Behavioral signatures related to genetic disorders in autism / Hilgo BRUINING in Molecular Autism, (February 2014)  

Public ISBD [article]  inMolecular Autism > (February 2014) Titre : Behavioral signatures related to genetic disorders in autism Type de document : Texte imprimé et/ou numérique Auteurs : Hilgo BRUINING, Auteur ; Marinus EIJKEMANS, Auteur ; Martien KAS, Auteur ; Sarah CURRAN, Auteur ; Jacob VORSTMAN, Auteur ; Patrick BOLTON, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is well recognized to be genetically heterogeneous. It is assumed that the genetic risk factors give rise to a broad spectrum of indistinguishable behavioral presentations. We tested this assumption by analyzing the Autism Diagnostic Interview-Revised (ADI-R) symptom profiles in samples comprising six genetic disorders that carry an increased risk for ASD (22q11.2 deletion, Down's syndrome, Prader-Willi, supernumerary marker chromosome 15, tuberous sclerosis complex and Klinefelter syndrome; total n=322 cases, groups ranging in sample sizes from 21 to 90 cases). We mined the data to test the existence and specificity of ADI-R profiles using a multiclass extension of support vector machine (SVM) learning. We subsequently applied the SVM genetic disorder algorithm on idiopathic ASD profiles from the Autism Genetics Resource Exchange (AGRE). Genetic disorders were associated with behavioral specificity, indicated by the accuracy and certainty of SVM predictions; one-by-one genetic disorder stratifications were highly accurate leading to 63% accuracy of correct genotype prediction when all six genetic disorder groups were analyzed simultaneously. Application of the SVM algorithm to AGRE cases indicated that the algorithm could detect similarity of genetic behavioral signatures in idiopathic ASD subjects. Also, affected sib pairs in the AGRE were behaviorally more similar when they had been allocated to the same genetic disorder group. Our findings provide evidence for genotype-phenotype correlations in relation to autistic symptomatology. SVM algorithms may be used to stratify idiopathic cases of ASD according to behavioral signature patterns associated with genetic disorders. Together, the results suggest a new approach for disentangling the heterogeneity of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Behavioral signatures related to genetic disorders in autism [Texte imprimé et/ou numérique] / Hilgo BRUINING, Auteur ; Marinus EIJKEMANS, Auteur ; Martien KAS, Auteur ; Sarah CURRAN, Auteur ; Jacob VORSTMAN, Auteur ; Patrick BOLTON, Auteur. Langues : Anglais (eng) in Molecular Autism > (February 2014) Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is well recognized to be genetically heterogeneous. It is assumed that the genetic risk factors give rise to a broad spectrum of indistinguishable behavioral presentations. We tested this assumption by analyzing the Autism Diagnostic Interview-Revised (ADI-R) symptom profiles in samples comprising six genetic disorders that carry an increased risk for ASD (22q11.2 deletion, Down's syndrome, Prader-Willi, supernumerary marker chromosome 15, tuberous sclerosis complex and Klinefelter syndrome; total n=322 cases, groups ranging in sample sizes from 21 to 90 cases). We mined the data to test the existence and specificity of ADI-R profiles using a multiclass extension of support vector machine (SVM) learning. We subsequently applied the SVM genetic disorder algorithm on idiopathic ASD profiles from the Autism Genetics Resource Exchange (AGRE). Genetic disorders were associated with behavioral specificity, indicated by the accuracy and certainty of SVM predictions; one-by-one genetic disorder stratifications were highly accurate leading to 63% accuracy of correct genotype prediction when all six genetic disorder groups were analyzed simultaneously. Application of the SVM algorithm to AGRE cases indicated that the algorithm could detect similarity of genetic behavioral signatures in idiopathic ASD subjects. Also, affected sib pairs in the AGRE were behaviorally more similar when they had been allocated to the same genetic disorder group. Our findings provide evidence for genotype-phenotype correlations in relation to autistic symptomatology. SVM algorithms may be used to stratify idiopathic cases of ASD according to behavioral signature patterns associated with genetic disorders. Together, the results suggest a new approach for disentangling the heterogeneity of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Diagnosing autism spectrum disorder in community settings using the Development and Well-Being Assessment: validation in a UK population-based twin sample / Fiona S. MCEWEN in Journal of Child Psychology and Psychiatry, 57-2 (February 2016)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 57-2 (February 2016) . - p.161-170 Titre : Diagnosing autism spectrum disorder in community settings using the Development and Well-Being Assessment: validation in a UK population-based twin sample Type de document : Texte imprimé et/ou numérique Auteurs : Fiona S. MCEWEN, Auteur ; Catherine S. STEWART, Auteur ; Emma COLVERT, Auteur ; Emma WOODHOUSE, Auteur ; Sarah CURRAN, Auteur ; Nicola GILLAN, Auteur ; Victoria HALLETT, Auteur ; Stephanie LIETZ, Auteur ; Tracy GARNETT, Auteur ; Angelica RONALD, Auteur ; Declan MURPHY, Auteur ; Francesca HAPPE, Auteur ; Patrick BOLTON, Auteur Article en page(s) : p.161-170 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  adolescence  assessment  diagnosis Index. décimale : PER Périodiques Résumé : Background Increasing numbers of people are being referred for the assessment of autism spectrum disorder (ASD). The NICE (UK) and the American Academy of Pediatrics recommend gathering a developmental history using a tool that operationalises ICD/DSM criteria. However, the best-established diagnostic interview instruments are time consuming, costly and rarely used outside national specialist centres. What is needed is a brief, cost-effective measure validated in community settings. We tested the Development and Well-Being Assessment (DAWBA) for diagnosing ASD in a sample of children/adolescents representative of those presenting in community mental health settings. Methods A general population sample of twins (TEDS) was screened and 276 adolescents were selected as at low (CAST score < 12; n = 164) or high risk for ASD (CAST score ? 15 and/or parent reported that ASD suspected/previously diagnosed; n = 112). Parents completed the ASD module of the DAWBA interview by telephone or online. Families were visited at home: the ADI-R and autism diagnostic observation schedule (ADOS) were completed to allow a best-estimate research diagnosis of ASD to be made. Results Development and Well-Being Assessment ASD symptom scores correlated highly with ADI-R algorithm scores (? = .82, p < .001). Good sensitivity (0.88) and specificity (0.85) were achieved using DAWBA computerised algorithms. Clinician review of responses to DAWBA questions minimally changed sensitivity (0.86) and specificity (0.87). Positive (0.82–0.95) and negative (0.90) predictive values were high. Eighty-six per cent of children were correctly classified. Performance was improved by using it in conjunction with the ADOS. Conclusions The DAWBA is a brief structured interview that showed good sensitivity and specificity in this general population sample. It requires little training, is easy to administer (online or by interview) and diagnosis is aided by an algorithm. It holds promise as a tool for assisting with assessment in community settings and may help services implement the recommendations made by NICE and the American Academy of Pediatrics regarding diagnosis of young people on the autism spectrum. En ligne : http://dx.doi.org/10.1111/jcpp.12447 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=280 [article] Diagnosing autism spectrum disorder in community settings using the Development and Well-Being Assessment: validation in a UK population-based twin sample [Texte imprimé et/ou numérique] / Fiona S. MCEWEN, Auteur ; Catherine S. STEWART, Auteur ; Emma COLVERT, Auteur ; Emma WOODHOUSE, Auteur ; Sarah CURRAN, Auteur ; Nicola GILLAN, Auteur ; Victoria HALLETT, Auteur ; Stephanie LIETZ, Auteur ; Tracy GARNETT, Auteur ; Angelica RONALD, Auteur ; Declan MURPHY, Auteur ; Francesca HAPPE, Auteur ; Patrick BOLTON, Auteur . - p.161-170. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 57-2 (February 2016) . - p.161-170 Mots-clés : Autism spectrum disorder  adolescence  assessment  diagnosis Index. décimale : PER Périodiques Résumé : Background Increasing numbers of people are being referred for the assessment of autism spectrum disorder (ASD). The NICE (UK) and the American Academy of Pediatrics recommend gathering a developmental history using a tool that operationalises ICD/DSM criteria. However, the best-established diagnostic interview instruments are time consuming, costly and rarely used outside national specialist centres. What is needed is a brief, cost-effective measure validated in community settings. We tested the Development and Well-Being Assessment (DAWBA) for diagnosing ASD in a sample of children/adolescents representative of those presenting in community mental health settings. Methods A general population sample of twins (TEDS) was screened and 276 adolescents were selected as at low (CAST score < 12; n = 164) or high risk for ASD (CAST score ? 15 and/or parent reported that ASD suspected/previously diagnosed; n = 112). Parents completed the ASD module of the DAWBA interview by telephone or online. Families were visited at home: the ADI-R and autism diagnostic observation schedule (ADOS) were completed to allow a best-estimate research diagnosis of ASD to be made. Results Development and Well-Being Assessment ASD symptom scores correlated highly with ADI-R algorithm scores (? = .82, p < .001). Good sensitivity (0.88) and specificity (0.85) were achieved using DAWBA computerised algorithms. Clinician review of responses to DAWBA questions minimally changed sensitivity (0.86) and specificity (0.87). Positive (0.82–0.95) and negative (0.90) predictive values were high. Eighty-six per cent of children were correctly classified. Performance was improved by using it in conjunction with the ADOS. Conclusions The DAWBA is a brief structured interview that showed good sensitivity and specificity in this general population sample. It requires little training, is easy to administer (online or by interview) and diagnosis is aided by an algorithm. It holds promise as a tool for assisting with assessment in community settings and may help services implement the recommendations made by NICE and the American Academy of Pediatrics regarding diagnosis of young people on the autism spectrum. En ligne : http://dx.doi.org/10.1111/jcpp.12447 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=280

