Dépouillements

Fragile X and autism: Intertwined at the molecular level leading to targeted treatments / Randi J. HAGERMAN in Molecular Autism, (September 2010)  

Public ISBD [article]  inMolecular Autism > (September 2010) . - 14 p. Titre : Fragile X and autism: Intertwined at the molecular level leading to targeted treatments Type de document : Texte imprimé et/ou numérique Auteurs : Randi J. HAGERMAN, Auteur ; Gry HOEM, Auteur ; Paul J. HAGERMAN, Auteur Année de publication : 2010 Article en page(s) : 14 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is caused by an expanded CGG repeat (> 200 repeats) in the 5' untranslated portion of the fragile mental retardation 1 gene (FMR1), leading to deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA carrier protein that controls the translation of several other genes that regulate synaptic development and plasticity. Autism occurs in approximately 30% of FXS cases, and pervasive developmental disorder, not otherwise specified (PDD-NOS) occurs in an additional 30% of cases. Premutation repeat expansions (55 to 200 CGG repeats) may also give rise to autism spectrum disorders (ASD), including both autism and PDD-NOS, through a different molecular mechanism that involves a direct toxic effect of the expanded CGG repeat FMR1 mRNA. RNA toxicity can also lead to aging effects including tremor, ataxia and cognitive decline, termed fragile X-associated tremor ataxia syndrome (FXTAS), in premutation carriers in late life. In studies of mice bearing premutation expansions, there is evidence of early postnatal neuronal cell toxicity, presenting as reduced cell longevity, decreased dendritic arborization and altered synaptic morphology. There is also evidence of mitochondrial dysfunction in premutation carriers. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in autism without fragile X mutations. Research regarding dysregulation of neurotransmitter systems in FXS, including the metabotropic glutamate receptor (mGluR)1/5 pathway and γ aminobutyric acid (GABA)A pathways, have led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-1-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=114 [article] Fragile X and autism: Intertwined at the molecular level leading to targeted treatments [Texte imprimé et/ou numérique] / Randi J. HAGERMAN, Auteur ; Gry HOEM, Auteur ; Paul J. HAGERMAN, Auteur . - 2010 . - 14 p. Langues : Anglais (eng) in Molecular Autism > (September 2010) . - 14 p. Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is caused by an expanded CGG repeat (> 200 repeats) in the 5' untranslated portion of the fragile mental retardation 1 gene (FMR1), leading to deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA carrier protein that controls the translation of several other genes that regulate synaptic development and plasticity. Autism occurs in approximately 30% of FXS cases, and pervasive developmental disorder, not otherwise specified (PDD-NOS) occurs in an additional 30% of cases. Premutation repeat expansions (55 to 200 CGG repeats) may also give rise to autism spectrum disorders (ASD), including both autism and PDD-NOS, through a different molecular mechanism that involves a direct toxic effect of the expanded CGG repeat FMR1 mRNA. RNA toxicity can also lead to aging effects including tremor, ataxia and cognitive decline, termed fragile X-associated tremor ataxia syndrome (FXTAS), in premutation carriers in late life. In studies of mice bearing premutation expansions, there is evidence of early postnatal neuronal cell toxicity, presenting as reduced cell longevity, decreased dendritic arborization and altered synaptic morphology. There is also evidence of mitochondrial dysfunction in premutation carriers. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in autism without fragile X mutations. Research regarding dysregulation of neurotransmitter systems in FXS, including the metabotropic glutamate receptor (mGluR)1/5 pathway and γ aminobutyric acid (GABA)A pathways, have led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-1-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=114

Elevated cortisol during play is associated with age and social engagement in children with autism / Blythe A. CORBETT in Molecular Autism, (September 2010)  

