiety symptomatology (categorized into clinical-level, sub-threshold, or none for each). Bivariate relations between life events/trauma and mood/anxiety symptomatology were assessed using analysis of variance and chi-square. Ordinal logistic regression models were used to test whether significant bivariate relations remained after controlling for the sex of the youth with ASD and his/her IQ. RESULTS: Over 50 % of youth had experienced at least one trauma. Nearly one half had clinical-level mood or anxiety symptomatology. There was a statistically significant relation between absence/presence of trauma and mood symptomatology; nearly 90 % of the youth with clinical-level mood symptoms had at least one trauma, compared to 40 % of those with no mood symptomatology. CONCLUSIONS: Our findings suggest that contextual factors such as trauma might be important for the development of mood symptomatology in individuals with ASD. Although this idea is well-accepted in typically developing populations, contextual factors are rarely studied in investigations of psychopathology or transition outcomes in ASD. Given the high rates of psychiatric comorbidities in this population, future research should continue to identify the range of possible factors-both behavioral and contextual-that might influence the emergence of these disorders. En ligne : http://dx.doi.org/10.1186/s11689-016-9160-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Neurophysiological hyperresponsivity to sensory input in autism spectrum disorders / Y. TAKARAE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.29 Titre : Neurophysiological hyperresponsivity to sensory input in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Y. TAKARAE, Auteur ; S. R. SABLICH, Auteur ; S. P. WHITE, Auteur ; J. A. SWEENEY, Auteur Article en page(s) : p.29 Langues : Anglais (eng) Mots-clés : Autism  Contrast sensitivity  Heterogeneity  Individual differences  Sensory hypersensitivity Index. décimale : PER Périodiques Résumé : BACKGROUND: Atypical sensory processing is a common clinical observation in autism spectrum disorder (ASD). Neural hyperexcitability has been suggested as the cause for sensory hypersensitivity, a frequently reported clinical observation in ASD. We examined visual evoked responses to parametric increases in stimulus contrast in order to model neural responsivity of sensory systems in ASD. METHODS: Thirteen high-functioning individuals with ASD and 12 typically developing (TD) individuals completed a steady-state visual evoked potential study. Stimuli were vertical circular gratings oscillating at 3.76 Hz at varying contrasts (5, 10, 20,..., 90 % contrast, 10 levels). The average spectral power at the stimulus oscillation frequency was calculated for each contrast level. RESULTS: The magnitude of evoked sensory responses increased at a significantly greater rate and resulted in disproportionately elevated activation with higher contrasts in the ASD group. Approximately 45 % of ASD participants had rates of response increases greater than any TD participant. This alteration was highly associated with parental reports of these participants' sensory difficulties. CONCLUSIONS: Greater increases in visual responses over contrast manipulation suggest heightened excitability in the sensory cortex in ASD participants. Heightened neural excitability was observed in a substantial portion but not all of the ASD participants. This pattern suggests that individuals with higher excitability may constitute a neurobiologically distinct subgroup requiring individualized treatment interventions. En ligne : http://dx.doi.org/10.1186/s11689-016-9162-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Neurophysiological hyperresponsivity to sensory input in autism spectrum disorders [Texte imprimé et/ou numérique] / Y. TAKARAE, Auteur ; S. R. SABLICH, Auteur ; S. P. WHITE, Auteur ; J. A. SWEENEY, Auteur . - p.29. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.29 Mots-clés : Autism  Contrast sensitivity  Heterogeneity  Individual differences  Sensory hypersensitivity Index. décimale : PER Périodiques Résumé : BACKGROUND: Atypical sensory processing is a common clinical observation in autism spectrum disorder (ASD). Neural hyperexcitability has been suggested as the cause for sensory hypersensitivity, a frequently reported clinical observation in ASD. We examined visual evoked responses to parametric increases in stimulus contrast in order to model neural responsivity of sensory systems in ASD. METHODS: Thirteen high-functioning individuals with ASD and 12 typically developing (TD) individuals completed a steady-state visual evoked potential study. Stimuli were vertical circular gratings oscillating at 3.76 Hz at varying contrasts (5, 10, 20,..., 90 % contrast, 10 levels). The average spectral power at the stimulus oscillation frequency was calculated for each contrast level. RESULTS: The magnitude of evoked sensory responses increased at a significantly greater rate and resulted in disproportionately elevated activation with higher contrasts in the ASD group. Approximately 45 % of ASD participants had rates of response increases greater than any TD participant. This alteration was highly associated with parental reports of these participants' sensory difficulties. CONCLUSIONS: Greater increases in visual responses over contrast manipulation suggest heightened excitability in the sensory cortex in ASD participants. Heightened neural excitability was observed in a substantial portion but not all of the ASD participants. This pattern suggests that individuals with higher excitability may constitute a neurobiologically distinct subgroup requiring individualized treatment interventions. En ligne : http://dx.doi.org/10.1186/s11689-016-9162-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition / K. L. MCCABE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.30 Titre : Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition Type de document : Texte imprimé et/ou numérique Auteurs : K. L. MCCABE, Auteur ; S. MARLIN, Auteur ; Gavin COOPER, Auteur ; R. MORRIS, Auteur ; U. SCHALL, Auteur ; D. G. MURPHY, Auteur ; K. C. MURPHY, Auteur ; Linda E. CAMPBELL, Auteur Article en page(s) : p.30 Langues : Anglais (eng) Mots-clés : 22q11.2 deletion syndrome (22q11DS)  Face processing  Object recognition  Perceptual organisation  Social cognition  Visual integration Index. décimale : PER Périodiques Résumé : BACKGROUND: People with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may play a role in difficulties observed with these social cognitive skills. METHODS: A cross-sectional study investigated visual perception and processing as well as facial processing abilities in a group of 49 children and adolescents with 22q11DS and 30 age and socio-economic status-matched healthy sibling controls using the Birmingham Object Recognition Battery and face processing sub-tests from the MRC face processing skills battery. RESULTS: The 22q11DS group demonstrated poorer performance on all measures of visual perception and processing, with greatest impairment on perceptual processes relating to form perception as well as object recognition and memory. In addition, form perception was found to make a significant and unique contribution to higher order social-perceptual processing (face identity) in the 22q11DS group. CONCLUSIONS: The findings indicate evidence for impaired visual perception and processing capabilities in 22q11DS. In turn, these were found to influence cognitive skills needed for social processes such as facial identity recognition in the children with 22q11DS. En ligne : http://dx.doi.org/10.1186/s11689-016-9164-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition [Texte imprimé et/ou numérique] / K. L. MCCABE, Auteur ; S. MARLIN, Auteur ; Gavin COOPER, Auteur ; R. MORRIS, Auteur ; U. SCHALL, Auteur ; D. G. MURPHY, Auteur ; K. C. MURPHY, Auteur ; Linda E. CAMPBELL, Auteur . - p.30. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.30 Mots-clés : 22q11.2 deletion syndrome (22q11DS)  Face processing  Object recognition  Perceptual organisation  Social cognition  Visual integration Index. décimale : PER Périodiques Résumé : BACKGROUND: People with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may play a role in difficulties observed with these social cognitive skills. METHODS: A cross-sectional study investigated visual perception and processing as well as facial processing abilities in a group of 49 children and adolescents with 22q11DS and 30 age and socio-economic status-matched healthy sibling controls using the Birmingham Object Recognition Battery and face processing sub-tests from the MRC face processing skills battery. RESULTS: The 22q11DS group demonstrated poorer performance on all measures of visual perception and processing, with greatest impairment on perceptual processes relating to form perception as well as object recognition and memory. In addition, form perception was found to make a significant and unique contribution to higher order social-perceptual processing (face identity) in the 22q11DS group. CONCLUSIONS: The findings indicate evidence for impaired visual perception and processing capabilities in 22q11DS. In turn, these were found to influence cognitive skills needed for social processes such as facial identity recognition in the children with 22q11DS. En ligne : http://dx.doi.org/10.1186/s11689-016-9164-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Erratum to: Neural correlates of reward processing in adults with 22q11 deletion syndrome / E. D. A. VAN DUIN in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.31 Titre : Erratum to: Neural correlates of reward processing in adults with 22q11 deletion syndrome Type de document : Texte imprimé et/ou numérique Auteurs : E. D. A. VAN DUIN, Auteur ; L. GOOSSENS, Auteur ; D. HERNAUS, Auteur ; F. D. S. ALVES, Auteur ; N. SCHMITZ, Auteur ; K. SCHRUERS, Auteur ; T. VAN AMELSVOORT, Auteur Article en page(s) : p.31 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s11689-016-9158-5.]. En ligne : http://dx.doi.org/10.1186/s11689-016-9163-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Erratum to: Neural correlates of reward processing in adults with 22q11 deletion syndrome [Texte imprimé et/ou numérique] / E. D. A. VAN DUIN, Auteur ; L. GOOSSENS, Auteur ; D. HERNAUS, Auteur ; F. D. S. ALVES, Auteur ; N. SCHMITZ, Auteur ; K. SCHRUERS, Auteur ; T. VAN AMELSVOORT, Auteur . - p.31. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.31 Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s11689-016-9158-5.]