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Auteur Jean FRAZIER |
Documents disponibles écrits par cet auteur (2)
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A multi-omic approach identifies an autism spectrum disorder (ASD) regulatory complex of functional epimutations in placentas from children born preterm / Anastasia N. FREEDMAN in Autism Research, 16-5 (May 2023)
[article]
Titre : A multi-omic approach identifies an autism spectrum disorder (ASD) regulatory complex of functional epimutations in placentas from children born preterm Type de document : Texte imprimé et/ou numérique Auteurs : Anastasia N. FREEDMAN, Auteur ; Jeliyah CLARK, Auteur ; Lauren A. EAVES, Auteur ; Kyle ROELL, Auteur ; Ali ORAN, Auteur ; Lauren KOVAL, Auteur ; Julia RAGER, Auteur ; Hudson P. SANTOS JR., Auteur ; Karl KUBAN, Auteur ; Robert M. JOSEPH, Auteur ; Jean FRAZIER, Auteur ; Carmen J. MARSIT, Auteur ; Amber A. BURT, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur Article en page(s) : p.918-934 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Children born preterm are at heightened risk of neurodevelopmental impairments, including Autism Spectrum Disorder (ASD). The placenta is a key regulator of neurodevelopmental processes, though the precise underlying molecular mechanisms remain unclear. Here, we employed a multi-omic approach to identify placental transcriptomic and epigenetic modifications related to ASD diagnosis at age 10, among children born preterm. Working with the extremely low gestational age (ELGAN) cohort, we hypothesized that a pro-inflammatory placental environment would be predictive of ASD diagnosis at age 10. Placental messenger RNA (mRNA) expression, CpG methylation, and microRNA (miRNA) expression were compared among 368 ELGANs (28 children diagnosed with ASD and 340 children without ASD). A total of 111 genes displayed expression levels in the placenta that were associated with ASD. Within these ASD-associated genes is an ASD regulatory complex comprising key genes that predicted ASD case status. Genes with expression that predicted ASD case status included Ewing Sarcoma Breakpoint Region 1 (EWSR1) (OR: 6.57 (95% CI: 2.34, 23.58)) and Bromodomain Adjacent To Zinc Finger Domain 2A (BAZ2A) (OR: 0.12 (95% CI: 0.03, 0.35)). Moreover, of the 111 ASD-associated genes, nine (8.1%) displayed associations with CpG methylation levels, while 14 (12.6%) displayed associations with miRNA expression levels. Among these, LRR Binding FLII Interacting Protein 1 (LRRFIP1) was identified as being under the control of both CpG methylation and miRNAs, displaying an OR of 0.42 (95% CI: 0.17, 0.95). This gene, as well as others identified as having functional epimutations, plays a critical role in immune system regulation and inflammatory response. In summary, a multi-omic approach was used to identify functional epimutations in the placenta that are associated with the development of ASD in children born preterm, highlighting future avenues for intervention. En ligne : http://dx.doi.org/https://doi.org/10.1002/aur.2915 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=503
in Autism Research > 16-5 (May 2023) . - p.918-934[article] A multi-omic approach identifies an autism spectrum disorder (ASD) regulatory complex of functional epimutations in placentas from children born preterm [Texte imprimé et/ou numérique] / Anastasia N. FREEDMAN, Auteur ; Jeliyah CLARK, Auteur ; Lauren A. EAVES, Auteur ; Kyle ROELL, Auteur ; Ali ORAN, Auteur ; Lauren KOVAL, Auteur ; Julia RAGER, Auteur ; Hudson P. SANTOS JR., Auteur ; Karl KUBAN, Auteur ; Robert M. JOSEPH, Auteur ; Jean FRAZIER, Auteur ; Carmen J. MARSIT, Auteur ; Amber A. BURT, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur . - p.918-934.
