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Distinct neural bases of disruptive behavior and autism symptom severity in boys with autism spectrum disorder / Y. J. YANG in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.1 Titre : Distinct neural bases of disruptive behavior and autism symptom severity in boys with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Y. J. YANG, Auteur ; D. G. SUKHODOLSKY, Auteur ; J. LEI, Auteur ; E. DAYAN, Auteur ; Kevin A. PELPHREY, Auteur ; Pamela VENTOLA, Auteur Article en page(s) : p.1 Langues : Anglais (eng) Mots-clés : Adhd  Anxiety disorders  Autism spectrum disorder  Comorbidity  Default mode network  Disruptive behavior  Neuroimaging  Oppositional defiant disorder  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings of disruptive behavior in ASD, while addressing whether the neural basis is shared with or separable from that of core ASD symptoms. METHODS: Participants consisted of 48 male children and adolescents: 31 ASD (7 had high disruptive behavior) and 17 typically developing (TD) controls, well-matched on sex, age, and IQ. For ASD participants, autism symptom severity, disruptive behavior, anxiety symptoms, and ADHD symptoms were measured. All participants were scanned while viewing biological motion (BIO) and scrambled motion (SCR). Two fMRI contrasts were analyzed: social perception (BIO > SCR) and Default Mode Network (DMN) deactivation (fixation > BIO). Age and IQ were included as covariates of no interest in all analyses. RESULTS: First, the between-group analyses on BIO > SCR showed that ASD is characterized by hypoactivation in the social perception circuitry, and ASD with high or low disruptive behavior exhibited similar patterns of hypoactivation. Second, the between-group analyses on fixation > BIO showed that ASD with high disruptive behavior exhibited more restricted and less DMN deactivation, when compared to ASD with low disruptive behavior or TD. Third, the within-ASD analyses showed that (a) autism symptom severity (but not disruptive behavior) was uniquely associated with less activation in the social perception regions including the posterior superior temporal sulcus and inferior frontal gyrus; (b) disruptive behavior (but not autism symptom severity) was uniquely associated with less DMN deactivation in the medial prefrontal cortex (MPFC) and lateral parietal cortex; and (c) anxiety symptoms mediated the link between disruptive behavior and less DMN deactivation in both anterior cingulate cortex (ACC) and MPFC, while ADHD symptoms mediated the link primarily in ACC. CONCLUSIONS: In boys with ASD, disruptive behavior has a neural basis in reduced DMN deactivation, which is distinct and separable from that of core ASD symptoms, with the latter characterized by hypoactivation in the social perception circuitry. These differential neurobiological markers may potentially serve as neural targets or predictors for interventions when treating disruptive behavior vs. core symptoms in ASD. En ligne : http://dx.doi.org/10.1186/s11689-017-9183-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Distinct neural bases of disruptive behavior and autism symptom severity in boys with autism spectrum disorder [Texte imprimé et/ou numérique] / Y. J. YANG, Auteur ; D. G. SUKHODOLSKY, Auteur ; J. LEI, Auteur ; E. DAYAN, Auteur ; Kevin A. PELPHREY, Auteur ; Pamela VENTOLA, Auteur . - p.1. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.1 Mots-clés : Adhd  Anxiety disorders  Autism spectrum disorder  Comorbidity  Default mode network  Disruptive behavior  Neuroimaging  Oppositional defiant disorder  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings of disruptive behavior in ASD, while addressing whether the neural basis is shared with or separable from that of core ASD symptoms. METHODS: Participants consisted of 48 male children and adolescents: 31 ASD (7 had high disruptive behavior) and 17 typically developing (TD) controls, well-matched on sex, age, and IQ. For ASD participants, autism symptom severity, disruptive behavior, anxiety symptoms, and ADHD symptoms were measured. All participants were scanned while viewing biological motion (BIO) and scrambled motion (SCR). Two fMRI contrasts were analyzed: social perception (BIO > SCR) and Default Mode Network (DMN) deactivation (fixation > BIO). Age and IQ were included as covariates of no interest in all analyses. RESULTS: First, the between-group analyses on BIO > SCR showed that ASD is characterized by hypoactivation in the social perception circuitry, and ASD with high or low disruptive behavior exhibited similar patterns of hypoactivation. Second, the between-group analyses on fixation > BIO showed that ASD with high disruptive behavior exhibited more restricted and less DMN deactivation, when compared to ASD with low disruptive behavior or TD. Third, the within-ASD analyses showed that (a) autism symptom severity (but not disruptive behavior) was uniquely associated with less activation in the social perception regions including the posterior superior temporal sulcus and inferior frontal gyrus; (b) disruptive behavior (but not autism symptom severity) was uniquely associated with less DMN deactivation in the medial prefrontal cortex (MPFC) and lateral parietal cortex; and (c) anxiety symptoms mediated the link between disruptive behavior and less DMN deactivation in both anterior cingulate cortex (ACC) and MPFC, while ADHD symptoms mediated the link primarily in ACC. CONCLUSIONS: In boys with ASD, disruptive behavior has a neural basis in reduced DMN deactivation, which is distinct and separable from that of core ASD symptoms, with the latter characterized by hypoactivation in the social perception circuitry. These differential neurobiological markers may potentially serve as neural targets or predictors for interventions when treating disruptive behavior vs. core symptoms in ASD. En ligne : http://dx.doi.org/10.1186/s11689-017-9183-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Genotype- and sex-dependent effects of altered Cntnap2 expression on the function of visual cortical areas / L. B. TOWNSEND in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.2 Titre : Genotype- and sex-dependent effects of altered Cntnap2 expression on the function of visual cortical areas Type de document : Texte imprimé et/ou numérique Auteurs : L. B. TOWNSEND, Auteur ; S. L. SMITH, Auteur Article en page(s) : p.2 Langues : Anglais (eng) Mots-clés : Autism  Cortical circuits  Higher visual areas  Intrinsic signal optical imaging  Mouse models  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a heritable, heterogeneous neurodevelopmental disorder that is four times more likely to affect males than females. Despite this overt sex bias, it is unclear how genetic mutations associated with ASD alter cortical circuitry to produce the behavioral phenotypes by which ASD is diagnosed. Contactin-associated protein-like 2 (CNTNAP2) is an ASD-associated gene, and while Cntnap2 knockout (KO) mice recapitulate many of the features of ASD, the effect on cortical circuitry is poorly understood. Moreover, although heterozygous (Het) mice are the more relevant genotype for ASD-linked CNTNAP2 mutations in humans, to our knowledge, no effects in Het mice have been previously reported. METHODS: Intrinsic signal optical imaging was used to measure functional visual responses in primary and higher visual cortical areas in male and female Cntnap2 KO, Het, and wild-type (WT) mice. Main effect of genotype was assessed with one-way ANOVA. Visual responses were also measured in P17-18 and P30-32 KO and WT mice. Main effects of age and genotype were assessed using two-way ANOVA. RESULTS: Visually evoked activity in dorsal stream associated higher visual areas in both KO and Het adult males was decreased relative to WT adult males. This decrease was not observed in adult females. Additionally, no significant difference was observed between WT and KO males at P17-18 with differences beginning to emerge at P30-32. CONCLUSIONS: The functional responses of cortical circuitry in male mice are more strongly affected by Cntnap2 mutations than females, an effect present even in Hets. The observed differences in males emerge with development beginning at P30-32. These results reveal genotype- and sex-dependent effects of altered Cntnap2 expression and can shed light on the sex-dependent incidence of ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9182-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Genotype- and sex-dependent effects of altered Cntnap2 expression on the function of visual cortical areas [Texte imprimé et/ou numérique] / L. B. TOWNSEND, Auteur ; S. L. SMITH, Auteur . - p.2. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.2 Mots-clés : Autism  Cortical circuits  Higher visual areas  Intrinsic signal optical imaging  Mouse models  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a heritable, heterogeneous neurodevelopmental disorder that is four times more likely to affect males than females. Despite this overt sex bias, it is unclear how genetic mutations associated with ASD alter cortical circuitry to produce the behavioral phenotypes by which ASD is diagnosed. Contactin-associated protein-like 2 (CNTNAP2) is an ASD-associated gene, and while Cntnap2 knockout (KO) mice recapitulate many of the features of ASD, the effect on cortical circuitry is poorly understood. Moreover, although heterozygous (Het) mice are the more relevant genotype for ASD-linked CNTNAP2 mutations in humans, to our knowledge, no effects in Het mice have been previously reported. METHODS: Intrinsic signal optical imaging was used to measure functional visual responses in primary and higher visual cortical areas in male and female Cntnap2 KO, Het, and wild-type (WT) mice. Main effect of genotype was assessed with one-way ANOVA. Visual responses were also measured in P17-18 and P30-32 KO and WT mice. Main effects of age and genotype were assessed using two-way ANOVA. RESULTS: Visually evoked activity in dorsal stream associated higher visual areas in both KO and Het adult males was decreased relative to WT adult males. This decrease was not observed in adult females. Additionally, no significant difference was observed between WT and KO males at P17-18 with differences beginning to emerge at P30-32. CONCLUSIONS: The functional responses of cortical circuitry in male mice are more strongly affected by Cntnap2 mutations than females, an effect present even in Hets. The observed differences in males emerge with development beginning at P30-32. These results reveal genotype- and sex-dependent effects of altered Cntnap2 expression and can shed light on the sex-dependent incidence of ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9182-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Arbaclofen in fragile X syndrome: results of phase 3 trials / Elizabeth BERRY-KRAVIS in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.3 Titre : Arbaclofen in fragile X syndrome: results of phase 3 trials Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth BERRY-KRAVIS, Auteur ; Randi J. HAGERMAN, Auteur ; J. VISOOTSAK, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; W. E. KAUFMANN, Auteur ; M. CHERUBINI, Auteur ; P. ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; P. WANG, Auteur ; Mark F. BEAR, Auteur ; Randall L. CARPENTER, Auteur Article en page(s) : p.3 Langues : Anglais (eng) Mots-clés : Arbaclofen  Fmr1  Fragile X syndrome  GABA agonist  Neurodevelopmental disorder  Targeted treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: Arbaclofen improved multiple abnormal phenotypes in animal models of fragile X syndrome (FXS) and showed promising results in a phase 2 clinical study. The objective of the study is to determine safety and efficacy of arbaclofen for social avoidance in FXS. METHODS: Two phase 3 placebo-controlled trials were conducted, a flexible dose trial in subjects age 12-50 (209FX301, adolescent/adult study) and a fixed dose trial in subjects age 5-11 (209FX302, child study). The primary endpoint for both trials was the Social Avoidance subscale of the Aberrant Behavior Checklist-Community Edition, FXS-specific (ABC-CFX). Secondary outcomes included other ABC-CFX subscale scores, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S), and Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Socialization domain score. RESULTS: A total 119 of 125 randomized subjects completed the adolescent/adult study (n = 57 arbaclofen, 62 placebo) and 159/172 completed the child study (arbaclofen 5 BID n = 38; 10 BID n = 39; 10 TID n = 38; placebo n = 44). There were no serious adverse events (AEs); the most common AEs included somatic (headache, vomiting, nausea), neurobehavioral (irritability/agitation, anxiety, hyperactivity), decreased appetite, and infectious conditions, many of which were also common on placebo. In the combined studies, there were 13 discontinuations (n = 12 arbaclofen, 1 placebo) due to AEs (all neurobehavioral). The adolescent/adult study did not show benefit for arbaclofen over placebo for any measure. In the child study, the highest dose group showed benefit over placebo on the ABC-CFX Irritability subscale (p = 0.03) and Parenting Stress Index (PSI, p = 0.03) and trends toward benefit on the ABC-CFX Social Avoidance and Hyperactivity subscales (both p < 0.1) and CGI-I (p = 0.119). Effect size in the highest dose group was similar to effect sizes for FDA-approved serotonin reuptake inhibitors (SSRIs). CONCLUSIONS: Arbaclofen did not meet the primary outcome of improved social avoidance in FXS in either study. Data from secondary measures in the child study suggests younger patients may derive benefit, but additional studies with a larger cohort on higher doses would be required to confirm this finding. The reported studies illustrate the challenges but represent a significant step forward in translating targeted treatments from preclinical models to clinical trials in humans with FXS. En ligne : http://dx.doi.org/10.1186/s11689-016-9181-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Arbaclofen in fragile X syndrome: results of phase 3 trials [Texte imprimé et/ou numérique] / Elizabeth BERRY-KRAVIS, Auteur ; Randi J. HAGERMAN, Auteur ; J. VISOOTSAK, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; W. E. KAUFMANN, Auteur ; M. CHERUBINI, Auteur ; P. ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; P. WANG, Auteur ; Mark F. BEAR, Auteur ; Randall L. CARPENTER, Auteur . - p.3. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.3 Mots-clés : Arbaclofen  Fmr1  Fragile X syndrome  GABA agonist  Neurodevelopmental disorder  Targeted treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: Arbaclofen improved multiple abnormal phenotypes in animal models of fragile X syndrome (FXS) and showed promising results in a phase 2 clinical study. The objective of the study is to determine safety and efficacy of arbaclofen for social avoidance in FXS. METHODS: Two phase 3 placebo-controlled trials were conducted, a flexible dose trial in subjects age 12-50 (209FX301, adolescent/adult study) and a fixed dose trial in subjects age 5-11 (209FX302, child study). The primary endpoint for both trials was the Social Avoidance subscale of the Aberrant Behavior Checklist-Community Edition, FXS-specific (ABC-CFX). Secondary outcomes included other ABC-CFX subscale scores, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S), and Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Socialization domain score. RESULTS: A total 119 of 125 randomized subjects completed the adolescent/adult study (n = 57 arbaclofen, 62 placebo) and 159/172 completed the child study (arbaclofen 5 BID n = 38; 10 BID n = 39; 10 TID n = 38; placebo n = 44). There were no serious adverse events (AEs); the most common AEs included somatic (headache, vomiting, nausea), neurobehavioral (irritability/agitation, anxiety, hyperactivity), decreased appetite, and infectious conditions, many of which were also common on placebo. In the combined studies, there were 13 discontinuations (n = 12 arbaclofen, 1 placebo) due to AEs (all neurobehavioral). The adolescent/adult study did not show benefit for arbaclofen over placebo for any measure. In the child study, the highest dose group showed benefit over placebo on the ABC-CFX Irritability subscale (p = 0.03) and Parenting Stress Index (PSI, p = 0.03) and trends toward benefit on the ABC-CFX Social Avoidance and Hyperactivity subscales (both p < 0.1) and CGI-I (p = 0.119). Effect size in the highest dose group was similar to effect sizes for FDA-approved serotonin reuptake inhibitors (SSRIs). CONCLUSIONS: Arbaclofen did not meet the primary outcome of improved social avoidance in FXS in either study. Data from secondary measures in the child study suggests younger patients may derive benefit, but additional studies with a larger cohort on higher doses would be required to confirm this finding. The reported studies illustrate the challenges but represent a significant step forward in translating targeted treatments from preclinical models to clinical trials in humans with FXS. En ligne : http://dx.doi.org/10.1186/s11689-016-9181-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder / K. H. FINCH in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.4 Titre : Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : K. H. FINCH, Auteur ; A. M. SEERY, Auteur ; Meagan R. TALBOTT, Auteur ; C. A. NELSON, Auteur ; Helen TAGER-FLUSBERG, Auteur Article en page(s) : p.4 Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  Event-related potentials  Handedness  Lateralization  Speech processing Index. décimale : PER Périodiques Résumé : BACKGROUND: Language is a highly lateralized function, with typically developing individuals showing left hemispheric specialization. Individuals with autism spectrum disorder (ASD) often show reduced or reversed hemispheric lateralization in response to language. However, it is unclear when this difference emerges and whether or not it can serve as an early ASD biomarker. Additionally, atypical language lateralization is not specific to ASD as it is also seen more frequently in individuals with mixed- and left-handedness. Here, we examined early asymmetry patterns measured through neural responses to speech sounds at 12 months and behavioral observations of handedness at 36 months in children with and without ASD. METHODS: Three different groups of children participated in the study: low-risk controls (LRC), high risk for ASD (HRA; infants with older sibling with ASD) without ASD, and HRA infants who later receive a diagnosis of ASD (ASD). Event-related potentials (ERPs) to speech sounds were recorded at 12 months. Utilizing a novel observational approach, handedness was measured by hand preference on a variety of behaviors at 36 months. RESULTS: At 12 months, lateralization patterns of ERPs to speech stimuli differed across the groups with the ASD group showing reversed lateralization compared to the LRC group. At 36 months, factor analysis of behavioral observations of hand preferences indicated a one-factor model with medium to high factor loadings. A composite handedness score was derived; no group differences were observed. There was no association between lateralization to speech at 12 months and handedness at 36 months in the LRC and HRA groups. However, children with ASD did show an association such that infants with lateralization patterns more similar to the LRC group at 12 months were stronger right-handers at 36 months. CONCLUSIONS: These results highlight early developmental patterns that might be specific to ASD, including a potential early biomarker of reversed lateralization to speech stimuli at 12 months, and a relation between behavioral and neural asymmetries. Future investigations of early asymmetry patterns, especially atypical hemispheric specialization, may be informative in the early identification of ASD. En ligne : http://dx.doi.org/10.1186/s11689-017-9185-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder [Texte imprimé et/ou numérique] / K. H. FINCH, Auteur ; A. M. SEERY, Auteur ; Meagan R. TALBOTT, Auteur ; C. A. NELSON, Auteur ; Helen TAGER-FLUSBERG, Auteur . - p.4. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.4 Mots-clés : Autism spectrum disorders  Event-related potentials  Handedness  Lateralization  Speech processing Index. décimale : PER Périodiques Résumé : BACKGROUND: Language is a highly lateralized function, with typically developing individuals showing left hemispheric specialization. Individuals with autism spectrum disorder (ASD) often show reduced or reversed hemispheric lateralization in response to language. However, it is unclear when this difference emerges and whether or not it can serve as an early ASD biomarker. Additionally, atypical language lateralization is not specific to ASD as it is also seen more frequently in individuals with mixed- and left-handedness. Here, we examined early asymmetry patterns measured through neural responses to speech sounds at 12 months and behavioral observations of handedness at 36 months in children with and without ASD. METHODS: Three different groups of children participated in the study: low-risk controls (LRC), high risk for ASD (HRA; infants with older sibling with ASD) without ASD, and HRA infants who later receive a diagnosis of ASD (ASD). Event-related potentials (ERPs) to speech sounds were recorded at 12 months. Utilizing a novel observational approach, handedness was measured by hand preference on a variety of behaviors at 36 months. RESULTS: At 12 months, lateralization patterns of ERPs to speech stimuli differed across the groups with the ASD group showing reversed lateralization compared to the LRC group. At 36 months, factor analysis of behavioral observations of hand preferences indicated a one-factor model with medium to high factor loadings. A composite handedness score was derived; no group differences were observed. There was no association between lateralization to speech at 12 months and handedness at 36 months in the LRC and HRA groups. However, children with ASD did show an association such that infants with lateralization patterns more similar to the LRC group at 12 months were stronger right-handers at 36 months. CONCLUSIONS: These results highlight early developmental patterns that might be specific to ASD, including a potential early biomarker of reversed lateralization to speech stimuli at 12 months, and a relation between behavioral and neural asymmetries. Future investigations of early asymmetry patterns, especially atypical hemispheric specialization, may be informative in the early identification of ASD. En ligne : http://dx.doi.org/10.1186/s11689-017-9185-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families / M. WOODBURY-SMITH in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.5 Titre : Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families Type de document : Texte imprimé et/ou numérique Auteurs : M. WOODBURY-SMITH, Auteur ; Deborah A. BILDER, Auteur ; J. MORGAN, Auteur ; L. JEROMINSKI, Auteur ; T. DARLINGTON, Auteur ; T. DYER, Auteur ; Andrew D. PATERSON, Auteur ; H. COON, Auteur Article en page(s) : p.5 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Genetic association  Genome-wide linkage  Head circumference (HC) Index. décimale : PER Périodiques Résumé : BACKGROUND: It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. METHODS: HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. RESULTS: We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p = 1.72E-07). CONCLUSIONS: Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD. En ligne : http://dx.doi.org/10.1186/s11689-017-9187-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families [Texte imprimé et/ou numérique] / M. WOODBURY-SMITH, Auteur ; Deborah A. BILDER, Auteur ; J. MORGAN, Auteur ; L. JEROMINSKI, Auteur ; T. DARLINGTON, Auteur ; T. DYER, Auteur ; Andrew D. PATERSON, Auteur ; H. COON, Auteur . - p.5. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.5 Mots-clés : Autism spectrum disorder (ASD)  Genetic association  Genome-wide linkage  Head circumference (HC) Index. décimale : PER Périodiques Résumé : BACKGROUND: It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. METHODS: HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. RESULTS: We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p = 1.72E-07). CONCLUSIONS: Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD. En ligne : http://dx.doi.org/10.1186/s11689-017-9187-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety / T. L. SCHAEFER in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.6 Titre : Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety Type de document : Texte imprimé et/ou numérique Auteurs : T. L. SCHAEFER, Auteur ; M. H. DAVENPORT, Auteur ; L. M. GRAINGER, Auteur ; C. K. ROBINSON, Auteur ; A. T. EARNHEART, Auteur ; M. S. STEGMAN, Auteur ; A. L. LANG, Auteur ; A. ASHWORTH, Auteur ; G. MOLINARO, Auteur ; K. M. HUBER, Auteur ; C. A. ERICKSON, Auteur Article en page(s) : p.6 Langues : Anglais (eng) Mots-clés : Anxiety  Dendritic spine density  Electrophysiology  Extracellular signal-related kinase  Fragile X syndrome  Hippocampus  Hyperactivity  Open field  Striatum Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X Syndrome (FXS) occurs as a result of a silenced fragile X mental retardation 1 gene (FMR1) and subsequent loss of fragile X mental retardation protein (FMRP) expression. Loss of FMRP alters excitatory/inhibitory signaling balance, leading to increased neuronal hyperexcitability and altered behavior. Acamprosate (the calcium salt of N-acetylhomotaurinate), a drug FDA-approved for relapse prevention in the treatment of alcohol dependence in adults, is a novel agent with multiple mechanisms that may be beneficial for people with FXS. There are questions regarding the neuroactive effects of acamprosate and the significance of the molecule's calcium moiety. Therefore, the electrophysiological, cellular, molecular, and behavioral effects of acamprosate were assessed in the Fmr1(-/y) (knock out; KO) mouse model of FXS controlling for the calcium salt in several experiments. METHODS: Fmr1 KO mice and their wild-type (WT) littermates were utilized to assess acamprosate treatment on cortical UP state parameters, dendritic spine density, and seizure susceptibility. Brain extracellular-signal regulated kinase 1/2 (ERK1/2) activation was used to investigate this signaling molecule as a potential biomarker for treatment response. Additional adult mice were used to assess chronic acamprosate treatment and any potential effects of the calcium moiety using CaCl2 treatment on behavior and nuclear ERK1/2 activation. RESULTS: Acamprosate attenuated prolonged cortical UP state duration, decreased elevated ERK1/2 activation in brain tissue, and reduced nuclear ERK1/2 activation in the dentate gyrus in KO mice. Acamprosate treatment modified behavior in anxiety and locomotor tests in Fmr1 KO mice in which control-treated KO mice were shown to deviate from control-treated WT mice. Mice treated with CaCl2 were not different from saline-treated mice in the adult behavior battery or nuclear ERK1/2 activation. CONCLUSIONS: These data indicate that acamprosate, and not calcium, improves function reminiscent of reduced anxiety-like behavior and hyperactivity in Fmr1 KO mice and that acamprosate attenuates select electrophysiological and molecular dysregulation that may play a role in the pathophysiology of FXS. Differences between control-treated KO and WT mice were not evident in a recognition memory test or in examination of acoustic startle response/prepulse inhibition which impeded conclusions from being made about the treatment effects of acamprosate in these instances. En ligne : http://dx.doi.org/10.1186/s11689-017-9184-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety [Texte imprimé et/ou numérique] / T. L. SCHAEFER, Auteur ; M. H. DAVENPORT, Auteur ; L. M. GRAINGER, Auteur ; C. K. ROBINSON, Auteur ; A. T. EARNHEART, Auteur ; M. S. STEGMAN, Auteur ; A. L. LANG, Auteur ; A. ASHWORTH, Auteur ; G. MOLINARO, Auteur ; K. M. HUBER, Auteur ; C. A. ERICKSON, Auteur . - p.6. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.6 Mots-clés : Anxiety  Dendritic spine density  Electrophysiology  Extracellular signal-related kinase  Fragile X syndrome  Hippocampus  Hyperactivity  Open field  Striatum Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X Syndrome (FXS) occurs as a result of a silenced fragile X mental retardation 1 gene (FMR1) and subsequent loss of fragile X mental retardation protein (FMRP) expression. Loss of FMRP alters excitatory/inhibitory signaling balance, leading to increased neuronal hyperexcitability and altered behavior. Acamprosate (the calcium salt of N-acetylhomotaurinate), a drug FDA-approved for relapse prevention in the treatment of alcohol dependence in adults, is a novel agent with multiple mechanisms that may be beneficial for people with FXS. There are questions regarding the neuroactive effects of acamprosate and the significance of the molecule's calcium moiety. Therefore, the electrophysiological, cellular, molecular, and behavioral effects of acamprosate were assessed in the Fmr1(-/y) (knock out; KO) mouse model of FXS controlling for the calcium salt in several experiments. METHODS: Fmr1 KO mice and their wild-type (WT) littermates were utilized to assess acamprosate treatment on cortical UP state parameters, dendritic spine density, and seizure susceptibility. Brain extracellular-signal regulated kinase 1/2 (ERK1/2) activation was used to investigate this signaling molecule as a potential biomarker for treatment response. Additional adult mice were used to assess chronic acamprosate treatment and any potential effects of the calcium moiety using CaCl2 treatment on behavior and nuclear ERK1/2 activation. RESULTS: Acamprosate attenuated prolonged cortical UP state duration, decreased elevated ERK1/2 activation in brain tissue, and reduced nuclear ERK1/2 activation in the dentate gyrus in KO mice. Acamprosate treatment modified behavior in anxiety and locomotor tests in Fmr1 KO mice in which control-treated KO mice were shown to deviate from control-treated WT mice. Mice treated with CaCl2 were not different from saline-treated mice in the adult behavior battery or nuclear ERK1/2 activation. CONCLUSIONS: These data indicate that acamprosate, and not calcium, improves function reminiscent of reduced anxiety-like behavior and hyperactivity in Fmr1 KO mice and that acamprosate attenuates select electrophysiological and molecular dysregulation that may play a role in the pathophysiology of FXS. Differences between control-treated KO and WT mice were not evident in a recognition memory test or in examination of acoustic startle response/prepulse inhibition which impeded conclusions from being made about the treatment effects of acamprosate in these instances. En ligne : http://dx.doi.org/10.1186/s11689-017-9184-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Fragile X targeted pharmacotherapy: lessons learned and future directions / C. A. ERICKSON in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.7 Titre : Fragile X targeted pharmacotherapy: lessons learned and future directions Type de document : Texte imprimé et/ou numérique Auteurs : C. A. ERICKSON, Auteur ; M. H. DAVENPORT, Auteur ; T. L. SCHAEFER, Auteur ; L. K. WINK, Auteur ; Ernest V. PEDAPATI, Auteur ; J. A. SWEENEY, Auteur ; S. E. FITZPATRICK, Auteur ; W. Ted BROWN, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; Randi J. HAGERMAN, Auteur ; D. HESSL, Auteur ; W. E. KAUFMANN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur Article en page(s) : p.7 Langues : Anglais (eng) Mots-clés : Drug development  Fragile X syndrome  Genetic disorder  Targeted treatments  Translational treatment Index. décimale : PER Périodiques Résumé : Our understanding of fragile X syndrome (FXS) pathophysiology continues to improve and numerous potential drug targets have been identified. Yet, current prescribing practices are only symptom-based in order to manage difficult behaviors, as no drug to date is approved for the treatment of FXS. Drugs impacting a diversity of targets in the brain have been studied in recent FXS-specific clinical trials. While many drugs have focused on regulation of enhanced glutamatergic or deficient GABAergic neurotransmission, compounds studied have not been limited to these mechanisms. As a single-gene disorder, it was thought that FXS would have consistent drug targets that could be modulated with pharmacotherapy and lead to significant improvement. Unfortunately, despite promising results in FXS animal models, translational drug treatment development in FXS has largely failed. Future success in this field will depend on learning from past challenges to improve clinical trial design, choose appropriate outcome measures and age range choices, and find readily modulated drug targets. Even with many negative placebo-controlled study results, the field continues to move forward exploring both the new mechanistic drug approaches combined with ways to improve trial execution. This review summarizes the known phenotype and pathophysiology of FXS and past clinical trial rationale and results, and discusses current challenges facing the field and lessons from which to learn for future treatment development efforts. En ligne : http://dx.doi.org/10.1186/s11689-017-9186-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Fragile X targeted pharmacotherapy: lessons learned and future directions [Texte imprimé et/ou numérique] / C. A. ERICKSON, Auteur ; M. H. DAVENPORT, Auteur ; T. L. SCHAEFER, Auteur ; L. K. WINK, Auteur ; Ernest V. PEDAPATI, Auteur ; J. A. SWEENEY, Auteur ; S. E. FITZPATRICK, Auteur ; W. Ted BROWN, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; Randi J. HAGERMAN, Auteur ; D. HESSL, Auteur ; W. E. KAUFMANN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur . - p.7. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.7 Mots-clés : Drug development  Fragile X syndrome  Genetic disorder  Targeted treatments  Translational treatment Index. décimale : PER Périodiques Résumé : Our understanding of fragile X syndrome (FXS) pathophysiology continues to improve and numerous potential drug targets have been identified. Yet, current prescribing practices are only symptom-based in order to manage difficult behaviors, as no drug to date is approved for the treatment of FXS. Drugs impacting a diversity of targets in the brain have been studied in recent FXS-specific clinical trials. While many drugs have focused on regulation of enhanced glutamatergic or deficient GABAergic neurotransmission, compounds studied have not been limited to these mechanisms. As a single-gene disorder, it was thought that FXS would have consistent drug targets that could be modulated with pharmacotherapy and lead to significant improvement. Unfortunately, despite promising results in FXS animal models, translational drug treatment development in FXS has largely failed. Future success in this field will depend on learning from past challenges to improve clinical trial design, choose appropriate outcome measures and age range choices, and find readily modulated drug targets. Even with many negative placebo-controlled study results, the field continues to move forward exploring both the new mechanistic drug approaches combined with ways to improve trial execution. This review summarizes the known phenotype and pathophysiology of FXS and past clinical trial rationale and results, and discusses current challenges facing the field and lessons from which to learn for future treatment development efforts. En ligne : http://dx.doi.org/10.1186/s11689-017-9186-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Preserved search asymmetry in the detection of fearful faces among neutral faces in individuals with Williams syndrome revealed by measurement of both manual responses and eye tracking / M. HIRAI in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.8 Titre : Preserved search asymmetry in the detection of fearful faces among neutral faces in individuals with Williams syndrome revealed by measurement of both manual responses and eye tracking 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.8 Langues : Anglais (eng) Mots-clés : Attention  Eye tracking  Fearful face detection  Search asymmetry  Visual search  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with Williams syndrome (WS) exhibit an atypical social phenotype termed hypersociability. One theory accounting for hypersociability presumes an atypical function of the amygdala, which processes fear-related information. However, evidence is lacking regarding the detection mechanisms of fearful faces for individuals with WS. Here, we introduce a visual search paradigm to elucidate the mechanisms for detecting fearful faces by evaluating the search asymmetry; the reaction time when both the target and distractors were swapped was asymmetrical. METHODS: Eye movements reflect subtle atypical attentional properties, whereas, manual responses are unable to capture atypical attentional profiles toward faces in individuals with WS. Therefore, we measured both eye movements and manual responses of individuals with WS and typically developed children and adults in visual searching for a fearful face among neutral faces or a neutral face among fearful faces. Two task measures, namely reaction time and performance accuracy, were analyzed for each stimulus as well as gaze behavior and the initial fixation onset latency. RESULTS: Overall, reaction times in the WS group and the mentally age-matched control group were significantly longer than those in the chronologically age-matched group. We observed a search asymmetry effect in all groups: when a neutral target facial expression was presented among fearful faces, the reaction times were significantly prolonged in comparison with when a fearful target facial expression was displayed among neutral distractor faces. Furthermore, the first fixation onset latency of eye movement toward a target facial expression showed a similar tendency for manual responses. CONCLUSIONS: Although overall responses in detecting fearful faces for individuals with WS are slower than those for control groups, search asymmetry was observed. Therefore, cognitive mechanisms underlying the detection of fearful faces seem to be typical in individuals with WS. This finding is discussed with reference to the amygdala account explaining hypersociability in individuals with WS. En ligne : http://dx.doi.org/10.1186/s11689-017-9190-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Preserved search asymmetry in the detection of fearful faces among neutral faces in individuals with Williams syndrome revealed by measurement of both manual responses and eye tracking [Texte imprimé et/ou numérique] / M. HIRAI, Auteur ; Y. MURAMATSU, Auteur ; S. MIZUNO, Auteur ; N. KURAHASHI, Auteur ; H. KURAHASHI, Auteur ; M. NAKAMURA, Auteur . - p.8. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.8 Mots-clés : Attention  Eye tracking  Fearful face detection  Search asymmetry  Visual search  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with Williams syndrome (WS) exhibit an atypical social phenotype termed hypersociability. One theory accounting for hypersociability presumes an atypical function of the amygdala, which processes fear-related information. However, evidence is lacking regarding the detection mechanisms of fearful faces for individuals with WS. Here, we introduce a visual search paradigm to elucidate the mechanisms for detecting fearful faces by evaluating the search asymmetry; the reaction time when both the target and distractors were swapped was asymmetrical. METHODS: Eye movements reflect subtle atypical attentional properties, whereas, manual responses are unable to capture atypical attentional profiles toward faces in individuals with WS. Therefore, we measured both eye movements and manual responses of individuals with WS and typically developed children and adults in visual searching for a fearful face among neutral faces or a neutral face among fearful faces. Two task measures, namely reaction time and performance accuracy, were analyzed for each stimulus as well as gaze behavior and the initial fixation onset latency. RESULTS: Overall, reaction times in the WS group and the mentally age-matched control group were significantly longer than those in the chronologically age-matched group. We observed a search asymmetry effect in all groups: when a neutral target facial expression was presented among fearful faces, the reaction times were significantly prolonged in comparison with when a fearful target facial expression was displayed among neutral distractor faces. Furthermore, the first fixation onset latency of eye movement toward a target facial expression showed a similar tendency for manual responses. CONCLUSIONS: Although overall responses in detecting fearful faces for individuals with WS are slower than those for control groups, search asymmetry was observed. Therefore, cognitive mechanisms underlying the detection of fearful faces seem to be typical in individuals with WS. This finding is discussed with reference to the amygdala account explaining hypersociability in individuals with WS. En ligne : http://dx.doi.org/10.1186/s11689-017-9190-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Differential effects of anxiety and autism on social scene scanning in males with fragile X syndrome / Hayley CRAWFORD in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.9 Titre : Differential effects of anxiety and autism on social scene scanning in males with fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Hayley CRAWFORD, Auteur ; J. MOSS, Auteur ; C. OLIVER, Auteur ; D. RIBY, Auteur Article en page(s) : p.9 Langues : Anglais (eng) Mots-clés : Anxiety  Autism spectrum disorder  Eye tracking  Fragile X syndrome  Social attention Index. décimale : PER Périodiques Résumé : BACKGROUND: Existing literature draws links between social attention and socio-behavioural profiles in neurodevelopmental disorders. Fragile X syndrome (FXS) is associated with a known socio-behavioural phenotype of social anxiety and social communication difficulties alongside high social motivation. However, studies investigating social attention in males with FXS are scarce. Using eye tracking, this study investigates social attention and its relationship with both anxiety and autism symptomatology in males with FXS. METHODS: We compared dwell times to the background, body, and face regions of naturalistic social scenes in 11 males with FXS (M age = 26.29) and 11 typically developing (TD) children who were matched on gender and receptive language ability (M age = 6.28). Using informant-report measures, we then investigated the relationships between social scene scanning and anxiety, and social scene scanning and social communicative impairments. RESULTS: Males with FXS did not differ to TD children on overall dwell time to the background, body, or face regions of the naturalistic social scenes. Whilst males with FXS displayed developmentally 'typical' social attention, increased looking at faces was associated with both heightened anxiety and fewer social communication impairments in this group. CONCLUSIONS: These results offer novel insights into the mechanisms associated with social attention in FXS and provide evidence to suggest that anxiety and autism symptomatology, which are both heightened in FXS, have differential effects on social attention. En ligne : http://dx.doi.org/10.1186/s11689-017-9189-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Differential effects of anxiety and autism on social scene scanning in males with fragile X syndrome [Texte imprimé et/ou numérique] / Hayley CRAWFORD, Auteur ; J. MOSS, Auteur ; C. OLIVER, Auteur ; D. RIBY, Auteur . - p.9. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.9 Mots-clés : Anxiety  Autism spectrum disorder  Eye tracking  Fragile X syndrome  Social attention Index. décimale : PER Périodiques Résumé : BACKGROUND: Existing literature draws links between social attention and socio-behavioural profiles in neurodevelopmental disorders. Fragile X syndrome (FXS) is associated with a known socio-behavioural phenotype of social anxiety and social communication difficulties alongside high social motivation. However, studies investigating social attention in males with FXS are scarce. Using eye tracking, this study investigates social attention and its relationship with both anxiety and autism symptomatology in males with FXS. METHODS: We compared dwell times to the background, body, and face regions of naturalistic social scenes in 11 males with FXS (M age = 26.29) and 11 typically developing (TD) children who were matched on gender and receptive language ability (M age = 6.28). Using informant-report measures, we then investigated the relationships between social scene scanning and anxiety, and social scene scanning and social communicative impairments. RESULTS: Males with FXS did not differ to TD children on overall dwell time to the background, body, or face regions of the naturalistic social scenes. Whilst males with FXS displayed developmentally 'typical' social attention, increased looking at faces was associated with both heightened anxiety and fewer social communication impairments in this group. CONCLUSIONS: These results offer novel insights into the mechanisms associated with social attention in FXS and provide evidence to suggest that anxiety and autism symptomatology, which are both heightened in FXS, have differential effects on social attention. En ligne : http://dx.doi.org/10.1186/s11689-017-9189-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Erratum to: A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome / M. LEE in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.10 Titre : Erratum to: 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.10 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s11689-016-9179-0.]