. En ligne : http://dx.doi.org/10.1186/s11689-016-9163-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development / B. A. CORBETT in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.32 Titre : Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development Type de document : Texte imprimé et/ou numérique Auteurs : B. A. CORBETT, Auteur ; Karen L. BALES, Auteur ; D. SWAIN, Auteur ; K. SANDERS, Auteur ; T. A. WEINSTEIN, Auteur ; L. J. MUGLIA, Auteur Article en page(s) : p.32 Langues : Anglais (eng) Mots-clés : Arginine vasopressin  Autism  Autism spectrum disorder  Cortisol  Hormone  Hydrocortisone  LHPA axis  Oxytocin  Stress Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic effect, and have been implicated in the neuropathological profile in ASD. However, they are rarely investigated together. The purpose of the pilot study was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions. Arginine vasopressin (AVP), structurally similar to OT, was also examined. METHODS: A double-blind, placebo-controlled, randomly assigned, crossover design was employed in 25 children 8-to-12 years with ASD (N = 14) or typical development (TD, N = 11). A low dose of hydrocortisone and placebo were administered via liquid suspension. Analysis of variance (ANOVA) was used to examine the within-subject factor "Condition" (hydrocortisone/placebo) and "Time" (pre and post) and the between-subject factor "Group" (ASD vs. TD). Pearson correlations examined the relationship between hormone levels and clinical profile. RESULTS: There was a significant Time x Condition x Group interaction F (1.23) = 4.18, p = 0.05 showing a rise in OT during the experimental condition (hydrocortisone) and a drop during the placebo condition for the TD group but not the ASD group. There were no group differences for AVP. Hormone levels were associated with social profiles. CONCLUSIONS: For the TD group, an inverse relationship was observed. OT increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT remained unchanged or decreased during both the physiological challenge and the placebo condition, suggesting that OT failed to serve as a stress buffer under conditions of physiological stress. While OT has been tied to the social ability of children with ASD, the diminished moderating effect of OT on cortisol may also play a contributory role in the heightened stress often observed in children with ASD. These results contribute to our understanding of the growing complexity of the effects of OT on social behavior as well as the functional interplay and differential regulation OT may have on stress modulation. En ligne : http://dx.doi.org/10.1186/s11689-016-9165-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development [Texte imprimé et/ou numérique] / B. A. CORBETT, Auteur ; Karen L. BALES, Auteur ; D. SWAIN, Auteur ; K. SANDERS, Auteur ; T. A. WEINSTEIN, Auteur ; L. J. MUGLIA, Auteur . - p.32. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.32 Mots-clés : Arginine vasopressin  Autism  Autism spectrum disorder  Cortisol  Hormone  Hydrocortisone  LHPA axis  Oxytocin  Stress Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic effect, and have been implicated in the neuropathological profile in ASD. However, they are rarely investigated together. The purpose of the pilot study was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions. Arginine vasopressin (AVP), structurally similar to OT, was also examined. METHODS: A double-blind, placebo-controlled, randomly assigned, crossover design was employed in 25 children 8-to-12 years with ASD (N = 14) or typical development (TD, N = 11). A low dose of hydrocortisone and placebo were administered via liquid suspension. Analysis of variance (ANOVA) was used to examine the within-subject factor "Condition" (hydrocortisone/placebo) and "Time" (pre and post) and the between-subject factor "Group" (ASD vs. TD). Pearson correlations examined the relationship between hormone levels and clinical profile. RESULTS: There was a significant Time x Condition x Group interaction F (1.23) = 4.18, p = 0.05 showing a rise in OT during the experimental condition (hydrocortisone) and a drop during the placebo condition for the TD group but not the ASD group. There were no group differences for AVP. Hormone levels were associated with social profiles. CONCLUSIONS: For the TD group, an inverse relationship was observed. OT increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT remained unchanged or decreased during both the physiological challenge and the placebo condition, suggesting that OT failed to serve as a stress buffer under conditions of physiological stress. While OT has been tied to the social ability of children with ASD, the diminished moderating effect of OT on cortisol may also play a contributory role in the heightened stress often observed in children with ASD. These results contribute to our understanding of the growing complexity of the effects of OT on social behavior as well as the functional interplay and differential regulation OT may have on stress modulation. En ligne : http://dx.doi.org/10.1186/s11689-016-9165-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Atypical audiovisual word processing in school-age children with a history of specific language impairment: an event-related potential study / N. KAGANOVICH in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.33 Titre : Atypical audiovisual word processing in school-age children with a history of specific language impairment: an event-related potential study Type de document : Texte imprimé et/ou numérique Auteurs : N. KAGANOVICH, Auteur ; J. SCHUMAKER, Auteur ; C. ROWLAND, Auteur Article en page(s) : p.33 Langues : Anglais (eng) Mots-clés : Audiovisual matching  Event-related potentials  Lexical processing  Specific language impairment  Speech-in-noise perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Visual speech cues influence different aspects of language acquisition. However, whether developmental language disorders may be associated with atypical processing of visual speech is unknown. In this study, we used behavioral and ERP measures to determine whether children with a history of SLI (H-SLI) differ from their age-matched typically developing (TD) peers in the ability to match auditory words with corresponding silent visual articulations. METHODS: Nineteen 7-13-year-old H-SLI children and 19 age-matched TD children participated in the study. Children first heard a word and then saw a speaker silently articulating a word. In half of trials, the articulated word matched the auditory word (congruent trials), while in another half, it did not (incongruent trials). Children specified whether the auditory and the articulated words matched. We examined ERPs elicited by the onset of visual stimuli (visual P1, N1, and P2) as well as ERPs elicited by the articulatory movements themselves-namely, N400 to incongruent articulations and late positive complex (LPC) to congruent articulations. We also examined whether ERP measures of visual speech processing could predict (1) children's linguistic skills and (2) the use of visual speech cues when listening to speech-in-noise (SIN). RESULTS: H-SLI children were less accurate in matching auditory words with visual articulations. They had a significantly reduced P1 to the talker's face and a smaller N400 to incongruent articulations. In contrast, congruent articulations elicited LPCs of similar amplitude in both groups of children. The P1 and N400 amplitude was significantly correlated with accuracy enhancement on the SIN task when seeing the talker's face. CONCLUSIONS: H-SLI children have poorly defined correspondences between speech sounds and visually observed articulatory movements that produce them. En ligne : http://dx.doi.org/10.1186/s11689-016-9168-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Atypical audiovisual word processing in school-age children with a history of specific language impairment: an event-related potential study [Texte imprimé et/ou numérique] / N. KAGANOVICH, Auteur ; J. SCHUMAKER, Auteur ; C. ROWLAND, Auteur . - p.33. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.33 Mots-clés : Audiovisual matching  Event-related potentials  Lexical processing  Specific language impairment  Speech-in-noise perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Visual speech cues influence different aspects of language acquisition. However, whether developmental language disorders may be associated with atypical processing of visual speech is unknown. In this study, we used behavioral and ERP measures to determine whether children with a history of SLI (H-SLI) differ from their age-matched typically developing (TD) peers in the ability to match auditory words with corresponding silent visual articulations. METHODS: Nineteen 7-13-year-old H-SLI children and 19 age-matched TD children participated in the study. Children first heard a word and then saw a speaker silently articulating a word. In half of trials, the articulated word matched the auditory word (congruent trials), while in another half, it did not (incongruent trials). Children specified whether the auditory and the articulated words matched. We examined ERPs elicited by the onset of visual stimuli (visual P1, N1, and P2) as well as ERPs elicited by the articulatory movements themselves-namely, N400 to incongruent articulations and late positive complex (LPC) to congruent articulations. We also examined whether ERP measures of visual speech processing could predict (1) children's linguistic skills and (2) the use of visual speech cues when listening to speech-in-noise (SIN). RESULTS: H-SLI children were less accurate in matching auditory words with visual articulations. They had a significantly reduced P1 to the talker's face and a smaller N400 to incongruent articulations. In contrast, congruent articulations elicited LPCs of similar amplitude in both groups of children. The P1 and N400 amplitude was significantly correlated with accuracy enhancement on the SIN task when seeing the talker's face. CONCLUSIONS: H-SLI children have poorly defined correspondences between speech sounds and visually observed articulatory movements that produce them. En ligne : http://dx.doi.org/10.1186/s11689-016-9168-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Automatic cortical representation of auditory pitch changes in Rett syndrome / J. J. FOXE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.34 Titre : Automatic cortical representation of auditory pitch changes in Rett syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. J. FOXE, Auteur ; K. M. BURKE, Auteur ; G. N. ANDRADE, Auteur ; A. DJUKIC, Auteur ; H. P. FREY, Auteur ; S. MOLHOLM, Auteur Article en page(s) : p.34 Langues : Anglais (eng) Mots-clés : Aep  Auditory evoked potential  Eeg  Erp  Event-related potential  Females  High-density electrical mapping  Mecp2  Mmn  Mismatch negativity Index. décimale : PER Périodiques Résumé : BACKGROUND: Over the typical course of Rett syndrome, initial language and communication abilities deteriorate dramatically between the ages of 1 and 4 years, and a majority of these children go on to lose all oral communication abilities. It becomes extremely difficult for clinicians and caretakers to accurately assess the level of preserved auditory functioning in these children, an issue of obvious clinical import. Non-invasive electrophysiological techniques allow for the interrogation of auditory cortical processing without the need for overt behavioral responses. In particular, the mismatch negativity (MMN) component of the auditory evoked potential (AEP) provides an excellent and robust dependent measure of change detection and auditory sensory memory. Here, we asked whether females with Rett syndrome would produce the MMN to occasional changes in pitch in a regularly occurring stream of auditory tones. METHODS: Fourteen girls with genetically confirmed Rett syndrome and 22 age-matched neurotypical controls participated (ages 3.9-21.1 years). High-density electrophysiological recordings from 64 scalp electrodes were made while participants passively listened to a regularly occurring stream of 503-Hz auditory tone pips that was occasionally (15 % of presentations) interrupted by a higher-pitched deviant tone of 996 Hz. The MMN was derived by subtracting the AEP to these deviants from the AEP produced to the standard. RESULTS: Despite clearly anomalous morphology and latency of the AEP to simple pure-tone inputs in Rett syndrome, the MMN response was evident in both neurotypicals and Rett patients. However, we found that the pitch-evoked MMN was both delayed and protracted in duration in Rett, pointing to slowing of auditory responsiveness. CONCLUSIONS: The presence of the MMN in Rett patients suggests preserved abilities to process pitch changes in auditory sensory memory. This work represents a beginning step in an effort to comprehensively map the extent of auditory cortical functioning in Rett syndrome. These easily obtained objective brain measures of auditory processing have promise as biomarkers against which future therapeutic efforts can be assayed. En ligne : http://dx.doi.org/10.1186/s11689-016-9166-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Automatic cortical representation of auditory pitch changes in Rett syndrome [Texte imprimé et/ou numérique] / J. J. FOXE, Auteur ; K. M. BURKE, Auteur ; G. N. ANDRADE, Auteur ; A. DJUKIC, Auteur ; H. P. FREY, Auteur ; S. MOLHOLM, Auteur . - p.34. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.34 Mots-clés : Aep  Auditory evoked potential  Eeg  Erp  Event-related potential  Females  High-density electrical mapping  Mecp2  Mmn  Mismatch negativity Index. décimale : PER Périodiques Résumé : BACKGROUND: Over the typical course of Rett syndrome, initial language and communication abilities deteriorate dramatically between the ages of 1 and 4 years, and a majority of these children go on to lose all oral communication abilities. It becomes extremely difficult for clinicians and caretakers to accurately assess the level of preserved auditory functioning in these children, an issue of obvious clinical import. Non-invasive electrophysiological techniques allow for the interrogation of auditory cortical processing without the need for overt behavioral responses. In particular, the mismatch negativity (MMN) component of the auditory evoked potential (AEP) provides an excellent and robust dependent measure of change detection and auditory sensory memory. Here, we asked whether females with Rett syndrome would produce the MMN to occasional changes in pitch in a regularly occurring stream of auditory tones. METHODS: Fourteen girls with genetically confirmed Rett syndrome and 22 age-matched neurotypical controls participated (ages 3.9-21.1 years). High-density electrophysiological recordings from 64 scalp electrodes were made while participants passively listened to a regularly occurring stream of 503-Hz auditory tone pips that was occasionally (15 % of presentations) interrupted by a higher-pitched deviant tone of 996 Hz. The MMN was derived by subtracting the AEP to these deviants from the AEP produced to the standard. RESULTS: Despite clearly anomalous morphology and latency of the AEP to simple pure-tone inputs in Rett syndrome, the MMN response was evident in both neurotypicals and Rett patients. However, we found that the pitch-evoked MMN was both delayed and protracted in duration in Rett, pointing to slowing of auditory responsiveness. CONCLUSIONS: The presence of the MMN in Rett patients suggests preserved abilities to process pitch changes in auditory sensory memory. This work represents a beginning step in an effort to comprehensively map the extent of auditory cortical functioning in Rett syndrome. These easily obtained objective brain measures of auditory processing have promise as biomarkers against which future therapeutic efforts can be assayed. En ligne : http://dx.doi.org/10.1186/s11689-016-9166-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions / D. HESSL in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.35 Titre : The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions Type de document : Texte imprimé et/ou numérique Auteurs : D. HESSL, Auteur ; Stephanie M. SANSONE, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; K. RILEY, Auteur ; K. F. WIDAMAN, Auteur ; Leonard ABBEDUTO, Auteur ; A. SCHNEIDER, Auteur ; J. COLEMAN, Auteur ; D. OAKLANDER, Auteur ; K. C. RHODES, Auteur ; R. C. GERSHON, Auteur Article en page(s) : p.35 Langues : Anglais (eng) Mots-clés : Assessment  Cognition  Down syndrome  FMR1 gene  Fragile X syndrome  Outcome measures Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent advances in understanding molecular and synaptic mechanisms of intellectual disabilities (ID) in fragile X syndrome (FXS) and Down syndrome (DS) through animal models have led to targeted controlled trials with pharmacological agents designed to normalize these underlying mechanisms and improve clinical outcomes. However, several human clinical trials have failed to demonstrate efficacy of these targeted treatments to improve surrogate behavioral endpoints. Because the ultimate index of disease modification in these disorders is amelioration of ID, the validation of cognitive measures for tracking treatment response is essential. Here, we present preliminary research to validate the National Institutes of Health Toolbox Cognitive Battery (NIH-TCB) for ID. METHODS: We completed three pilot studies of patients with FXS (total n = 63; mean age 19.3 +/- 8.3 years, mean mental age 5.3 +/- 1.6 years), DS (n = 47; mean age 16.1 +/- 6.2, mean mental age 5.4 +/- 2.0), and idiopathic ID (IID; n = 16; mean age 16.1 +/- 5.0, mean mental age 6.6 +/- 2.3) measuring processing speed, executive function, episodic memory, word/letter reading, receptive vocabulary, and working memory using the web-based NIH-TB-CB, addressing feasibility, test-retest reliability, construct validity, ecological validity, and syndrome differences and profiles. RESULTS: Feasibility was good to excellent (>/=80 % of participants with valid scores) for above mental age 4 years for all tests except list sorting (working memory). Test-retest stability was good to excellent, and convergent validity was similar to or better than results obtained from typically developing children in the normal sample for executive function and language measures. Examination of ecological validity revealed moderate to very strong correlations between the NIH-TCB composite and adaptive behavior and full-scale IQ measures. Syndrome/group comparisons demonstrated significant deficits for the FXS and DS groups relative to IID on attention and inhibitory control, a significant reading weakness for FXS, and a receptive vocabulary weakness for DS. CONCLUSIONS: The NIH-TCB has potential for assessing important dimensions of cognition in persons with ID, and several tests may be useful for tracking response to intervention. However, more extensive psychometric studies, evaluation of the NIH-TCB's sensitivity to change, both developmentally and in the context of treatment, and perhaps establishing links to brain function in these populations, are required to determine the true utility of the battery as a set of outcome measures. En ligne : http://dx.doi.org/10.1186/s11689-016-9167-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions [Texte imprimé et/ou numérique] / D. HESSL, Auteur ; Stephanie M. SANSONE, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; K. RILEY, Auteur ; K. F. WIDAMAN, Auteur ; Leonard ABBEDUTO, Auteur ; A. SCHNEIDER, Auteur ; J. COLEMAN, Auteur ; D. OAKLANDER, Auteur ; K. C. RHODES, Auteur ; R. C. GERSHON, Auteur . - p.35. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.35 Mots-clés : Assessment  Cognition  Down syndrome  FMR1 gene  Fragile X syndrome  Outcome measures Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent advances in understanding molecular and synaptic mechanisms of intellectual disabilities (ID) in fragile X syndrome (FXS) and Down syndrome (DS) through animal models have led to targeted controlled trials with pharmacological agents designed to normalize these underlying mechanisms and improve clinical outcomes. However, several human clinical trials have failed to demonstrate efficacy of these targeted treatments to improve surrogate behavioral endpoints. Because the ultimate index of disease modification in these disorders is amelioration of ID, the validation of cognitive measures for tracking treatment response is essential. Here, we present preliminary research to validate the National Institutes of Health Toolbox Cognitive Battery (NIH-TCB) for ID. METHODS: We completed three pilot studies of patients with FXS (total n = 63; mean age 19.3 +/- 8.3 years, mean mental age 5.3 +/- 1.6 years), DS (n = 47; mean age 16.1 +/- 6.2, mean mental age 5.4 +/- 2.0), and idiopathic ID (IID; n = 16; mean age 16.1 +/- 5.0, mean mental age 6.6 +/- 2.3) measuring processing speed, executive function, episodic memory, word/letter reading, receptive vocabulary, and working memory using the web-based NIH-TB-CB, addressing feasibility, test-retest reliability, construct validity, ecological validity, and syndrome differences and profiles. RESULTS: Feasibility was good to excellent (>/=80 % of participants with valid scores) for above mental age 4 years for all tests except list sorting (working memory). Test-retest stability was good to excellent, and convergent validity was similar to or better than results obtained from typically developing children in the normal sample for executive function and language measures. Examination of ecological validity revealed moderate to very strong correlations between the NIH-TCB composite and adaptive behavior and full-scale IQ measures. Syndrome/group comparisons demonstrated significant deficits for the FXS and DS groups relative to IID on attention and inhibitory control, a significant reading weakness for FXS, and a receptive vocabulary weakness for DS. CONCLUSIONS: The NIH-TCB has potential for assessing important dimensions of cognition in persons with ID, and several tests may be useful for tracking response to intervention. However, more extensive psychometric studies, evaluation of the NIH-TCB's sensitivity to change, both developmentally and in the context of treatment, and perhaps establishing links to brain function in these populations, are required to determine the true utility of the battery as a set of outcome measures. En ligne : http://dx.doi.org/10.1186/s11689-016-9167-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation / M. J. GAZZELLONE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.36 Titre : Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation Type de document : Texte imprimé et/ou numérique Auteurs : M. J. GAZZELLONE, Auteur ; M. ZARREI, Auteur ; C. L. BURTON, Auteur ; S. WALKER, Auteur ; M. UDDIN, Auteur ; S. M. SHAHEEN, Auteur ; J. COSTE, Auteur ; R. RAJENDRAM, Auteur ; R. J. SCHACHTER, Auteur ; M. COLASANTO, Auteur ; G. L. HANNA, Auteur ; D. R. ROSENBERG, Auteur ; N. SORENI, Auteur ; K. D. FITZGERALD, Auteur ; C. R. MARSHALL, Auteur ; J. A. BUCHANAN, Auteur ; D. MERICO, Auteur ; P. D. ARNOLD, Auteur ; Stephen SCHERER, Auteur Article en page(s) : p.36 Langues : Anglais (eng) Mots-clés : Copy number variation  Obsessive-compulsive disorder  Pediatrics  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. METHODS: We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. RESULTS: We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 x 10(-03); FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten "CNV positive" trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. CONCLUSIONS: Our findings suggest that rare CNVs may contribute to the etiology of OCD. En ligne : http://dx.doi.org/10.1186/s11689-016-9170-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation [Texte imprimé et/ou numérique] / M. J. GAZZELLONE, Auteur ; M. ZARREI, Auteur ; C. L. BURTON, Auteur ; S. WALKER, Auteur ; M. UDDIN, Auteur ; S. M. SHAHEEN, Auteur ; J. COSTE, Auteur ; R. RAJENDRAM, Auteur ; R. J. SCHACHTER, Auteur ; M. COLASANTO, Auteur ; G. L. HANNA, Auteur ; D. R. ROSENBERG, Auteur ; N. SORENI, Auteur ; K. D. FITZGERALD, Auteur ; C. R. MARSHALL, Auteur ; J. A. BUCHANAN, Auteur ; D. MERICO, Auteur ; P. D. ARNOLD, Auteur ; Stephen SCHERER, Auteur . - p.36. