Dépouillements

Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial / Evdokia ANAGNOSTOU in Molecular Autism, (December 2012)  

Public ISBD [article]  inMolecular Autism > (December 2012) . - 9 p. Titre : Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial Type de document : Texte imprimé et/ou numérique Auteurs : Evdokia ANAGNOSTOU, Auteur ; Latha V. SOORYA, Auteur ; William CHAPLIN, Auteur ; Jennifer BARTZ, Auteur ; Danielle B. HALPERN, Auteur ; Stacey WASSERMAN, Auteur ; A. Ting WANG, Auteur ; Lauren PEPA, Auteur ; Nadia TANEL, Auteur ; Azadeh KUSHKI, Auteur ; Eric HOLLANDER, Auteur Année de publication : 2012 Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Autism  Adults  Oxytocin  Clinical trial  Social cognition Index. décimale : PER Périodiques Résumé : BACKGROUND:There are no effective medications for the treatment of social cognition/function deficits in autism spectrum disorder (ASD), and adult intervention literature in this area is sparse. Emerging data from animal models and genetic association studies as well as early, single-dose intervention studies suggest that the oxytocin system may be a potential therapeutic target for social cognition/function deficits in ASD. The primary aim of this study was to examine the safety/therapeutic effects of intranasal oxytocin versus placebo in adults with ASD, with respect to the two core symptom domains of social cognition/functioning and repetitive behaviors.METHODS:This was a pilot, randomized, double-blind, placebo-controlled, parallel design trial of intranasal oxytocin versus placebo in 19 adults with ASD (16 males; 33.20 +/- 13.29 years). Subjects were randomized to 24 IU intranasal oxytocin or placebo in the morning and afternoon for 6 weeks. Measures of social function/cognition (the Diagnostic Analysis of Nonverbal Accuracy) and repetitive behaviors (Repetitive Behavior Scale Revised) were administered. Secondary measures included the Social Responsiveness Scale, Reading-the-Mind-in-the-Eyes Test and the Yale Brown Obsessive Compulsive Scale - compulsion subscale and quality of life (World Health Organization Quality of Life Questionnaire - emotional/social subscales). Full-information maximum-likelihood parameter estimates were obtained and tested using mixed-effects regression analyses.RESULTS:Although no significant changes were detected in the primary outcome measures after correcting for baseline differences, results suggested improvements after 6 weeks in measures of social cognition (Reading-the-Mind-in-the-Eyes Test, p = 0.002, d = 1.2), and quality of life (World Health Organization Quality of Life Questionnaire - emotion, p = 0.031, d = 0.84), both secondary measures. Oxytocin was well tolerated and no serious adverse effects were reported.CONCLUSIONS:This pilot study suggests that there is therapeutic potential to daily administration of intranasal oxytocin in adults with ASD and that larger and longer studies are warranted.TRIAL REGISTRATION:NCT00490802 En ligne : http://dx.doi.org/10.1186/2040-2392-3-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial [Texte imprimé et/ou numérique] / Evdokia ANAGNOSTOU, Auteur ; Latha V. SOORYA, Auteur ; William CHAPLIN, Auteur ; Jennifer BARTZ, Auteur ; Danielle B. HALPERN, Auteur ; Stacey WASSERMAN, Auteur ; A. Ting WANG, Auteur ; Lauren PEPA, Auteur ; Nadia TANEL, Auteur ; Azadeh KUSHKI, Auteur ; Eric HOLLANDER, Auteur . - 2012 . - 9 p. Langues : Anglais (eng) in Molecular Autism > (December 2012) . - 9 p. Mots-clés : Autism  Adults  Oxytocin  Clinical trial  Social cognition Index. décimale : PER Périodiques Résumé : BACKGROUND:There are no effective medications for the treatment of social cognition/function deficits in autism spectrum disorder (ASD), and adult intervention literature in this area is sparse. Emerging data from animal models and genetic association studies as well as early, single-dose intervention studies suggest that the oxytocin system may be a potential therapeutic target for social cognition/function deficits in ASD. The primary aim of this study was to examine the safety/therapeutic effects of intranasal oxytocin versus placebo in adults with ASD, with respect to the two core symptom domains of social cognition/functioning and repetitive behaviors.METHODS:This was a pilot, randomized, double-blind, placebo-controlled, parallel design trial of intranasal oxytocin versus placebo in 19 adults with ASD (16 males; 33.20 +/- 13.29 years). Subjects were randomized to 24 IU intranasal oxytocin or placebo in the morning and afternoon for 6 weeks. Measures of social function/cognition (the Diagnostic Analysis of Nonverbal Accuracy) and repetitive behaviors (Repetitive Behavior Scale Revised) were administered. Secondary measures included the Social Responsiveness Scale, Reading-the-Mind-in-the-Eyes Test and the Yale Brown Obsessive Compulsive Scale - compulsion subscale and quality of life (World Health Organization Quality of Life Questionnaire - emotional/social subscales). Full-information maximum-likelihood parameter estimates were obtained and tested using mixed-effects regression analyses.RESULTS:Although no significant changes were detected in the primary outcome measures after correcting for baseline differences, results suggested improvements after 6 weeks in measures of social cognition (Reading-the-Mind-in-the-Eyes Test, p = 0.002, d = 1.2), and quality of life (World Health Organization Quality of Life Questionnaire - emotion, p = 0.031, d = 0.84), both secondary measures. Oxytocin was well tolerated and no serious adverse effects were reported.CONCLUSIONS:This pilot study suggests that there is therapeutic potential to daily administration of intranasal oxytocin in adults with ASD and that larger and longer studies are warranted.TRIAL REGISTRATION:NCT00490802 En ligne : http://dx.doi.org/10.1186/2040-2392-3-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age / Bonnie AUYEUNG in Molecular Autism, (December 2012)  

