Dépouillements

DSM-5: the debate continues / Joseph D. BUXBAUM in Molecular Autism, (May 2013)  

Public ISBD [article]  inMolecular Autism > (May 2013) . - 2 p. Titre : DSM-5: the debate continues Type de document : Texte imprimé et/ou numérique Auteurs : Joseph D. BUXBAUM, Auteur ; Simon BARON-COHEN, Auteur Année de publication : 2013 Article en page(s) : 2 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : We are fortunate to have invited commentaries from the laboratories of Dr Cathy Lord and Dr Fred Volkmar offering their perspectives on the new Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for the autism spectrum. Both commentaries note how DSM-5 collapses the earlier diagnostic categories of the pervasive developmental disorders into a single category of autism spectrum disorder. In addition, DSM-5 collapses social and communication domains into a single combined domain. The commentaries go on to discuss the positive aspects of these changes and raise some areas of potential concern. We support the evidence-based changes to autism diagnosis found in DSM-5, and look forward to further studies on the autism phenotype as this has implications for diagnosis and treatment. As our mechanistic understanding of autism improves, diagnoses based on behavioral parameters will continue to provide opportunities for interventions targeting the behaviors, while etiological diagnoses will provide opportunities for interventions tailored to etiology. En ligne : http://dx.doi.org/10.1186/2040-2392-4-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] DSM-5: the debate continues [Texte imprimé et/ou numérique] / Joseph D. BUXBAUM, Auteur ; Simon BARON-COHEN, Auteur . - 2013 . - 2 p. Langues : Anglais (eng) in Molecular Autism > (May 2013) . - 2 p. Index. décimale : PER Périodiques Résumé : We are fortunate to have invited commentaries from the laboratories of Dr Cathy Lord and Dr Fred Volkmar offering their perspectives on the new Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for the autism spectrum. Both commentaries note how DSM-5 collapses the earlier diagnostic categories of the pervasive developmental disorders into a single category of autism spectrum disorder. In addition, DSM-5 collapses social and communication domains into a single combined domain. The commentaries go on to discuss the positive aspects of these changes and raise some areas of potential concern. We support the evidence-based changes to autism diagnosis found in DSM-5, and look forward to further studies on the autism phenotype as this has implications for diagnosis and treatment. As our mechanistic understanding of autism improves, diagnoses based on behavioral parameters will continue to provide opportunities for interventions targeting the behaviors, while etiological diagnoses will provide opportunities for interventions tailored to etiology. En ligne : http://dx.doi.org/10.1186/2040-2392-4-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

DSM-5 and autism spectrum disorders (ASDs): an opportunity for identifying ASD subtypes / Rebecca GRZADZINSKI in Molecular Autism, (May 2013)  

Public ISBD [article]  inMolecular Autism > (May 2013) . - 6 p. Titre : DSM-5 and autism spectrum disorders (ASDs): an opportunity for identifying ASD subtypes Type de document : Texte imprimé et/ou numérique Auteurs : Rebecca GRZADZINSKI, Auteur ; Marisela HUERTA, Auteur ; Catherine LORD, Auteur Année de publication : 2013 Article en page(s) : 6 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The heterogeneous clinical presentations of individuals with autism spectrum disorders (ASDs) poses a significant challenge for sample characterization and limits the interpretability and replicability of research studies. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria for ASD, with its dimensional approach, may be a useful framework to increase the homogeneity of research samples. In this review, we summarize the revisions to the diagnostic criteria for ASD, briefly highlight the literature supporting these changes, and illustrate how DSM-5 can improve sample characterization and provide opportunities for researchers to identify possible subtypes within ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-4-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] DSM-5 and autism spectrum disorders (ASDs): an opportunity for identifying ASD subtypes [Texte imprimé et/ou numérique] / Rebecca GRZADZINSKI, Auteur ; Marisela HUERTA, Auteur ; Catherine LORD, Auteur . - 2013 . - 6 p. Langues : Anglais (eng) in Molecular Autism > (May 2013) . - 6 p. Index. décimale : PER Périodiques Résumé : The heterogeneous clinical presentations of individuals with autism spectrum disorders (ASDs) poses a significant challenge for sample characterization and limits the interpretability and replicability of research studies. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria for ASD, with its dimensional approach, may be a useful framework to increase the homogeneity of research samples. In this review, we summarize the revisions to the diagnostic criteria for ASD, briefly highlight the literature supporting these changes, and illustrate how DSM-5 can improve sample characterization and provide opportunities for researchers to identify possible subtypes within ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-4-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome? / Talakad LOHITH in Molecular Autism, (May 2013)  