No major effect of twinning on autistic traits / Sarah CURRAN in Autism Research, 4-5 (October 2011)  

Public ISBD [article]  inAutism Research > 4-5 (October 2011) . - p.377-382 Titre : No major effect of twinning on autistic traits Type de document : Texte imprimé et/ou numérique Auteurs : Sarah CURRAN, Auteur ; Katharina DWORZYNSKI, Auteur ; Francesca HAPPE, Auteur ; Angelica RONALD, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur ; Carol BRAYNE, Auteur ; Patrick BOLTON, Auteur Année de publication : 2011 Article en page(s) : p.377-382 Langues : Anglais (eng) Mots-clés : clinical psychiatry  developmental psychology  diagnosis  epidemiology  social cognition Index. décimale : PER Périodiques Résumé : Background: It has been questioned whether the process of twinning might be a risk factor for autism spectrum conditions (ASC) and autistic traits. Aim: We sought to determine whether autistic traits and probable disorder, as measured by the Childhood Autism Spectrum Test (CAST), were more pronounced in twins compared to singletons. Samples: Data were analyzed from two large population-based samples of UK children, twins (n = 5,142 twin pairs, aged 8 years) and singletons (n = 2,805, aged 5–9 years). Results: Distributions of CAST scores in both groups were negatively skewed and scores for twins were more variable than singletons. Mean CAST total scores and standard errors (SE) were not significantly different for twins (5.1; SE 0.04) compared to singletons (4.9; SE 0.08). Moreover, contrary to expectations, the likelihood of scoring above the threshold for possible ASC was significantly lower in the twins than the singletons (OR = 0.69; P = 0.002). Subsidiary analyses of CAST scores according to sex, twin type, and subscale scores representing the subdomains of autism found a few significant differences (P<0.01), but the effect sizes for these differences were small and none exceeded η2 = 0.005. The explanation for these small differences remains obscure, but the very small effect sizes mean they are of little importance. Conclusions: Our results do not provide evidence to support twinning as a risk factor in the development of autistic traits. Autism Res2011,4:377–382. © 2011 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.207 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=145 [article] No major effect of twinning on autistic traits [Texte imprimé et/ou numérique] / Sarah CURRAN, Auteur ; Katharina DWORZYNSKI, Auteur ; Francesca HAPPE, Auteur ; Angelica RONALD, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur ; Carol BRAYNE, Auteur ; Patrick BOLTON, Auteur . - 2011 . - p.377-382. Langues : Anglais (eng) in Autism Research > 4-5 (October 2011) . - p.377-382 Mots-clés : clinical psychiatry  developmental psychology  diagnosis  epidemiology  social cognition Index. décimale : PER Périodiques Résumé : Background: It has been questioned whether the process of twinning might be a risk factor for autism spectrum conditions (ASC) and autistic traits. Aim: We sought to determine whether autistic traits and probable disorder, as measured by the Childhood Autism Spectrum Test (CAST), were more pronounced in twins compared to singletons. Samples: Data were analyzed from two large population-based samples of UK children, twins (n = 5,142 twin pairs, aged 8 years) and singletons (n = 2,805, aged 5–9 years). Results: Distributions of CAST scores in both groups were negatively skewed and scores for twins were more variable than singletons. Mean CAST total scores and standard errors (SE) were not significantly different for twins (5.1; SE 0.04) compared to singletons (4.9; SE 0.08). Moreover, contrary to expectations, the likelihood of scoring above the threshold for possible ASC was significantly lower in the twins than the singletons (OR = 0.69; P = 0.002). Subsidiary analyses of CAST scores according to sex, twin type, and subscale scores representing the subdomains of autism found a few significant differences (P<0.01), but the effect sizes for these differences were small and none exceeded η2 = 0.005. The explanation for these small differences remains obscure, but the very small effect sizes mean they are of little importance. Conclusions: Our results do not provide evidence to support twinning as a risk factor in the development of autistic traits. Autism Res2011,4:377–382. © 2011 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.207 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=145

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