Public ISBD [article]  inMolecular Autism > (December 2012) . - 5 p. Titre : Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age Type de document : Texte imprimé et/ou numérique Auteurs : Bonnie AUYEUNG, Auteur ; Jag AHLUWALIA, Auteur ; Lynn THOMSON, Auteur ; Kevin TAYLOR, Auteur ; Gerald HACKETT, Auteur ; Kieran J. O'DONNELL, Auteur ; Simon BARON-COHEN, Auteur Année de publication : 2012 Article en page(s) : 5 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:Studies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children.Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old.FINDING:fT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores.CONCLUSIONS:These preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life. En ligne : http://dx.doi.org/10.1186/2040-2392-3-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age [Texte imprimé et/ou numérique] / Bonnie AUYEUNG, Auteur ; Jag AHLUWALIA, Auteur ; Lynn THOMSON, Auteur ; Kevin TAYLOR, Auteur ; Gerald HACKETT, Auteur ; Kieran J. O'DONNELL, Auteur ; Simon BARON-COHEN, Auteur . - 2012 . - 5 p. Langues : Anglais (eng) in Molecular Autism > (December 2012) . - 5 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:Studies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children.Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old.FINDING:fT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores.CONCLUSIONS:These preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life. En ligne : http://dx.doi.org/10.1186/2040-2392-3-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Support for calcium channel gene defects in autism spectrum disorders / Ake Tzu-Hui LU in Molecular Autism, (December 2012)  