Public ISBD [article]  inMolecular Autism > (May 2013) . - 8 p. Titre : Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome? Type de document : Texte imprimé et/ou numérique Auteurs : Talakad LOHITH, Auteur ; Emily OSTERWEIL, Auteur ; Masahiro FUJITA, Auteur ; Kimberly JENKO, Auteur ; Mark F. BEAR, Auteur ; Robert INNIS, Auteur Année de publication : 2013 Article en page(s) : 8 p. Langues : Anglais (eng) Mots-clés : Fragile X mental retardation protein  Fragile X syndrome  Glutamate receptor  mGluR5  Receptor density  Receptor expression Index. décimale : PER Périodiques Résumé : BACKGROUND:Fragile X syndrome (FXS) is a common inherited form of intellectual disability caused by loss of function of the fragile X mental retardation protein. Recent animal studies suggest that upregulated downstream signaling by metabotropic glutamate receptor 5 (mGluR5) might be an important mechanism for cognitive and behavioral abnormalities associated with FXS. However, mGluR5 density in human FXS remains unknown.METHODS:Receptor binding and protein expression were measured in the postmortem prefrontal cortex of 14 FXS patients or carriers and 17 age- and sex-matched control subjects without neurological disorders. In-vitro binding assays were performed using [3H]-labeled 3-methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity negative allosteric modulator of mGluR5, to measure receptor density and the radioligand's dissociation constant, which is inversely proportional to affinity. Immunoblotting was also performed, to measure mGluR5 protein expression.RESULTS:The mGluR5 density increased with marginal significance (+16%; P = 0.058) in the prefrontal cortex of FXS patients or carriers compared with matched healthy controls. No significant change in dissociation constant (-4%; P = 0.293) was observed. Immunoblotting found a significant elevation (+32%; P = 0.048) in mGluR5 protein expression.CONCLUSIONS:Both mGluR5 binding density and protein expression were increased in the brains of FXS patients or carriers, but only expression was significantly different, which could be because of the small sample size and moderate variability. Another important caveat is that the effects of psychotropic medications on mGluR5 expression are largely unknown. Future in-vivo measurement of mGluR5 with positron emission tomography might characterize the role of this receptor in the pathophysiology of FXS and facilitate trials of mGluR5-oriented treatments for this disorder. En ligne : http://dx.doi.org/10.1186/2040-2392-4-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome? [Texte imprimé et/ou numérique] / Talakad LOHITH, Auteur ; Emily OSTERWEIL, Auteur ; Masahiro FUJITA, Auteur ; Kimberly JENKO, Auteur ; Mark F. BEAR, Auteur ; Robert INNIS, Auteur . - 2013 . - 8 p. Langues : Anglais (eng) in Molecular Autism > (May 2013) . - 8 p. Mots-clés : Fragile X mental retardation protein  Fragile X syndrome  Glutamate receptor  mGluR5  Receptor density  Receptor expression Index. décimale : PER Périodiques Résumé : BACKGROUND:Fragile X syndrome (FXS) is a common inherited form of intellectual disability caused by loss of function of the fragile X mental retardation protein. Recent animal studies suggest that upregulated downstream signaling by metabotropic glutamate receptor 5 (mGluR5) might be an important mechanism for cognitive and behavioral abnormalities associated with FXS. However, mGluR5 density in human FXS remains unknown.METHODS:Receptor binding and protein expression were measured in the postmortem prefrontal cortex of 14 FXS patients or carriers and 17 age- and sex-matched control subjects without neurological disorders. In-vitro binding assays were performed using [3H]-labeled 3-methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity negative allosteric modulator of mGluR5, to measure receptor density and the radioligand's dissociation constant, which is inversely proportional to affinity. Immunoblotting was also performed, to measure mGluR5 protein expression.RESULTS:The mGluR5 density increased with marginal significance (+16%; P = 0.058) in the prefrontal cortex of FXS patients or carriers compared with matched healthy controls. No significant change in dissociation constant (-4%; P = 0.293) was observed. Immunoblotting found a significant elevation (+32%; P = 0.048) in mGluR5 protein expression.CONCLUSIONS:Both mGluR5 binding density and protein expression were increased in the brains of FXS patients or carriers, but only expression was significantly different, which could be because of the small sample size and moderate variability. Another important caveat is that the effects of psychotropic medications on mGluR5 expression are largely unknown. Future in-vivo measurement of mGluR5 with positron emission tomography might characterize the role of this receptor in the pathophysiology of FXS and facilitate trials of mGluR5-oriented treatments for this disorder. En ligne : http://dx.doi.org/10.1186/2040-2392-4-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder / Tewarit SARACHANA in Molecular Autism, (May 2013)  