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.36 Mots-clés : Copy number variation  Obsessive-compulsive disorder  Pediatrics  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. METHODS: We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. RESULTS: We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 x 10(-03); FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten "CNV positive" trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. CONCLUSIONS: Our findings suggest that rare CNVs may contribute to the etiology of OCD. En ligne : http://dx.doi.org/10.1186/s11689-016-9170-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome / W. ZHONG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.37 Titre : Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome Type de document : Texte imprimé et/ou numérique Auteurs : W. ZHONG, Auteur ; C. M. JOHNSON, Auteur ; Y. WU, Auteur ; N. CUI, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur Article en page(s) : p.37 Langues : Anglais (eng) Mots-clés : Behavior  Gaboxadol  Locus coeruleus  Mecp2  Rett syndrome  Thip Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by disruptions in the MECP2 gene. MECP2-null mice show imbalances in neuronal excitability and synaptic communications. Several previous studies indicate that augmenting synaptic GABA receptors (GABAARs) can alleviate RTT-like symptoms in mice. In addition to the synaptic GABAARs, there is a group of GABAARs found outside the synaptic cleft with the capability to produce sustained inhibition, which may be potential therapeutic targets for the control of neuronal excitability in RTT. METHODS: Wild-type and MECP2-null mice were randomly divided into four groups, receiving the extrasynaptic GABAAR agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP) and vehicle control, respectively. Low-dose THIP was administered to neonatal mice through lactation. RTT-like symptoms including lifespan, breathing, motor function, and social behaviors were studied when mice became mature. Changes in neuronal excitability and norepinephrine biosynthesis enzyme expression were studied in electrophysiology and molecular biology. RESULTS: With no evident sedation and other adverse side effects, early-life exposure to THIP extended the lifespan, alleviated breathing abnormalities, enhanced motor function, and improved social behaviors of MECP2-null mice. Such beneficial effects were associated with stabilization of locus coeruleus neuronal excitability and improvement of norepinephrine biosynthesis enzyme expression. CONCLUSIONS: THIP treatment in early lives might be a therapeutic approach to RTT-like symptoms in MECP2-null mice and perhaps in people with RTT as well. En ligne : http://dx.doi.org/10.1186/s11689-016-9169-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome [Texte imprimé et/ou numérique] / W. ZHONG, Auteur ; C. M. JOHNSON, Auteur ; Y. WU, Auteur ; N. CUI, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur . - p.37. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.37 Mots-clés : Behavior  Gaboxadol  Locus coeruleus  Mecp2  Rett syndrome  Thip Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by disruptions in the MECP2 gene. MECP2-null mice show imbalances in neuronal excitability and synaptic communications. Several previous studies indicate that augmenting synaptic GABA receptors (GABAARs) can alleviate RTT-like symptoms in mice. In addition to the synaptic GABAARs, there is a group of GABAARs found outside the synaptic cleft with the capability to produce sustained inhibition, which may be potential therapeutic targets for the control of neuronal excitability in RTT. METHODS: Wild-type and MECP2-null mice were randomly divided into four groups, receiving the extrasynaptic GABAAR agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP) and vehicle control, respectively. Low-dose THIP was administered to neonatal mice through lactation. RTT-like symptoms including lifespan, breathing, motor function, and social behaviors were studied when mice became mature. Changes in neuronal excitability and norepinephrine biosynthesis enzyme expression were studied in electrophysiology and molecular biology. RESULTS: With no evident sedation and other adverse side effects, early-life exposure to THIP extended the lifespan, alleviated breathing abnormalities, enhanced motor function, and improved social behaviors of MECP2-null mice. Such beneficial effects were associated with stabilization of locus coeruleus neuronal excitability and improvement of norepinephrine biosynthesis enzyme expression. CONCLUSIONS: THIP treatment in early lives might be a therapeutic approach to RTT-like symptoms in MECP2-null mice and perhaps in people with RTT as well. En ligne : http://dx.doi.org/10.1186/s11689-016-9169-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Typical visual search performance and atypical gaze behaviors in response to faces in Williams syndrome / M. HIRAI in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.38 Titre : Typical visual search performance and atypical gaze behaviors in response to faces in Williams syndrome Type de document : Texte imprimé et/ou numérique Auteurs : M. HIRAI, Auteur ; Y. MURAMATSU, Auteur ; S. MIZUNO, Auteur ; N. KURAHASHI, Auteur ; H. KURAHASHI, Auteur ; M. NAKAMURA, Auteur Article en page(s) : p.38 Langues : Anglais (eng) Mots-clés : Attention  Eye tracking  Face perception  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Evidence indicates that individuals with Williams syndrome (WS) exhibit atypical attentional characteristics when viewing faces. However, the dynamics of visual attention captured by faces remain unclear, especially when explicit attentional forces are present. To clarify this, we introduced a visual search paradigm and assessed how the relative strength of visual attention captured by a face and explicit attentional control changes as search progresses. METHODS: Participants (WS and controls) searched for a target (butterfly) within an array of distractors, which sometimes contained an upright face. We analyzed reaction time and location of the first fixation-which reflect the attentional profile at the initial stage-and fixation durations. These features represent aspects of attention at later stages of visual search. The strength of visual attention captured by faces and explicit attentional control (toward the butterfly) was characterized by the frequency of first fixations on a face or butterfly and on the duration of face or butterfly fixations. RESULTS: Although reaction time was longer in all groups when faces were present, and visual attention was not dominated by faces in any group during the initial stages of the search, when faces were present, attention to faces dominated in the WS group during the later search stages. Furthermore, for the WS group, reaction time correlated with eye-movement measures at different stages of searching such that longer reaction times were associated with longer face-fixations, specifically at the initial stage of searching. Moreover, longer reaction times were associated with longer face-fixations at the later stages of searching, while shorter reaction times were associated with longer butterfly fixations. CONCLUSIONS: The relative strength of attention captured by faces in people with WS is not observed at the initial stage of searching but becomes dominant as the search progresses. Furthermore, although behavioral responses are associated with some aspects of eye movements, they are not as sensitive as eye-movement measurements themselves at detecting atypical attentional characteristics in people with WS. En ligne : http://dx.doi.org/10.1186/s11689-016-9172-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Typical visual search performance and atypical gaze behaviors in response to faces in Williams syndrome [Texte imprimé et/ou numérique] / M. HIRAI, Auteur ; Y. MURAMATSU, Auteur ; S. MIZUNO, Auteur ; N. KURAHASHI, Auteur ; H. KURAHASHI, Auteur ; M. NAKAMURA, Auteur . - p.38. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.38 Mots-clés : Attention  Eye tracking  Face perception  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Evidence indicates that individuals with Williams syndrome (WS) exhibit atypical attentional characteristics when viewing faces. However, the dynamics of visual attention captured by faces remain unclear, especially when explicit attentional forces are present. To clarify this, we introduced a visual search paradigm and assessed how the relative strength of visual attention captured by a face and explicit attentional control changes as search progresses. METHODS: Participants (WS and controls) searched for a target (butterfly) within an array of distractors, which sometimes contained an upright face. We analyzed reaction time and location of the first fixation-which reflect the attentional profile at the initial stage-and fixation durations. These features represent aspects of attention at later stages of visual search. The strength of visual attention captured by faces and explicit attentional control (toward the butterfly) was characterized by the frequency of first fixations on a face or butterfly and on the duration of face or butterfly fixations. RESULTS: Although reaction time was longer in all groups when faces were present, and visual attention was not dominated by faces in any group during the initial stages of the search, when faces were present, attention to faces dominated in the WS group during the later search stages. Furthermore, for the WS group, reaction time correlated with eye-movement measures at different stages of searching such that longer reaction times were associated with longer face-fixations, specifically at the initial stage of searching. Moreover, longer reaction times were associated with longer face-fixations at the later stages of searching, while shorter reaction times were associated with longer butterfly fixations. CONCLUSIONS: The relative strength of attention captured by faces in people with WS is not observed at the initial stage of searching but becomes dominant as the search progresses. Furthermore, although behavioral responses are associated with some aspects of eye movements, they are not as sensitive as eye-movement measurements themselves at detecting atypical attentional characteristics in people with WS. En ligne : http://dx.doi.org/10.1186/s11689-016-9172-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Erratum to: Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol / A. DE GIORGIO in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.39 Titre : Erratum to: Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol Type de document : Texte imprimé et/ou numérique Auteurs : A. DE GIORGIO, Auteur ; S. E. COMPARINI, Auteur ; F. SANGIULIANO INTRA, Auteur ; A. GRANATO, Auteur Article en page(s) : p.39 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/1866-1955-4-18.]