Dépouillements

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study / McLeod Frampton GWYNETTE in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.346-351 Titre : Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study Type de document : Texte imprimé et/ou numérique Auteurs : McLeod Frampton GWYNETTE, Auteur ; Danielle W. LOWE, Auteur ; Erin A. HENNEBERRY, Auteur ; Gregory L. SAHLEM, Auteur ; Melanie Gail WILEY, Auteur ; Hussam ALSARRAF, Auteur ; Sarah Brice RUSSO, Auteur ; Jane E. JOSEPH, Auteur ; Philipp M. SUMMERS, Auteur ; Laura LOHNES, Auteur ; Mark S. GEORGE, Auteur Article en page(s) : p.346-351 Langues : Anglais (eng) Mots-clés : adults with autism spectrum disorder  autism spectrum disorder  major depressive disorder  mood  psychiatric comorbidity  transcranial stimulation  treatment research Index. décimale : PER Périodiques Résumé : Patients with autism spectrum disorder (ASD) are at high risk for comorbid major depressive disorder (MDD), which can severely impair functioning and quality of life. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique, which is Food and Drug Administration (FDA) cleared for the treatment of MDD in adults. Despite demonstrated efficacy in the treatment of depression, there are limited data on the use of rTMS in patients with ASD and comorbid MDD. We hypothesized that a standard rTMS protocol for MDD would reduce depressive symptoms for adults with ASD and MDD. Secondarily, we investigated whether this treatment would also reduce core ASD symptoms. Participants of 18-65 years old with ASD and MDD without any medication changes in the last month were eligible for this open-label trial. Participants underwent 25 sessions of rTMS (figure-of-eight coil, 100-120% resting motor threshold, 10 Hz, 3,000 pulses per session) applied to the left dorsolateral prefrontal cortex. Thirteen participants enrolled in the study, with two withdrawing due to tolerability, and one excluded from analysis. Overall, side effects were mild and rTMS was well tolerated. The Hamilton rating scale for depression (HAM-D17 ) improved 13.5 points (IQR 5-15), and 40% of participants achieved remission (HAM-D17 En ligne : http://dx.doi.org/10.1002/aur.2266 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study [Texte imprimé et/ou numérique] / McLeod Frampton GWYNETTE, Auteur ; Danielle W. LOWE, Auteur ; Erin A. HENNEBERRY, Auteur ; Gregory L. SAHLEM, Auteur ; Melanie Gail WILEY, Auteur ; Hussam ALSARRAF, Auteur ; Sarah Brice RUSSO, Auteur ; Jane E. JOSEPH, Auteur ; Philipp M. SUMMERS, Auteur ; Laura LOHNES, Auteur ; Mark S. GEORGE, Auteur . - p.346-351. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.346-351 Mots-clés : adults with autism spectrum disorder  autism spectrum disorder  major depressive disorder  mood  psychiatric comorbidity  transcranial stimulation  treatment research Index. décimale : PER Périodiques Résumé : Patients with autism spectrum disorder (ASD) are at high risk for comorbid major depressive disorder (MDD), which can severely impair functioning and quality of life. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique, which is Food and Drug Administration (FDA) cleared for the treatment of MDD in adults. Despite demonstrated efficacy in the treatment of depression, there are limited data on the use of rTMS in patients with ASD and comorbid MDD. We hypothesized that a standard rTMS protocol for MDD would reduce depressive symptoms for adults with ASD and MDD. Secondarily, we investigated whether this treatment would also reduce core ASD symptoms. Participants of 18-65 years old with ASD and MDD without any medication changes in the last month were eligible for this open-label trial. Participants underwent 25 sessions of rTMS (figure-of-eight coil, 100-120% resting motor threshold, 10 Hz, 3,000 pulses per session) applied to the left dorsolateral prefrontal cortex. Thirteen participants enrolled in the study, with two withdrawing due to tolerability, and one excluded from analysis. Overall, side effects were mild and rTMS was well tolerated. The Hamilton rating scale for depression (HAM-D17 ) improved 13.5 points (IQR 5-15), and 40% of participants achieved remission (HAM-D17 En ligne : http://dx.doi.org/10.1002/aur.2266 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism / Weicheng DUAN in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.352-368 Titre : Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism Type de document : Texte imprimé et/ou numérique Auteurs : Weicheng DUAN, Auteur ; Kang WANG, Auteur ; Yijie DUAN, Auteur ; Xufeng CHU, Auteur ; Ruoyun MA, Auteur ; Ping HU, Auteur ; Bo XIONG, Auteur Article en page(s) : p.352-368 Langues : Anglais (eng) Mots-clés : PPI network  autism  gene regulation  integrated analysis  synaptic transmission  transcriptome Index. décimale : PER Périodiques Résumé : Genetic mutations are the major pathogenic factor of Autism Spectrum Disorder (ASD). In recent years, more and more ASD risk genes have been revealed, among which there are a group of transcriptional regulators. Considering the similarity of the core clinical phenotypes, it is possible that these different factors may regulate the expression levels of certain key targets. Identification of these targets could facilitate the understanding of the etiology and developing of novel diagnostic and therapeutic methods. Therefore, we performed integrated transcriptome analyses of RNA-Seq and microarray data in multiple ASD mouse models and identified a number of common downstream genes in various brain regions, many of which are related to the structure and function of the synapse components or drug addiction. We then established protein-protein interaction networks of the overlapped targets and isolated the hub genes by 11 algorithms based on the topological structure of the networks, including Sdc4, Vegfa, and Cp in the Cortex-Adult subgroup, Gria1 in the Cortex-Juvenile subgroup, and Kdr, S1pr1, Ubc, Grm2, Grin2b, Nrxn1, Pdyn, Grin3a, Itgam, Grin2a, Gabra2, and Camk4 in the Hippocampus-Adult subgroup, many of which have been associated with ASD in previous studies. Finally, we cross compared our results with human brain transcriptional data sets and verified several key candidates, which may play important role in the pathology process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRIN2A, GABRA2, and CAMK4. In summary, by integrated bioinformatics analysis, we have identified a series of potentially important molecules for future ASD research. Autism Res 2020, 13: 352-368. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Abnormal transcriptional regulation accounts for a significant portion of Autism Spectrum Disorder. In this study, we performed transcriptome analyses of mouse models to identify common downstream targets of transcriptional regulators involved in ASD. We identified several recurrent target genes that are close related to the common pathological process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRM2, NRXN1, GRIN3A, ITGAM, GRIN2A, GABRA2, and CAMK4. These results provide potentially important targets for understanding the molecular mechanism of ASD. En ligne : http://dx.doi.org/10.1002/aur.2240 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism [Texte imprimé et/ou numérique] / Weicheng DUAN, Auteur ; Kang WANG, Auteur ; Yijie DUAN, Auteur ; Xufeng CHU, Auteur ; Ruoyun MA, Auteur ; Ping HU, Auteur ; Bo XIONG, Auteur . - p.352-368. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.352-368 Mots-clés : PPI network  autism  gene regulation  integrated analysis  synaptic transmission  transcriptome Index. décimale : PER Périodiques Résumé : Genetic mutations are the major pathogenic factor of Autism Spectrum Disorder (ASD). In recent years, more and more ASD risk genes have been revealed, among which there are a group of transcriptional regulators. Considering the similarity of the core clinical phenotypes, it is possible that these different factors may regulate the expression levels of certain key targets. Identification of these targets could facilitate the understanding of the etiology and developing of novel diagnostic and therapeutic methods. Therefore, we performed integrated transcriptome analyses of RNA-Seq and microarray data in multiple ASD mouse models and identified a number of common downstream genes in various brain regions, many of which are related to the structure and function of the synapse components or drug addiction. We then established protein-protein interaction networks of the overlapped targets and isolated the hub genes by 11 algorithms based on the topological structure of the networks, including Sdc4, Vegfa, and Cp in the Cortex-Adult subgroup, Gria1 in the Cortex-Juvenile subgroup, and Kdr, S1pr1, Ubc, Grm2, Grin2b, Nrxn1, Pdyn, Grin3a, Itgam, Grin2a, Gabra2, and Camk4 in the Hippocampus-Adult subgroup, many of which have been associated with ASD in previous studies. Finally, we cross compared our results with human brain transcriptional data sets and verified several key candidates, which may play important role in the pathology process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRIN2A, GABRA2, and CAMK4. In summary, by integrated bioinformatics analysis, we have identified a series of potentially important molecules for future ASD research. Autism Res 2020, 13: 352-368. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Abnormal transcriptional regulation accounts for a significant portion of Autism Spectrum Disorder. In this study, we performed transcriptome analyses of mouse models to identify common downstream targets of transcriptional regulators involved in ASD. We identified several recurrent target genes that are close related to the common pathological process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRM2, NRXN1, GRIN3A, ITGAM, GRIN2A, GABRA2, and CAMK4. These results provide potentially important targets for understanding the molecular mechanism of ASD. En ligne : http://dx.doi.org/10.1002/aur.2240 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Language deficits in specific language impairment, attention deficit/hyperactivity disorder, and autism spectrum disorder: An analysis of polygenic risk / Ron NUDEL in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.369-381 Titre : Language deficits in specific language impairment, attention deficit/hyperactivity disorder, and autism spectrum disorder: An analysis of polygenic risk Type de document : Texte imprimé et/ou numérique Auteurs : Ron NUDEL, Auteur ; Camilla A. J. CHRISTIANI, Auteur ; Jessica OHLAND, Auteur ; Md Jamal UDDIN, Auteur ; Nicoline HEMAGER, Auteur ; Ditte ELLERSGAARD, Auteur ; Katrine S. SPANG, Auteur ; Birgitte K. BURTON, Auteur ; Aja N. GREVE, Auteur ; Ditte L. GANTRIIS, Auteur ; Jonas BYBJERG-GRAUHOLM, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; Anne A. E. THORUP, Auteur ; Ole MORS, Auteur ; Merete NORDENTOFT, Auteur ; Thomas WERGE, Auteur Article en page(s) : p.369-381 Langues : Anglais (eng) Mots-clés : attention deficit hyperactivity disorder  autism spectrum disorder  genome-wide association study  polygenic risk score  specific language impairment Index. décimale : PER Périodiques Résumé : Language is one of the cognitive domains often impaired across many neurodevelopmental disorders. While for some disorders the linguistic deficit is the primary impairment (e.g., specific language impairment, SLI), for others it may accompany broader behavioral problems (e.g., autism). The precise nature of this phenotypic overlap has been the subject of debate. Moreover, several studies have found genetic overlaps across neurodevelopmental disorders. This raises the question of whether these genetic overlaps may correlate with phenotypic overlaps and, if so, in what manner. Here, we apply a genome-wide approach to the study of the linguistic deficit in SLI, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Using a discovery genome-wide association study of SLI, we generate polygenic risk scores (PRS) in an independent sample which includes children with language impairment, SLI, ASD or ADHD and age-matched controls and perform regression analyses across groups. The SLI-trained PRS significantly predicted risk in the SLI case-control group (adjusted R(2) = 6.24%; P = 0.024) but not in the ASD or ADHD case-control groups (adjusted R(2) = 0.0004%, 0.01%; P = 0.984, 0.889, respectively) nor for height, used as a negative control (R(2) = 0.2%; P = 0.452). Additionally, there was a significant difference in the normalized PRS between children with SLI and children with ASD (common language effect size = 0.66; P = 0.044). Our study suggests no additive common-variant genetic overlap between SLI and ASD and ADHD. This is discussed in the context of phenotypic studies of SLI and related disorders. Autism Res 2020, 13: 369-381. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Language deficits are characteristic of specific language impairment (SLI), but may also be found in other neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Many studies examined the overlaps and differences across the language deficits in these disorders, but few studies have examined the genetic aspect thereof. In this study, we use a genome-wide approach to evaluate whether common genetic variants increasing risk of SLI may also be associated with ASD and ADHD in the same manner. Our results suggest that this is not the case, and we discuss this finding in the context of theories concerning the etiologies of these disorders. En ligne : http://dx.doi.org/10.1002/aur.2211 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Language deficits in specific language impairment, attention deficit/hyperactivity disorder, and autism spectrum disorder: An analysis of polygenic risk [Texte imprimé et/ou numérique] / Ron NUDEL, Auteur ; Camilla A. J. CHRISTIANI, Auteur ; Jessica OHLAND, Auteur ; Md Jamal UDDIN, Auteur ; Nicoline HEMAGER, Auteur ; Ditte ELLERSGAARD, Auteur ; Katrine S. SPANG, Auteur ; Birgitte K. BURTON, Auteur ; Aja N. GREVE, Auteur ; Ditte L. GANTRIIS, Auteur ; Jonas BYBJERG-GRAUHOLM, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; Anne A. E. THORUP, Auteur ; Ole MORS, Auteur ; Merete NORDENTOFT, Auteur ; Thomas WERGE, Auteur . - p.369-381. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.369-381 Mots-clés : attention deficit hyperactivity disorder  autism spectrum disorder  genome-wide association study  polygenic risk score  specific language impairment Index. décimale : PER Périodiques Résumé : Language is one of the cognitive domains often impaired across many neurodevelopmental disorders. While for some disorders the linguistic deficit is the primary impairment (e.g., specific language impairment, SLI), for others it may accompany broader behavioral problems (e.g., autism). The precise nature of this phenotypic overlap has been the subject of debate. Moreover, several studies have found genetic overlaps across neurodevelopmental disorders. This raises the question of whether these genetic overlaps may correlate with phenotypic overlaps and, if so, in what manner. Here, we apply a genome-wide approach to the study of the linguistic deficit in SLI, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Using a discovery genome-wide association study of SLI, we generate polygenic risk scores (PRS) in an independent sample which includes children with language impairment, SLI, ASD or ADHD and age-matched controls and perform regression analyses across groups. The SLI-trained PRS significantly predicted risk in the SLI case-control group (adjusted R(2) = 6.24%; P = 0.024) but not in the ASD or ADHD case-control groups (adjusted R(2) = 0.0004%, 0.01%; P = 0.984, 0.889, respectively) nor for height, used as a negative control (R(2) = 0.2%; P = 0.452). Additionally, there was a significant difference in the normalized PRS between children with SLI and children with ASD (common language effect size = 0.66; P = 0.044). Our study suggests no additive common-variant genetic overlap between SLI and ASD and ADHD. This is discussed in the context of phenotypic studies of SLI and related disorders. Autism Res 2020, 13: 369-381. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Language deficits are characteristic of specific language impairment (SLI), but may also be found in other neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Many studies examined the overlaps and differences across the language deficits in these disorders, but few studies have examined the genetic aspect thereof. In this study, we use a genome-wide approach to evaluate whether common genetic variants increasing risk of SLI may also be associated with ASD and ADHD in the same manner. Our results suggest that this is not the case, and we discuss this finding in the context of theories concerning the etiologies of these disorders. En ligne : http://dx.doi.org/10.1002/aur.2211 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Genome-wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders / Lu XIA in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.382-396 Titre : Genome-wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders Type de document : Texte imprimé et/ou numérique Auteurs : Lu XIA, Auteur ; Jianjun OU, Auteur ; Kuokuo LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Ting BAI, Auteur ; Jingping ZHAO, Auteur ; Kun XIA, Auteur ; Fengyu ZHANG, Auteur Article en page(s) : p.382-396 Langues : Anglais (eng) Mots-clés : autism  genome-wide association study  neuropsychiatric disorders  transmission disequilibrium test Index. décimale : PER Périodiques Résumé : Autism is a common neurodevelopmental disorder with a moderate to a high degree of heritability, but only a few common genetic variants that explain the heritability have been associated. We performed a genome-wide transmission disequilibrium test analysis of a newly genotyped autism case-parent triad samples (127 trios) in Han Chinese, identified top association signals at multiple single nucleotide polymorphisms (SNPs), including rs9839376 (OR = 2.59, P = 1.27 x 10(-05) ) at KCNMB2, rs6044680 (OR = 0.319, P = 4.82 x 10(-05) ) and rs7274133 (OR = 0.313, P = 3.22 x 10(-05) ) at PCSK2, and rs310619 (OR = 2.40, P = 7.44 x 10(-05) ) at EEF1A2. Furthermore, a genome-wide combined P-value of individual SNPs in two independent case-parent triad samples (total 402 triads, n = 1,206) identified SNPs at EGFLAM, ZDHHC2, AGBL1, and SNX29 as additional association signals for autism. While none of these signals achieved a genome-wide significance in the two samples of our study, they have been reported in a previous genome-wide association study of neuropsychiatric disorders, and the majority of these SNP have a significant cis-regulatory association with mRNA in human tissues (false discovery rate (FDR) < 0.05). Our study warrants further study or replication with additional sample for association with autism and other neuropsychiatric disorders. Autism Res 2020, 13: 382-396. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism is a common neurodevelopmental disorder, heritable, but only a few common genetic variants that explain the heritability have been associated. We conducted a genome-wide association study with two cohorts of autism case-parent triad samples in Han Chinese and identified multiple single nucleotide polymorphisms that were reported as strong association signals in a previous genome-wide association study of other neuropsychiatric disorders or related traits. Our study provides evidence for shared genetic variants among autism and other neuropsychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2229 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Genome-wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders [Texte imprimé et/ou numérique] / Lu XIA, Auteur ; Jianjun OU, Auteur ; Kuokuo LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Ting BAI, Auteur ; Jingping ZHAO, Auteur ; Kun XIA, Auteur ; Fengyu ZHANG, Auteur . - p.382-396. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.382-396 Mots-clés : autism  genome-wide association study  neuropsychiatric disorders  transmission disequilibrium test Index. décimale : PER Périodiques Résumé : Autism is a common neurodevelopmental disorder with a moderate to a high degree of heritability, but only a few common genetic variants that explain the heritability have been associated. We performed a genome-wide transmission disequilibrium test analysis of a newly genotyped autism case-parent triad samples (127 trios) in Han Chinese, identified top association signals at multiple single nucleotide polymorphisms (SNPs), including rs9839376 (OR = 2.59, P = 1.27 x 10(-05) ) at KCNMB2, rs6044680 (OR = 0.319, P = 4.82 x 10(-05) ) and rs7274133 (OR = 0.313, P = 3.22 x 10(-05) ) at PCSK2, and rs310619 (OR = 2.40, P = 7.44 x 10(-05) ) at EEF1A2. Furthermore, a genome-wide combined P-value of individual SNPs in two independent case-parent triad samples (total 402 triads, n = 1,206) identified SNPs at EGFLAM, ZDHHC2, AGBL1, and SNX29 as additional association signals for autism. While none of these signals achieved a genome-wide significance in the two samples of our study, they have been reported in a previous genome-wide association study of neuropsychiatric disorders, and the majority of these SNP have a significant cis-regulatory association with mRNA in human tissues (false discovery rate (FDR) < 0.05). Our study warrants further study or replication with additional sample for association with autism and other neuropsychiatric disorders. Autism Res 2020, 13: 382-396. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism is a common neurodevelopmental disorder, heritable, but only a few common genetic variants that explain the heritability have been associated. We conducted a genome-wide association study with two cohorts of autism case-parent triad samples in Han Chinese and identified multiple single nucleotide polymorphisms that were reported as strong association signals in a previous genome-wide association study of other neuropsychiatric disorders or related traits. Our study provides evidence for shared genetic variants among autism and other neuropsychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2229 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion / Andie DODGE in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.397-409 Titre : Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion Type de document : Texte imprimé et/ou numérique Auteurs : Andie DODGE, Auteur ; Melinda M. PETERS, Auteur ; Hayden E. GREENE, Auteur ; Clifton DIETRICK, Auteur ; Robert BOTELHO, Auteur ; Diana CHUNG, Auteur ; Jonathan WILLMAN, Auteur ; Austin W NENNINGER, Auteur ; Stephanie CIARLONE, Auteur ; Siddharth G. KAMATH, Auteur ; Pavel HOUDEK, Auteur ; Alena SUMOVA, Auteur ; Anne E. ANDERSON, Auteur ; Scott V. DINDOT, Auteur ; Elizabeth L. BERG, Auteur ; Henriette O'GEEN, Auteur ; David J. SEGAL, Auteur ; Jill L. SILVERMAN, Auteur ; Edwin J. WEEBER, Auteur ; Kevin R. NASH, Auteur Article en page(s) : p.397-409 Langues : Anglais (eng) Mots-clés : Angelman syndrome  E6ap  Ube3a  cognitive deficits  rat model Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397-409. (c) 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. En ligne : http://dx.doi.org/10.1002/aur.2267 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion [Texte imprimé et/ou numérique] / Andie DODGE, Auteur ; Melinda M. PETERS, Auteur ; Hayden E. GREENE, Auteur ; Clifton DIETRICK, Auteur ; Robert BOTELHO, Auteur ; Diana CHUNG, Auteur ; Jonathan WILLMAN, Auteur ; Austin W NENNINGER, Auteur ; Stephanie CIARLONE, Auteur ; Siddharth G. KAMATH, Auteur ; Pavel HOUDEK, Auteur ; Alena SUMOVA, Auteur ; Anne E. ANDERSON, Auteur ; Scott V. DINDOT, Auteur ; Elizabeth L. BERG, Auteur ; Henriette O'GEEN, Auteur ; David J. SEGAL, Auteur ; Jill L. SILVERMAN, Auteur ; Edwin J. WEEBER, Auteur ; Kevin R. NASH, Auteur . - p.397-409. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.397-409 Mots-clés : Angelman syndrome  E6ap  Ube3a  cognitive deficits  rat model Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397-409. (c) 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. En ligne : http://dx.doi.org/10.1002/aur.2267 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Specific Functional Connectivity Patterns of Middle Temporal Gyrus Subregions in Children and Adults with Autism Spectrum Disorder / Jinping XU in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.410-422 Titre : Specific Functional Connectivity Patterns of Middle Temporal Gyrus Subregions in Children and Adults with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Jinping XU, Auteur ; Chao WANG, Auteur ; Ziyun XU, Auteur ; Tian LI, Auteur ; Fangfang CHEN, Auteur ; Kai CHEN, Auteur ; Jingjing GAO, Auteur ; Jiaojian WANG, Auteur ; Qingmao HU, Auteur Article en page(s) : p.410-422 Langues : Anglais (eng) Mots-clés : autism spectrum disorders  coactivation-based parcellation  functional characterization  middle temporal gyrus  resting-state functional connectivity Index. décimale : PER Périodiques Résumé : As one of the key regions in the "social brain" network, the middle temporal gyrus (MTG) has been widely reported to be associated with autism spectrum disorder (ASD), but there have been contradictory results in terms of whether it shows hyperconnectivity or hypoconnectivity. Delineating roles of MTG at the subregional level may eliminate the observed inconsistencies and provide a new avenue to reveal the neurophysiologic mechanism of ASD. Thus, we first performed connectivity-based parcellation using the BrainMap database to identify fine-grained functional topography of the MTG. Then, the MTG subregions were used to investigate differences in the functional connectivity in children and adults with ASD using two data sets from Autism Brain Imaging Data Exchange database. Four distinct subregions in the human left and right MTG were identified, including the anterior MTG (aMTG), middle-anterior MTG (maMTG), middle-posterior MTG, and posterior MTG (pMTG). The bilateral pMTG was more vulnerable in both children and adults with ASD than in the typically developing (TD) group, mainly showing hypoconnectivity with different brain regions. In addition, the bilateral aMTG and right maMTG also showed altered functional connectivity in adults with ASD compared to the TD group. Moreover, all these altered MTG subregions were mainly associated with social cognition and language, as revealed by functional characterization. Further correlation analyses also showed trends of association between altered connectivity of the left aMTG and the Autism Diagnostic Observation Schedule scores in adults with ASD. Together, these results suggest a potential objective way to explore sub-regional differences associated with such disorders. Autism Res 2020, 13: 410-422. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Four distinct subregions in the human left and right middle temporal gyrus (MTG) were identified, including the anterior MTG (aMTG), middle-anterior MTG (maMTG), middle-posterior MTG, and posterior MTG (pMTG). The bilateral pMTG was more vulnerable in both children and adults with autism spectrum disorder (ASD) than in the typically developing (TD) group, mainly showing hypoconnectivity with different brain regions. In addition, the bilateral aMTG and right maMTG also showed altered functional connectivity in adults with ASD compared to the TD group. Moreover, all these altered MTG subregions were mainly associated with social cognition and language, as revealed by functional characterization. Further correlation analyses also showed trends of association between altered connectivity of the left aMTG and the Autism Diagnostic Observation Schedule scores in adults with ASD. En ligne : http://dx.doi.org/10.1002/aur.2239 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Specific Functional Connectivity Patterns of Middle Temporal Gyrus Subregions in Children and Adults with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Jinping XU, Auteur ; Chao WANG, Auteur ; Ziyun XU, Auteur ; Tian LI, Auteur ; Fangfang CHEN, Auteur ; Kai CHEN, Auteur ; Jingjing GAO, Auteur ; Jiaojian WANG, Auteur ; Qingmao HU, Auteur . - p.410-422. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.410-422 Mots-clés : autism spectrum disorders  coactivation-based parcellation  functional characterization  middle temporal gyrus  resting-state functional connectivity Index. décimale : PER Périodiques Résumé : As one of the key regions in the "social brain" network, the middle temporal gyrus (MTG) has been widely reported to be associated with autism spectrum disorder (ASD), but there have been contradictory results in terms of whether it shows hyperconnectivity or hypoconnectivity. Delineating roles of MTG at the subregional level may eliminate the observed inconsistencies and provide a new avenue to reveal the neurophysiologic mechanism of ASD. Thus, we first performed connectivity-based parcellation using the BrainMap database to identify fine-grained functional topography of the MTG. Then, the MTG subregions were used to investigate differences in the functional connectivity in children and adults with ASD using two data sets from Autism Brain Imaging Data Exchange database. Four distinct subregions in the human left and right MTG were identified, including the anterior MTG (aMTG), middle-anterior MTG (maMTG), middle-posterior MTG, and posterior MTG (pMTG). The bilateral pMTG was more vulnerable in both children and adults with ASD than in the typically developing (TD) group, mainly showing hypoconnectivity with different brain regions. In addition, the bilateral aMTG and right maMTG also showed altered functional connectivity in adults with ASD compared to the TD group. Moreover, all these altered MTG subregions were mainly associated with social cognition and language, as revealed by functional characterization. Further correlation analyses also showed trends of association between altered connectivity of the left aMTG and the Autism Diagnostic Observation Schedule scores in adults with ASD. Together, these results suggest a potential objective way to explore sub-regional differences associated with such disorders. Autism Res 2020, 13: 410-422. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Four distinct subregions in the human left and right middle temporal gyrus (MTG) were identified, including the anterior MTG (aMTG), middle-anterior MTG (maMTG), middle-posterior MTG, and posterior MTG (pMTG). The bilateral pMTG was more vulnerable in both children and adults with autism spectrum disorder (ASD) than in the typically developing (TD) group, mainly showing hypoconnectivity with different brain regions. In addition, the bilateral aMTG and right maMTG also showed altered functional connectivity in adults with ASD compared to the TD group. Moreover, all these altered MTG subregions were mainly associated with social cognition and language, as revealed by functional characterization. Further correlation analyses also showed trends of association between altered connectivity of the left aMTG and the Autism Diagnostic Observation Schedule scores in adults with ASD. En ligne : http://dx.doi.org/10.1002/aur.2239 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Getting Off to a Shaky Start: Specificity in Planning and Feedforward Control During Sensorimotor Learning in Autism Spectrum Disorder / Nathan C. FOSTER in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.423-435 Titre : Getting Off to a Shaky Start: Specificity in Planning and Feedforward Control During Sensorimotor Learning in Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Nathan C. FOSTER, Auteur ; Simon J. BENNETT, Auteur ; Joe CAUSER, Auteur ; Digby ELLIOTT, Auteur ; Geoffrey BIRD, Auteur ; Spencer J. HAYES, Auteur Article en page(s) : p.423-435 Langues : Anglais (eng) Mots-clés : autism  feedforward and feedback motor control  sensorimotor learning Index. décimale : PER Périodiques Résumé : Whilst autistic individuals develop new internal action models during sensorimotor learning, the acquired movements are executed less accurately and with greater variability. Such movement profiles are related to differences in sensorimotor integration and/or altered feedforward/feedback sensorimotor control. We investigated the processes underlying sensorimotor learning in autism by quantifying accuracy and variability, relative timing, and feedforward and feedback control. Although autistic individuals demonstrated significant sensorimotor learning across trials, which was facilitated by processing knowledge-of-results feedback, motor execution was less accurate than non-autistic individuals. Kinematic analysis indicated that autistic individuals showed significantly greater spatial variability at peak acceleration, but comparable spatial variability at peak velocity. These kinematic markers suggest that autistic movement profiles are driven by specific differences in sensorimotor control processes (i.e., internal action models) associated with planning and regulating the forces required to execute the movement. The reduction of variability at peak velocity indicates intact early feedback-based sensorimotor control in autism. Understanding how feedforward and feedback-based control processes operate provides an opportunity to explore how these control processes influence the acquisition of socio-motor actions in autism. Autism Res 2020, 13: 423-435. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autistic adults successfully learned a new movement skill by physically practising it, and using feedback about how well they had done to become more accurate. When looking at the movements in detail, autistic adults were more variable than non-autistic adults when planning (e.g., how much force to use), and performing, the movement. These differences impact how autistic individuals learn different types of movement skills, which might influence how other behaviours (e.g., imitation) are acquired that support social interaction. En ligne : http://dx.doi.org/10.1002/aur.2214 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Getting Off to a Shaky Start: Specificity in Planning and Feedforward Control During Sensorimotor Learning in Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Nathan C. FOSTER, Auteur ; Simon J. BENNETT, Auteur ; Joe CAUSER, Auteur ; Digby ELLIOTT, Auteur ; Geoffrey BIRD, Auteur ; Spencer J. HAYES, Auteur . - p.423-435. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.423-435 Mots-clés : autism  feedforward and feedback motor control  sensorimotor learning Index. décimale : PER Périodiques Résumé : Whilst autistic individuals develop new internal action models during sensorimotor learning, the acquired movements are executed less accurately and with greater variability. Such movement profiles are related to differences in sensorimotor integration and/or altered feedforward/feedback sensorimotor control. We investigated the processes underlying sensorimotor learning in autism by quantifying accuracy and variability, relative timing, and feedforward and feedback control. Although autistic individuals demonstrated significant sensorimotor learning across trials, which was facilitated by processing knowledge-of-results feedback, motor execution was less accurate than non-autistic individuals. Kinematic analysis indicated that autistic individuals showed significantly greater spatial variability at peak acceleration, but comparable spatial variability at peak velocity. These kinematic markers suggest that autistic movement profiles are driven by specific differences in sensorimotor control processes (i.e., internal action models) associated with planning and regulating the forces required to execute the movement. The reduction of variability at peak velocity indicates intact early feedback-based sensorimotor control in autism. Understanding how feedforward and feedback-based control processes operate provides an opportunity to explore how these control processes influence the acquisition of socio-motor actions in autism. Autism Res 2020, 13: 423-435. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autistic adults successfully learned a new movement skill by physically practising it, and using feedback about how well they had done to become more accurate. When looking at the movements in detail, autistic adults were more variable than non-autistic adults when planning (e.g., how much force to use), and performing, the movement. These differences impact how autistic individuals learn different types of movement skills, which might influence how other behaviours (e.g., imitation) are acquired that support social interaction. En ligne : http://dx.doi.org/10.1002/aur.2214 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Investigating the factor structure of the child behavior checklist dysregulation profile in children and adolescents with autism spectrum disorder / Amy KEEFER in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.436-443 Titre : Investigating the factor structure of the child behavior checklist dysregulation profile in children and adolescents with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Amy KEEFER, Auteur ; Vini SINGH, Auteur ; Luther G. KALB, Auteur ; Carla A. MAZEFSKY, Auteur ; Roma A. VASA, Auteur Article en page(s) : p.436-443 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  child behavior checklist  dysregulation  factor analysis Index. décimale : PER Périodiques Résumé : Dysregulation has been identified as an important risk factor for the development of psychiatric disorders in individuals with autism spectrum disorder (ASD). Therefore, it is necessary to empirically characterize dysregulation and identify psychometrically sound and readily available assessment methods in the ASD population. We sought to evaluate the factor structure of the Child Behavior Checklist-Dysregulation Profile (CBCL-DP), an established dysregulation measure in neurotypical children that is derived from the CBCL, in a large, clinically referred sample of children, ages 6-18 years, with ASD (n = 727). Confirmatory factor analysis was used to characterize dysregulation and assess the validity of the CBCL-DP in children with ASD. Our findings support a bi-factor model of dysregulation in which dysregulation is a broad and distinct syndrome that is associated with the three subdomains of the CBCL-DP, anxiety/depression (AD), attention problems (AP), and aggressive behavior (AGG). Dysregulation was associated with most items in the AD and AGG domains and few items in the AP domain. This association with AD and AGG indicates that dysregulation in ASD may be conceptualized as the combined experience of internalized, negative mood states and externalized, reactive behaviors. These findings provide support as well as important caveats for the use of the CBCL-DP as a measure of dysregulation in the ASD population. Autism Res 2020, 13: 436-443. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Dysregulation is a risk factor for psychiatric disorders in ASD. This study examined if the CBCL-DP, an established measure of dysregulation in neurotypical children, can be used to assess dysregulation in children with ASD. Findings provide evidence that in ASD, dysregulation is a broad construct that exists alongside anxiety/depression, attention problems, and aggression. These findings indicate that the CBCL-DP can be considered a valid measure of dysregulation in the ASD population and could be used in clinical settings. En ligne : http://dx.doi.org/10.1002/aur.2233 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Investigating the factor structure of the child behavior checklist dysregulation profile in children and adolescents with autism spectrum disorder [Texte imprimé et/ou numérique] / Amy KEEFER, Auteur ; Vini SINGH, Auteur ; Luther G. KALB, Auteur ; Carla A. MAZEFSKY, Auteur ; Roma A. VASA, Auteur . - p.436-443. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.436-443 Mots-clés : autism spectrum disorder  child behavior checklist  dysregulation  factor analysis Index. décimale : PER Périodiques Résumé : Dysregulation has been identified as an important risk factor for the development of psychiatric disorders in individuals with autism spectrum disorder (ASD). Therefore, it is necessary to empirically characterize dysregulation and identify psychometrically sound and readily available assessment methods in the ASD population. We sought to evaluate the factor structure of the Child Behavior Checklist-Dysregulation Profile (CBCL-DP), an established dysregulation measure in neurotypical children that is derived from the CBCL, in a large, clinically referred sample of children, ages 6-18 years, with ASD (n = 727). Confirmatory factor analysis was used to characterize dysregulation and assess the validity of the CBCL-DP in children with ASD. Our findings support a bi-factor model of dysregulation in which dysregulation is a broad and distinct syndrome that is associated with the three subdomains of the CBCL-DP, anxiety/depression (AD), attention problems (AP), and aggressive behavior (AGG). Dysregulation was associated with most items in the AD and AGG domains and few items in the AP domain. This association with AD and AGG indicates that dysregulation in ASD may be conceptualized as the combined experience of internalized, negative mood states and externalized, reactive behaviors. These findings provide support as well as important caveats for the use of the CBCL-DP as a measure of dysregulation in the ASD population. Autism Res 2020, 13: 436-443. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Dysregulation is a risk factor for psychiatric disorders in ASD. This study examined if the CBCL-DP, an established measure of dysregulation in neurotypical children, can be used to assess dysregulation in children with ASD. Findings provide evidence that in ASD, dysregulation is a broad construct that exists alongside anxiety/depression, attention problems, and aggression. These findings indicate that the CBCL-DP can be considered a valid measure of dysregulation in the ASD population and could be used in clinical settings. En ligne : http://dx.doi.org/10.1002/aur.2233 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Neonatal Thyroid Stimulating Hormone and Subsequent Diagnosis of Autism Spectrum Disorders and Intellectual Disability / Jennifer L. AMES in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.444-455 Titre : Neonatal Thyroid Stimulating Hormone and Subsequent Diagnosis of Autism Spectrum Disorders and Intellectual Disability Type de document : Texte imprimé et/ou numérique Auteurs : Jennifer L. AMES, Auteur ; Gayle C. WINDHAM, Auteur ; Kristen LYALL, Auteur ; Michelle PEARL, Auteur ; Martin KHARRAZI, Auteur ; Cathleen K. YOSHIDA, Auteur ; Judy VAN DE WATER, Auteur ; Paul ASHWOOD, Auteur ; Lisa A. CROEN, Auteur Article en page(s) : p.444-455 Langues : Anglais (eng) Mots-clés : Asd  autism  intellectual disability  neonatal  thyroid  thyroid-stimulating hormone Index. décimale : PER Périodiques Résumé : Hypothyroid conditions in early life, if left untreated, are associated with adverse neurodevelopmental outcomes, including intellectual disability (ID). However, evidence addressing the role of neonatal thyroid hormone insufficiencies in the altered neurobiology underlying autism spectrum disorders (ASD), particularly among its subphenotypes, is limited. We conducted a population-based, case-control study among a sample of children born during 2000-2003 in Southern California. We examined neonatal thyroid-stimulating hormone (TSH) measured during routine newborn screening among children later diagnosed with ASD (n = 518) or ID (n = 145) and general population (GP) controls (n = 399). TSH was further analyzed in relation to ASD subgroups of intellectual ability and onset type (early-onset ASD vs. ASD with regression) ascertained by expert review of developmental services records. Odds ratios (ORs) of the differences in TSH between groups were obtained from multivariate logistic regression. We examined neonatal TSH as continuous (ln-transformed) and as quartiles. We found no association between continuous neonatal TSH levels and ASD (adj-OR: 1.00, 95% CI: 0.79-1.26) nor ID (adj-OR = 1.01, 95% CI: 0.73-1.40). Among ASD subphenotypes, we observed a suggestive inverse trend between ASD with regression and TSH, though the association only reached statistical significance in the highest TSH quartile (adj-OR: 0.50, 95% CI: 0.26-0.98). While there was little evidence that neonatal TSH is related to overall ASD risk, more work is needed to understand the influence of thyroid hormones on ASD subphenotypes. Autism Res 2020, 13: 444-455. (c) 2019 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Low levels of thyroid hormone at birth can negatively impact brain development. We studied whether newborn levels of thyroid stimulating hormone (TSH) were associated with autism spectrum disorder (ASD) and its subtypes in a sample of children born in California. Newborn TSH was not related to the overall risk of ASD or intellectual disability. However, the relationships of thyroid hormone levels at birth and specific subtypes of ASD, particularly ASD with developmental regression, may need more research. En ligne : http://dx.doi.org/10.1002/aur.2247 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Neonatal Thyroid Stimulating Hormone and Subsequent Diagnosis of Autism Spectrum Disorders and Intellectual Disability [Texte imprimé et/ou numérique] / Jennifer L. AMES, Auteur ; Gayle C. WINDHAM, Auteur ; Kristen LYALL, Auteur ; Michelle PEARL, Auteur ; Martin KHARRAZI, Auteur ; Cathleen K. YOSHIDA, Auteur ; Judy VAN DE WATER, Auteur ; Paul ASHWOOD, Auteur ; Lisa A. CROEN, Auteur . - p.444-455. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.444-455 Mots-clés : Asd  autism  intellectual disability  neonatal  thyroid  thyroid-stimulating hormone Index. décimale : PER Périodiques Résumé : Hypothyroid conditions in early life, if left untreated, are associated with adverse neurodevelopmental outcomes, including intellectual disability (ID). However, evidence addressing the role of neonatal thyroid hormone insufficiencies in the altered neurobiology underlying autism spectrum disorders (ASD), particularly among its subphenotypes, is limited. We conducted a population-based, case-control study among a sample of children born during 2000-2003 in Southern California. We examined neonatal thyroid-stimulating hormone (TSH) measured during routine newborn screening among children later diagnosed with ASD (n = 518) or ID (n = 145) and general population (GP) controls (n = 399). TSH was further analyzed in relation to ASD subgroups of intellectual ability and onset type (early-onset ASD vs. ASD with regression) ascertained by expert review of developmental services records. Odds ratios (ORs) of the differences in TSH between groups were obtained from multivariate logistic regression. We examined neonatal TSH as continuous (ln-transformed) and as quartiles. We found no association between continuous neonatal TSH levels and ASD (adj-OR: 1.00, 95% CI: 0.79-1.26) nor ID (adj-OR = 1.01, 95% CI: 0.73-1.40). Among ASD subphenotypes, we observed a suggestive inverse trend between ASD with regression and TSH, though the association only reached statistical significance in the highest TSH quartile (adj-OR: 0.50, 95% CI: 0.26-0.98). While there was little evidence that neonatal TSH is related to overall ASD risk, more work is needed to understand the influence of thyroid hormones on ASD subphenotypes. Autism Res 2020, 13: 444-455. (c) 2019 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Low levels of thyroid hormone at birth can negatively impact brain development. We studied whether newborn levels of thyroid stimulating hormone (TSH) were associated with autism spectrum disorder (ASD) and its subtypes in a sample of children born in California. Newborn TSH was not related to the overall risk of ASD or intellectual disability. However, the relationships of thyroid hormone levels at birth and specific subtypes of ASD, particularly ASD with developmental regression, may need more research. En ligne : http://dx.doi.org/10.1002/aur.2247 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Identification of Pediatric Autism Spectrum Disorder Cases Using Health Administrative Data / Celeste D. BICKFORD in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.456-463 Titre : Identification of Pediatric Autism Spectrum Disorder Cases Using Health Administrative Data Type de document : Texte imprimé et/ou numérique Auteurs : Celeste D. BICKFORD, Auteur ; Tim F. OBERLANDER, Auteur ; Nancy E. LANPHEAR, Auteur ; Whitney M. WEIKUM, Auteur ; Patricia A. JANSSEN, Auteur ; Hélène OUELLETTE-KUNTZ, Auteur ; Gillian E. HANLEY, Auteur Article en page(s) : p.456-463 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  diagnostic accuracy  health administrative data  validation Index. décimale : PER Périodiques Résumé : Administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases in epidemiological studies. However, validation studies on this mode of case ascertainment have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We report on the diagnostic accuracy of using readily available health administrative data for pediatric ASD case ascertainment. The validation cohort included almost all the ASD-positive children born in British Columbia, Canada from April 1, 2000 to December 31, 2009 and consisted of 8,670 children in total. 4,079 ASD-positive and 2,787 ASD-negative children were identified using Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) assessments done through the British Columbia Autism Assessment Network (BCAAN). An additional 1,804 ADOS/ADI-R assessed ASD-positive children were identified using Ministry of Education records. This prospectively collected clinical data (the diagnostic gold standard) was then linked to each child's physician billing and hospital discharge data. The diagnostic accuracy of 11 algorithms that used the administrative data to assign ASD case status was assessed. For all algorithms, high positive predictive values (PPVs) were observed alongside low values for other measures of diagnostic accuracy illustrating that PPVs alone are not an adequate measure of diagnostic accuracy. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders. Utilizing these data may result in misclassification bias. Methodologically sound, region-specific validation studies are needed to support the use of administrative data for ASD case ascertainment. Autism Res 2020, 13: 456-463. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Health administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases for research purposes. However, previous validation studies on this sort of case identification have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders. En ligne : http://dx.doi.org/10.1002/aur.2252 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Identification of Pediatric Autism Spectrum Disorder Cases Using Health Administrative Data [Texte imprimé et/ou numérique] / Celeste D. BICKFORD, Auteur ; Tim F. OBERLANDER, Auteur ; Nancy E. LANPHEAR, Auteur ; Whitney M. WEIKUM, Auteur ; Patricia A. JANSSEN, Auteur ; Hélène OUELLETTE-KUNTZ, Auteur ; Gillian E. HANLEY, Auteur . - p.456-463. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.456-463 Mots-clés : Autism spectrum disorder  diagnostic accuracy  health administrative data  validation Index. décimale : PER Périodiques Résumé : Administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases in epidemiological studies. However, validation studies on this mode of case ascertainment have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We report on the diagnostic accuracy of using readily available health administrative data for pediatric ASD case ascertainment. The validation cohort included almost all the ASD-positive children born in British Columbia, Canada from April 1, 2000 to December 31, 2009 and consisted of 8,670 children in total. 4,079 ASD-positive and 2,787 ASD-negative children were identified using Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) assessments done through the British Columbia Autism Assessment Network (BCAAN). An additional 1,804 ADOS/ADI-R assessed ASD-positive children were identified using Ministry of Education records. This prospectively collected clinical data (the diagnostic gold standard) was then linked to each child's physician billing and hospital discharge data. The diagnostic accuracy of 11 algorithms that used the administrative data to assign ASD case status was assessed. For all algorithms, high positive predictive values (PPVs) were observed alongside low values for other measures of diagnostic accuracy illustrating that PPVs alone are not an adequate measure of diagnostic accuracy. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders. Utilizing these data may result in misclassification bias. Methodologically sound, region-specific validation studies are needed to support the use of administrative data for ASD case ascertainment. Autism Res 2020, 13: 456-463. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Health administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases for research purposes. However, previous validation studies on this sort of case identification have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders. En ligne : http://dx.doi.org/10.1002/aur.2252 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Disparities in Documented Diagnoses of Autism Spectrum Disorder Based on Demographic, Individual, and Service Factors / Lisa D. WIGGINS in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.464-473 Titre : Disparities in Documented Diagnoses of Autism Spectrum Disorder Based on Demographic, Individual, and Service Factors Type de document : Texte imprimé et/ou numérique Auteurs : Lisa D. WIGGINS, Auteur ; Maureen DURKIN, Auteur ; Amy ESLER, Auteur ; Li-Ching LEE, Auteur ; Walter ZAHORODNY, Auteur ; Catherine RICE, Auteur ; Marshalyn YEARGIN-ALLSOPP, Auteur ; Nicole F. DOWLING, Auteur ; Jennifer HALL-LANDE, Auteur ; Michael J. MORRIER, Auteur ; Deborah CHRISTENSEN, Auteur ; Josephine SHENOUDA, Auteur ; Jon BAIO, Auteur Article en page(s) : p.464-473 Langues : Anglais (eng) Mots-clés : autism  diagnosis  disparities  surveillance Index. décimale : PER Périodiques Résumé : The objectives of our study were to (a) report how many children met an autism spectrum disorder (ASD) surveillance definition but had no clinical diagnosis of ASD in health or education records and (b) evaluate differences in demographic, individual, and service factors between children with and without a documented ASD diagnosis. ASD surveillance was conducted in selected areas of Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin. Children were defined as having ASD if sufficient social and behavioral deficits and/or an ASD diagnosis were noted in health and/or education records. Among 4,498 children, 1,135 (25%) had ASD indicators without having an ASD diagnosis. Of those 1,135 children without a documented ASD diagnosis, 628 (55%) were not known to receive ASD services in public school. Factors associated with not having a clinical diagnosis of ASD were non-White race, no intellectual disability, older age at first developmental concern, older age at first developmental evaluation, special education eligibility other than ASD, and need for fewer supports. These results highlight the importance of reducing disparities in the diagnosis of children with ASD characteristics so that appropriate interventions can be promoted across communities. Autism Res 2020, 13: 464-473. (c) 2019 International Society for AutismResearch,Wiley Periodicals, Inc. LAY SUMMARY: Children who did not have a clinical diagnosis of autism spectrum disorder (ASD) documented in health or education records were more likely to be non-White and have fewer developmental problems than children with a clinical diagnosis of ASD. They were brought to the attention of healthcare providers at older ages and needed fewer supports than children with a clinical diagnosis of ASD. All children with ASD symptoms who meet diagnostic criteria should be given a clinical diagnosis so they can receive treatment specific to their needs. En ligne : http://dx.doi.org/10.1002/aur.2255 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Disparities in Documented Diagnoses of Autism Spectrum Disorder Based on Demographic, Individual, and Service Factors [Texte imprimé et/ou numérique] / Lisa D. WIGGINS, Auteur ; Maureen DURKIN, Auteur ; Amy ESLER, Auteur ; Li-Ching LEE, Auteur ; Walter ZAHORODNY, Auteur ; Catherine RICE, Auteur ; Marshalyn YEARGIN-ALLSOPP, Auteur ; Nicole F. DOWLING, Auteur ; Jennifer HALL-LANDE, Auteur ; Michael J. MORRIER, Auteur ; Deborah CHRISTENSEN, Auteur ; Josephine SHENOUDA, Auteur ; Jon BAIO, Auteur . - p.464-473. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.464-473 Mots-clés : autism  diagnosis  disparities  surveillance Index. décimale : PER Périodiques Résumé : The objectives of our study were to (a) report how many children met an autism spectrum disorder (ASD) surveillance definition but had no clinical diagnosis of ASD in health or education records and (b) evaluate differences in demographic, individual, and service factors between children with and without a documented ASD diagnosis. ASD surveillance was conducted in selected areas of Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin. Children were defined as having ASD if sufficient social and behavioral deficits and/or an ASD diagnosis were noted in health and/or education records. Among 4,498 children, 1,135 (25%) had ASD indicators without having an ASD diagnosis. Of those 1,135 children without a documented ASD diagnosis, 628 (55%) were not known to receive ASD services in public school. Factors associated with not having a clinical diagnosis of ASD were non-White race, no intellectual disability, older age at first developmental concern, older age at first developmental evaluation, special education eligibility other than ASD, and need for fewer supports. These results highlight the importance of reducing disparities in the diagnosis of children with ASD characteristics so that appropriate interventions can be promoted across communities. Autism Res 2020, 13: 464-473. (c) 2019 International Society for AutismResearch,Wiley Periodicals, Inc. LAY SUMMARY: Children who did not have a clinical diagnosis of autism spectrum disorder (ASD) documented in health or education records were more likely to be non-White and have fewer developmental problems than children with a clinical diagnosis of ASD. They were brought to the attention of healthcare providers at older ages and needed fewer supports than children with a clinical diagnosis of ASD. All children with ASD symptoms who meet diagnostic criteria should be given a clinical diagnosis so they can receive treatment specific to their needs. En ligne : http://dx.doi.org/10.1002/aur.2255 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Autism Heterogeneity in a Densely Sampled U.S. Population: Results From the First 1,000 Participants in the RI-CART Study / Carolyn E. B. MCCORMICK in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.474-488 Titre : Autism Heterogeneity in a Densely Sampled U.S. Population: Results From the First 1,000 Participants in the RI-CART Study Type de document : Texte imprimé et/ou numérique Auteurs : Carolyn E. B. MCCORMICK, Auteur ; Brian C. KAVANAUGH, Auteur ; Danielle SIPSOCK, Auteur ; Giulia RIGHI, Auteur ; Lindsay M. OBERMAN, Auteur ; Daniel MORENO DE LUCA, Auteur ; Ece D. GAMSIZ UZUN, Auteur ; Carrie R. BEST, Auteur ; Beth A. JERSKEY, Auteur ; Joanne G. QUINN, Auteur ; Susan B. JEWEL, Auteur ; Pei-Chi WU, Auteur ; Rebecca L. MCLEAN, Auteur ; Todd P. LEVINE, Auteur ; Hasmik TOKADJIAN, Auteur ; Kayla A. PERKINS, Auteur ; Elaine B. CLARKE, Auteur ; Brittany DUNN, Auteur ; Alan H. GERBER, Auteur ; Elena J. TENENBAUM, Auteur ; Thomas F. ANDERS, Auteur Article en page(s) : p.474-488 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  comorbidity  female autism  population study  registry Index. décimale : PER Périodiques Résumé : The objective of this study was to establish a large, densely sampled, U.S. population-based cohort of people with autism spectrum disorder (ASD). The Rhode Island Consortium for Autism Research and Treatment (RI-CART) represents a unique public-private-academic collaboration involving all major points of service for families in Rhode Island affected by ASD. Diagnosis was based on direct behavioral observation via the Autism Diagnostic Observation Schedule, Second Edition. For the first 1,000 participants, ages ranged from 21 months to 64 years. Using Geographic Information System and published prevalence rates, the overall cohort is estimated to represent between 20% and 49% of pediatric age persons in Rhode Island with ASD, with demographics representative of U.S. Census. We observed a high rate of co-occurring medical and psychiatric conditions in affected individuals. Among the most prominent findings of immediate clinical importance, we found that females received a first diagnosis of ASD at a later age than males, potentially due to more advanced language abilities in females with ASD. In summary, this is the first analysis of a large, population-based U.S. cohort with ASD. Given the depth of sampling, the RI-CART study reflects an important new resource for studying ASD in a representative U.S. population. Psychiatric and medical comorbidities in ASD constitute a substantial burden and warrant adequate attention as part of overall treatment. Our study also suggests that new strategies for earlier diagnosis of ASD in females may be warranted. Autism Res 2020, 13: 474-488. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The Rhode Island Consortium for Autism Research and Treatment (RI-CART) represents a unique public-private-academic collaboration involving all major points of service for families in Rhode Island affected by autism spectrum disorder (ASD). In this article, we provide results from the first 1,000 participants, estimated to represent >20% of affected families in the state. Importantly, we find a later age at first diagnosis of ASD in females, which potentially calls attention to the need for improved early diagnosis in girls. Also, we report a high rate of co-occurring medical and psychiatric conditions in affected individuals. En ligne : http://dx.doi.org/10.1002/aur.2261 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Autism Heterogeneity in a Densely Sampled U.S. Population: Results From the First 1,000 Participants in the RI-CART Study [Texte imprimé et/ou numérique] / Carolyn E. B. MCCORMICK, Auteur ; Brian C. KAVANAUGH, Auteur ; Danielle SIPSOCK, Auteur ; Giulia RIGHI, Auteur ; Lindsay M. OBERMAN, Auteur ; Daniel MORENO DE LUCA, Auteur ; Ece D. GAMSIZ UZUN, Auteur ; Carrie R. BEST, Auteur ; Beth A. JERSKEY, Auteur ; Joanne G. QUINN, Auteur ; Susan B. JEWEL, Auteur ; Pei-Chi WU, Auteur ; Rebecca L. MCLEAN, Auteur ; Todd P. LEVINE, Auteur ; Hasmik TOKADJIAN, Auteur ; Kayla A. PERKINS, Auteur ; Elaine B. CLARKE, Auteur ; Brittany DUNN, Auteur ; Alan H. GERBER, Auteur ; Elena J. TENENBAUM, Auteur ; Thomas F. ANDERS, Auteur . - p.474-488. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.474-488 Mots-clés : autism spectrum disorder  comorbidity  female autism  population study  registry Index. décimale : PER Périodiques Résumé : The objective of this study was to establish a large, densely sampled, U.S. population-based cohort of people with autism spectrum disorder (ASD). The Rhode Island Consortium for Autism Research and Treatment (RI-CART) represents a unique public-private-academic collaboration involving all major points of service for families in Rhode Island affected by ASD. Diagnosis was based on direct behavioral observation via the Autism Diagnostic Observation Schedule, Second Edition. For the first 1,000 participants, ages ranged from 21 months to 64 years. Using Geographic Information System and published prevalence rates, the overall cohort is estimated to represent between 20% and 49% of pediatric age persons in Rhode Island with ASD, with demographics representative of U.S. Census. We observed a high rate of co-occurring medical and psychiatric conditions in affected individuals. Among the most prominent findings of immediate clinical importance, we found that females received a first diagnosis of ASD at a later age than males, potentially due to more advanced language abilities in females with ASD. In summary, this is the first analysis of a large, population-based U.S. cohort with ASD. Given the depth of sampling, the RI-CART study reflects an important new resource for studying ASD in a representative U.S. population. Psychiatric and medical comorbidities in ASD constitute a substantial burden and warrant adequate attention as part of overall treatment. Our study also suggests that new strategies for earlier diagnosis of ASD in females may be warranted. Autism Res 2020, 13: 474-488. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The Rhode Island Consortium for Autism Research and Treatment (RI-CART) represents a unique public-private-academic collaboration involving all major points of service for families in Rhode Island affected by autism spectrum disorder (ASD). In this article, we provide results from the first 1,000 participants, estimated to represent >20% of affected families in the state. Importantly, we find a later age at first diagnosis of ASD in females, which potentially calls attention to the need for improved early diagnosis in girls. Also, we report a high rate of co-occurring medical and psychiatric conditions in affected individuals. En ligne : http://dx.doi.org/10.1002/aur.2261 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Development of the Behavioral Inflexibility Scale for Children with Autism Spectrum Disorder and Other Developmental Disabilities / Luc LECAVALIER in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.489-499 Titre : Development of the Behavioral Inflexibility Scale for Children with Autism Spectrum Disorder and Other Developmental Disabilities Type de document : Texte imprimé et/ou numérique Auteurs : Luc LECAVALIER, Auteur ; James W. BODFISH, Auteur ; Clare HARROP, Auteur ; Allison WHITTEN, Auteur ; Desiree R. JONES, Auteur ; Jill PRITCHETT, Auteur ; Richard FALDOWSKI, Auteur ; Brian A. BOYD, Auteur Article en page(s) : p.489-499 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  behavior inflexibility  development  measurement  outcome  repetitive behavior Index. décimale : PER Périodiques Résumé : Behavior inflexibility (BI) refers to rigid patterns of behavior that contrast with the need to be adaptable to changing environmental demands. We developed a parent-reported outcome measure of BI for children with autism spectrum disorder (ASD) and other developmental disabilities with a multi-step iterative process. A pool of 62 candidate items was generated through expert panel feedback, review of existing scales and focus groups. A consensus process was used to generate the final 38 items. Parents of 943 children (age range, 3-18 years; average, 11.4 years; 79% boys) with ASD completed an online survey. One hundred thirty-three parents rated their child twice within 3 weeks (average = 16.5 days). A series of factor analyses suggested that the 38 items measured a single construct. Scores had a weak correlation with level of functioning (-0.12) and did not differ based on sex. Scores had a negligible correlation with age (-0.07), although measurement invariance was not supported. The mean total score for the Behavioral Inflexibility Scale (BIS) was normally distributed. Internal consistency was alpha = 0.97 and temporal stability was r = 0.92. Correlations with parent ratings on the subscales of the Repetitive Behavior Scale-Revised varied from 0.48 to 0.89. The correlation with parent ratings on the Social Communication Questionnaire total score was 0.52. Our data show that BI in children with ASD ranges significantly from mild to severe and that the 38-item BIS is valid and reliable. Autism Res 2020, 13: 489-499. (c) 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: We developed a parent-completed rating scale of behavior inflexibility (BI) for children with developmental disabilities using a multistep process. The Behavioral Inflexibility Scale (BIS) contains 38 questions rated on a 6-point scale. Parents of 943 children with autism spectrum disorder (ASD) completed an online survey. We examined associations between the BIS and other scales and demographic variables. The BIS is valid and reliable. BI in children with ASD ranges from mild to severe. En ligne : http://dx.doi.org/10.1002/aur.2257 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Development of the Behavioral Inflexibility Scale for Children with Autism Spectrum Disorder and Other Developmental Disabilities [Texte imprimé et/ou numérique] / Luc LECAVALIER, Auteur ; James W. BODFISH, Auteur ; Clare HARROP, Auteur ; Allison WHITTEN, Auteur ; Desiree R. JONES, Auteur ; Jill PRITCHETT, Auteur ; Richard FALDOWSKI, Auteur ; Brian A. BOYD, Auteur . - p.489-499. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.489-499 Mots-clés : autism spectrum disorder  behavior inflexibility  development  measurement  outcome  repetitive behavior Index. décimale : PER Périodiques Résumé : Behavior inflexibility (BI) refers to rigid patterns of behavior that contrast with the need to be adaptable to changing environmental demands. We developed a parent-reported outcome measure of BI for children with autism spectrum disorder (ASD) and other developmental disabilities with a multi-step iterative process. A pool of 62 candidate items was generated through expert panel feedback, review of existing scales and focus groups. A consensus process was used to generate the final 38 items. Parents of 943 children (age range, 3-18 years; average, 11.4 years; 79% boys) with ASD completed an online survey. One hundred thirty-three parents rated their child twice within 3 weeks (average = 16.5 days). A series of factor analyses suggested that the 38 items measured a single construct. Scores had a weak correlation with level of functioning (-0.12) and did not differ based on sex. Scores had a negligible correlation with age (-0.07), although measurement invariance was not supported. The mean total score for the Behavioral Inflexibility Scale (BIS) was normally distributed. Internal consistency was alpha = 0.97 and temporal stability was r = 0.92. Correlations with parent ratings on the subscales of the Repetitive Behavior Scale-Revised varied from 0.48 to 0.89. The correlation with parent ratings on the Social Communication Questionnaire total score was 0.52. Our data show that BI in children with ASD ranges significantly from mild to severe and that the 38-item BIS is valid and reliable. Autism Res 2020, 13: 489-499. (c) 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: We developed a parent-completed rating scale of behavior inflexibility (BI) for children with developmental disabilities using a multistep process. The Behavioral Inflexibility Scale (BIS) contains 38 questions rated on a 6-point scale. Parents of 943 children with autism spectrum disorder (ASD) completed an online survey. We examined associations between the BIS and other scales and demographic variables. The BIS is valid and reliable. BI in children with ASD ranges from mild to severe. En ligne : http://dx.doi.org/10.1002/aur.2257 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421