Public ISBD [article]  inMolecular Autism > (May 2013) . - 19 p. Titre : Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Tewarit SARACHANA, Auteur ; Valerie W. HU, Auteur Année de publication : 2013 Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : RORA  Autism  Nuclear hormone receptor  Transcriptional targets  Chromatin immunoprecipitation  Promoter microarray Index. décimale : PER Périodiques Résumé : BACKGROUND:We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as in the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans.METHODS:Here we identify transcriptional targets of RORA in human neuronal cells on a genome-wide level using chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then validated by an independent ChIP followed by quantitative PCR analysis. To further demonstrate that reduced RORA expression results in reduced transcription of RORA targets, we determined the expression levels of the selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression.RESULTS:The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 2,764 genomic locations corresponding to promoter regions of 2,544 genes across the human genome. Gene ontology analysis of this dataset of genes that are potentially directly regulated by RORA1 reveals statistically significant enrichment in biological functions negatively impacted in individuals with ASD, including neuronal differentiation, adhesion and survival, synaptogenesis, synaptic transmission and plasticity, and axonogenesis, as well as higher level functions such as development of the cortex and cerebellum, cognition, memory, and spatial learning. Independent ChIP-quantitative PCR analyses confirm binding of RORA1 to promoter regions of selected ASD-associated genes, including A2BP1, CYP19A1, ITPR1, NLGN1, and NTRK2, whose expression levels (in addition to HSD17B10) are also decreased in RORA1-repressed human neuronal cells and in prefrontal cortex tissues from individuals with ASD.CONCLUSIONS:Findings from this study indicate that RORA transcriptionally regulates A2BP1, CYP19A1, HSD17B10, ITPR1, NLGN1, and NTRK2, and strongly suggest that reduction of this sex hormone-sensitive nuclear receptor in the brain causes dysregulated expression of these ASD-relevant genes as well as their associated pathways and functions which, in turn, may contribute to the underlying pathobiology of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-4-14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder [Texte imprimé et/ou numérique] / Tewarit SARACHANA, Auteur ; Valerie W. HU, Auteur . - 2013 . - 19 p. Langues : Anglais (eng) in Molecular Autism > (May 2013) . - 19 p. Mots-clés : RORA  Autism  Nuclear hormone receptor  Transcriptional targets  Chromatin immunoprecipitation  Promoter microarray Index. décimale : PER Périodiques Résumé : BACKGROUND:We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as in the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans.METHODS:Here we identify transcriptional targets of RORA in human neuronal cells on a genome-wide level using chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then validated by an independent ChIP followed by quantitative PCR analysis. To further demonstrate that reduced RORA expression results in reduced transcription of RORA targets, we determined the expression levels of the selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression.RESULTS:The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 2,764 genomic locations corresponding to promoter regions of 2,544 genes across the human genome. Gene ontology analysis of this dataset of genes that are potentially directly regulated by RORA1 reveals statistically significant enrichment in biological functions negatively impacted in individuals with ASD, including neuronal differentiation, adhesion and survival, synaptogenesis, synaptic transmission and plasticity, and axonogenesis, as well as higher level functions such as development of the cortex and cerebellum, cognition, memory, and spatial learning. Independent ChIP-quantitative PCR analyses confirm binding of RORA1 to promoter regions of selected ASD-associated genes, including A2BP1, CYP19A1, ITPR1, NLGN1, and NTRK2, whose expression levels (in addition to HSD17B10) are also decreased in RORA1-repressed human neuronal cells and in prefrontal cortex tissues from individuals with ASD.CONCLUSIONS:Findings from this study indicate that RORA transcriptionally regulates A2BP1, CYP19A1, HSD17B10, ITPR1, NLGN1, and NTRK2, and strongly suggest that reduction of this sex hormone-sensitive nuclear receptor in the brain causes dysregulated expression of these ASD-relevant genes as well as their associated pathways and functions which, in turn, may contribute to the underlying pathobiology of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-4-14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Autism in DSM-5: progress and challenges / Fred R. VOLKMAR in Molecular Autism, (May 2013)  