. En ligne : http://dx.doi.org/10.1186/s11689-017-9192-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Erratum to: 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.10. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.10 Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s11689-016-9179-0.]. En ligne : http://dx.doi.org/10.1186/s11689-017-9192-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome / J. WANG in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.11 Titre : A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. WANG, Auteur ; L. E. ETHRIDGE, Auteur ; M. W. MOSCONI, Auteur ; S. P. WHITE, Auteur ; D. K. BINDER, Auteur ; Ernest V. PEDAPATI, Auteur ; C. A. ERICKSON, Auteur ; M. J. BYERLY, Auteur ; J. A. SWEENEY, Auteur Article en page(s) : p.11 Langues : Anglais (eng) Mots-clés : Cross-frequency coupling  Eeg  Fragile X syndrome  Gamma  Hyperexcitability  Top-down modulation Index. décimale : PER Périodiques Résumé : BACKGROUND: Cortical hyperexcitability due to abnormal fast-spiking inhibitory interneuron function has been documented in fmr1 KO mice, a mouse model of the fragile X syndrome which is the most common single gene cause of autism and intellectual disability. METHODS: We collected resting state dense-array electroencephalography data from 21 fragile X syndrome (FXS) patients and 21 age-matched healthy participants. RESULTS: FXS patients exhibited greater gamma frequency band power, which was correlated with social and sensory processing difficulties. Second, FXS patients showed increased spatial spreading of phase-synchronized high frequency neural activity in the gamma band. Third, we observed increased negative theta-to-gamma but decreased alpha-to-gamma band amplitude coupling, and the level of increased theta power was inversely related to the level of resting gamma power in FXS. CONCLUSIONS: Increased theta band power and coupling from frontal sources may represent a mechanism providing compensatory inhibition of high-frequency gamma band activity, potentially contributing to the widely varying level of neurophysiological and behavioral abnormalities and treatment response seen in full-mutation FXS patients. These findings extend preclinical observations and provide new mechanistic insights into brain alterations and their variability across FXS patients. Electrophysiological measures may provide useful translational biomarkers for advancing drug development and individualizing treatments for neurodevelopmental disorders with associated neuronal hyperexcitability. En ligne : http://dx.doi.org/10.1186/s11689-017-9191-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome [Texte imprimé et/ou numérique] / J. WANG, Auteur ; L. E. ETHRIDGE, Auteur ; M. W. MOSCONI, Auteur ; S. P. WHITE, Auteur ; D. K. BINDER, Auteur ; Ernest V. PEDAPATI, Auteur ; C. A. ERICKSON, Auteur ; M. J. BYERLY, Auteur ; J. A. SWEENEY, Auteur . - p.11. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.11 Mots-clés : Cross-frequency coupling  Eeg  Fragile X syndrome  Gamma  Hyperexcitability  Top-down modulation Index. décimale : PER Périodiques Résumé : BACKGROUND: Cortical hyperexcitability due to abnormal fast-spiking inhibitory interneuron function has been documented in fmr1 KO mice, a mouse model of the fragile X syndrome which is the most common single gene cause of autism and intellectual disability. METHODS: We collected resting state dense-array electroencephalography data from 21 fragile X syndrome (FXS) patients and 21 age-matched healthy participants. RESULTS: FXS patients exhibited greater gamma frequency band power, which was correlated with social and sensory processing difficulties. Second, FXS patients showed increased spatial spreading of phase-synchronized high frequency neural activity in the gamma band. Third, we observed increased negative theta-to-gamma but decreased alpha-to-gamma band amplitude coupling, and the level of increased theta power was inversely related to the level of resting gamma power in FXS. CONCLUSIONS: Increased theta band power and coupling from frontal sources may represent a mechanism providing compensatory inhibition of high-frequency gamma band activity, potentially contributing to the widely varying level of neurophysiological and behavioral abnormalities and treatment response seen in full-mutation FXS patients. These findings extend preclinical observations and provide new mechanistic insights into brain alterations and their variability across FXS patients. Electrophysiological measures may provide useful translational biomarkers for advancing drug development and individualizing treatments for neurodevelopmental disorders with associated neuronal hyperexcitability. En ligne : http://dx.doi.org/10.1186/s11689-017-9191-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome / A. LUKOSHE in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.12 Titre : Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. LUKOSHE, Auteur ; S. E. VAN DIJK, Auteur ; G. E. VAN DEN BOSCH, Auteur ; A. VAN DER LUGT, Auteur ; T. WHITE, Auteur ; A. C. HOKKEN-KOELEGA, Auteur Article en page(s) : p.12 Langues : Anglais (eng) Mots-clés : 15q11-q13  Functional resting-state connectivity  Hypothalamus  Neurodevelopmental disorders  Pituitary gland  Prader-Willi syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional connectivity with other brain regions. Thus, the aim of this study was to examine the anatomical differences of the hypothalamus, mammillary bodies, and pituitary gland as well as resting state functional connectivity of the hypothalamus in children with PWS. METHODS: Twenty-seven children with PWS (13 DEL, 14 mUPD) and 28 typically developing children were included. Manual segmentations by a blinded investigator were performed to determine the volumes of the hypothalamus, mammillary bodies, and pituitary gland. In addition, brain-wide functional connectivity analysis was performed using the obtained masks of the hypothalamus. RESULTS: Children with PWS showed altered resting state functional connectivity between hypothalamus and right and left lateral occipital complex, compared to healthy controls. In addition, children with PWS had on average a 50% smaller pituitary volume, an irregular shape of the pituitary, and a longer pituitary stalk. Pituitary volume did not increase in volume during puberty in PWS. No volumetric differences in the hypothalamus and mammillary bodies were found. In all subjects, the posterior pituitary bright spot was observed. CONCLUSIONS: We report altered functional hypothalamic connectivity with lateral occipital complexes in both hemispheres, which are implicated in response to food and reward system, and absence of connectivity might therefore at least partially contribute to the preoccupation with food in PWS. En ligne : http://dx.doi.org/10.1186/s11689-017-9188-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome [Texte imprimé et/ou numérique] / A. LUKOSHE, Auteur ; S. E. VAN DIJK, Auteur ; G. E. VAN DEN BOSCH, Auteur ; A. VAN DER LUGT, Auteur ; T. WHITE, Auteur ; A. C. HOKKEN-KOELEGA, Auteur . - p.12. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.12 Mots-clés : 15q11-q13  Functional resting-state connectivity  Hypothalamus  Neurodevelopmental disorders  Pituitary gland  Prader-Willi syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional connectivity with other brain regions. Thus, the aim of this study was to examine the anatomical differences of the hypothalamus, mammillary bodies, and pituitary gland as well as resting state functional connectivity of the hypothalamus in children with PWS. METHODS: Twenty-seven children with PWS (13 DEL, 14 mUPD) and 28 typically developing children were included. Manual segmentations by a blinded investigator were performed to determine the volumes of the hypothalamus, mammillary bodies, and pituitary gland. In addition, brain-wide functional connectivity analysis was performed using the obtained masks of the hypothalamus. RESULTS: Children with PWS showed altered resting state functional connectivity between hypothalamus and right and left lateral occipital complex, compared to healthy controls. In addition, children with PWS had on average a 50% smaller pituitary volume, an irregular shape of the pituitary, and a longer pituitary stalk. Pituitary volume did not increase in volume during puberty in PWS. No volumetric differences in the hypothalamus and mammillary bodies were found. In all subjects, the posterior pituitary bright spot was observed. CONCLUSIONS: We report altered functional hypothalamic connectivity with lateral occipital complexes in both hemispheres, which are implicated in response to food and reward system, and absence of connectivity might therefore at least partially contribute to the preoccupation with food in PWS. En ligne : http://dx.doi.org/10.1186/s11689-017-9188-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Atypical sound discrimination in children with ASD as indicated by cortical ERPs / Aurélie BIDET-CAULET in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.13 Titre : Atypical sound discrimination in children with ASD as indicated by cortical ERPs Type de document : Texte imprimé et/ou numérique Auteurs : Aurélie BIDET-CAULET, Auteur ; Marianne LATINUS, Auteur ; S. ROUX, Auteur ; J. MALVY, Auteur ; Frédérique BONNET-BRILHAULT, Auteur ; N. BRUNEAU, Auteur Article en page(s) : p.13 Langues : Anglais (eng) Mots-clés : Auditory  Autism  Development  Ftpv  Speech  Voice Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with autism spectrum disorder (ASD) show a relative indifference to the human voice. Accordingly, and contrarily to their typically developed peers, adults with autism do not show a preferential response to voices in the superior temporal sulcus; this lack of voice-specific response was previously linked to atypical processing of voices. In electroencephalography, a slow event-related potential (ERP) called the fronto-temporal positivity to voice (FTPV) is larger for vocal than for non-vocal sounds, resulting in a voice-sensitive response over right fronto-temporal sites. Here, we investigated the neurophysiological correlates of voice perception in children with and without ASD. METHODS: Sixteen children with autism and 16 age-matched typically developing children heard vocal (speech and non-speech) and non-vocal sounds while their electroencephalographic activity was recorded; overall IQ was smaller in the group of children with ASD. ERP amplitudes were compared using non-parametric statistical tests at each electrode and in successive 20-ms time windows. Within each group, differences between conditions were assessed using a non-parametric Quade test between 0 and 400 ms post-stimulus. Inter-group comparisons of ERP amplitudes were performed using non-paired Kruskal-Wallis tests between 140 and 180 ms post-stimulus. RESULTS: Typically developing children showed the classical voice-sensitive response over right fronto-temporal electrodes, for both speech and non-speech vocal sounds. Children with ASD did not show a preferential response to vocal sounds. Inter-group analysis showed no difference in the processing of vocal sounds, both speech and non-speech, but significant differences in the processing of non-vocal sounds over right fronto-temporal sites. CONCLUSIONS: Our results demonstrate a lack of voice-preferential response in children with autism spectrum disorders. In contrast to observations in adults with ASD, the lack of voice-preferential response was attributed to an atypical response to non-vocal sounds, which was overall more similar to the event-related potentials evoked by vocal sounds in both groups. This result suggests atypical maturation processes in ASD impeding the specialization of temporal regions in voice processing. En ligne : http://dx.doi.org/10.1186/s11689-017-9194-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Atypical sound discrimination in children with ASD as indicated by cortical ERPs [Texte imprimé et/ou numérique] / Aurélie BIDET-CAULET, Auteur ; Marianne LATINUS, Auteur ; S. ROUX, Auteur ; J. MALVY, Auteur ; Frédérique BONNET-BRILHAULT, Auteur ; N. BRUNEAU, Auteur . - p.13. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.13 Mots-clés : Auditory  Autism  Development  Ftpv  Speech  Voice Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with autism spectrum disorder (ASD) show a relative indifference to the human voice. Accordingly, and contrarily to their typically developed peers, adults with autism do not show a preferential response to voices in the superior temporal sulcus; this lack of voice-specific response was previously linked to atypical processing of voices. In electroencephalography, a slow event-related potential (ERP) called the fronto-temporal positivity to voice (FTPV) is larger for vocal than for non-vocal sounds, resulting in a voice-sensitive response over right fronto-temporal sites. Here, we investigated the neurophysiological correlates of voice perception in children with and without ASD. METHODS: Sixteen children with autism and 16 age-matched typically developing children heard vocal (speech and non-speech) and non-vocal sounds while their electroencephalographic activity was recorded; overall IQ was smaller in the group of children with ASD. ERP amplitudes were compared using non-parametric statistical tests at each electrode and in successive 20-ms time windows. Within each group, differences between conditions were assessed using a non-parametric Quade test between 0 and 400 ms post-stimulus. Inter-group comparisons of ERP amplitudes were performed using non-paired Kruskal-Wallis tests between 140 and 180 ms post-stimulus. RESULTS: Typically developing children showed the classical voice-sensitive response over right fronto-temporal electrodes, for both speech and non-speech vocal sounds. Children with ASD did not show a preferential response to vocal sounds. Inter-group analysis showed no difference in the processing of vocal sounds, both speech and non-speech, but significant differences in the processing of non-vocal sounds over right fronto-temporal sites. CONCLUSIONS: Our results demonstrate a lack of voice-preferential response in children with autism spectrum disorders. In contrast to observations in adults with ASD, the lack of voice-preferential response was attributed to an atypical response to non-vocal sounds, which was overall more similar to the event-related potentials evoked by vocal sounds in both groups. This result suggests atypical maturation processes in ASD impeding the specialization of temporal regions in voice processing. En ligne : http://dx.doi.org/10.1186/s11689-017-9194-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Updated report on tools to measure outcomes of clinical trials in fragile X syndrome / Dejan B. BUDIMIROVIC in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.14 Titre : Updated report on tools to measure outcomes of clinical trials in fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Dejan B. BUDIMIROVIC, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; C. A. ERICKSON, Auteur ; S. S. HALL, Auteur ; D. HESSL, Auteur ; A. L. REISS, Auteur ; M. K. KING, Auteur ; Leonard ABBEDUTO, Auteur ; W. E. KAUFMANN, Auteur Article en page(s) : p.14 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Clinical trials  Fragile X syndrome  Intellectual disability  Outcome measures Index. décimale : PER Périodiques Résumé : OBJECTIVE: Fragile X syndrome (FXS) has been the neurodevelopmental disorder with the most active translation of preclinical breakthroughs into clinical trials. This process has led to a critical assessment of outcome measures, which resulted in a comprehensive review published in 2013. Nevertheless, the disappointing outcome of several recent phase III drug trials in FXS, and parallel efforts at evaluating behavioral endpoints for trials in autism spectrum disorder (ASD), has emphasized the need for re-assessing outcome measures and revising recommendations for FXS. METHODS: After performing an extensive database search (PubMed, Food and Drug Administration (FDA)/National Institutes of Health (NIH)'s www.ClinicalTrials.gov, etc.) to determine progress since 2013, members of the Working Groups who published the 2013 Report evaluated the available outcome measures for FXS and related neurodevelopmental disorders using the COSMIN grading system of levels of evidence. The latter has also been applied to a British survey of endpoints for ASD. In addition, we also generated an informal classification of outcome measures for use in FXS intervention studies as instruments appropriate to detect shorter- or longer-term changes. RESULTS: To date, a total of 22 double-blind controlled clinical trials in FXS have been identified through www.ClinicalTrials.gov and an extensive literature search. The vast majority of these FDA/NIH-registered clinical trials has been completed between 2008 and 2015 and has targeted the core excitatory/inhibitory imbalance present in FXS and other neurodevelopmental disorders. Limited data exist on reliability and validity for most tools used to measure cognitive, behavioral, and other problems in FXS in these trials and other studies. Overall, evidence for most tools supports a moderate tool quality grading. Data on sensitivity to treatment, currently under evaluation, could improve ratings for some cognitive and behavioral tools. Some progress has also been made at identifying promising biomarkers, mainly on blood-based and neurophysiological measures. CONCLUSION: Despite the tangible progress in implementing clinical trials in FXS, the increasing data on measurement properties of endpoints, and the ongoing process of new tool development, the vast majority of outcome measures are at the moderate quality level with limited information on reliability, validity, and sensitivity to treatment. This situation is not unique to FXS, since reviews of endpoints for ASD have arrived at similar conclusions. These findings, in conjunction with the predominance of parent-based measures particularly in the behavioral domain, indicate that endpoint development in FXS needs to continue with an emphasis on more objective measures (observational, direct testing, biomarkers) that reflect meaningful improvements in quality of life. A major continuous challenge is the development of measurement tools concurrently with testing drug safety and efficacy in clinical trials. En ligne : http://dx.doi.org/10.1186/s11689-017-9193-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Updated report on tools to measure outcomes of clinical trials in fragile X syndrome [Texte imprimé et/ou numérique] / Dejan B. BUDIMIROVIC, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; C. A. ERICKSON, Auteur ; S. S. HALL, Auteur ; D. HESSL, Auteur ; A. L. REISS, Auteur ; M. K. KING, Auteur ; Leonard ABBEDUTO, Auteur ; W. E. KAUFMANN, Auteur . - p.14. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.14 Mots-clés : Autism spectrum disorder  Clinical trials  Fragile X syndrome  Intellectual disability  Outcome measures Index. décimale : PER Périodiques Résumé : OBJECTIVE: Fragile X syndrome (FXS) has been the neurodevelopmental disorder with the most active translation of preclinical breakthroughs into clinical trials. This process has led to a critical assessment of outcome measures, which resulted in a comprehensive review published in 2013. Nevertheless, the disappointing outcome of several recent phase III drug trials in FXS, and parallel efforts at evaluating behavioral endpoints for trials in autism spectrum disorder (ASD), has emphasized the need for re-assessing outcome measures and revising recommendations for FXS. METHODS: After performing an extensive database search (PubMed, Food and Drug Administration (FDA)/National Institutes of Health (NIH)'s www.ClinicalTrials.gov, etc.) to determine progress since 2013, members of the Working Groups who published the 2013 Report evaluated the available outcome measures for FXS and related neurodevelopmental disorders using the COSMIN grading system of levels of evidence. The latter has also been applied to a British survey of endpoints for ASD. In addition, we also generated an informal classification of outcome measures for use in FXS intervention studies as instruments appropriate to detect shorter- or longer-term changes. RESULTS: To date, a total of 22 double-blind controlled clinical trials in FXS have been identified through www.ClinicalTrials.gov and an extensive literature search. The vast majority of these FDA/NIH-registered clinical trials has been completed between 2008 and 2015 and has targeted the core excitatory/inhibitory imbalance present in FXS and other neurodevelopmental disorders. Limited data exist on reliability and validity for most tools used to measure cognitive, behavioral, and other problems in FXS in these trials and other studies. Overall, evidence for most tools supports a moderate tool quality grading. Data on sensitivity to treatment, currently under evaluation, could improve ratings for some cognitive and behavioral tools. Some progress has also been made at identifying promising biomarkers, mainly on blood-based and neurophysiological measures. CONCLUSION: Despite the tangible progress in implementing clinical trials in FXS, the increasing data on measurement properties of endpoints, and the ongoing process of new tool development, the vast majority of outcome measures are at the moderate quality level with limited information on reliability, validity, and sensitivity to treatment. This situation is not unique to FXS, since reviews of endpoints for ASD have arrived at similar conclusions. These findings, in conjunction with the predominance of parent-based measures particularly in the behavioral domain, indicate that endpoint development in FXS needs to continue with an emphasis on more objective measures (observational, direct testing, biomarkers) that reflect meaningful improvements in quality of life. A major continuous challenge is the development of measurement tools concurrently with testing drug safety and efficacy in clinical trials. En ligne : http://dx.doi.org/10.1186/s11689-017-9193-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Autonomic breathing abnormalities in Rett syndrome: caregiver perspectives in an international database study / J. MACKAY in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.15 Titre : Autonomic breathing abnormalities in Rett syndrome: caregiver perspectives in an international database study Type de document : Texte imprimé et/ou numérique Auteurs : J. MACKAY, Auteur ; J. DOWNS, Auteur ; K. WONG, Auteur ; J. HEYWORTH, Auteur ; A. EPSTEIN, Auteur ; H. LEONARD, Auteur Article en page(s) : p.15 Langues : Anglais (eng) Mots-clés : Breathing disorders  Developmental disability  Genotype  International database  Mecp2  Rare disorder  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder associated with mutations in the MECP2 gene. Irregular breathing patterns and abdominal bloating are prominent but poorly understood features. Our aims were to characterize the abnormal breathing patterns and abdominal bloating, investigate the distribution of these by age and mutation type and examine their impact and management from a caregiver perspective. METHODS: We invited previously recruited families from the International Rett Syndrome Study to complete a web-based questionnaire concerning their family member with Rett syndrome aged between 2 and 57 years. We used logistic regression to investigate presence, frequency and impact of breath-holding, hyperventilation, or abdominal bloating by age group and mutation type. Age of onset for both breathing abnormalities was investigated using time-to-onset analysis, and the Kaplan-Meier method was used to estimate the failure function for the study sample. Descriptive statistics were used to characterize the management of irregular breathing. RESULTS: Questionnaires were returned by 413/482 (85.7%) families. Breath-holding was reported for 68.8%, hyperventilation for 46.4% and abdominal bloating for 42.4%. Hyperventilation was more prevalent and frequent in those younger than 7 years of age and abdominal bloating in those aged over 20 years. Onset of breathing irregularities usually occurred during early childhood. Caregivers perceived that daily life was considerably impacted for almost half (44.1%) of those with abdominal bloating and in just over than a third of those with breath-holding (35.8%) or hyperventilation (35.1%). Although perceived impact was broadly comparable between age and mutation groups for breath-holding, hyperventilation and abdominal bloating, girls and women with a p.Arg294* mutation were considered to be more affected by all three conditions. Only 31 individuals had received medically prescribed treatments including 12 different medications, added oxygen, rebreathing apparatus or non-invasive ventilation. CONCLUSIONS: Autonomic disturbances are prevalent and burdensome in Rett syndrome. This information may guide the design of inclusion criteria and outcome measures for clinical intervention trials targeting autonomic abnormalities. Further investigation of available treatments is necessary to delineate evidence-based management pathways. En ligne : http://dx.doi.org/10.1186/s11689-017-9196-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Autonomic breathing abnormalities in Rett syndrome: caregiver perspectives in an international database study [Texte imprimé et/ou numérique] / J. MACKAY, Auteur ; J. DOWNS, Auteur ; K. WONG, Auteur ; J. HEYWORTH, Auteur ; A. EPSTEIN, Auteur ; H. LEONARD, Auteur . - p.15. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.15 Mots-clés : Breathing disorders  Developmental disability  Genotype  International database  Mecp2  Rare disorder  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder associated with mutations in the MECP2 gene. Irregular breathing patterns and abdominal bloating are prominent but poorly understood features. Our aims were to characterize the abnormal breathing patterns and abdominal bloating, investigate the distribution of these by age and mutation type and examine their impact and management from a caregiver perspective. METHODS: We invited previously recruited families from the International Rett Syndrome Study to complete a web-based questionnaire concerning their family member with Rett syndrome aged between 2 and 57 years. We used logistic regression to investigate presence, frequency and impact of breath-holding, hyperventilation, or abdominal bloating by age group and mutation type. Age of onset for both breathing abnormalities was investigated using time-to-onset analysis, and the Kaplan-Meier method was used to estimate the failure function for the study sample. Descriptive statistics were used to characterize the management of irregular breathing. RESULTS: Questionnaires were returned by 413/482 (85.7%) families. Breath-holding was reported for 68.8%, hyperventilation for 46.4% and abdominal bloating for 42.4%. Hyperventilation was more prevalent and frequent in those younger than 7 years of age and abdominal bloating in those aged over 20 years. Onset of breathing irregularities usually occurred during early childhood. Caregivers perceived that daily life was considerably impacted for almost half (44.1%) of those with abdominal bloating and in just over than a third of those with breath-holding (35.8%) or hyperventilation (35.1%). Although perceived impact was broadly comparable between age and mutation groups for breath-holding, hyperventilation and abdominal bloating, girls and women with a p.Arg294* mutation were considered to be more affected by all three conditions. Only 31 individuals had received medically prescribed treatments including 12 different medications, added oxygen, rebreathing apparatus or non-invasive ventilation. CONCLUSIONS: Autonomic disturbances are prevalent and burdensome in Rett syndrome. This information may guide the design of inclusion criteria and outcome measures for clinical intervention trials targeting autonomic abnormalities. Further investigation of available treatments is necessary to delineate evidence-based management pathways. En ligne : http://dx.doi.org/10.1186/s11689-017-9196-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Reduced vagal tone in women with the FMR1 premutation is associated with FMR1 mRNA but not depression or anxiety / J. KLUSEK in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.16 Titre : Reduced vagal tone in women with the FMR1 premutation is associated with FMR1 mRNA but not depression or anxiety Type de document : Texte imprimé et/ou numérique Auteurs : J. KLUSEK, Auteur ; G. LAFAUCI, Auteur ; T. ADAYEV, Auteur ; W. Ted BROWN, Auteur ; F. TASSONE, Auteur ; J. E. ROBERTS, Auteur Article en page(s) : p.16 Langues : Anglais (eng) Mots-clés : FMR1 mRNA  Fmrp  Fragile X carriers  Heart rate  Physiological arousal  Vagal tone Index. décimale : PER Périodiques Résumé : BACKGROUND: Autonomic dysfunction is implicated in a range of psychological conditions, including depression and anxiety. The fragile X mental retardation-1 (FMR1) premutation is a common genetic mutation that affects ~1:150 women and is associated with psychological vulnerability. This study examined cardiac indicators of autonomic function among women with the FMR1 premutation and control women as potential biomarkers for psychological risk that may be linked to FMR1. METHODS: Baseline inter-beat interval and respiratory sinus arrhythmia (a measure of parasympathetic vagal tone) were measured in 35 women with the FMR1 premutation and 28 controls. The women completed anxiety and depression questionnaires. FMR1 genetic indices (i.e., CGG repeat, quantitative FMRP, FMR1 mRNA, activation ratio) were obtained for the premutation group. RESULTS: Respiratory sinus arrhythmia was reduced in the FMR1 premutation group relative to controls. While depression symptoms were associated with reduced respiratory sinus arrhythmia among control women, these variables were unrelated in the FMR1 premutation. Elevated FMR1 mRNA was associated with higher respiratory sinus arrhythmia. CONCLUSIONS: Women with the FMR1 premutation demonstrated autonomic dysregulation characterized by reduced vagal tone. Unlike patterns observed in the general population and in study controls, vagal activity and depression symptoms were decoupled in women with the FMR1 premutation, suggesting independence between autonomic regulation and psychopathological symptoms that is atypical and potentially specific to the FMR1 premutation. The association between vagal tone and mRNA suggests that molecular variation associated with FMR1 plays a role in autonomic regulation. En ligne : http://dx.doi.org/10.1186/s11689-017-9197-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Reduced vagal tone in women with the FMR1 premutation is associated with FMR1 mRNA but not depression or anxiety [Texte imprimé et/ou numérique] / J. KLUSEK, Auteur ; G. LAFAUCI, Auteur ; T. ADAYEV, Auteur ; W. Ted BROWN, Auteur ; F. TASSONE, Auteur ; J. E. ROBERTS, Auteur . - p.16. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.16 Mots-clés : FMR1 mRNA  Fmrp  Fragile X carriers  Heart rate  Physiological arousal  Vagal tone Index. décimale : PER Périodiques Résumé : BACKGROUND: Autonomic dysfunction is implicated in a range of psychological conditions, including depression and anxiety. The fragile X mental retardation-1 (FMR1) premutation is a common genetic mutation that affects ~1:150 women and is associated with psychological vulnerability. This study examined cardiac indicators of autonomic function among women with the FMR1 premutation and control women as potential biomarkers for psychological risk that may be linked to FMR1. METHODS: Baseline inter-beat interval and respiratory sinus arrhythmia (a measure of parasympathetic vagal tone) were measured in 35 women with the FMR1 premutation and 28 controls. The women completed anxiety and depression questionnaires. FMR1 genetic indices (i.e., CGG repeat, quantitative FMRP, FMR1 mRNA, activation ratio) were obtained for the premutation group. RESULTS: Respiratory sinus arrhythmia was reduced in the FMR1 premutation group relative to controls. While depression symptoms were associated with reduced respiratory sinus arrhythmia among control women, these variables were unrelated in the FMR1 premutation. Elevated FMR1 mRNA was associated with higher respiratory sinus arrhythmia. CONCLUSIONS: Women with the FMR1 premutation demonstrated autonomic dysregulation characterized by reduced vagal tone. Unlike patterns observed in the general population and in study controls, vagal activity and depression symptoms were decoupled in women with the FMR1 premutation, suggesting independence between autonomic regulation and psychopathological symptoms that is atypical and potentially specific to the FMR1 premutation. The association between vagal tone and mRNA suggests that molecular variation associated with FMR1 plays a role in autonomic regulation. En ligne : http://dx.doi.org/10.1186/s11689-017-9197-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis / M. S. SIDOROV in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.17 Titre : Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis Type de document : Texte imprimé et/ou numérique Auteurs : M. S. SIDOROV, Auteur ; G. M. DECK, Auteur ; M. DOLATSHAHI, Auteur ; R. L. THIBERT, Auteur ; L. M. BIRD, Auteur ; C. J. CHU, Auteur ; B. D. PHILPOT, Auteur Article en page(s) : p.17 Langues : Anglais (eng) Mots-clés : Angelman syndrome  Biomarker  Delta  Eeg  Mouse model  Outcome measure  Ube3a Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinicians have qualitatively described rhythmic delta activity as a prominent EEG abnormality in individuals with Angelman syndrome, but this phenotype has yet to be rigorously quantified in the clinical population or validated in a preclinical model. Here, we sought to quantitatively measure delta rhythmicity and evaluate its fidelity as a biomarker. METHODS: We quantified delta oscillations in mouse and human using parallel spectral analysis methods and measured regional, state-specific, and developmental changes in delta rhythms in a patient population. RESULTS: Delta power was broadly increased and more dynamic in both the Angelman syndrome mouse model, relative to wild-type littermates, and in children with Angelman syndrome, relative to age-matched neurotypical controls. Enhanced delta oscillations in children with Angelman syndrome were present during wakefulness and sleep, were generalized across the neocortex, and were more pronounced at earlier ages. CONCLUSIONS: Delta rhythmicity phenotypes can serve as reliable biomarkers for Angelman syndrome in both preclinical and clinical settings. En ligne : http://dx.doi.org/10.1186/s11689-017-9195-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis [Texte imprimé et/ou numérique] / M. S. SIDOROV, Auteur ; G. M. DECK, Auteur ; M. DOLATSHAHI, Auteur ; R. L. THIBERT, Auteur ; L. M. BIRD, Auteur ; C. J. CHU, Auteur ; B. D. PHILPOT, Auteur . - p.17. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.17 Mots-clés : Angelman syndrome  Biomarker  Delta  Eeg  Mouse model  Outcome measure  Ube3a Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinicians have qualitatively described rhythmic delta activity as a prominent EEG abnormality in individuals with Angelman syndrome, but this phenotype has yet to be rigorously quantified in the clinical population or validated in a preclinical model. Here, we sought to quantitatively measure delta rhythmicity and evaluate its fidelity as a biomarker. METHODS: We quantified delta oscillations in mouse and human using parallel spectral analysis methods and measured regional, state-specific, and developmental changes in delta rhythms in a patient population. RESULTS: Delta power was broadly increased and more dynamic in both the Angelman syndrome mouse model, relative to wild-type littermates, and in children with Angelman syndrome, relative to age-matched neurotypical controls. Enhanced delta oscillations in children with Angelman syndrome were present during wakefulness and sleep, were generalized across the neocortex, and were more pronounced at earlier ages. CONCLUSIONS: Delta rhythmicity phenotypes can serve as reliable biomarkers for Angelman syndrome in both preclinical and clinical settings. En ligne : http://dx.doi.org/10.1186/s11689-017-9195-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Diagnoses and characteristics of autism spectrum disorders in children with Prader-Willi syndrome / E. M. DYKENS in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.18 Titre : Diagnoses and characteristics of autism spectrum disorders in children with Prader-Willi syndrome Type de document : Texte imprimé et/ou numérique Auteurs : E. M. DYKENS, Auteur ; E. ROOF, Auteur ; Hailee HUNT-HAWKINS, Auteur ; N. DANKNER, Auteur ; E. B. LEE, Auteur ; C. M. SHIVERS, Auteur ; C. DANIELL, Auteur ; S. J. KIM, Auteur Article en page(s) : p.18 Langues : Anglais (eng) Mots-clés : ASD screeners  Autism spectrum disorder (ASD)  Best-estimate diagnoses  Insistence on sameness  Prader-Willi syndrome (PWS)  Repetitive behavior  Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: A small percentage of people with autism spectrum disorders (ASD) have alterations in chromosome 15q11.2-q3, the critical region for Prader-Willi syndrome (PWS). Data are limited, however, on the rates and characteristics of ASD in PWS. Previous estimates of ASD in PWS (25 to 41%) are questionable as they are based solely on autism screeners given to parents. Inaccurate diagnoses of ASD in PWS can mislead intervention and future research. METHODS: One hundred forty-six children and youth with PWS aged 4 to 21 years (M = 11) were assessed with the Autism Diagnostic Observation Schedule-2 (ADOS-2). An expert clinical team-made best-estimate ASD diagnoses based on ADOS-2 videotapes, calibrated severity scores, and children's developmental histories and indices of current functioning. Children were also administered the Kaufman Brief Intelligence Test-2, and parents completed the Repetitive Behavior Scale-Revised and Vineland Adaptive Behavior Scales. Scores were compared across children with PWS + ASD versus PWS only. The performance of an ASD screener, the Social Communication Questionnaire (SCQ) and the ADOS-2 were evaluated in relation to best-estimate diagnoses. RESULTS: Best-estimate diagnoses of ASD were made in 18 children, or 12.3% of the sample, and the majority of them had the maternal uniparental disomy (mUPD) PWS genetic subtype. Compared to the PWS-only group, children with PWS + ASD had lower verbal and composite IQ's and adaptive daily living and socialization skills, as well as elevated stereotypies and restricted interests. Regardless of ASD status, compulsivity and insistence on sameness in routines or events were seen in 76-100% of children and were robustly correlated with lower adaptive functioning. The SCQ yielded a 29-49% chance that screen-positive cases will indeed have ASD. The ADOS-2 had higher sensitivity, specificity and predictive values. Communication problems were seen in children who were ADOS-2 positive but deemed not to have ASD by the clinical team. CONCLUSIONS: Autism screeners should not be the sole index of probable ASD in PWS; children need to be directly observed and evaluated. Compulsivity and insistence on sameness are salient in PWS and likely impede adaptive functioning. Most children with PWS only evidenced sub-threshold problems in social interactions that could signal risks for other psychopathologies. En ligne : http://dx.doi.org/10.1186/s11689-017-9200-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Diagnoses and characteristics of autism spectrum disorders in children with Prader-Willi syndrome [Texte imprimé et/ou numérique] / E. M. DYKENS, Auteur ; E. ROOF, Auteur ; Hailee HUNT-HAWKINS, Auteur ; N. DANKNER, Auteur ; E. B. LEE, Auteur ; C. M. SHIVERS, Auteur ; C. DANIELL, Auteur ; S. J. KIM, Auteur . - p.18. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.18 Mots-clés : ASD screeners  Autism spectrum disorder (ASD)  Best-estimate diagnoses  Insistence on sameness  Prader-Willi syndrome (PWS)  Repetitive behavior  Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: A small percentage of people with autism spectrum disorders (ASD) have alterations in chromosome 15q11.2-q3, the critical region for Prader-Willi syndrome (PWS). Data are limited, however, on the rates and characteristics of ASD in PWS. Previous estimates of ASD in PWS (25 to 41%) are questionable as they are based solely on autism screeners given to parents. Inaccurate diagnoses of ASD in PWS can mislead intervention and future research. METHODS: One hundred forty-six children and youth with PWS aged 4 to 21 years (M = 11) were assessed with the Autism Diagnostic Observation Schedule-2 (ADOS-2). An expert clinical team-made best-estimate ASD diagnoses based on ADOS-2 videotapes, calibrated severity scores, and children's developmental histories and indices of current functioning. Children were also administered the Kaufman Brief Intelligence Test-2, and parents completed the Repetitive Behavior Scale-Revised and Vineland Adaptive Behavior Scales. Scores were compared across children with PWS + ASD versus PWS only. The performance of an ASD screener, the Social Communication Questionnaire (SCQ) and the ADOS-2 were evaluated in relation to best-estimate diagnoses. RESULTS: Best-estimate diagnoses of ASD were made in 18 children, or 12.3% of the sample, and the majority of them had the maternal uniparental disomy (mUPD) PWS genetic subtype. Compared to the PWS-only group, children with PWS + ASD had lower verbal and composite IQ's and adaptive daily living and socialization skills, as well as elevated stereotypies and restricted interests. Regardless of ASD status, compulsivity and insistence on sameness in routines or events were seen in 76-100% of children and were robustly correlated with lower adaptive functioning. The SCQ yielded a 29-49% chance that screen-positive cases will indeed have ASD. The ADOS-2 had higher sensitivity, specificity and predictive values. Communication problems were seen in children who were ADOS-2 positive but deemed not to have ASD by the clinical team. CONCLUSIONS: Autism screeners should not be the sole index of probable ASD in PWS; children need to be directly observed and evaluated. Compulsivity and insistence on sameness are salient in PWS and likely impede adaptive functioning. Most children with PWS only evidenced sub-threshold problems in social interactions that could signal risks for other psychopathologies. En ligne : http://dx.doi.org/10.1186/s11689-017-9200-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Motor problems in children with neurofibromatosis type 1 / A. B. RIETMAN in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.19 Titre : Motor problems in children with neurofibromatosis type 1 Type de document : Texte imprimé et/ou numérique Auteurs : A. B. RIETMAN, Auteur ; R. OOSTENBRINK, Auteur ; S. BONGERS, Auteur ; E. GAUKEMA, Auteur ; S. VAN ABEELEN, Auteur ; J. G. HENDRIKSEN, Auteur ; C. W. N. LOOMAN, Auteur ; P. F. A. DE NIJS, Auteur ; M. C. DE WIT, Auteur Article en page(s) : p.19 Langues : Anglais (eng) Mots-clés : Dcd  Emotional and behavioural problems  Intelligence  Motor problems  Neurofibromatosis type 1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with the neurogenetic disorder neurofibromatosis type 1 (NF1) often have problems with learning and behaviour. In both parent reports and neuropsychological assessment, motor problems are reported in approximately one third to one half of the children with NF1. Studies using broad motor performance test batteries with relatively large groups of children with NF1 are limited. The aim of this cross-sectional observational study was to describe the severity of motor problems in children with NF1 and to explore the predictive value of demographics, intelligence, and behavioural problems. METHODS: From 2002 to 2014, 69 children with NF1, aged 4 to 16 years (age = 9.5 +/- 2.8 years; 29 girls) had a motor, psychological, and neurological evaluation in an NF1 expertise centre. Data were collected about (1) motor performance (M-ABC: Movement Assessment Battery for Children), (2) intelligence, and (3) emotional and behavioural problems as rated by parents. RESULTS: Sixty-one percent of these children scored within the clinical range of the M-ABC. In ordinal logistic regression analyses, motor problems were associated with symptoms of attention-deficit/hyperactivity disorder (ADHD), symptoms of autism spectrum disorder (ASD), and externalising behavioural problems. Motor outcome was not predicted by age, intelligence, scoliosis, hypotonia, nor hypermobility. CONCLUSIONS: Motor problems are among the most common comorbid developmental problems in children with NF1, and these problems do not diminish with age. Because of their impact on daily functioning, motor problems need to be specifically addressed in diagnosis, follow-up, and treatment of NF1. En ligne : http://dx.doi.org/10.1186/s11689-017-9198-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Motor problems in children with neurofibromatosis type 1 [Texte imprimé et/ou numérique] / A. B. RIETMAN, Auteur ; R. OOSTENBRINK, Auteur ; S. BONGERS, Auteur ; E. GAUKEMA, Auteur ; S. VAN ABEELEN, Auteur ; J. G. HENDRIKSEN, Auteur ; C. W. N. LOOMAN, Auteur ; P. F. A. DE NIJS, Auteur ; M. C. DE WIT, Auteur . - p.19. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.19 Mots-clés : Dcd  Emotional and behavioural problems  Intelligence  Motor problems  Neurofibromatosis type 1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with the neurogenetic disorder neurofibromatosis type 1 (NF1) often have problems with learning and behaviour. In both parent reports and neuropsychological assessment, motor problems are reported in approximately one third to one half of the children with NF1. Studies using broad motor performance test batteries with relatively large groups of children with NF1 are limited. The aim of this cross-sectional observational study was to describe the severity of motor problems in children with NF1 and to explore the predictive value of demographics, intelligence, and behavioural problems. METHODS: From 2002 to 2014, 69 children with NF1, aged 4 to 16 years (age = 9.5 +/- 2.8 years; 29 girls) had a motor, psychological, and neurological evaluation in an NF1 expertise centre. Data were collected about (1) motor performance (M-ABC: Movement Assessment Battery for Children), (2) intelligence, and (3) emotional and behavioural problems as rated by parents. RESULTS: Sixty-one percent of these children scored within the clinical range of the M-ABC. In ordinal logistic regression analyses, motor problems were associated with symptoms of attention-deficit/hyperactivity disorder (ADHD), symptoms of autism spectrum disorder (ASD), and externalising behavioural problems. Motor outcome was not predicted by age, intelligence, scoliosis, hypotonia, nor hypermobility. CONCLUSIONS: Motor problems are among the most common comorbid developmental problems in children with NF1, and these problems do not diminish with age. Because of their impact on daily functioning, motor problems need to be specifically addressed in diagnosis, follow-up, and treatment of NF1. En ligne : http://dx.doi.org/10.1186/s11689-017-9198-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism and other neurodevelopmental disorders / C. T. ENGINEER in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.20 Titre : Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism and other neurodevelopmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : C. T. ENGINEER, Auteur ; S. A. HAYS, Auteur ; M. P. KILGARD, Auteur Article en page(s) : p.20 Langues : Anglais (eng) Mots-clés : Autism  Cortex  Cortical reorganization  Plasticity  Vagal nerve Index. décimale : PER Périodiques Résumé : BACKGROUND: Many children with autism and other neurodevelopmental disorders undergo expensive, time-consuming behavioral interventions that often yield only modest improvements. The development of adjunctive interventions that can increase the benefit of rehabilitation therapies is essential in order to improve the lives of individuals with neurodevelopmental disorders. MAIN TEXT: Vagus nerve stimulation (VNS) is an FDA approved therapy that is safe and effective in reducing seizure frequency and duration in individuals with epilepsy. Individuals with neurodevelopmental disorders often exhibit decreased vagal tone, and studies indicate that VNS can be used to overcome an insufficient vagal response. Multiple studies have also documented significant improvements in quality of life after VNS therapy in individuals with neurodevelopmental disorders. Moreover, recent findings indicate that VNS significantly enhances the benefits of rehabilitative training in animal models and patients, leading to greater recovery in a variety of neurological diseases. Here, we review these findings and provide a discussion of how VNS paired with rehabilitation may yield benefits in the context of neurodevelopmental disorders. CONCLUSIONS: VNS paired with behavioral therapy may represent a potential new approach to enhance rehabilitation that could significantly improve the outcomes of individuals with neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/s11689-017-9203-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism and other neurodevelopmental disorders [Texte imprimé et/ou numérique] / C. T. ENGINEER, Auteur ; S. A. HAYS, Auteur ; M. P. KILGARD, Auteur . - p.20. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.20 Mots-clés : Autism  Cortex  Cortical reorganization  Plasticity  Vagal nerve Index. décimale : PER Périodiques Résumé : BACKGROUND: Many children with autism and other neurodevelopmental disorders undergo expensive, time-consuming behavioral interventions that often yield only modest improvements. The development of adjunctive interventions that can increase the benefit of rehabilitation therapies is essential in order to improve the lives of individuals with neurodevelopmental disorders. MAIN TEXT: Vagus nerve stimulation (VNS) is an FDA approved therapy that is safe and effective in reducing seizure frequency and duration in individuals with epilepsy. Individuals with neurodevelopmental disorders often exhibit decreased vagal tone, and studies indicate that VNS can be used to overcome an insufficient vagal response. Multiple studies have also documented significant improvements in quality of life after VNS therapy in individuals with neurodevelopmental disorders. Moreover, recent findings indicate that VNS significantly enhances the benefits of rehabilitative training in animal models and patients, leading to greater recovery in a variety of neurological diseases. Here, we review these findings and provide a discussion of how VNS paired with rehabilitation may yield benefits in the context of neurodevelopmental disorders. CONCLUSIONS: VNS paired with behavioral therapy may represent a potential new approach to enhance rehabilitation that could significantly improve the outcomes of individuals with neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/s11689-017-9203-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Translation in fragile X: no home runs in the first at-bat / J. VEENSTRA-VANDERWEELE in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.21 Titre : Translation in fragile X: no home runs in the first at-bat Type de document : Texte imprimé et/ou numérique Auteurs : J. VEENSTRA-VANDERWEELE, Auteur Article en page(s) : p.21 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s11689-017-9204-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Translation in fragile X: no home runs in the first at-bat [Texte imprimé et/ou numérique] / J. VEENSTRA-VANDERWEELE, Auteur . - p.21. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.21 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s11689-017-9204-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Neural patterns elicited by sentence processing uniquely characterize typical development, SLI recovery, and SLI persistence / Eileen HAEBIG in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.22 Titre : Neural patterns elicited by sentence processing uniquely characterize typical development, SLI recovery, and SLI persistence Type de document : Texte imprimé et/ou numérique Auteurs : Eileen HAEBIG, Auteur ; C. WEBER, Auteur ; L. B. LEONARD, Auteur ; P. DEEVY, Auteur ; J. B. TOMBLIN, Auteur Article en page(s) : p.22 Langues : Anglais (eng) Mots-clés : Event-related brain potentials  Language trajectories  N400  P600  Sentence processing  Specific language impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: A substantial amount of work has examined language abilities in young children with specific language impairment (SLI); however, our understanding of the developmental trajectory of language impairment is limited. Along with studying the behavioral changes that occur across development, it is important to examine the neural indices of language processing for children with different language trajectories. The current study sought to examine behavioral and neural bases of language processing in adolescents showing three different trajectories: those with normal language development (NL), those exhibiting persistent SLI (SLI-Persistent), and those with a history of SLI who appear to have recovered (SLI-Recovered). METHODS: Through a sentence judgment task, we examined semantic and syntactic processing. Adolescents judged whether or not each sentence was semantically and syntactically correct. Stimuli consisted of naturally spoken sentences that were either correct, contained a semantic verb error, or contained a syntactic verb agreement error. Verb agreement errors consisted of omission and commission violations of the third-person singular -s. Behavioral button-press responses and electroencephalographic recordings were collected. Behavioral judgments and mean amplitude of the N400 and P600 components were examined. RESULTS: Adolescents in the SLI-Persistent group had lower sentence judgment accuracy overall, relative to the NL and SLI-Recovered groups. Accuracy in judging omission and commission syntactic errors were marginally different, with marginally lower accuracy for commission errors. All groups demonstrated an N400 component elicited by semantic violations. However, adolescents in the SLI-Persistent group demonstrated a less robust P600 component for syntactic violations. Furthermore, adolescents in the SLI-Recovered group exhibited a similar neural profile to the NL group for the semantic and syntactic omission violations. However, a unique profile with initial negativity was observed in the SLI-Recovered group in the commission violation condition. CONCLUSIONS: Adolescents with persistent language impairment continue to demonstrate delays in language processing at the behavioral and neural levels. Conversely, the adolescents in the SLI-Recovered group appear to have made gains in language processing skills to overcome their initial impairments. However, our findings suggest that the adolescents in the SLI-Recovered group may have compensatory processing strategies for some aspects of language, as evidenced by a unique event-related potential profile. En ligne : http://dx.doi.org/10.1186/s11689-017-9201-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Neural patterns elicited by sentence processing uniquely characterize typical development, SLI recovery, and SLI persistence [Texte imprimé et/ou numérique] / Eileen HAEBIG, Auteur ; C. WEBER, Auteur ; L. B. LEONARD, Auteur ; P. DEEVY, Auteur ; J. B. TOMBLIN, Auteur . - p.22. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.22 Mots-clés : Event-related brain potentials  Language trajectories  N400  P600  Sentence processing  Specific language impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: A substantial amount of work has examined language abilities in young children with specific language impairment (SLI); however, our understanding of the developmental trajectory of language impairment is limited. Along with studying the behavioral changes that occur across development, it is important to examine the neural indices of language processing for children with different language trajectories. The current study sought to examine behavioral and neural bases of language processing in adolescents showing three different trajectories: those with normal language development (NL), those exhibiting persistent SLI (SLI-Persistent), and those with a history of SLI who appear to have recovered (SLI-Recovered). METHODS: Through a sentence judgment task, we examined semantic and syntactic processing. Adolescents judged whether or not each sentence was semantically and syntactically correct. Stimuli consisted of naturally spoken sentences that were either correct, contained a semantic verb error, or contained a syntactic verb agreement error. Verb agreement errors consisted of omission and commission violations of the third-person singular -s. Behavioral button-press responses and electroencephalographic recordings were collected. Behavioral judgments and mean amplitude of the N400 and P600 components were examined. RESULTS: Adolescents in the SLI-Persistent group had lower sentence judgment accuracy overall, relative to the NL and SLI-Recovered groups. Accuracy in judging omission and commission syntactic errors were marginally different, with marginally lower accuracy for commission errors. All groups demonstrated an N400 component elicited by semantic violations. However, adolescents in the SLI-Persistent group demonstrated a less robust P600 component for syntactic violations. Furthermore, adolescents in the SLI-Recovered group exhibited a similar neural profile to the NL group for the semantic and syntactic omission violations. However, a unique profile with initial negativity was observed in the SLI-Recovered group in the commission violation condition. CONCLUSIONS: Adolescents with persistent language impairment continue to demonstrate delays in language processing at the behavioral and neural levels. Conversely, the adolescents in the SLI-Recovered group appear to have made gains in language processing skills to overcome their initial impairments. However, our findings suggest that the adolescents in the SLI-Recovered group may have compensatory processing strategies for some aspects of language, as evidenced by a unique event-related potential profile. En ligne : http://dx.doi.org/10.1186/s11689-017-9201-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Autism spectrum disorder and epileptic encephalopathy: common causes, many questions / S. SRIVASTAVA in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.23 Titre : Autism spectrum disorder and epileptic encephalopathy: common causes, many questions Type de document : Texte imprimé et/ou numérique Auteurs : S. SRIVASTAVA, Auteur ; M. SAHIN, Auteur Article en page(s) : p.23 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Epileptic encephalopathy  Mendelian disorders Index. décimale : PER Périodiques Résumé : Epileptic encephalopathies represent a particularly severe form of epilepsy, associated with cognitive and behavioral deficits, including impaired social-communication and restricted, repetitive behaviors that are the hallmarks of autism spectrum disorder (ASD). With the advent of next-generation sequencing, the genetic landscape of epileptic encephalopathies is growing and demonstrates overlap with genes separately implicated in ASD. However, many questions remain about this connection, including whether epileptiform activity itself contributes to the development of ASD symptomatology. In this review, we compiled a database of genes associated with both epileptic encephalopathy and ASD, limiting our purview to Mendelian disorders not including inborn errors of metabolism, and we focused on the connection between ASD and epileptic encephalopathy rather than epilepsy broadly. Our review has four goals: to (1) discuss the overlapping presentations of ASD and monogenic epileptic encephalopathies; (2) examine the impact of the epilepsy itself on neurocognitive features, including ASD, in monogenic epileptic encephalopathies; (3) outline many of the genetic causes responsible for both ASD and epileptic encephalopathy; (4) provide an illustrative example of a final common pathway that may be implicated in both ASD and epileptic encephalopathy. We demonstrate that autistic features are a common association with monogenic epileptic encephalopathies. Certain epileptic encephalopathy syndromes, like infantile spasms, are especially linked to the development of ASD. The connection between seizures themselves and neurobehavioral deficits in these monogenic encephalopathies remains open to debate. Finally, advances in genetics have revealed many genes that overlap in ties to both ASD and epileptic encephalopathy and that play a role in diverse central nervous system processes. Increased attention to the autistic features of monogenic epileptic encephalopathies is warranted for both researchers and clinicians alike. En ligne : http://dx.doi.org/10.1186/s11689-017-9202-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Autism spectrum disorder and epileptic encephalopathy: common causes, many questions [Texte imprimé et/ou numérique] / S. SRIVASTAVA, Auteur ; M. SAHIN, Auteur . - p.23. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.23 Mots-clés : Autism spectrum disorder  Epileptic encephalopathy  Mendelian disorders Index. décimale : PER Périodiques Résumé : Epileptic encephalopathies represent a particularly severe form of epilepsy, associated with cognitive and behavioral deficits, including impaired social-communication and restricted, repetitive behaviors that are the hallmarks of autism spectrum disorder (ASD). With the advent of next-generation sequencing, the genetic landscape of epileptic encephalopathies is growing and demonstrates overlap with genes separately implicated in ASD. However, many questions remain about this connection, including whether epileptiform activity itself contributes to the development of ASD symptomatology. In this review, we compiled a database of genes associated with both epileptic encephalopathy and ASD, limiting our purview to Mendelian disorders not including inborn errors of metabolism, and we focused on the connection between ASD and epileptic encephalopathy rather than epilepsy broadly. Our review has four goals: to (1) discuss the overlapping presentations of ASD and monogenic epileptic encephalopathies; (2) examine the impact of the epilepsy itself on neurocognitive features, including ASD, in monogenic epileptic encephalopathies; (3) outline many of the genetic causes responsible for both ASD and epileptic encephalopathy; (4) provide an illustrative example of a final common pathway that may be implicated in both ASD and epileptic encephalopathy. We demonstrate that autistic features are a common association with monogenic epileptic encephalopathies. Certain epileptic encephalopathy syndromes, like infantile spasms, are especially linked to the development of ASD. The connection between seizures themselves and neurobehavioral deficits in these monogenic encephalopathies remains open to debate. Finally, advances in genetics have revealed many genes that overlap in ties to both ASD and epileptic encephalopathy and that play a role in diverse central nervous system processes. Increased attention to the autistic features of monogenic epileptic encephalopathies is warranted for both researchers and clinicians alike. En ligne : http://dx.doi.org/10.1186/s11689-017-9202-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Exploring the heterogeneity of neural social indices for genetically distinct etiologies of autism / C. M. HUDAC in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.24 Titre : Exploring the heterogeneity of neural social indices for genetically distinct etiologies of autism Type de document : Texte imprimé et/ou numérique Auteurs : C. M. HUDAC, Auteur ; H. A. F. STESSMAN, Auteur ; Trent D. DESCHAMPS, Auteur ; A. KRESSE, Auteur ; S. FAJA, Auteur ; E. NEUHAUS, Auteur ; S. J. WEBB, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur Article en page(s) : p.24 Langues : Anglais (eng) Mots-clés : Autism spectrum disorders (ASD)  Electroencephalography (EEG)  Likely gene-disrupting mutations  Molecular subtyping  Mu rhythm attenuation  Social cognition  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder. Promising initiatives utilizing interdisciplinary characterization of ASD suggest phenotypic subtypes related to specific likely gene-disrupting mutations (LGDMs). However, the role of functionally associated LGDMs in the neural social phenotype is unknown. METHODS: In this study of 26 children with ASD (n = 13 with an LGDM) and 13 control children, we characterized patterns of mu attenuation and habituation as children watched videos containing social and nonsocial motions during electroencephalography acquisition. RESULTS: Diagnostic comparisons were consistent with prior work suggesting aberrant mu attenuation in ASD within the upper mu band (10-12 Hz), but typical patterns within the lower mu band (8-10 Hz). Preliminary exploration indicated distinct social sensitization patterns (i.e., increasing mu attenuation for social motion) for children with an LGDM that is primarily expressed during embryonic development. In contrast, children with an LGDM primarily expressed post-embryonic development exhibited stable typical patterns of lower mu attenuation. Neural social indices were associated with social responsiveness, but not cognition. CONCLUSIONS: These findings suggest unique neurophysiological profiles for certain genetic etiologies of ASD, further clarifying possible genetic functional subtypes of ASD and providing insight into mechanisms for targeted treatment approaches. En ligne : http://dx.doi.org/10.1186/s11689-017-9199-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Exploring the heterogeneity of neural social indices for genetically distinct etiologies of autism [Texte imprimé et/ou numérique] / C. M. HUDAC, Auteur ; H. A. F. STESSMAN, Auteur ; Trent D. DESCHAMPS, Auteur ; A. KRESSE, Auteur ; S. FAJA, Auteur ; E. NEUHAUS, Auteur ; S. J. WEBB, Auteur ; E. E. EICHLER, Auteur ; Raphael BERNIER, Auteur . - p.24. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.24 Mots-clés : Autism spectrum disorders (ASD)  Electroencephalography (EEG)  Likely gene-disrupting mutations  Molecular subtyping  Mu rhythm attenuation  Social cognition  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder. Promising initiatives utilizing interdisciplinary characterization of ASD suggest phenotypic subtypes related to specific likely gene-disrupting mutations (LGDMs). However, the role of functionally associated LGDMs in the neural social phenotype is unknown. METHODS: In this study of 26 children with ASD (n = 13 with an LGDM) and 13 control children, we characterized patterns of mu attenuation and habituation as children watched videos containing social and nonsocial motions during electroencephalography acquisition. RESULTS: Diagnostic comparisons were consistent with prior work suggesting aberrant mu attenuation in ASD within the upper mu band (10-12 Hz), but typical patterns within the lower mu band (8-10 Hz). Preliminary exploration indicated distinct social sensitization patterns (i.e., increasing mu attenuation for social motion) for children with an LGDM that is primarily expressed during embryonic development. In contrast, children with an LGDM primarily expressed post-embryonic development exhibited stable typical patterns of lower mu attenuation. Neural social indices were associated with social responsiveness, but not cognition. CONCLUSIONS: These findings suggest unique neurophysiological profiles for certain genetic etiologies of ASD, further clarifying possible genetic functional subtypes of ASD and providing insight into mechanisms for targeted treatment approaches. En ligne : http://dx.doi.org/10.1186/s11689-017-9199-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Attention deficit hyperactivity disorder (ADHD) in phenotypically similar neurogenetic conditions: Turner syndrome and the RASopathies / T. GREEN in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.25 Titre : Attention deficit hyperactivity disorder (ADHD) in phenotypically similar neurogenetic conditions: Turner syndrome and the RASopathies Type de document : Texte imprimé et/ou numérique Auteurs : T. GREEN, Auteur ; P. E. NAYLOR, Auteur ; W. DAVIES, Auteur Article en page(s) : p.25 Langues : Anglais (eng) Mots-clés : Attention deficit hyperactivity disorder  Neurofibromatosis type 1  Noonan syndrome  RASopathies  Turner syndrome  X chromosome Index. décimale : PER Périodiques Résumé : BACKGROUND: ADHD (attention deficit hyperactivity disorder) is a common neurodevelopmental disorder. There has been extensive clinical and basic research in the field of ADHD over the past 20 years, but the mechanisms underlying ADHD risk are multifactorial, complex and heterogeneous and, as yet, are poorly defined. In this review, we argue that one approach to address this challenge is to study well-defined disorders to provide insights into potential biological pathways that may be involved in idiopathic ADHD. MAIN BODY: To address this premise, we selected two neurogenetic conditions that are associated with significantly increased ADHD risk: Turner syndrome and the RASopathies (of which Noonan syndrome and neurofibromatosis type 1 are the best-defined with regard to ADHD-related phenotypes). These syndromes were chosen for two main reasons: first, because intellectual functioning is relatively preserved, and second, because they are strikingly phenotypically similar but are etiologically distinct. We review the cognitive, behavioural, neural and cellular phenotypes associated with these conditions and examine their relevance as a model for idiopathic ADHD. CONCLUSION: We conclude by discussing current and future opportunities in the clinical and basic research of these conditions, which, in turn, may shed light upon the biological pathways underlying idiopathic ADHD. En ligne : http://dx.doi.org/10.1186/s11689-017-9205-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Attention deficit hyperactivity disorder (ADHD) in phenotypically similar neurogenetic conditions: Turner syndrome and the RASopathies [Texte imprimé et/ou numérique] / T. GREEN, Auteur ; P. E. NAYLOR, Auteur ; W. DAVIES, Auteur . - p.25. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.25 Mots-clés : Attention deficit hyperactivity disorder  Neurofibromatosis type 1  Noonan syndrome  RASopathies  Turner syndrome  X chromosome Index. décimale : PER Périodiques Résumé : BACKGROUND: ADHD (attention deficit hyperactivity disorder) is a common neurodevelopmental disorder. There has been extensive clinical and basic research in the field of ADHD over the past 20 years, but the mechanisms underlying ADHD risk are multifactorial, complex and heterogeneous and, as yet, are poorly defined. In this review, we argue that one approach to address this challenge is to study well-defined disorders to provide insights into potential biological pathways that may be involved in idiopathic ADHD. MAIN BODY: To address this premise, we selected two neurogenetic conditions that are associated with significantly increased ADHD risk: Turner syndrome and the RASopathies (of which Noonan syndrome and neurofibromatosis type 1 are the best-defined with regard to ADHD-related phenotypes). These syndromes were chosen for two main reasons: first, because intellectual functioning is relatively preserved, and second, because they are strikingly phenotypically similar but are etiologically distinct. We review the cognitive, behavioural, neural and cellular phenotypes associated with these conditions and examine their relevance as a model for idiopathic ADHD. CONCLUSION: We conclude by discussing current and future opportunities in the clinical and basic research of these conditions, which, in turn, may shed light upon the biological pathways underlying idiopathic ADHD. En ligne : http://dx.doi.org/10.1186/s11689-017-9205-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome / A. LIGSAY in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.26 Titre : A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. LIGSAY, Auteur ; A. VAN DIJCK, Auteur ; D. V. NGUYEN, Auteur ; R. LOZANO, Auteur ; Y. CHEN, Auteur ; E. S. BICKEL, Auteur ; D. HESSL, Auteur ; A. SCHNEIDER, Auteur ; Kathleen ANGKUSTSIRI, Auteur ; F. TASSONE, Auteur ; B. CEULEMANS, Auteur ; R. F. KOOY, Auteur ; Randi J. HAGERMAN, Auteur Article en page(s) : p.26 Langues : Anglais (eng) Mots-clés : Adolescents  Children  Clinical trial  Fragile X syndrome  Ganaxolone Index. décimale : PER Périodiques Résumé : BACKGROUND: Gamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA receptor positive allosteric modulator, is hypothesized to improve symptoms such as anxiety, hyperactivity, and attention deficits in children with FXS. METHODS: This study was a randomized, double-blind, placebo-controlled, crossover trial of ganaxolone in children with FXS, aged 6-17 years. RESULTS: Sixty-one participants were assessed for eligibility, and 59 were randomized to the study. Fifty-five participants completed at least the first arm and were included in the intention-to-treat analysis; 51 participants completed both treatment arms. There were no statistically significant improvements observed on the primary outcome measure (Clinical Global Impression-Improvement), the key secondary outcome measure (Pediatric Anxiety Rating Scale-R), or any other secondary outcome measures in the overall study population. However, post-hoc analyses revealed positive trends in areas of anxiety, attention, and hyperactivity in participants with higher baseline anxiety and low full-scale IQ scores. No serious adverse events (AEs) occurred, although there was a significant increase in the frequency and severity of AEs related to ganaxolone compared to placebo. CONCLUSIONS: While ganaxolone was found to be safe, there were no significant improvements in the outcome measures in the overall study population. However, ganaxolone in subgroups of children with FXS, including those with higher anxiety or lower cognitive abilities, might have beneficial effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01725152. En ligne : http://dx.doi.org/10.1186/s11689-017-9207-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome [Texte imprimé et/ou numérique] / A. LIGSAY, Auteur ; A. VAN DIJCK, Auteur ; D. V. NGUYEN, Auteur ; R. LOZANO, Auteur ; Y. CHEN, Auteur ; E. S. BICKEL, Auteur ; D. HESSL, Auteur ; A. SCHNEIDER, Auteur ; Kathleen ANGKUSTSIRI, Auteur ; F. TASSONE, Auteur ; B. CEULEMANS, Auteur ; R. F. KOOY, Auteur ; Randi J. HAGERMAN, Auteur . - p.26. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.26 Mots-clés : Adolescents  Children  Clinical trial  Fragile X syndrome  Ganaxolone Index. décimale : PER Périodiques Résumé : BACKGROUND: Gamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA receptor positive allosteric modulator, is hypothesized to improve symptoms such as anxiety, hyperactivity, and attention deficits in children with FXS. METHODS: This study was a randomized, double-blind, placebo-controlled, crossover trial of ganaxolone in children with FXS, aged 6-17 years. RESULTS: Sixty-one participants were assessed for eligibility, and 59 were randomized to the study. Fifty-five participants completed at least the first arm and were included in the intention-to-treat analysis; 51 participants completed both treatment arms. There were no statistically significant improvements observed on the primary outcome measure (Clinical Global Impression-Improvement), the key secondary outcome measure (Pediatric Anxiety Rating Scale-R), or any other secondary outcome measures in the overall study population. However, post-hoc analyses revealed positive trends in areas of anxiety, attention, and hyperactivity in participants with higher baseline anxiety and low full-scale IQ scores. No serious adverse events (AEs) occurred, although there was a significant increase in the frequency and severity of AEs related to ganaxolone compared to placebo. CONCLUSIONS: While ganaxolone was found to be safe, there were no significant improvements in the outcome measures in the overall study population. However, ganaxolone in subgroups of children with FXS, including those with higher anxiety or lower cognitive abilities, might have beneficial effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01725152. En ligne : http://dx.doi.org/10.1186/s11689-017-9207-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Social brain circuitry and social cognition in infants born preterm / A. FENOGLIO in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.27 Titre : Social brain circuitry and social cognition in infants born preterm Type de document : Texte imprimé et/ou numérique Auteurs : A. FENOGLIO, Auteur ; Michael K. GEORGIEFF, Auteur ; J. T. ELISON, Auteur Article en page(s) : p.27 Langues : Anglais (eng) Mots-clés : Neurodevelopment  Neuroplasticity  Prematurity  Social brain  Social cognition Index. décimale : PER Périodiques Résumé : Preterm birth is associated with an increased risk of adverse neurologic, psychiatric, and cognitive outcomes. The brain circuits involved in processing social information are critical to all of these domains, but little work has been done to examine whether and how these circuits may be especially sensitive to prematurity. This paper contains a brief summary of some of the cognitive, psychiatric, and social outcomes associated with prematurity, followed by a description of findings from the modest body of research into social-cognitive development in infants and children born preterm. Next, findings from studies of structural and functional brain development in infants born preterm are reviewed, with an eye toward the distinctive role of the brain circuits implicated in social functioning. The goal of this review is to investigate the extent to which the putative "social brain" may have particular developmental susceptibilities to the insults associated with preterm birth, and the role of early social-cognitive development in later neurodevelopmental outcomes. Much work has been done to characterize neurobehavioral outcomes in the preterm population, but future research must incorporate both brain and behavioral measures to identify early biomarkers linked to later emerging social-cognitive clinical impairment in order to guide effective, targeted intervention. En ligne : http://dx.doi.org/10.1186/s11689-017-9206-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Social brain circuitry and social cognition in infants born preterm [Texte imprimé et/ou numérique] / A. FENOGLIO, Auteur ; Michael K. GEORGIEFF, Auteur ; J. T. ELISON, Auteur . - p.27. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.27 Mots-clés : Neurodevelopment  Neuroplasticity  Prematurity  Social brain  Social cognition Index. décimale : PER Périodiques Résumé : Preterm birth is associated with an increased risk of adverse neurologic, psychiatric, and cognitive outcomes. The brain circuits involved in processing social information are critical to all of these domains, but little work has been done to examine whether and how these circuits may be especially sensitive to prematurity. This paper contains a brief summary of some of the cognitive, psychiatric, and social outcomes associated with prematurity, followed by a description of findings from the modest body of research into social-cognitive development in infants and children born preterm. Next, findings from studies of structural and functional brain development in infants born preterm are reviewed, with an eye toward the distinctive role of the brain circuits implicated in social functioning. The goal of this review is to investigate the extent to which the putative "social brain" may have particular developmental susceptibilities to the insults associated with preterm birth, and the role of early social-cognitive development in later neurodevelopmental outcomes. Much work has been done to characterize neurobehavioral outcomes in the preterm population, but future research must incorporate both brain and behavioral measures to identify early biomarkers linked to later emerging social-cognitive clinical impairment in order to guide effective, targeted intervention. En ligne : http://dx.doi.org/10.1186/s11689-017-9206-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Social brain circuitry and social cognition in infants born preterm / A. FENOGLIO in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.27 Titre : Social brain circuitry and social cognition in infants born preterm Type de document : Texte imprimé et/ou numérique Auteurs : A. FENOGLIO, Auteur ; Michael K. GEORGIEFF, Auteur ; J. T. ELISON, Auteur Article en page(s) : p.27 Langues : Anglais (eng) Mots-clés : Neurodevelopment  Neuroplasticity  Prematurity  Social brain  Social cognition Index. décimale : PER Périodiques Résumé : Preterm birth is associated with an increased risk of adverse neurologic, psychiatric, and cognitive outcomes. The brain circuits involved in processing social information are critical to all of these domains, but little work has been done to examine whether and how these circuits may be especially sensitive to prematurity. This paper contains a brief summary of some of the cognitive, psychiatric, and social outcomes associated with prematurity, followed by a description of findings from the modest body of research into social-cognitive development in infants and children born preterm. Next, findings from studies of structural and functional brain development in infants born preterm are reviewed, with an eye toward the distinctive role of the brain circuits implicated in social functioning. The goal of this review is to investigate the extent to which the putative "social brain" may have particular developmental susceptibilities to the insults associated with preterm birth, and the role of early social-cognitive development in later neurodevelopmental outcomes. Much work has been done to characterize neurobehavioral outcomes in the preterm population, but future research must incorporate both brain and behavioral measures to identify early biomarkers linked to later emerging social-cognitive clinical impairment in order to guide effective, targeted intervention. En ligne : http://dx.doi.org/10.1186/s11689-017-9206-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Social brain circuitry and social cognition in infants born preterm [Texte imprimé et/ou numérique] / A. FENOGLIO, Auteur ; Michael K. GEORGIEFF, Auteur ; J. T. ELISON, Auteur . - p.27. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.27 Mots-clés : Neurodevelopment  Neuroplasticity  Prematurity  Social brain  Social cognition Index. décimale : PER Périodiques Résumé : Preterm birth is associated with an increased risk of adverse neurologic, psychiatric, and cognitive outcomes. The brain circuits involved in processing social information are critical to all of these domains, but little work has been done to examine whether and how these circuits may be especially sensitive to prematurity. This paper contains a brief summary of some of the cognitive, psychiatric, and social outcomes associated with prematurity, followed by a description of findings from the modest body of research into social-cognitive development in infants and children born preterm. Next, findings from studies of structural and functional brain development in infants born preterm are reviewed, with an eye toward the distinctive role of the brain circuits implicated in social functioning. The goal of this review is to investigate the extent to which the putative "social brain" may have particular developmental susceptibilities to the insults associated with preterm birth, and the role of early social-cognitive development in later neurodevelopmental outcomes. Much work has been done to characterize neurobehavioral outcomes in the preterm population, but future research must incorporate both brain and behavioral measures to identify early biomarkers linked to later emerging social-cognitive clinical impairment in order to guide effective, targeted intervention. En ligne : http://dx.doi.org/10.1186/s11689-017-9206-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

The role of nonverbal working memory in morphosyntactic processing by children with specific language impairment and autism spectrum disorders / S. ELLIS WEISMER in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.28 Titre : The role of nonverbal working memory in morphosyntactic processing by children with specific language impairment and autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : S. ELLIS WEISMER, Auteur ; M. M. DAVIDSON, Auteur ; I. GANGOPADHYAY, Auteur ; H. SINDBERG, Auteur ; H. ROEBUCK, Auteur ; M. KAUSHANSKAYA, Auteur Article en page(s) : p.28 Langues : Anglais (eng) Mots-clés : Autism  Grammatical judgment  Specific language impairment  Working memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Both children with autism spectrum disorders (ASD) and children with specific language impairment (SLI) have been shown to have difficulties with grammatical processing. A comparison of these two populations with neurodevelopmental disorders was undertaken to examine similarities and differences in the mechanisms that may underlie grammatical processing. Research has shown that working memory (WM) is recruited during grammatical processing. The goal of this study was to examine morphosyntactic processing on a grammatical judgment task in children who varied in clinical diagnosis and language abilities and to assess the extent to which performance is predicted by nonverbal working memory (WM). Two theoretical perspectives were evaluated relative to performance on the grammatical judgment task-the "working memory" account and the "wrap-up" account. These accounts make contrasting predictions about the detection of grammatical errors occurring early versus late in the sentence. METHODS: Participants were 84 school-age children with SLI (n = 21), ASD (n = 27), and typical development (TD, n = 36). Performance was analyzed based on diagnostic group as well as language status (normal language, NL, n = 54, and language impairment, LI, n = 30). A grammatical judgment task was used in which the position of the error in the sentence (early versus late) was manipulated. A visual WM task (N-back) was administered and the ability of WM to predict morphosyntactic processing was assessed. RESULTS: Groups differed significantly in their sensitivity to grammatical errors (TD > SLI and NL > LI) but did not differ in nonverbal WM. Overall, children in all groups were more sensitive and quicker at detecting errors occurring late in the sentence than early in the sentence. Nonverbal WM predicted morphosyntactic processing across groups, but the specific profile of association between WM and early versus late error detection was reversed for children with and without language impairment. CONCLUSIONS: Findings primarily support a "wrap up" account whereby the accumulating sentence context for errors positioned late in the sentence (rather than early) appeared to facilitate morphosyntactic processing. Although none of the groups displayed deficits in visual WM, individual differences in these nonverbal WM resources predicted proficiency in morphosyntactic processing. En ligne : http://dx.doi.org/10.1186/s11689-017-9209-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] The role of nonverbal working memory in morphosyntactic processing by children with specific language impairment and autism spectrum disorders [Texte imprimé et/ou numérique] / S. ELLIS WEISMER, Auteur ; M. M. DAVIDSON, Auteur ; I. GANGOPADHYAY, Auteur ; H. SINDBERG, Auteur ; H. ROEBUCK, Auteur ; M. KAUSHANSKAYA, Auteur . - p.28. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.28 Mots-clés : Autism  Grammatical judgment  Specific language impairment  Working memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Both children with autism spectrum disorders (ASD) and children with specific language impairment (SLI) have been shown to have difficulties with grammatical processing. A comparison of these two populations with neurodevelopmental disorders was undertaken to examine similarities and differences in the mechanisms that may underlie grammatical processing. Research has shown that working memory (WM) is recruited during grammatical processing. The goal of this study was to examine morphosyntactic processing on a grammatical judgment task in children who varied in clinical diagnosis and language abilities and to assess the extent to which performance is predicted by nonverbal working memory (WM). Two theoretical perspectives were evaluated relative to performance on the grammatical judgment task-the "working memory" account and the "wrap-up" account. These accounts make contrasting predictions about the detection of grammatical errors occurring early versus late in the sentence. METHODS: Participants were 84 school-age children with SLI (n = 21), ASD (n = 27), and typical development (TD, n = 36). Performance was analyzed based on diagnostic group as well as language status (normal language, NL, n = 54, and language impairment, LI, n = 30). A grammatical judgment task was used in which the position of the error in the sentence (early versus late) was manipulated. A visual WM task (N-back) was administered and the ability of WM to predict morphosyntactic processing was assessed. RESULTS: Groups differed significantly in their sensitivity to grammatical errors (TD > SLI and NL > LI) but did not differ in nonverbal WM. Overall, children in all groups were more sensitive and quicker at detecting errors occurring late in the sentence than early in the sentence. Nonverbal WM predicted morphosyntactic processing across groups, but the specific profile of association between WM and early versus late error detection was reversed for children with and without language impairment. CONCLUSIONS: Findings primarily support a "wrap up" account whereby the accumulating sentence context for errors positioned late in the sentence (rather than early) appeared to facilitate morphosyntactic processing. Although none of the groups displayed deficits in visual WM, individual differences in these nonverbal WM resources predicted proficiency in morphosyntactic processing. En ligne : http://dx.doi.org/10.1186/s11689-017-9209-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance / D. REID in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.29 Titre : Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance Type de document : Texte imprimé et/ou numérique Auteurs : D. REID, Auteur ; J. MOSS, Auteur ; L. NELSON, Auteur ; L. GROVES, Auteur ; C. OLIVER, Auteur Article en page(s) : p.29 Langues : Anglais (eng) Mots-clés : Behavioural phenotype  CdLS  Cornelia de Lange  Executive functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. METHODS: Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. RESULTS: Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. CONCLUSIONS: The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important. En ligne : http://dx.doi.org/10.1186/s11689-017-9208-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance [Texte imprimé et/ou numérique] / D. REID, Auteur ; J. MOSS, Auteur ; L. NELSON, Auteur ; L. GROVES, Auteur ; C. OLIVER, Auteur . - p.29. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.29 Mots-clés : Behavioural phenotype  CdLS  Cornelia de Lange  Executive functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. METHODS: Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. RESULTS: Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. CONCLUSIONS: The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important. En ligne : http://dx.doi.org/10.1186/s11689-017-9208-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance / D. REID in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.29 Titre : Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance Type de document : Texte imprimé et/ou numérique Auteurs : D. REID, Auteur ; J. MOSS, Auteur ; L. NELSON, Auteur ; L. GROVES, Auteur ; C. OLIVER, Auteur Article en page(s) : p.29 Langues : Anglais (eng) Mots-clés : Behavioural phenotype  CdLS  Cornelia de Lange  Executive functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. METHODS: Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. RESULTS: Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. CONCLUSIONS: The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important. En ligne : http://dx.doi.org/10.1186/s11689-017-9208-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance [Texte imprimé et/ou numérique] / D. REID, Auteur ; J. MOSS, Auteur ; L. NELSON, Auteur ; L. GROVES, Auteur ; C. OLIVER, Auteur . - p.29. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.29 Mots-clés : Behavioural phenotype  CdLS  Cornelia de Lange  Executive functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. METHODS: Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. RESULTS: Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. CONCLUSIONS: The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important. En ligne : http://dx.doi.org/10.1186/s11689-017-9208-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Erratum to: Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis / M. S. SIDOROV in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.30 Titre : Erratum to: Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis Type de document : Texte imprimé et/ou numérique Auteurs : M. S. SIDOROV, Auteur ; G. M. DECK, Auteur ; M. DOLATSHAHI, Auteur ; R. L. THIBERT, Auteur ; L. M. BIRD, Auteur ; C. J. CHU, Auteur ; B. D. PHILPOT, Auteur Article en page(s) : p.30 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s11689-017-9195-8.]. En ligne : http://dx.doi.org/10.1186/s11689-017-9210-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Erratum to: Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis [Texte imprimé et/ou numérique] / M. S. SIDOROV, Auteur ; G. M. DECK, Auteur ; M. DOLATSHAHI, Auteur ; R. L. THIBERT, Auteur ; L. M. BIRD, Auteur ; C. J. CHU, Auteur ; B. D. PHILPOT, Auteur . - p.30. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.30 Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s11689-017-9195-8.]. En ligne : http://dx.doi.org/10.1186/s11689-017-9210-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Altered sensitivity to social gaze in the FMR1 premutation and pragmatic language competence / J. KLUSEK in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.31 Titre : Altered sensitivity to social gaze in the FMR1 premutation and pragmatic language competence Type de document : Texte imprimé et/ou numérique Auteurs : J. KLUSEK, Auteur ; J. SCHMIDT, Auteur ; A. J. FAIRCHILD, Auteur ; A. PORTER, Auteur ; J. E. ROBERTS, Auteur Article en page(s) : p.31 Langues : Anglais (eng) Mots-clés : Direct gaze  Eye contact  Fragile X carriers  Social cognition  Social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: The FMR1 premutation affects 1:291 women and is associated with a range of cognitive, affective, and physical health complications, including deficits in pragmatic language (i.e., social language). This study investigated attention to eye gaze as a fundamental social-cognitive skill that may be impaired in the FMR1 premutation and could underlie pragmatic deficits. Given the high prevalence of the FMR1 premutation, efforts to define its phenotype and mechanistic underpinnings have significant public health implications. METHODS: Thirty-five women with the FMR1 premutation and 20 control women completed an eye-tracking paradigm that recorded time spent dwelling within the eye region in response to a face displaying either direct or averted gaze. Pragmatic language ability was coded from a conversational sample using the Pragmatic Rating Scale. RESULTS: Women with the FMR1 premutation failed to show attentional preference to direct gaze and spent more time dwelling on the averted eyes relative to controls. While dwelling on the eyes was associated with better pragmatic language performance in controls, these variables were unrelated in the women with the FMR1 premutation. CONCLUSIONS: Altered sensitivity to social gaze, characterized by increased salience of averted gaze, was observed among women with the FMR1 premutation. Furthermore, women with the FMR1 premutation were unable to capitalize on information conveyed through the eyes to enhance social-communicative engagement, which differed from patterns seen in controls. These findings contribute to the growing characterization of social and communication phenotypes associated with the FMR1 premutation. En ligne : http://dx.doi.org/10.1186/s11689-017-9211-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Altered sensitivity to social gaze in the FMR1 premutation and pragmatic language competence [Texte imprimé et/ou numérique] / J. KLUSEK, Auteur ; J. SCHMIDT, Auteur ; A. J. FAIRCHILD, Auteur ; A. PORTER, Auteur ; J. E. ROBERTS, Auteur . - p.31. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.31 Mots-clés : Direct gaze  Eye contact  Fragile X carriers  Social cognition  Social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: The FMR1 premutation affects 1:291 women and is associated with a range of cognitive, affective, and physical health complications, including deficits in pragmatic language (i.e., social language). This study investigated attention to eye gaze as a fundamental social-cognitive skill that may be impaired in the FMR1 premutation and could underlie pragmatic deficits. Given the high prevalence of the FMR1 premutation, efforts to define its phenotype and mechanistic underpinnings have significant public health implications. METHODS: Thirty-five women with the FMR1 premutation and 20 control women completed an eye-tracking paradigm that recorded time spent dwelling within the eye region in response to a face displaying either direct or averted gaze. Pragmatic language ability was coded from a conversational sample using the Pragmatic Rating Scale. RESULTS: Women with the FMR1 premutation failed to show attentional preference to direct gaze and spent more time dwelling on the averted eyes relative to controls. While dwelling on the eyes was associated with better pragmatic language performance in controls, these variables were unrelated in the women with the FMR1 premutation. CONCLUSIONS: Altered sensitivity to social gaze, characterized by increased salience of averted gaze, was observed among women with the FMR1 premutation. Furthermore, women with the FMR1 premutation were unable to capitalize on information conveyed through the eyes to enhance social-communicative engagement, which differed from patterns seen in controls. These findings contribute to the growing characterization of social and communication phenotypes associated with the FMR1 premutation. En ligne : http://dx.doi.org/10.1186/s11689-017-9211-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Attention and motor deficits index non-specific background liabilities that predict autism recurrence in siblings / S. E. MOUS in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.32 Titre : Attention and motor deficits index non-specific background liabilities that predict autism recurrence in siblings Type de document : Texte imprimé et/ou numérique Auteurs : S. E. MOUS, Auteur ; A. JIANG, Auteur ; Arpana AGRAWAL, Auteur ; John N. CONSTANTINO, Auteur Article en page(s) : p.32 Langues : Anglais (eng) Mots-clés : Adhd  Autism  Family studies  Motor coordination  Sibling recurrence Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent research has demonstrated that subclinical autistic traits of parents amplify the effects of deleterious mutations in the causation of autism spectrum disorder (ASD) in their offspring. Here, we examined the extent to which two neurodevelopmental traits that are non-specific to ASD-inattention/hyperactivity and motor coordination-might contribute to ASD recurrence in siblings of ASD probands. METHODS: Data from a quantitative trait study of 114 ASD probands and their brothers, 26% of whom also had ASD, were analyzed. Autistic trait severity was ascertained using the Social Responsiveness Scale-2, attention/hyperactivity problems using the Achenbach System of Empirically Based Assessment, and motor coordination (in a subset of participants) using the Developmental Coordination Disorder Questionnaire. RESULTS: Among siblings (affected and unaffected), both categorical recurrence of ASD (Nagelkerke R (2) = 0.53) and quantitative ASD trait burden (R (2) = 0.55) were predicted by sibling ADHD and motor coordination impairment scores, even though these traits, on average, were not elevated among the unaffected siblings. CONCLUSIONS: These findings in a clinical family cohort confirm observations from general population studies that inattention/hyperactivity and motor impairment-axes of behavioral development that are non-specific to ASD, and often appreciable before ASD is typically diagnosed-jointly account for over 50% of the variation in autistic impairment of siblings, whether ascertained quantitatively or categorically. This finding within a sibling design suggests that background ASD susceptibilities that are inherited but non-specific ("BASINS") may contribute to additive genetic liability in the same manner that ASD-specific susceptibilities (such as parental subclinical ASD traits and deleterious mutations) engender ASD risk. En ligne : http://dx.doi.org/10.1186/s11689-017-9212-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Attention and motor deficits index non-specific background liabilities that predict autism recurrence in siblings [Texte imprimé et/ou numérique] / S. E. MOUS, Auteur ; A. JIANG, Auteur ; Arpana AGRAWAL, Auteur ; John N. CONSTANTINO, Auteur . - p.32. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.32 Mots-clés : Adhd  Autism  Family studies  Motor coordination  Sibling recurrence Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent research has demonstrated that subclinical autistic traits of parents amplify the effects of deleterious mutations in the causation of autism spectrum disorder (ASD) in their offspring. Here, we examined the extent to which two neurodevelopmental traits that are non-specific to ASD-inattention/hyperactivity and motor coordination-might contribute to ASD recurrence in siblings of ASD probands. METHODS: Data from a quantitative trait study of 114 ASD probands and their brothers, 26% of whom also had ASD, were analyzed. Autistic trait severity was ascertained using the Social Responsiveness Scale-2, attention/hyperactivity problems using the Achenbach System of Empirically Based Assessment, and motor coordination (in a subset of participants) using the Developmental Coordination Disorder Questionnaire. RESULTS: Among siblings (affected and unaffected), both categorical recurrence of ASD (Nagelkerke R (2) = 0.53) and quantitative ASD trait burden (R (2) = 0.55) were predicted by sibling ADHD and motor coordination impairment scores, even though these traits, on average, were not elevated among the unaffected siblings. CONCLUSIONS: These findings in a clinical family cohort confirm observations from general population studies that inattention/hyperactivity and motor impairment-axes of behavioral development that are non-specific to ASD, and often appreciable before ASD is typically diagnosed-jointly account for over 50% of the variation in autistic impairment of siblings, whether ascertained quantitatively or categorically. This finding within a sibling design suggests that background ASD susceptibilities that are inherited but non-specific ("BASINS") may contribute to additive genetic liability in the same manner that ASD-specific susceptibilities (such as parental subclinical ASD traits and deleterious mutations) engender ASD risk. En ligne : http://dx.doi.org/10.1186/s11689-017-9212-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

An experimental study of executive function and social impairment in Cornelia de Lange syndrome / L. NELSON in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.33 Titre : An experimental study of executive function and social impairment in Cornelia de Lange syndrome Type de document : Texte imprimé et/ou numérique Auteurs : L. NELSON, Auteur ; Hayley CRAWFORD, Auteur ; D. REID, Auteur ; J. MOSS, Auteur ; C. OLIVER, Auteur Article en page(s) : p.33 Langues : Anglais (eng) Mots-clés : Cornelia de Lange syndrome  Down syndrome  Executive function  Social anxiety Index. décimale : PER Périodiques Résumé : BACKGROUND: Extreme shyness and social anxiety is reported to be characteristic of adolescents and adults with Cornelia de Lange syndrome (CdLS); however, the nature of these characteristics is not well documented. In this study, we develop and apply an experimental assessment of social anxiety in a group of adolescents and adults with CdLS to determine the nature of the social difficulties and whether they are related to impairments in executive functioning. METHODS: A familiar and unfamiliar examiner separately engaged in socially demanding tasks comprising three experimental conditions with a group of individuals with CdLS (n = 25; % male = 44; mean age = 22.16; SD = 8.81) and a comparable group of individuals with Down syndrome (DS; n = 20; % male = 35; mean age = 24.35; SD = 5.97). Behaviours indicative of social anxiety were coded. The Behavior Rating Inventory of Executive Function-Preschool version, an informant measure of executive function, was completed by participants' caregivers. RESULTS: Significantly less verbalisation was observed in the CdLS group than the DS group in conditions requiring the initiation of speech. In the CdLS group, impairments in verbalisation were not associated with a greater degree of intellectual disability but were significantly correlated with impairments in both planning and working memory. This association was not evident in the DS group. CONCLUSIONS: Adolescents and adults with CdLS have a specific difficulty with the initiation of speech when social demands are placed upon them. This impairment in verbalisation may be underpinned by specific cognitive deficits, although further research is needed to investigate this fully. En ligne : http://dx.doi.org/10.1186/s11689-017-9213-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] An experimental study of executive function and social impairment in Cornelia de Lange syndrome [Texte imprimé et/ou numérique] / L. NELSON, Auteur ; Hayley CRAWFORD, Auteur ; D. REID, Auteur ; J. MOSS, Auteur ; C. OLIVER, Auteur . - p.33. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.33 Mots-clés : Cornelia de Lange syndrome  Down syndrome  Executive function  Social anxiety Index. décimale : PER Périodiques Résumé : BACKGROUND: Extreme shyness and social anxiety is reported to be characteristic of adolescents and adults with Cornelia de Lange syndrome (CdLS); however, the nature of these characteristics is not well documented. In this study, we develop and apply an experimental assessment of social anxiety in a group of adolescents and adults with CdLS to determine the nature of the social difficulties and whether they are related to impairments in executive functioning. METHODS: A familiar and unfamiliar examiner separately engaged in socially demanding tasks comprising three experimental conditions with a group of individuals with CdLS (n = 25; % male = 44; mean age = 22.16; SD = 8.81) and a comparable group of individuals with Down syndrome (DS; n = 20; % male = 35; mean age = 24.35; SD = 5.97). Behaviours indicative of social anxiety were coded. The Behavior Rating Inventory of Executive Function-Preschool version, an informant measure of executive function, was completed by participants' caregivers. RESULTS: Significantly less verbalisation was observed in the CdLS group than the DS group in conditions requiring the initiation of speech. In the CdLS group, impairments in verbalisation were not associated with a greater degree of intellectual disability but were significantly correlated with impairments in both planning and working memory. This association was not evident in the DS group. CONCLUSIONS: Adolescents and adults with CdLS have a specific difficulty with the initiation of speech when social demands are placed upon them. This impairment in verbalisation may be underpinned by specific cognitive deficits, although further research is needed to investigate this fully. En ligne : http://dx.doi.org/10.1186/s11689-017-9213-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

EEG power at 3 months in infants at high familial risk for autism / A. R. LEVIN in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.34 Titre : EEG power at 3 months in infants at high familial risk for autism Type de document : Texte imprimé et/ou numérique Auteurs : A. R. LEVIN, Auteur ; Kandice J. VARCIN, Auteur ; H. M. O'LEARY, Auteur ; Helen TAGER-FLUSBERG, Auteur ; C. A. NELSON, Auteur Article en page(s) : p.34 Langues : Anglais (eng) Mots-clés : Autism  Biomarker  Early development  Electroencephalography  Infant siblings Index. décimale : PER Périodiques Résumé : BACKGROUND: Alterations in brain development during infancy may precede the behavioral manifestation of developmental disorders. Infants at increased risk for autism are also at increased risk for other developmental disorders, including, quite commonly, language disorders. Here we assess the extent to which electroencephalographic (EEG) differences in infants at high versus low familial risk for autism are present by 3 months of age, and elucidate the functional significance of EEG power at 3 months in predicting later development. METHODS: EEG data were acquired at 3 months in infant siblings of children with autism (high risk; n = 29) and infant siblings of typically developing children (low risk; n = 19) as part of a prospective, longitudinal investigation. Development across multiple domains was assessed at 6, 9, 12, 18, 24, and 36 months. Diagnosis of autism was determined at 18-36 months. We assessed relationships between 3-month-olds' frontal EEG power and autism risk, autism outcome, language development, and development in other domains. RESULTS: Infants at high familial risk for autism had reduced frontal power at 3 months compared to infants at low familial risk for autism, across several frequency bands. Reduced frontal high-alpha power at 3 months was robustly associated with poorer expressive language at 12 months. CONCLUSIONS: Reduced frontal power at 3 months may indicate increased risk for reduced expressive language skills at 12 months. This finding aligns with prior studies suggesting reduced power is a marker for atypical brain function, and infants at familial risk for autism are also at increased risk for altered developmental functioning in non-autism-specific domains. En ligne : http://dx.doi.org/10.1186/s11689-017-9214-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] EEG power at 3 months in infants at high familial risk for autism [Texte imprimé et/ou numérique] / A. R. LEVIN, Auteur ; Kandice J. VARCIN, Auteur ; H. M. O'LEARY, Auteur ; Helen TAGER-FLUSBERG, Auteur ; C. A. NELSON, Auteur . - p.34. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.34 Mots-clés : Autism  Biomarker  Early development  Electroencephalography  Infant siblings Index. décimale : PER Périodiques Résumé : BACKGROUND: Alterations in brain development during infancy may precede the behavioral manifestation of developmental disorders. Infants at increased risk for autism are also at increased risk for other developmental disorders, including, quite commonly, language disorders. Here we assess the extent to which electroencephalographic (EEG) differences in infants at high versus low familial risk for autism are present by 3 months of age, and elucidate the functional significance of EEG power at 3 months in predicting later development. METHODS: EEG data were acquired at 3 months in infant siblings of children with autism (high risk; n = 29) and infant siblings of typically developing children (low risk; n = 19) as part of a prospective, longitudinal investigation. Development across multiple domains was assessed at 6, 9, 12, 18, 24, and 36 months. Diagnosis of autism was determined at 18-36 months. We assessed relationships between 3-month-olds' frontal EEG power and autism risk, autism outcome, language development, and development in other domains. RESULTS: Infants at high familial risk for autism had reduced frontal power at 3 months compared to infants at low familial risk for autism, across several frequency bands. Reduced frontal high-alpha power at 3 months was robustly associated with poorer expressive language at 12 months. CONCLUSIONS: Reduced frontal power at 3 months may indicate increased risk for reduced expressive language skills at 12 months. This finding aligns with prior studies suggesting reduced power is a marker for atypical brain function, and infants at familial risk for autism are also at increased risk for altered developmental functioning in non-autism-specific domains. En ligne : http://dx.doi.org/10.1186/s11689-017-9214-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Understanding others: a pilot investigation of cognitive and affective facets of social cognition in patients with 22q11.2 deletion syndrome (22q11DS) / D. BADOUD in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.35 Titre : Understanding others: a pilot investigation of cognitive and affective facets of social cognition in patients with 22q11.2 deletion syndrome (22q11DS) Type de document : Texte imprimé et/ou numérique Auteurs : D. BADOUD, Auteur ; M. SCHNEIDER, Auteur ; S. MENGHETTI, Auteur ; B. GLASER, Auteur ; M. DEBBANE, Auteur ; S. ELIEZ, Auteur Article en page(s) : p.35 Langues : Anglais (eng) Mots-clés : 22q11.2 deletion syndrome  Adolescence  Emotion recognition  Perspective taking  Psychosis  Social cognition  Social functioning  Theory of mind Index. décimale : PER Périodiques Résumé : BACKGROUND: Although significant impairments in the affective and cognitive facets of social cognition have been highlighted in patients with 22q11.2 deletion syndrome (22q11DS) in previous studies, these domains have never been investigated simultaneously within the same group of participants. Furthermore, despite theoretical evidence, associations between these two processes and schizotypal symptoms or social difficulties in this population have been scarcely examined. METHODS: Twenty-nine participants with 22q11DS and 27 typically developing controls (N = 5 siblings; N = 22 unrelated controls) aged between 11 and 21 years participated in the study. Both groups were matched for age and gender distribution. Two computerized social cognition tasks evaluating perspective and emotion recognition abilities were administered to all participants. The levels of schizotypal trait expression and social functioning were further investigated in both groups, based on a validated self-report questionnaire (Schizotypal Personality Questionnaire) and parental interview (Vineland Adaptive Behavior Scales). RESULTS: Participants with 22q11DS exhibited lower perspective-taking and emotion recognition capacities than typically developing controls. The two socio-cognitive dimensions investigated here were further correlated in healthy controls. The efficiency of perspective-taking processes (response time) was marginally related to the degree of schizotypal trait expression in patients with 22q11DS. CONCLUSIONS: This study first provides support for significant deficits in two core facets of social cognition in 22q11DS. The associations observed between the experimental tasks and measures of social functioning or schizotypal symptoms in 22q11DS open promising research avenue, which should be more deeply investigated in future studies. En ligne : http://dx.doi.org/10.1186/s11689-017-9216-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Understanding others: a pilot investigation of cognitive and affective facets of social cognition in patients with 22q11.2 deletion syndrome (22q11DS) [Texte imprimé et/ou numérique] / D. BADOUD, Auteur ; M. SCHNEIDER, Auteur ; S. MENGHETTI, Auteur ; B. GLASER, Auteur ; M. DEBBANE, Auteur ; S. ELIEZ, Auteur . - p.35. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.35 Mots-clés : 22q11.2 deletion syndrome  Adolescence  Emotion recognition  Perspective taking  Psychosis  Social cognition  Social functioning  Theory of mind Index. décimale : PER Périodiques Résumé : BACKGROUND: Although significant impairments in the affective and cognitive facets of social cognition have been highlighted in patients with 22q11.2 deletion syndrome (22q11DS) in previous studies, these domains have never been investigated simultaneously within the same group of participants. Furthermore, despite theoretical evidence, associations between these two processes and schizotypal symptoms or social difficulties in this population have been scarcely examined. METHODS: Twenty-nine participants with 22q11DS and 27 typically developing controls (N = 5 siblings; N = 22 unrelated controls) aged between 11 and 21 years participated in the study. Both groups were matched for age and gender distribution. Two computerized social cognition tasks evaluating perspective and emotion recognition abilities were administered to all participants. The levels of schizotypal trait expression and social functioning were further investigated in both groups, based on a validated self-report questionnaire (Schizotypal Personality Questionnaire) and parental interview (Vineland Adaptive Behavior Scales). RESULTS: Participants with 22q11DS exhibited lower perspective-taking and emotion recognition capacities than typically developing controls. The two socio-cognitive dimensions investigated here were further correlated in healthy controls. The efficiency of perspective-taking processes (response time) was marginally related to the degree of schizotypal trait expression in patients with 22q11DS. CONCLUSIONS: This study first provides support for significant deficits in two core facets of social cognition in 22q11DS. The associations observed between the experimental tasks and measures of social functioning or schizotypal symptoms in 22q11DS open promising research avenue, which should be more deeply investigated in future studies. En ligne : http://dx.doi.org/10.1186/s11689-017-9216-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Saccade adaptation deficits in developmental dyslexia suggest disruption of cerebellar-dependent learning / E. G. FREEDMAN in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.36 Titre : Saccade adaptation deficits in developmental dyslexia suggest disruption of cerebellar-dependent learning Type de document : Texte imprimé et/ou numérique Auteurs : E. G. FREEDMAN, Auteur ; S. MOLHOLM, Auteur ; M. J. GRAY, Auteur ; D. BELYUSAR, Auteur ; J. J. FOXE, Auteur Article en page(s) : p.36 Langues : Anglais (eng) Mots-clés : Adaptation  Cerebellum  Dyslexia  Eye movements  Reading  Saccades Index. décimale : PER Périodiques Résumé : BACKGROUND: Estimates of the prevalence of developmental dyslexia in the general population range from 5% to as many as 10%. Symptoms include reading, writing, and language deficits, but the severity and mix of symptoms can vary widely across individuals. In at least some people with dyslexia, the structure and function of the cerebellum may be disordered. Saccadic adaptation requires proper function of the cerebellum and brainstem circuitry and might provide a simple, noninvasive assay for early identification and sub-phenotyping in populations of children who may have dyslexia. METHODS: Children between the ages of 7 and 15 served as participants in this experiment. Fifteen had been diagnosed with developmental dyslexia and an additional 15 were typically developing children. Five of the participants diagnosed with dyslexia were also diagnosed with an attention deficit hyperactivity disroder and were excluded from further analyses. Participants performed in a saccadic adaptation task in which visual errors were introduced at the end of saccadic eye movements. The amplitudes of primary saccades were measured and plotted as a function of the order in which they occurred. Lines of best fit were calculated. Significant changes in the amplitude of primary saccades were identified. RESULTS: 12/15 typically developing children had significant adaptation of saccade amplitude in this experiment. 1/10 participants with dyslexia appropriately altered saccade amplitudes to reduce the visual error introduced in the saccade adaptation paradigm. CONCLUSIONS: Proper cerebellar function is required for saccadic adaptation, but in at least some children with dyslexia, cerebellar structure and function may be disordered. Consistent with this hypothesis, the data presented in this report clearly illustrate a difference in the ability of children with dyslexia to adapt saccade amplitudes in response to imposed visual errors. Saccadic adaptation might provide a noninvasive assay for early identification of dyslexia. Future work will determine whether reduced saccadic adaptation is pervasive in dyslexia or whether this identifies a sub-phenotype within the larger population of people identified with reading and language deficits. En ligne : http://dx.doi.org/10.1186/s11689-017-9218-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Saccade adaptation deficits in developmental dyslexia suggest disruption of cerebellar-dependent learning [Texte imprimé et/ou numérique] / E. G. FREEDMAN, Auteur ; S. MOLHOLM, Auteur ; M. J. GRAY, Auteur ; D. BELYUSAR, Auteur ; J. J. FOXE, Auteur . - p.36. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.36 Mots-clés : Adaptation  Cerebellum  Dyslexia  Eye movements  Reading  Saccades Index. décimale : PER Périodiques Résumé : BACKGROUND: Estimates of the prevalence of developmental dyslexia in the general population range from 5% to as many as 10%. Symptoms include reading, writing, and language deficits, but the severity and mix of symptoms can vary widely across individuals. In at least some people with dyslexia, the structure and function of the cerebellum may be disordered. Saccadic adaptation requires proper function of the cerebellum and brainstem circuitry and might provide a simple, noninvasive assay for early identification and sub-phenotyping in populations of children who may have dyslexia. METHODS: Children between the ages of 7 and 15 served as participants in this experiment. Fifteen had been diagnosed with developmental dyslexia and an additional 15 were typically developing children. Five of the participants diagnosed with dyslexia were also diagnosed with an attention deficit hyperactivity disroder and were excluded from further analyses. Participants performed in a saccadic adaptation task in which visual errors were introduced at the end of saccadic eye movements. The amplitudes of primary saccades were measured and plotted as a function of the order in which they occurred. Lines of best fit were calculated. Significant changes in the amplitude of primary saccades were identified. RESULTS: 12/15 typically developing children had significant adaptation of saccade amplitude in this experiment. 1/10 participants with dyslexia appropriately altered saccade amplitudes to reduce the visual error introduced in the saccade adaptation paradigm. CONCLUSIONS: Proper cerebellar function is required for saccadic adaptation, but in at least some children with dyslexia, cerebellar structure and function may be disordered. Consistent with this hypothesis, the data presented in this report clearly illustrate a difference in the ability of children with dyslexia to adapt saccade amplitudes in response to imposed visual errors. Saccadic adaptation might provide a noninvasive assay for early identification of dyslexia. Future work will determine whether reduced saccadic adaptation is pervasive in dyslexia or whether this identifies a sub-phenotype within the larger population of people identified with reading and language deficits. En ligne : http://dx.doi.org/10.1186/s11689-017-9218-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Prospective study of autism phenomenology and the behavioural phenotype of Phelan-McDermid syndrome: comparison to fragile X syndrome, Down syndrome and idiopathic autism spectrum disorder / C. RICHARDS in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.37 Titre : Prospective study of autism phenomenology and the behavioural phenotype of Phelan-McDermid syndrome: comparison to fragile X syndrome, Down syndrome and idiopathic autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : C. RICHARDS, Auteur ; L. POWIS, Auteur ; J. MOSS, Auteur ; C. STINTON, Auteur ; L. NELSON, Auteur ; C. OLIVER, Auteur Article en page(s) : p.37 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Behavioural phenotype  Hyperactivity  Impulsivity  Mood  Phelan-McDermid syndrome  Repetitive behaviour  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: The limited behavioural phenotype literature on Phelan-McDermid syndrome (PMS) indicates atypically high levels of activity, impulsivity and autism spectrum disorder (ASD) behaviours. Divergent profiles of ASD in PMS are also reported, with some studies demonstrating similarities to idiopathic ASD and others indicating an uneven profile of social and communication impairments and repetitive behaviours. An evaluation of the behavioural phenotype of PMS and the prevalence and phenomenology of ASD is warranted, particularly given the causal involvement of the SHANK3 gene in the aetiology of PMS. METHODS: Carers of individuals with PMS (N = 30; mean age = 10.55, SD = 7.08) completed questionnaires relating to impulsivity, overactivity, mood, interest and pleasure, repetitive behaviour and ASD phenomenology. These data were compared to data from matched samples of individuals with fragile X and Down syndromes and idiopathic ASD. In order to evaluate the profile of ASD phenomenology in PMS, two comparisons were made: first, including the total sample with PMS, and second, including only those who met the threshold indicative of autism on an ASD screening measure. RESULTS: The results revealed lower mood in individuals with PMS, but no differences in impulsivity and overactivity. Compulsive and routine-driven repetitive behaviours were less common in the total sample with PMS; however, motor-based stereotyped behaviours were more common. ASD phenomenology was highly prevalent, with 87% of the sample meeting the cutoff score for ASD and 57% meeting the cutoff for autism. The profile of ASD phenomenology in the total sample with PMS differed from those with idiopathic ASD across impairments in communication and social interaction and repetitive behaviour. However, the profile of those who met the threshold for autism was commensurate to those with idiopathic ASD. CONCLUSIONS: ASD phenomenology is common within PMS. Whilst the total sample may display an atypical profile of ASD behaviour, the profile in those who met the threshold for autism was very similar to those with idiopathic ASD. These results are discussed in relation to the wider behavioural phenotype and the emerging evidence of an autism endophenotype in PMS. En ligne : http://dx.doi.org/10.1186/s11689-017-9217-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Prospective study of autism phenomenology and the behavioural phenotype of Phelan-McDermid syndrome: comparison to fragile X syndrome, Down syndrome and idiopathic autism spectrum disorder [Texte imprimé et/ou numérique] / C. RICHARDS, Auteur ; L. POWIS, Auteur ; J. MOSS, Auteur ; C. STINTON, Auteur ; L. NELSON, Auteur ; C. OLIVER, Auteur . - p.37. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.37 Mots-clés : Autism spectrum disorder  Behavioural phenotype  Hyperactivity  Impulsivity  Mood  Phelan-McDermid syndrome  Repetitive behaviour  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: The limited behavioural phenotype literature on Phelan-McDermid syndrome (PMS) indicates atypically high levels of activity, impulsivity and autism spectrum disorder (ASD) behaviours. Divergent profiles of ASD in PMS are also reported, with some studies demonstrating similarities to idiopathic ASD and others indicating an uneven profile of social and communication impairments and repetitive behaviours. An evaluation of the behavioural phenotype of PMS and the prevalence and phenomenology of ASD is warranted, particularly given the causal involvement of the SHANK3 gene in the aetiology of PMS. METHODS: Carers of individuals with PMS (N = 30; mean age = 10.55, SD = 7.08) completed questionnaires relating to impulsivity, overactivity, mood, interest and pleasure, repetitive behaviour and ASD phenomenology. These data were compared to data from matched samples of individuals with fragile X and Down syndromes and idiopathic ASD. In order to evaluate the profile of ASD phenomenology in PMS, two comparisons were made: first, including the total sample with PMS, and second, including only those who met the threshold indicative of autism on an ASD screening measure. RESULTS: The results revealed lower mood in individuals with PMS, but no differences in impulsivity and overactivity. Compulsive and routine-driven repetitive behaviours were less common in the total sample with PMS; however, motor-based stereotyped behaviours were more common. ASD phenomenology was highly prevalent, with 87% of the sample meeting the cutoff score for ASD and 57% meeting the cutoff for autism. The profile of ASD phenomenology in the total sample with PMS differed from those with idiopathic ASD across impairments in communication and social interaction and repetitive behaviour. However, the profile of those who met the threshold for autism was commensurate to those with idiopathic ASD. CONCLUSIONS: ASD phenomenology is common within PMS. Whilst the total sample may display an atypical profile of ASD behaviour, the profile in those who met the threshold for autism was very similar to those with idiopathic ASD. These results are discussed in relation to the wider behavioural phenotype and the emerging evidence of an autism endophenotype in PMS. En ligne : http://dx.doi.org/10.1186/s11689-017-9217-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Is dopamine transporter-mediated dopaminergic signaling in the retina a noninvasive biomarker for attention-deficit/ hyperactivity disorder? A study in a novel dopamine transporter variant Val559 transgenic mouse model / H. DAI in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.38 Titre : Is dopamine transporter-mediated dopaminergic signaling in the retina a noninvasive biomarker for attention-deficit/ hyperactivity disorder? A study in a novel dopamine transporter variant Val559 transgenic mouse model Type de document : Texte imprimé et/ou numérique Auteurs : H. DAI, Auteur ; Carrie R. JACKSON, Auteur ; G. L. DAVIS, Auteur ; R. D. BLAKELY, Auteur ; D. G. MCMAHON, Auteur Article en page(s) : p.38 Langues : Anglais (eng) Mots-clés : Ala559Val coding substitution  Anomalous dopamine efflux  Attention-deficit/hyperactivity disorder  Biomarker  Dopamine transporter  Electroretinogram Index. décimale : PER Périodiques Résumé : BACKGROUND: Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes. To understand the broader impact of ADE on ADHD, noninvasive measures sensitive to DAT reversal are needed. METHODS: Here, we explored this question through ERG-based analysis of retinal light responses, as well as HPLC measurements of retinal DA in DAT Val559 mice. RESULTS: Male mice homozygous (HOM) for the DAT Val559 variant demonstrated increased, light-adapted ERG b-wave amplitudes compared to wild type (WT) and heterozygous (HET) mice, whereas dark-adapted responses were indistinguishable across genotypes. The elevated amplitude of the photopic light responses in HOM mice could be mimicked in WT mice by applying D1 and D4 DA receptor agonists and suppressed in HOM mice by introducing D4 antagonist, supporting elevated retinal DA signaling arising from ADE. Following the challenge with amphetamine, WT exhibited an increase in light-adapted response amplitudes, while HOM did not. Total retinal DA content was similar across genotypes. Interestingly, female DAT Val559 HOM animals revealed no significant difference in photopic ERG responses when compared with WT and HET littermates. CONCLUSIONS: These data reveal that noninvasive, in vivo evaluation of retinal responses to light can reveal physiological signatures of ADE, suggesting a possible approach to the segregation of neurobehavioral disorders based on the DAT-dependent control of DA signaling. En ligne : http://dx.doi.org/10.1186/s11689-017-9215-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] Is dopamine transporter-mediated dopaminergic signaling in the retina a noninvasive biomarker for attention-deficit/ hyperactivity disorder? A study in a novel dopamine transporter variant Val559 transgenic mouse model [Texte imprimé et/ou numérique] / H. DAI, Auteur ; Carrie R. JACKSON, Auteur ; G. L. DAVIS, Auteur ; R. D. BLAKELY, Auteur ; D. G. MCMAHON, Auteur . - p.38. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.38 Mots-clés : Ala559Val coding substitution  Anomalous dopamine efflux  Attention-deficit/hyperactivity disorder  Biomarker  Dopamine transporter  Electroretinogram Index. décimale : PER Périodiques Résumé : BACKGROUND: Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes. To understand the broader impact of ADE on ADHD, noninvasive measures sensitive to DAT reversal are needed. METHODS: Here, we explored this question through ERG-based analysis of retinal light responses, as well as HPLC measurements of retinal DA in DAT Val559 mice. RESULTS: Male mice homozygous (HOM) for the DAT Val559 variant demonstrated increased, light-adapted ERG b-wave amplitudes compared to wild type (WT) and heterozygous (HET) mice, whereas dark-adapted responses were indistinguishable across genotypes. The elevated amplitude of the photopic light responses in HOM mice could be mimicked in WT mice by applying D1 and D4 DA receptor agonists and suppressed in HOM mice by introducing D4 antagonist, supporting elevated retinal DA signaling arising from ADE. Following the challenge with amphetamine, WT exhibited an increase in light-adapted response amplitudes, while HOM did not. Total retinal DA content was similar across genotypes. Interestingly, female DAT Val559 HOM animals revealed no significant difference in photopic ERG responses when compared with WT and HET littermates. CONCLUSIONS: These data reveal that noninvasive, in vivo evaluation of retinal responses to light can reveal physiological signatures of ADE, suggesting a possible approach to the segregation of neurobehavioral disorders based on the DAT-dependent control of DA signaling. En ligne : http://dx.doi.org/10.1186/s11689-017-9215-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350