Public ISBD [article]  inMolecular Autism > (December 2012) . - 9 p. Titre : Support for calcium channel gene defects in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Ake Tzu-Hui LU, Auteur ; Xiaoxian DAI, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Rita M. CANTOR, Auteur Année de publication : 2012 Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  Calcium channel genes  Common variants  Imputed SNPs  Association studies Index. décimale : PER Périodiques Résumé : BACKGROUND:Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD). Calcium channel genes (CCG) contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS) data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis.METHODS:A total of 2,176 single-nucleotide polymorphisms (SNP) (703 genotyped and 1,473 imputed) covering the genes that encode the alpha1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE) and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP). SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel.RESULTS:Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations.CONCLUSIONS:These associations support a role for common CCG SNPs in ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-3-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Support for calcium channel gene defects in autism spectrum disorders [Texte imprimé et/ou numérique] / Ake Tzu-Hui LU, Auteur ; Xiaoxian DAI, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Rita M. CANTOR, Auteur . - 2012 . - 9 p. Langues : Anglais (eng) in Molecular Autism > (December 2012) . - 9 p. Mots-clés : Autism spectrum disorders  Calcium channel genes  Common variants  Imputed SNPs  Association studies Index. décimale : PER Périodiques Résumé : BACKGROUND:Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD). Calcium channel genes (CCG) contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS) data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis.METHODS:A total of 2,176 single-nucleotide polymorphisms (SNP) (703 genotyped and 1,473 imputed) covering the genes that encode the alpha1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE) and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP). SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel.RESULTS:Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations.CONCLUSIONS:These associations support a role for common CCG SNPs in ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-3-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Failure to deactivate the default mode network indicates a possible endophenotype of autism / Michael D. SPENCER in Molecular Autism, (December 2012)  

Public ISBD [article]  inMolecular Autism > (December 2012) . - 9 p. Titre : Failure to deactivate the default mode network indicates a possible endophenotype of autism Type de document : Texte imprimé et/ou numérique Auteurs : Michael D. SPENCER, Auteur ; Lindsay CHURA, Auteur ; Rosemary HOLT, Auteur ; John SUCKLING, Auteur ; Andrew J. CALDER, Auteur ; Edward T. BULLMORE, Auteur ; Simon BARON-COHEN, Auteur Année de publication : 2012 Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Autism  Default mode network  Functional MRI  Endophenotype Index. décimale : PER Périodiques Résumé : BACKGROUND:Reduced activity during cognitively demanding tasks has been reported in the default mode network in typically developing controls and individuals with autism. However, no study has investigated the default mode network (DMN) in first-degree relatives of those with autism (such as siblings) and it is not known whether atypical activation of the DMN is specific to autism or whether it is also present in unaffected relatives. Here we use functional magnetic resonance imaging to investigate the pattern of task-related deactivation during completion of a visual search task, the Embedded Figures Task, in teenagers with autism, their unaffected siblings and typically developing controls.FINDINGS:We identified striking reductions in deactivation during the Embedded Figures Task in unaffected siblings compared to controls in brain regions corresponding to the default mode network. Adolescents with autism and their unaffected siblings similarly failed to deactivate regions, including posterior cingulate and bilateral inferior parietal cortex.CONCLUSIONS:This suggests that a failure to deactivate these regions is a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. En ligne : http://dx.doi.org/10.1186/2040-2392-3-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Failure to deactivate the default mode network indicates a possible endophenotype of autism [Texte imprimé et/ou numérique] / Michael D. SPENCER, Auteur ; Lindsay CHURA, Auteur ; Rosemary HOLT, Auteur ; John SUCKLING, Auteur ; Andrew J. CALDER, Auteur ; Edward T. BULLMORE, Auteur ; Simon BARON-COHEN, Auteur . - 2012 . - 9 p. Langues : Anglais (eng) in Molecular Autism > (December 2012) . - 9 p. Mots-clés : Autism  Default mode network  Functional MRI  Endophenotype Index. décimale : PER Périodiques Résumé : BACKGROUND:Reduced activity during cognitively demanding tasks has been reported in the default mode network in typically developing controls and individuals with autism. However, no study has investigated the default mode network (DMN) in first-degree relatives of those with autism (such as siblings) and it is not known whether atypical activation of the DMN is specific to autism or whether it is also present in unaffected relatives. Here we use functional magnetic resonance imaging to investigate the pattern of task-related deactivation during completion of a visual search task, the Embedded Figures Task, in teenagers with autism, their unaffected siblings and typically developing controls.FINDINGS:We identified striking reductions in deactivation during the Embedded Figures Task in unaffected siblings compared to controls in brain regions corresponding to the default mode network. Adolescents with autism and their unaffected siblings similarly failed to deactivate regions, including posterior cingulate and bilateral inferior parietal cortex.CONCLUSIONS:This suggests that a failure to deactivate these regions is a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. En ligne : http://dx.doi.org/10.1186/2040-2392-3-15 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202