. En ligne : http://dx.doi.org/10.1186/s11689-016-9173-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Erratum to: Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol [Texte imprimé et/ou numérique] / A. DE GIORGIO, Auteur ; S. E. COMPARINI, Auteur ; F. SANGIULIANO INTRA, Auteur ; A. GRANATO, Auteur . - p.39. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.39 Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/1866-1955-4-18.]. En ligne : http://dx.doi.org/10.1186/s11689-016-9173-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Developmental profiles of infants with an FMR1 premutation / Anne C. WHEELER in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.40 Titre : Developmental profiles of infants with an FMR1 premutation Type de document : Texte imprimé et/ou numérique Auteurs : Anne C. WHEELER, Auteur ; J. SIDERIS, Auteur ; Randi J. HAGERMAN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; F. TASSONE, Auteur ; Donald B. Jr BAILEY, Auteur Article en page(s) : p.40 Langues : Anglais (eng) Mots-clés : Early development  FMR1 premutation  Newborn screening Index. décimale : PER Périodiques Résumé : BACKGROUND: Emerging evidence suggests that a subset of FMR1 premutation carriers is at an increased risk for cognitive, emotional, and medical conditions. However, because the premutation is rarely diagnosed at birth, the early developmental trajectories of children with a premutation are not known. METHODS: This exploratory study examined the cognitive, communication, and social-behavioral profiles of 26 infants with a premutation who were identified through participation in a newborn screening for fragile X syndrome pilot study. In this study, families whose newborn screened positive for an FMR1 premutation were invited to participate in a longitudinal study of early development. Twenty-six infants with the premutation and 21 matched, screen-negative comparison babies were assessed using validated standardized measures at 6-month intervals starting as young as 3 months of age. The babies were assessed up to seven times over a 4-year period. RESULTS: The premutation group was not statistically different from the comparison group on measures of cognitive development, adaptive behavior, temperament, or overall communication. However, the babies with the premutation had a significantly different developmental trajectory on measures of nonverbal communication and hyperresponsivity to sensory experiences. They also were significantly more hyporesponsive at all ages than the comparison group. Cytosine-guanine-guanine repeat length was linearly associated with overall cognitive development. CONCLUSIONS: These results suggest that infants with a premutation may present with subtle developmental differences as young as 12 months of age that may be early markers of later anxiety, social deficits, or other challenges thought to be experienced by a subset of carriers. En ligne : http://dx.doi.org/10.1186/s11689-016-9171-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Developmental profiles of infants with an FMR1 premutation [Texte imprimé et/ou numérique] / Anne C. WHEELER, Auteur ; J. SIDERIS, Auteur ; Randi J. HAGERMAN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; F. TASSONE, Auteur ; Donald B. Jr BAILEY, Auteur . - p.40. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.40 Mots-clés : Early development  FMR1 premutation  Newborn screening Index. décimale : PER Périodiques Résumé : BACKGROUND: Emerging evidence suggests that a subset of FMR1 premutation carriers is at an increased risk for cognitive, emotional, and medical conditions. However, because the premutation is rarely diagnosed at birth, the early developmental trajectories of children with a premutation are not known. METHODS: This exploratory study examined the cognitive, communication, and social-behavioral profiles of 26 infants with a premutation who were identified through participation in a newborn screening for fragile X syndrome pilot study. In this study, families whose newborn screened positive for an FMR1 premutation were invited to participate in a longitudinal study of early development. Twenty-six infants with the premutation and 21 matched, screen-negative comparison babies were assessed using validated standardized measures at 6-month intervals starting as young as 3 months of age. The babies were assessed up to seven times over a 4-year period. RESULTS: The premutation group was not statistically different from the comparison group on measures of cognitive development, adaptive behavior, temperament, or overall communication. However, the babies with the premutation had a significantly different developmental trajectory on measures of nonverbal communication and hyperresponsivity to sensory experiences. They also were significantly more hyporesponsive at all ages than the comparison group. Cytosine-guanine-guanine repeat length was linearly associated with overall cognitive development. CONCLUSIONS: These results suggest that infants with a premutation may present with subtle developmental differences as young as 12 months of age that may be early markers of later anxiety, social deficits, or other challenges thought to be experienced by a subset of carriers. En ligne : http://dx.doi.org/10.1186/s11689-016-9171-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Visual memory profile in 22q11.2 microdeletion syndrome: are there differences in performance and neurobiological substrates between tasks linked to ventral and dorsal visual brain structures? A cross-sectional and longitudinal study / M. BOSTELMANN in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.41 Titre : Visual memory profile in 22q11.2 microdeletion syndrome: are there differences in performance and neurobiological substrates between tasks linked to ventral and dorsal visual brain structures? A cross-sectional and longitudinal study Type de document : Texte imprimé et/ou numérique Auteurs : M. BOSTELMANN, Auteur ; M. SCHNEIDER, Auteur ; M. C. PADULA, Auteur ; J. MAEDER, Auteur ; M. SCHAER, Auteur ; E. SCARIATI, Auteur ; M. DEBBANE, Auteur ; B. GLASER, Auteur ; S. MENGHETTI, Auteur ; S. ELIEZ, Auteur Article en page(s) : p.41 Langues : Anglais (eng) Mots-clés : 22q11.2 deletion syndrome  Dorsal stream vulnerability hypothesis  Visual cognitive development  Visual memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Children affected by the 22q11.2 deletion syndrome (22q11.2DS) have a specific neuropsychological profile with strengths and weaknesses in several cognitive domains. Specifically, previous evidence has shown that patients with 22q11.2DS have more difficulties memorizing faces and visual-object characteristics of stimuli. In contrast, they have better performance in visuo-spatial memory tasks. The first focus of this study was to replicate these results in a larger sample of patients affected with 22q11.2DS and using a range of memory tasks. Moreover, we analyzed if the deficits were related to brain morphology in the structures typically underlying these abilities (ventral and dorsal visual streams). Finally, since the longitudinal development of visual memory is not clearly characterized in 22q11.2DS, we investigated its evolution from childhood to adolescence. METHODS: Seventy-one patients with 22q11.2DS and 49 control individuals aged between 9 and 16 years completed the Benton Visual Retention Test (BVRT) and specific subtests assessing visual memory from the Children's Memory Scale (CMS). The BVRT was used to compute spatial and object memory errors. For the CMS, specific subtests were classified into ventral, dorsal, and mixed subtests. Longitudinal data were obtained from a subset of 26 patients and 22 control individuals. RESULTS: Cross-sectional results showed that patients with 22q11.2DS were impaired in all visual memory measures, with stronger deficits in visual-object memory and memory of faces, compared to visuo-spatial memory. No correlations between morphological brain impairments and visual memory were found in patients with 22q11.2DS. Longitudinal findings revealed that participants with 22q11.2DS made more object memory errors than spatial memory errors at baseline. This difference was no longer significant at follow-up. CONCLUSIONS: Individuals with 22q11.2DS have impairments in visual memory abilities, with more pronounced difficulties in memorizing faces and visual-object characteristics. From childhood to adolescence, the visual cognitive profile of patients with 22q11.2DS seems globally stable even though some processes show an evolution with time. We hope that our results will help clinicians and caregivers to better understand the memory difficulties of young individuals with 22q11.2DS. This has a particular importance at school to facilitate recommendations concerning intervention strategies for these young patients. En ligne : http://dx.doi.org/10.1186/s11689-016-9174-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Visual memory profile in 22q11.2 microdeletion syndrome: are there differences in performance and neurobiological substrates between tasks linked to ventral and dorsal visual brain structures? A cross-sectional and longitudinal study [Texte imprimé et/ou numérique] / M. BOSTELMANN, Auteur ; M. SCHNEIDER, Auteur ; M. C. PADULA, Auteur ; J. MAEDER, Auteur ; M. SCHAER, Auteur ; E. SCARIATI, Auteur ; M. DEBBANE, Auteur ; B. GLASER, Auteur ; S. MENGHETTI, Auteur ; S. ELIEZ, Auteur . - p.41. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.41 Mots-clés : 22q11.2 deletion syndrome  Dorsal stream vulnerability hypothesis  Visual cognitive development  Visual memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Children affected by the 22q11.2 deletion syndrome (22q11.2DS) have a specific neuropsychological profile with strengths and weaknesses in several cognitive domains. Specifically, previous evidence has shown that patients with 22q11.2DS have more difficulties memorizing faces and visual-object characteristics of stimuli. In contrast, they have better performance in visuo-spatial memory tasks. The first focus of this study was to replicate these results in a larger sample of patients affected with 22q11.2DS and using a range of memory tasks. Moreover, we analyzed if the deficits were related to brain morphology in the structures typically underlying these abilities (ventral and dorsal visual streams). Finally, since the longitudinal development of visual memory is not clearly characterized in 22q11.2DS, we investigated its evolution from childhood to adolescence. METHODS: Seventy-one patients with 22q11.2DS and 49 control individuals aged between 9 and 16 years completed the Benton Visual Retention Test (BVRT) and specific subtests assessing visual memory from the Children's Memory Scale (CMS). The BVRT was used to compute spatial and object memory errors. For the CMS, specific subtests were classified into ventral, dorsal, and mixed subtests. Longitudinal data were obtained from a subset of 26 patients and 22 control individuals. RESULTS: Cross-sectional results showed that patients with 22q11.2DS were impaired in all visual memory measures, with stronger deficits in visual-object memory and memory of faces, compared to visuo-spatial memory. No correlations between morphological brain impairments and visual memory were found in patients with 22q11.2DS. Longitudinal findings revealed that participants with 22q11.2DS