Public ISBD [article]  inMolecular Autism > (May 2013) . - 12 p. Titre : Autism in DSM-5: progress and challenges Type de document : Texte imprimé et/ou numérique Auteurs : Fred R. VOLKMAR, Auteur ; Brian REICHOW, Auteur Année de publication : 2013 Article en page(s) : 12 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:Since Kanner's first description of autism there have been a number of changes in approaches to diagnosis with certain key continuities . Since the Fourth edition of the Diagnostic and Statistical Manual (DSM-IV) appeared in 1994 there has been an explosion in research publications. The advent of changes in DSM-5 presents some important moves forward as well as some potential challenges.METHODS:The various relevant studies are summarized.RESULTS:If research diagnostic instruments are available, many (but not all) cases with a DSM-IV diagnosis of autism continue to have this diagnosis. The overall efficiency of this system falls if only one source of information is available and, particularly, if the criteria are used outside the research context. The impact is probably greatest among the most cognitively able cases and those with less classic autism presentations.CONCLUSIONS:Significant discontinuities in diagnostic practice raise significant problems for both research and clinical services. For DSM-5, the impact of these changes remains unclear. En ligne : http://dx.doi.org/10.1186/2040-2392-4-13 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Autism in DSM-5: progress and challenges [Texte imprimé et/ou numérique] / Fred R. VOLKMAR, Auteur ; Brian REICHOW, Auteur . - 2013 . - 12 p. Langues : Anglais (eng) in Molecular Autism > (May 2013) . - 12 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:Since Kanner's first description of autism there have been a number of changes in approaches to diagnosis with certain key continuities . Since the Fourth edition of the Diagnostic and Statistical Manual (DSM-IV) appeared in 1994 there has been an explosion in research publications. The advent of changes in DSM-5 presents some important moves forward as well as some potential challenges.METHODS:The various relevant studies are summarized.RESULTS:If research diagnostic instruments are available, many (but not all) cases with a DSM-IV diagnosis of autism continue to have this diagnosis. The overall efficiency of this system falls if only one source of information is available and, particularly, if the criteria are used outside the research context. The impact is probably greatest among the most cognitively able cases and those with less classic autism presentations.CONCLUSIONS:Significant discontinuities in diagnostic practice raise significant problems for both research and clinical services. For DSM-5, the impact of these changes remains unclear. En ligne : http://dx.doi.org/10.1186/2040-2392-4-13 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Sex-biased gene expression in the developing brain: implications for autism spectrum disorders / Mark ZIATS in Molecular Autism, (May 2013)  

Public ISBD [article]  inMolecular Autism > (May 2013) . - 3 p. Titre : Sex-biased gene expression in the developing brain: implications for autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Mark ZIATS, Auteur ; Owen RENNERT, Auteur Année de publication : 2013 Article en page(s) : 3 p. Langues : Anglais (eng) Mots-clés : Autistic disorder  Gene expression  Sex differences Index. décimale : PER Périodiques Résumé : Autism spectrum disorders affect significantly more males than females. Understanding sex differences in normal human brain development may provide insight into the mechanism(s) underlying this disparity; however, studies of sex differences in brain development at the genomic level are lacking. Here, we report a re-analysis of sex-specific gene expression from a recent large transcriptomic study of normal human brain development, to determine whether sex-biased genes relate to specific mechanistic processes. We discovered that male-biased genes are enriched for the processes of extracellular matrix formation/glycoproteins, immune response, chromatin, and cell cytoskeleton. We highlight that these pathways have been repeatedly implicated in autism and demonstrate that autism candidate genes are also enriched for these pathways. We propose that the overlap of these male-specific brain transcriptional modules with the same pathways in autism spectrum disorders may partially explain the increased incidence of autism in males. En ligne : http://dx.doi.org/10.1186/2040-2392-4-10 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Sex-biased gene expression in the developing brain: implications for autism spectrum disorders [Texte imprimé et/ou numérique] / Mark ZIATS, Auteur ; Owen RENNERT, Auteur . - 2013 . - 3 p. Langues : Anglais (eng) in Molecular Autism > (May 2013) . - 3 p. Mots-clés : Autistic disorder  Gene expression  Sex differences Index. décimale : PER Périodiques Résumé : Autism spectrum disorders affect significantly more males than females. Understanding sex differences in normal human brain development may provide insight into the mechanism(s) underlying this disparity; however, studies of sex differences in brain development at the genomic level are lacking. Here, we report a re-analysis of sex-specific gene expression from a recent large transcriptomic study of normal human brain development, to determine whether sex-biased genes relate to specific mechanistic processes. We discovered that male-biased genes are enriched for the processes of extracellular matrix formation/glycoproteins, immune response, chromatin, and cell cytoskeleton. We highlight that these pathways have been repeatedly implicated in autism and demonstrate that autism candidate genes are also enriched for these pathways. We propose that the overlap of these male-specific brain transcriptional modules with the same pathways in autism spectrum disorders may partially explain the increased incidence of autism in males. En ligne : http://dx.doi.org/10.1186/2040-2392-4-10 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202