Public ISBD [article]  inMolecular Autism > (September 2010) . - 12 p. Titre : Elevated cortisol during play is associated with age and social engagement in children with autism Type de document : Texte imprimé et/ou numérique Auteurs : Blythe A. CORBETT, Auteur ; Clayton W. SCHUPP, Auteur ; David SIMON, Auteur ; Niles RYAN, Auteur ; Sally MENDOZA, Auteur Année de publication : 2010 Article en page(s) : 12 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background The hallmark characteristic of autism is impaired reciprocal social interaction. While children find social interaction stress-reducing, many children with autism may find social interaction stress-inducing. The current study was designed to examine stress responsivity as measured by cortisol by comparing children with autism to neurotypical peers during an ecologically valid 20-minute playground paradigm. Methods The experiment involved sets of three children: a child with autism, a neurotypical child, and a confederate. Participants included 45 prepubescent males between 8 and 12 years of age (21 with autism and 24 neurotypical children). Results Children with autism showed fewer initiations (χ²(1) = 4.03, P = 0.044), rejected initiations from others more (χ²(1) = 7.10, P = 0.008) and spent less time interacting during motor (F(1,43) = 16.7, P = 0.0002) and cooperative (F(1,43) = 14.78, P = 0.0004) play. Repeated measures analysis of the cortisol values revealed a significant model (χ²(4) = 22.76, P < 0.0005) that included time of measurement, diagnosis and age as main effects and an interaction between diagnosis and age. Thus, as age increased among children with autism, they experienced enhanced cortisol levels while age did not modify expected cortisol levels for typical children. Stress responsivity was associated with more peripheral equipment play for motor (χ²(3) = 12.3, P = 0.006) and cooperative (χ²(3) = 8.24, P = 0.04) play as well as reduced nonverbal social skills during motor (χ²(1) = 5.52, P = 0.018) and cooperative play (χ²(1) = 4.53, P = 0.033). Conclusions Overall, children with autism engaged in fewer social overtures and spent less time interacting than typically developing peers during play. The peer interaction paradigm resulted in significantly higher levels of cortisol in many children with autism. Distinct patterns emerged within the autism group based on developmental (older), biological (cortisol responder) and behavioral patterns (peripheral group interaction). The enhanced cortisol response was observed in children who voluntarily engaged in interaction; thus, it does not support the notion of a response to social threat. Rather, it appears to reflect attendant metabolic preparedness and enhanced arousal from engaging socially. The data suggest that many children with autism activate hypothalamic-pituitary-adrenal responses in relatively benign social situations, which appears to be a function of age and level of social engagement. The findings support the need to teach coping strategies in addition to fundamental social skills to youth with autism. En ligne : http://dx.doi.org/10.1186/2040-2392-1-13 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=114 [article] Elevated cortisol during play is associated with age and social engagement in children with autism [Texte imprimé et/ou numérique] / Blythe A. CORBETT, Auteur ; Clayton W. SCHUPP, Auteur ; David SIMON, Auteur ; Niles RYAN, Auteur ; Sally MENDOZA, Auteur . - 2010 . - 12 p. Langues : Anglais (eng) in Molecular Autism > (September 2010) . - 12 p. Index. décimale : PER Périodiques Résumé : Background The hallmark characteristic of autism is impaired reciprocal social interaction. While children find social interaction stress-reducing, many children with autism may find social interaction stress-inducing. The current study was designed to examine stress responsivity as measured by cortisol by comparing children with autism to neurotypical peers during an ecologically valid 20-minute playground paradigm. Methods The experiment involved sets of three children: a child with autism, a neurotypical child, and a confederate. Participants included 45 prepubescent males between 8 and 12 years of age (21 with autism and 24 neurotypical children). Results Children with autism showed fewer initiations (χ²(1) = 4.03, P = 0.044), rejected initiations from others more (χ²(1) = 7.10, P = 0.008) and spent less time interacting during motor (F(1,43) = 16.7, P = 0.0002) and cooperative (F(1,43) = 14.78, P = 0.0004) play. Repeated measures analysis of the cortisol values revealed a significant model (χ²(4) = 22.76, P < 0.0005) that included time of measurement, diagnosis and age as main effects and an interaction between diagnosis and age. Thus, as age increased among children with autism, they experienced enhanced cortisol levels while age did not modify expected cortisol levels for typical children. Stress responsivity was associated with more peripheral equipment play for motor (χ²(3) = 12.3, P = 0.006) and cooperative (χ²(3) = 8.24, P = 0.04) play as well as reduced nonverbal social skills during motor (χ²(1) = 5.52, P = 0.018) and cooperative play (χ²(1) = 4.53, P = 0.033). Conclusions Overall, children with autism engaged in fewer social overtures and spent less time interacting than typically developing peers during play. The peer interaction paradigm resulted in significantly higher levels of cortisol in many children with autism. Distinct patterns emerged within the autism group based on developmental (older), biological (cortisol responder) and behavioral patterns (peripheral group interaction). The enhanced cortisol response was observed in children who voluntarily engaged in interaction; thus, it does not support the notion of a response to social threat. Rather, it appears to reflect attendant metabolic preparedness and enhanced arousal from engaging socially. The data suggest that many children with autism activate hypothalamic-pituitary-adrenal responses in relatively benign social situations, which appears to be a function of age and level of social engagement. The findings support the need to teach coping strategies in addition to fundamental social skills to youth with autism. En ligne : http://dx.doi.org/10.1186/2040-2392-1-13 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=114