made more object memory errors than spatial memory errors at baseline. This difference was no longer significant at follow-up. CONCLUSIONS: Individuals with 22q11.2DS have impairments in visual memory abilities, with more pronounced difficulties in memorizing faces and visual-object characteristics. From childhood to adolescence, the visual cognitive profile of patients with 22q11.2DS seems globally stable even though some processes show an evolution with time. We hope that our results will help clinicians and caregivers to better understand the memory difficulties of young individuals with 22q11.2DS. This has a particular importance at school to facilitate recommendations concerning intervention strategies for these young patients. En ligne : http://dx.doi.org/10.1186/s11689-016-9174-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Associations between social cognition, skills, and function and subclinical negative and positive symptoms in 22q11.2 deletion syndrome / A. VANGKILDE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.42 Titre : Associations between social cognition, skills, and function and subclinical negative and positive symptoms in 22q11.2 deletion syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. VANGKILDE, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; H. SCHMOCK, Auteur ; C. OLESEN, Auteur ; S. ARNARSDOTTIR, Auteur ; W. F. BAARE, Auteur ; K. J. PLESSEN, Auteur ; M. DIDRIKSEN, Auteur ; H. R. SIEBNER, Auteur ; T. WERGE, Auteur ; L. OLSEN, Auteur Article en page(s) : p.42 Langues : Anglais (eng) Mots-clés : 22q11 deletion syndrome  Emotional recognition task  Negative symptoms  Positive symptoms  Schizophrenia  Social cognition  Social function  Social skills  Theory of mind Index. décimale : PER Périodiques Résumé : BACKGROUND: Identification of the early signs of schizophrenia would be a major achievement for the early intervention and prevention strategies in psychiatry. Social impairments are defining features of schizophrenia. Impairments of individual layers of social competencies are frequently described in individuals with 22q11.2 deletion syndrome (22q11.2DS), who have high risk of schizophrenia. It is unclear whether and to what extent social impairments associate with subclinical negative and positive symptoms in 22q11.2DS, and which layer of social impairments are more correlated with schizophrenia-related symptoms. The aims of this study were to conduct a comprehensive investigation of social impairments at three different levels (function, skill, and cognition) and their interrelationship and to determine to what degree the social impairments correlate to subclinical levels of negative and positive symptoms, respectively, in a young cohort of 22q11.2DS not diagnosed with schizophrenia. METHODS: The level of social impairment was addressed using questionnaires and objective measures of social functioning (The Adaptive Behavior Assessment System), skills (Social Responsiveness Scale), and cognition (The Awareness of Social Inference Test and CANTAB Emotional Recognition Task), and the presence of subclinical symptoms of schizophrenia were evaluated using the Structured Interview for Prodromal Syndromes in a cross-sectional case-control study of 29 cases and 29 controls, aged 12 to 25 years. Association between social impairment and negative and positive symptoms levels was examined in cases only. RESULTS: Subjects with 22q11.2DS were highly impaired in social function, social skills, and social cognition (p En ligne : http://dx.doi.org/10.1186/s11689-016-9175-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Associations between social cognition, skills, and function and subclinical negative and positive symptoms in 22q11.2 deletion syndrome [Texte imprimé et/ou numérique] / A. VANGKILDE, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; H. SCHMOCK, Auteur ; C. OLESEN, Auteur ; S. ARNARSDOTTIR, Auteur ; W. F. BAARE, Auteur ; K. J. PLESSEN, Auteur ; M. DIDRIKSEN, Auteur ; H. R. SIEBNER, Auteur ; T. WERGE, Auteur ; L. OLSEN, Auteur . - p.42. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.42 Mots-clés : 22q11 deletion syndrome  Emotional recognition task  Negative symptoms  Positive symptoms  Schizophrenia  Social cognition  Social function  Social skills  Theory of mind Index. décimale : PER Périodiques Résumé : BACKGROUND: Identification of the early signs of schizophrenia would be a major achievement for the early intervention and prevention strategies in psychiatry. Social impairments are defining features of schizophrenia. Impairments of individual layers of social competencies are frequently described in individuals with 22q11.2 deletion syndrome (22q11.2DS), who have high risk of schizophrenia. It is unclear whether and to what extent social impairments associate with subclinical negative and positive symptoms in 22q11.2DS, and which layer of social impairments are more correlated with schizophrenia-related symptoms. The aims of this study were to conduct a comprehensive investigation of social impairments at three different levels (function, skill, and cognition) and their interrelationship and to determine to what degree the social impairments correlate to subclinical levels of negative and positive symptoms, respectively, in a young cohort of 22q11.2DS not diagnosed with schizophrenia. METHODS: The level of social impairment was addressed using questionnaires and objective measures of social functioning (The Adaptive Behavior Assessment System), skills (Social Responsiveness Scale), and cognition (The Awareness of Social Inference Test and CANTAB Emotional Recognition Task), and the presence of subclinical symptoms of schizophrenia were evaluated using the Structured Interview for Prodromal Syndromes in a cross-sectional case-control study of 29 cases and 29 controls, aged 12 to 25 years. Association between social impairment and negative and positive symptoms levels was examined in cases only. RESULTS: Subjects with 22q11.2DS were highly impaired in social function, social skills, and social cognition (p En ligne : http://dx.doi.org/10.1186/s11689-016-9175-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Postural orientation and equilibrium processes associated with increased postural sway in autism spectrum disorder (ASD) / Z. WANG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.43 Titre : Postural orientation and equilibrium processes associated with increased postural sway in autism spectrum disorder (ASD) Type de document : Texte imprimé et/ou numérique Auteurs : Z. WANG, Auteur ; R. R. HALLAC, Auteur ; K. C. CONROY, Auteur ; S. P. WHITE, Auteur ; A. A. KANE, Auteur ; A. L. COLLINSWORTH, Auteur ; J. A. SWEENEY, Auteur ; M. W. MOSCONI, Auteur Article en page(s) : p.43 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Mutual information  Postural equilibrium  Postural orientation  Static and dynamic stances  Virtual time-to-contact Index. décimale : PER Périodiques Résumé : BACKGROUND: Increased postural sway has been repeatedly documented in children with autism spectrum disorder (ASD). Characterizing the control processes underlying this deficit, including postural orientation and equilibrium, may provide key insights into neurophysiological mechanisms associated with ASD. Postural orientation refers to children's ability to actively align their trunk and head with respect to their base of support, while postural equilibrium is an active process whereby children coordinate ankle dorsi-/plantar-flexion and hip abduction/adduction movements to stabilize their upper body. Dynamic engagement of each of these control processes is important for maintaining postural stability, though neither postural orientation nor equilibrium has been studied in ASD. METHODS: Twenty-two children with ASD and 21 age and performance IQ-matched typically developing (TD) controls completed three standing tests. During static stance, participants were instructed to stand as still as possible. During dynamic stances, participants swayed at a comfortable speed and magnitude in either anterior-posterior (AP) or mediolateral (ML) directions. The center of pressure (COP) standard deviation and trajectory length were examined to determine if children with ASD showed increased postural sway. Postural orientation was assessed using a novel virtual time-to-contact (VTC) approach that characterized spatiotemporal dimensions of children's postural sway (i.e., body alignment) relative to their postural limitation boundary, defined as the maximum extent to which each child could sway in each direction. Postural equilibrium was quantified by evaluating the amount of shared or mutual information of COP time series measured along the AP and ML directions. RESULTS: Consistent with prior studies, children with ASD showed increased postural sway during both static and dynamic stances relative to TD children. In regard to postural orientation processes, children with ASD demonstrated reduced spatial perception of their postural limitation boundary towards target directions and reduced time to correct this error during dynamic postural sways but not during static stance. Regarding postural equilibrium, they showed a compromised ability to decouple ankle dorsi-/plantar-flexion and hip abduction/adduction processes during dynamic stances. CONCLUSIONS: These results suggest that deficits in both postural orientation and equilibrium processes contribute to reduced postural stability in ASD. Specifically, increased postural sway in ASD appears to reflect patients' impaired perception of their body movement relative to their own postural limitation boundary as well as a reduced ability to decouple distinct ankle and hip movements to align their body during standing. Our findings that deficits in postural orientation and equilibrium are more pronounced during dynamic compared to static stances suggests that the increased demands of everyday activities in which children must dynamically shift their COP involve more severe postural control deficits in ASD relative to static stance conditions that often are studied. Systematic assessment of dynamic postural control processes in ASD may provide important insights into new treatment targets and neurodevelopmental mechanisms. En ligne : http://dx.doi.org/10.1186/s11689-016-9178-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Postural orientation and equilibrium processes associated with increased postural sway in autism spectrum disorder (ASD) [Texte imprimé et/ou numérique] / Z. WANG, Auteur ; R. R. HALLAC, Auteur ; K. C. CONROY, Auteur ; S. P. WHITE, Auteur ; A. A. KANE, Auteur ; A. L. COLLINSWORTH, Auteur ; J. A. SWEENEY, Auteur ; M. W. MOSCONI, Auteur . - p.43. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.43 Mots-clés : Autism spectrum disorder  Mutual information  Postural equilibrium  Postural orientation  Static and dynamic stances  Virtual time-to-contact Index. décimale : PER Périodiques Résumé : BACKGROUND: Increased postural sway has been repeatedly documented in children with autism spectrum disorder (ASD). Characterizing the control processes underlying this deficit, including postural orientation and equilibrium, may provide key insights into neurophysiological mechanisms associated with ASD. Postural orientation refers to children's ability to actively align their trunk and head with respect to their base of support, while postural equilibrium is an active process whereby children coordinate ankle dorsi-/plantar-flexion and hip abduction/adduction movements to stabilize their upper body. Dynamic engagement of each of these control processes is important for maintaining postural stability, though neither postural orientation nor equilibrium has been studied in ASD. METHODS: Twenty-two children with ASD and 21 age and performance IQ-matched typically developing (TD) controls completed three standing tests. During static stance, participants were instructed to stand as still as possible. During dynamic stances, participants swayed at a comfortable speed and magnitude in either anterior-posterior (AP) or mediolateral (ML) directions. The center of pressure (COP) standard deviation and trajectory length were examined to determine if children with ASD showed increased postural sway. Postural orientation was assessed using a novel virtual time-to-contact (VTC) approach that characterized spatiotemporal dimensions of children's postural sway (i.e., body alignment) relative to their postural limitation boundary, defined as the maximum extent to which each child could sway in each direction. Postural equilibrium was quantified by evaluating the amount of shared or mutual information of COP time series measured along the AP and ML directions. RESULTS: Consistent with prior studies, children with ASD showed increased postural sway during both static and dynamic stances relative to TD children. In regard to postural orientation processes, children with ASD demonstrated reduced spatial perception of their postural limitation boundary towards target directions and reduced time to correct this error during dynamic postural sways but not during static stance. Regarding postural equilibrium, they showed a compromised ability to decouple ankle dorsi-/plantar-flexion and hip abduction/adduction processes during dynamic stances. CONCLUSIONS: These results suggest that deficits in both postural orientation and equilibrium processes contribute to reduced postural stability in ASD. Specifically, increased postural sway in ASD appears to reflect patients' impaired perception of their body movement relative to their own postural limitation boundary as well as a reduced ability to decouple distinct ankle and hip movements to align their body during standing. Our findings that deficits in postural orientation and equilibrium are more pronounced during dynamic compared to static stances suggests that the increased demands of everyday activities in which children must dynamically shift their COP involve more severe postural control deficits in ASD relative to static stance conditions that often are studied. Systematic assessment of dynamic postural control processes in ASD may provide important insights into new treatment targets and neurodevelopmental mechanisms. En ligne : http://dx.doi.org/10.1186/s11689-016-9178-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Functional characterization of rare FOXP2 variants in neurodevelopmental disorder / S. B. ESTRUCH in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.44 Titre : Functional characterization of rare FOXP2 variants in neurodevelopmental disorder Type de document : Texte imprimé et/ou numérique Auteurs : S. B. ESTRUCH, Auteur ; S. A. GRAHAM, Auteur ; S. M. CHINNAPPA, Auteur ; P. DERIZIOTIS, Auteur ; S. E. FISHER, Auteur Article en page(s) : p.44 Langues : Anglais (eng) Mots-clés : Functional genetics  Language  Neuroscience  Speech  Transcription factor Index. décimale : PER Périodiques Résumé : BACKGROUND: Heterozygous disruption of FOXP2 causes a rare form of speech and language impairment. Screens of the FOXP2 sequence in individuals with speech/language-related disorders have identified several rare protein-altering variants, but their phenotypic relevance is often unclear. FOXP2 encodes a transcription factor with a forkhead box DNA-binding domain, but little is known about the functions of protein regions outside this domain. METHODS: We performed detailed functional analyses of seven rare FOXP2 variants found in affected cases, including three which have not been previously characterized, testing intracellular localization, transcriptional regulation, dimerization, and interaction with other proteins. To shed further light on molecular functions of FOXP2, we characterized the interaction between this transcription factor and co-repressor proteins of the C-terminal binding protein (CTBP) family. Finally, we analysed the functional significance of the polyglutamine tracts in FOXP2, since tract length variations have been reported in cases of neurodevelopmental disorder. RESULTS: We confirmed etiological roles of multiple FOXP2 variants. Of three variants that have been suggested to cause speech/language disorder, but never before been characterized, only one showed functional effects. For the other two, we found no effects on protein function in any assays, suggesting that they are incidental to the phenotype. We identified a CTBP-binding region within the N-terminal portion of FOXP2. This region includes two amino acid substitutions that occurred on the human lineage following the split from chimpanzees. However, we did not observe any effects of these amino acid changes on CTBP binding or other core aspects of FOXP2 function. Finally, we found that FOXP2 variants with reduced polyglutamine tracts did not exhibit altered behaviour in cellular assays, indicating that such tracts are non-essential for core aspects of FOXP2 function, and that tract variation is unlikely to be a highly penetrant cause of speech/language disorder. CONCLUSIONS: Our findings highlight the importance of functional characterization of novel rare variants in FOXP2 in assessing the contribution of such variants to speech/language disorder and provide further insights into the molecular function of the FOXP2 protein. En ligne : http://dx.doi.org/10.1186/s11689-016-9177-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Functional characterization of rare FOXP2 variants in neurodevelopmental disorder [Texte imprimé et/ou numérique] / S. B. ESTRUCH, Auteur ; S. A. GRAHAM, Auteur ; S. M. CHINNAPPA, Auteur ; P. DERIZIOTIS, Auteur ; S. E. FISHER, Auteur . - p.44. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.44 Mots-clés : Functional genetics  Language  Neuroscience  Speech  Transcription factor Index. décimale : PER Périodiques Résumé : BACKGROUND: Heterozygous disruption of FOXP2 causes a rare form of speech and language impairment. Screens of the FOXP2 sequence in individuals with speech/language-related disorders have identified several rare protein-altering variants, but their phenotypic relevance is often unclear. FOXP2 encodes a transcription factor with a forkhead box DNA-binding domain, but little is known about the functions of protein regions outside this domain. METHODS: We performed detailed functional analyses of seven rare FOXP2 variants found in affected cases, including three which have not been previously characterized, testing intracellular localization, transcriptional regulation, dimerization, and interaction with other proteins. To shed further light on molecular functions of FOXP2, we characterized the interaction between this transcription factor and co-repressor proteins of the C-terminal binding protein (CTBP) family. Finally, we analysed the functional significance of the polyglutamine tracts in FOXP2, since tract length variations have been reported in cases of neurodevelopmental disorder. RESULTS: We confirmed etiological roles of multiple FOXP2 variants. Of three variants that have been suggested to cause speech/language disorder, but never before been characterized, only one showed functional effects. For the other two, we found no effects on protein function in any assays, suggesting that they are incidental to the phenotype. We identified a CTBP-binding region within the N-terminal portion of FOXP2. This region includes two amino acid substitutions that occurred on the human lineage following the split from chimpanzees. However, we did not observe any effects of these amino acid changes on CTBP binding or other core aspects of FOXP2 function. Finally, we found that FOXP2 variants with reduced polyglutamine tracts did not exhibit altered behaviour in cellular assays, indicating that such tracts are non-essential for core aspects of FOXP2 function, and that tract variation is unlikely to be a highly penetrant cause of speech/language disorder. CONCLUSIONS: Our findings highlight the importance of functional characterization of novel rare variants in FOXP2 in assessing the contribution of such variants to speech/language disorder and provide further insights into the molecular function of the FOXP2 protein. En ligne : http://dx.doi.org/10.1186/s11689-016-9177-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Wnt signaling networks in autism spectrum disorder and intellectual disability / V. KWAN in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.45 Titre : Wnt signaling networks in autism spectrum disorder and intellectual disability Type de document : Texte imprimé et/ou numérique Auteurs : V. KWAN, Auteur ; B. K. UNDA, Auteur ; K. K. SINGH, Auteur Article en page(s) : p.45 Langues : Anglais (eng) Mots-clés : Asd  Autism spectrum disorders  Gsk3  Mutations  Neurodevelopment  Neurogenesis  Neuronal migration  Neurotransmission  Plasticity  Signaling  Synapse  Wnt signaling Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic factors play a major role in the risk for neurodevelopmental disorders such as autism spectrum disorders (ASDs) and intellectual disability (ID). The underlying genetic factors have become better understood in recent years due to advancements in next generation sequencing. These studies have uncovered a vast number of genes that are impacted by different types of mutations (e.g., de novo, missense, truncation, copy number variations). ABSTRACT: Given the large volume of genetic data, analyzing each gene on its own is not a feasible approach and will take years to complete, let alone attempt to use the information to develop novel therapeutics. To make sense of independent genomic data, one approach is to determine whether multiple risk genes function in common signaling pathways that identify signaling "hubs" where risk genes converge. This approach has led to multiple pathways being implicated, such as synaptic signaling, chromatin remodeling, alternative splicing, and protein translation, among many others. In this review, we analyze recent and historical evidence indicating that multiple risk genes, including genes denoted as high-confidence and likely causal, are part of the Wingless (Wnt signaling) pathway. In the brain, Wnt signaling is an evolutionarily conserved pathway that plays an instrumental role in developing neural circuits and adult brain function. CONCLUSIONS: We will also review evidence that pharmacological therapies and genetic mouse models further identify abnormal Wnt signaling, particularly at the synapse, as being disrupted in ASDs and contributing to disease pathology. En ligne : http://dx.doi.org/10.1186/s11689-016-9176-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Wnt signaling networks in autism spectrum disorder and intellectual disability [Texte imprimé et/ou numérique] / V. KWAN, Auteur ; B. K. UNDA, Auteur ; K. K. SINGH, Auteur . - p.45. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.45 Mots-clés : Asd  Autism spectrum disorders  Gsk3  Mutations  Neurodevelopment  Neurogenesis  Neuronal migration  Neurotransmission  Plasticity  Signaling  Synapse  Wnt signaling Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic factors play a major role in the risk for neurodevelopmental disorders such as autism spectrum disorders (ASDs) and intellectual disability (ID). The underlying genetic factors have become better understood in recent years due to advancements in next generation sequencing. These studies have uncovered a vast number of genes that are impacted by different types of mutations (e.g., de novo, missense, truncation, copy number variations). ABSTRACT: Given the large volume of genetic data, analyzing each gene on its own is not a feasible approach and will take years to complete, let alone attempt to use the information to develop novel therapeutics. To make sense of independent genomic data, one approach is to determine whether multiple risk genes function in common signaling pathways that identify signaling "hubs" where risk genes converge. This approach has led to multiple pathways being implicated, such as synaptic signaling, chromatin remodeling, alternative splicing, and protein translation, among many others. In this review, we analyze recent and historical evidence indicating that multiple risk genes, including genes denoted as high-confidence and likely causal, are part of the Wingless (Wnt signaling) pathway. In the brain, Wnt signaling is an evolutionarily conserved pathway that plays an instrumental role in developing neural circuits and adult brain function. CONCLUSIONS: We will also review evidence that pharmacological therapies and genetic mouse models further identify abnormal Wnt signaling, particularly at the synapse, as being disrupted in ASDs and contributing to disease pathology. En ligne : http://dx.doi.org/10.1186/s11689-016-9176-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Verbal labels increase the salience of novel objects for preschoolers with typical development and Williams syndrome, but not in autism / G. VIVANTI in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.46 Titre : Verbal labels increase the salience of novel objects for preschoolers with typical development and Williams syndrome, but not in autism Type de document : Texte imprimé et/ou numérique Auteurs : G. VIVANTI, Auteur ; D. R. HOCKING, Auteur ; P. FANNING, Auteur ; Cheryl DISSANAYAKE, Auteur Article en page(s) : p.46 Langues : Anglais (eng) Mots-clés : Autism  Referential communication  Social learning  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Early research has documented that young children show an increased interest toward objects that are verbally labeled by an adult, compared to objects that are presented without a label. It is unclear whether the same phenomenon occurs in neurodevelopmental disorders affecting social development, such as autism spectrum disorder (ASD) and Williams syndrome (WS). METHODS: The present study used a novel eye-tracking paradigm to determine whether hearing a verbal label increases the salience of novel objects in 35 preschoolers with ASD, 18 preschoolers with WS, and 20 typically developing peers. RESULTS: We found that typically developing children and those with WS, but not those with ASD, spent significantly more time looking at objects that are verbally labeled by an adult, compared to objects that are presented without a label. CONCLUSIONS: In children without ASD, information accompanied by the speaker's verbal label is accorded a "special status," and it is more likely to be attended to. In contrast, children with ASD do not appear to attribute a special salience to labeled objects compared to non-labeled objects. This result is consistent with the notion that reduced responsivity to pedagogical cues hinders social learning in young children with ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9180-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Verbal labels increase the salience of novel objects for preschoolers with typical development and Williams syndrome, but not in autism [Texte imprimé et/ou numérique] / G. VIVANTI, Auteur ; D. R. HOCKING, Auteur ; P. FANNING, Auteur ; Cheryl DISSANAYAKE, Auteur . - p.46. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.46 Mots-clés : Autism  Referential communication  Social learning  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Early research has documented that young children show an increased interest toward objects that are verbally labeled by an adult, compared to objects that are presented without a label. It is unclear whether the same phenomenon occurs in neurodevelopmental disorders affecting social development, such as autism spectrum disorder (ASD) and Williams syndrome (WS). METHODS: The present study used a novel eye-tracking paradigm to determine whether hearing a verbal label increases the salience of novel objects in 35 preschoolers with ASD, 18 preschoolers with WS, and 20 typically developing peers. RESULTS: We found that typically developing children and those with WS, but not those with ASD, spent significantly more time looking at objects that are verbally labeled by an adult, compared to objects that are presented without a label. CONCLUSIONS: In children without ASD, information accompanied by the speaker's verbal label is accorded a "special status," and it is more likely to be attended to. In contrast, children with ASD do not appear to attribute a special salience to labeled objects compared to non-labeled objects. This result is consistent with the notion that reduced responsivity to pedagogical cues hinders social learning in young children with ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9180-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome / M. LEE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.47 Titre : A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : M. LEE, Auteur ; G. E. MARTIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; M. LOSH, Auteur Article en page(s) : p.47 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Endophenotype  FMR1 gene  Fragile X syndrome  Language  Longitudinal  Pragmatics  Social behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Targeting overlapping behavioral phenotypes in neurogenetic disorders can help elucidate gene-behavior relationships. Fragile X syndrome (FXS) and autism spectrum disorder (ASD) have been studied as a model for this approach, and important areas of phenotypic overlap and divergence have been documented. However, few studies have examined how the manifestation of ASD-related phenotypes in FXS may change over development, a question which has important implications for conceptualizing shared etiologies of these disorders and their constituent phenotypes. The goal of this study was to characterize ASD phenotypes in boys and girls with FXS across development, as well as to compare individual component phenotypes among boys with FXS and boys with idiopathic ASD (ASD-O) over time. METHODS: Sixty-five boys and girls with FXS and 19 boys with ASD-O completed a battery of diagnostic, cognitive, and language assessments at two time points (mean 2.5 years apart). Nonparametric tests assessed changes in diagnostic classification in FXS over time, and hierarchical linear modeling and repeated measures assessed changes in individual ASD symptoms in FXS over time. Additionally, ANCOVAs compared ASD symptom severity and component phenotypes in boys with FXS-O, FXS-ASD, and ASD-O at both time points. RESULTS: Overall, ASD symptom manifestation for children with FXS significantly increased over time, and developmental predictors varied based on the domain of symptoms assessed. The greatest degree of overlap was observed between boys with FXS-ASD and ASD-O in the domain of reciprocal social communication across time points, whereas boys with ASD-O demonstrated greater impairment in restricted and repetitive behaviors at the later time point. CONCLUSIONS: ASD symptoms increased in FXS with age, and social language impairment emerged as a potential core shared feature of FXS and ASD that may help elucidate underlying molecular genetic variation related to phenotypic variance, and aid intervention planning for subgroups of children showing distinct phenotypes. Results highlight the value of a developmental perspective, and longitudinal data in particular, in evaluating shared behavioral phenotypes across genetic conditions, lending insight into underlying cognitive, neural, and genetic mechanisms associated with key developmental phenotypes in ASD and FXS. En ligne : http://dx.doi.org/10.1186/s11689-016-9179-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome [Texte imprimé et/ou numérique] / M. LEE, Auteur ; G. E. MARTIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; M. LOSH, Auteur . - p.47. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.47 Mots-clés : Autism spectrum disorder  Endophenotype  FMR1 gene  Fragile X syndrome  Language  Longitudinal  Pragmatics  Social behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Targeting overlapping behavioral phenotypes in neurogenetic disorders can help elucidate gene-behavior relationships. Fragile X syndrome (FXS) and autism spectrum disorder (ASD) have been studied as a model for this approach, and important areas of phenotypic overlap and divergence have been documented. However, few studies have examined how the manifestation of ASD-related phenotypes in FXS may change over development, a question which has important implications for conceptualizing shared etiologies of these disorders and their constituent phenotypes. The goal of this study was to characterize ASD phenotypes in boys and girls with FXS across development, as well as to compare individual component phenotypes among boys with FXS and boys with idiopathic ASD (ASD-O) over time. METHODS: Sixty-five boys and girls with FXS and 19 boys with ASD-O completed a battery of diagnostic, cognitive, and language assessments at two time points (mean 2.5 years apart). Nonparametric tests assessed changes in diagnostic classification in FXS over time, and hierarchical linear modeling and repeated measures assessed changes in individual ASD symptoms in FXS over time. Additionally, ANCOVAs compared ASD symptom severity and component phenotypes in boys with FXS-O, FXS-ASD, and ASD-O at both time points. RESULTS: Overall, ASD symptom manifestation for children with FXS significantly increased over time, and developmental predictors varied based on the domain of symptoms assessed. The greatest degree of overlap was observed between boys with FXS-ASD and ASD-O in the domain of reciprocal social communication across time points, whereas boys with ASD-O demonstrated greater impairment in restricted and repetitive behaviors at the later time point. CONCLUSIONS: ASD symptoms increased in FXS with age, and social language impairment emerged as a potential core shared feature of FXS and ASD that may help elucidate underlying molecular genetic variation related to phenotypic variance, and aid intervention planning for subgroups of children showing distinct phenotypes. Results highlight the value of a developmental perspective, and longitudinal data in particular, in evaluating shared behavioral phenotypes across genetic conditions, lending insight into underlying cognitive, neural, and genetic mechanisms associated with key developmental phenotypes in ASD and FXS. En ligne : http://dx.doi.org/10.1186/s11689-016-9179-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349