Langues : Anglais (eng)
in Autism Research > 16-5 (May 2023) . - p.918-934
Index. décimale : PER Périodiques Résumé : Abstract Children born preterm are at heightened risk of neurodevelopmental impairments, including Autism Spectrum Disorder (ASD). The placenta is a key regulator of neurodevelopmental processes, though the precise underlying molecular mechanisms remain unclear. Here, we employed a multi-omic approach to identify placental transcriptomic and epigenetic modifications related to ASD diagnosis at age 10, among children born preterm. Working with the extremely low gestational age (ELGAN) cohort, we hypothesized that a pro-inflammatory placental environment would be predictive of ASD diagnosis at age 10. Placental messenger RNA (mRNA) expression, CpG methylation, and microRNA (miRNA) expression were compared among 368 ELGANs (28 children diagnosed with ASD and 340 children without ASD). A total of 111 genes displayed expression levels in the placenta that were associated with ASD. Within these ASD-associated genes is an ASD regulatory complex comprising key genes that predicted ASD case status. Genes with expression that predicted ASD case status included Ewing Sarcoma Breakpoint Region 1 (EWSR1) (OR: 6.57 (95% CI: 2.34, 23.58)) and Bromodomain Adjacent To Zinc Finger Domain 2A (BAZ2A) (OR: 0.12 (95% CI: 0.03, 0.35)). Moreover, of the 111 ASD-associated genes, nine (8.1%) displayed associations with CpG methylation levels, while 14 (12.6%) displayed associations with miRNA expression levels. Among these, LRR Binding FLII Interacting Protein 1 (LRRFIP1) was identified as being under the control of both CpG methylation and miRNAs, displaying an OR of 0.42 (95% CI: 0.17, 0.95). This gene, as well as others identified as having functional epimutations, plays a critical role in immune system regulation and inflammatory response. In summary, a multi-omic approach was used to identify functional epimutations in the placenta that are associated with the development of ASD in children born preterm, highlighting future avenues for intervention. En ligne : http://dx.doi.org/https://doi.org/10.1002/aur.2915 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=503 The SOFIA Study: Negative Multi-center Study of Low Dose Fluoxetine on Repetitive Behaviors in Children and Adolescents with Autistic Disorder / Paul HERSCU in Journal of Autism and Developmental Disorders, 50-9 (September 2020)
[article]
Titre : The SOFIA Study: Negative Multi-center Study of Low Dose Fluoxetine on Repetitive Behaviors in Children and Adolescents with Autistic Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Paul HERSCU, Auteur ; Benjamin L. HANDEN, Auteur ; L. Eugene ARNOLD, Auteur ; Michael F. SNAPE, Auteur ; Joel D. BREGMAN, Auteur ; Lawrence GINSBERG, Auteur ; Robert HENDREN, Auteur ; Alexander KOLEVZON, Auteur ; Raun MELMED, Auteur ; Mark MINTZ, Auteur ; Nancy MINSHEW, Auteur ; Linmarie SIKICH, Auteur ; Ashraf ATTALLA, Auteur ; Brian KING, Auteur ; Thomas OWLEY, Auteur ; Ann CHILDRESS, Auteur ; Harry CHUGANI, Auteur ; Jean FRAZIER, Auteur ; Charles CARTWRIGHT, Auteur ; Tanya MURPHY, Auteur Article en page(s) : p.3233-3244 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Repetitive behavior Selective seretonin reuptake inhibitor Index. décimale : PER Périodiques Résumé : Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that reduces obsessive-compulsive symptoms. There is limited evidence supporting its efficacy for repetitive behaviors (RRBs) in autistic spectrum disorder (ASD). We conducted a randomized controlled trial (RCT) of fluoxetine in 158 individuals with ASD (5-17 years). Following 14 treatment weeks (mean dose 11.8 mg/day), no significant differences were noted on the Children's Yale-Brown Obsessive Compulsive Scale; the proportion of responders was similar (fluoxetine: 36%; placebo: 41%). There were similar rates of AEs (e.g., insomnia, diarrhea, vomiting); high rates of activation were reported in both groups (fluoxetine: 42%; placebo: 45%). Overly cautious dosing/duration may have prevented attainment of a therapeutic level. Results are consistent with other SSRI RCTs treating RRBs in ASD.Trial Registration: clinicaltrials.gov Identifier: NCT00515320. En ligne : http://dx.doi.org/10.1007/s10803-019-04120-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=430
in Journal of Autism and Developmental Disorders > 50-9 (September 2020) . - p.3233-3244[article] The SOFIA Study: Negative Multi-center Study of Low Dose Fluoxetine on Repetitive Behaviors in Children and Adolescents with Autistic Disorder [Texte imprimé et/ou numérique] / Paul HERSCU, Auteur ; Benjamin L. HANDEN, Auteur ; L. Eugene ARNOLD, Auteur ; Michael F. SNAPE, Auteur ; Joel D. BREGMAN, Auteur ; Lawrence GINSBERG, Auteur ; Robert HENDREN, Auteur ; Alexander KOLEVZON, Auteur ; Raun MELMED, Auteur ; Mark MINTZ, Auteur ; Nancy MINSHEW, Auteur ; Linmarie SIKICH, Auteur ; Ashraf ATTALLA, Auteur ; Brian KING, Auteur ; Thomas OWLEY, Auteur ; Ann CHILDRESS, Auteur ; Harry CHUGANI, Auteur ; Jean FRAZIER, Auteur ; Charles CARTWRIGHT, Auteur ; Tanya MURPHY, Auteur . - p.3233-3244.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 50-9 (September 2020) . - p.3233-3244
Mots-clés : Autism spectrum disorder Repetitive behavior Selective seretonin reuptake inhibitor Index. décimale : PER Périodiques Résumé : Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that reduces obsessive-compulsive symptoms. There is limited evidence supporting its efficacy for repetitive behaviors (RRBs) in autistic spectrum disorder (ASD). We conducted a randomized controlled trial (RCT) of fluoxetine in 158 individuals with ASD (5-17 years). Following 14 treatment weeks (mean dose 11.8 mg/day), no significant differences were noted on the Children's Yale-Brown Obsessive Compulsive Scale; the proportion of responders was similar (fluoxetine: 36%; placebo: 41%). There were similar rates of AEs (e.g., insomnia, diarrhea, vomiting); high rates of activation were reported in both groups (fluoxetine: 42%; placebo: 45%). Overly cautious dosing/duration may have prevented attainment of a therapeutic level. Results are consistent with other SSRI RCTs treating RRBs in ASD.Trial Registration: clinicaltrials.gov Identifier: NCT00515320. En ligne : http://dx.doi.org/10.1007/s10803-019-04120-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=430