Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations / M. ULJAREVIC in Journal of Autism and Developmental Disorders, 52-1 (January 2022)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 52-1 (January 2022) . - p.414-422 Titre : Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations Type de document : Texte imprimé et/ou numérique Auteurs : M. ULJAREVIC, Auteur ; T. W. FRAZIER, Auteur ; G. RACHED, Auteur ; Robyn M. BUSCH, Auteur ; P. KLAAS, Auteur ; S. SRIVASTAVA, Auteur ; J. A. MARTINEZ-AGOSTO, Auteur ; M. SAHIN, Auteur ; C. ENG, Auteur ; A. Y. HARDAN, Auteur Article en page(s) : p.414-422 Langues : Anglais (eng) Mots-clés : Anxiety/genetics  Autism Spectrum Disorder/genetics  Child  Child, Preschool  Germ Cells  Germ-Line Mutation  Humans  PTEN Phosphohydrolase/genetics  Parents  Anxiety  Executive functioning  Insistence on sameness  Macrocephaly  Pten Index. décimale : PER Périodiques Résumé : This study aimed to characterize the relationship between insistence on sameness (IS), executive functioning (EF) and anxiety among individuals with PTEN mutations and individuals with macrocephalic ASD. The sample included 38 individuals with PTEN mutation and ASD diagnosis (PTEN-ASD; M(age)?=?8.93 years, SD(age)?=?4.75), 23 with PTEN mutation without ASD (PTEN-no ASD; M(age)?=?8.94 years; SD(age)?=?4.85) and 25 with ASD and macrocephaly but with no PTEN mutation (Macro-ASD; M(age)?=?11.99 years; SD(age)?=?5.15). The final model accounted for 45.7% of variance in IS, with Set-Shifting EF subdomain as a unique independent predictor (t?=?4.12, p? En ligne : http://dx.doi.org/10.1007/s10803-021-04881-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455 [article] Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations [Texte imprimé et/ou numérique] / M. ULJAREVIC, Auteur ; T. W. FRAZIER, Auteur ; G. RACHED, Auteur ; Robyn M. BUSCH, Auteur ; P. KLAAS, Auteur ; S. SRIVASTAVA, Auteur ; J. A. MARTINEZ-AGOSTO, Auteur ; M. SAHIN, Auteur ; C. ENG, Auteur ; A. Y. HARDAN, Auteur . - p.414-422. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 52-1 (January 2022) . - p.414-422 Mots-clés : Anxiety/genetics  Autism Spectrum Disorder/genetics  Child  Child, Preschool  Germ Cells  Germ-Line Mutation  Humans  PTEN Phosphohydrolase/genetics  Parents  Anxiety  Executive functioning  Insistence on sameness  Macrocephaly  Pten Index. décimale : PER Périodiques Résumé : This study aimed to characterize the relationship between insistence on sameness (IS), executive functioning (EF) and anxiety among individuals with PTEN mutations and individuals with macrocephalic ASD. The sample included 38 individuals with PTEN mutation and ASD diagnosis (PTEN-ASD; M(age)?=?8.93 years, SD(age)?=?4.75), 23 with PTEN mutation without ASD (PTEN-no ASD; M(age)?=?8.94 years; SD(age)?=?4.85) and 25 with ASD and macrocephaly but with no PTEN mutation (Macro-ASD; M(age)?=?11.99 years; SD(age)?=?5.15). The final model accounted for 45.7% of variance in IS, with Set-Shifting EF subdomain as a unique independent predictor (t?=?4.12, p? En ligne : http://dx.doi.org/10.1007/s10803-021-04881-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455

Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism / Thomas W FRAZIER in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 5p. Titre : Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism Type de document : Texte imprimé et/ou numérique Auteurs : Thomas W FRAZIER, Auteur ; Ritika JAINI, Auteur ; Robyn M. BUSCH, Auteur ; Matthew WOLF, Auteur ; Tammy SADLER, Auteur ; Patricia KLAAS, Auteur ; Antonio Y. HARDAN, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Mustafa SAHIN, Auteur ; Chari ENG, Auteur Article en page(s) : 5p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Behavior  Cognition  Molecular  Pten  Protein Index. décimale : PER Périodiques Résumé : BACKGROUND: PTEN is a well-established risk gene for autism spectrum disorder (ASD). Yet, little is known about how PTEN mutations and associated molecular processes influence neurobehavioral function in mutation carriers with (PTEN-ASD) and without ASD (PTEN no-ASD). The primary aim of the present study was to examine group differences in peripheral blood-derived PTEN pathway protein levels between PTEN-ASD, PTEN no-ASD, and idiopathic macrocephalic ASD patients (macro-ASD). Secondarily, associations between protein levels and neurobehavioral functions were examined in the full cohort. METHODS: Patients were recruited at four tertiary medical centers. Peripheral blood-derived protein levels from canonical PTEN pathways (PI3K/AKT and MAPK/ERK) were analyzed using Western blot analyses blinded to genotype and ASD status. Neurobehavioral measures included standardized assessments of global cognitive ability and multiple neurobehavioral domains. Analysis of variance models examined group differences in demographic, neurobehavioral, and protein measures. Bivariate correlations, structural models, and statistical learning procedures estimated associations between molecular and neurobehavioral variables. To complement patient data, Western blots for downstream proteins were generated to evaluate canonical PTEN pathways in the PTEN-m3m4 mouse model. RESULTS: Participants included 61 patients (25 PTEN-ASD, 16 PTEN no-ASD, and 20 macro-ASD). Decreased PTEN and S6 were observed in both PTEN mutation groups. Reductions in MnSOD and increases in P-S6 were observed in ASD groups. Elevated neural P-AKT/AKT and P-S6/S6 from PTEN murine models parallel our patient observations. Patient PTEN and AKT levels were independently associated with global cognitive ability, and p27 expression was associated with frontal sub-cortical functions. As a group, molecular measures added significant predictive value to several neurobehavioral domains over and above PTEN mutation status. LIMITATIONS: Sample sizes were small, precluding within-group analyses. Protein and neurobehavioral data were limited to a single evaluation. A small number of patients were excluded with invalid protein data, and cognitively impaired patients had missing data on some assessments. CONCLUSIONS: Several canonical PTEN pathway molecules appear to influence the presence of ASD and modify neurobehavioral function in PTEN mutation patients. Protein assays of the PTEN pathway may be useful for predicting neurobehavioral outcomes in PTEN patients. Future longitudinal analyses are needed to replicate these findings and evaluate within-group relationships between protein and neurobehavioral measures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02461446. En ligne : http://dx.doi.org/10.1186/s13229-020-00406-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism [Texte imprimé et/ou numérique] / Thomas W FRAZIER, Auteur ; Ritika JAINI, Auteur ; Robyn M. BUSCH, Auteur ; Matthew WOLF, Auteur ; Tammy SADLER, Auteur ; Patricia KLAAS, Auteur ; Antonio Y. HARDAN, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Mustafa SAHIN, Auteur ; Chari ENG, Auteur . - 5p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 5p. Mots-clés : Autism spectrum disorder  Behavior  Cognition  Molecular  Pten  Protein Index. décimale : PER Périodiques Résumé : BACKGROUND: PTEN is a well-established risk gene for autism spectrum disorder (ASD). Yet, little is known about how PTEN mutations and associated molecular processes influence neurobehavioral function in mutation carriers with (PTEN-ASD) and without ASD (PTEN no-ASD). The primary aim of the present study was to examine group differences in peripheral blood-derived PTEN pathway protein levels between PTEN-ASD, PTEN no-ASD, and idiopathic macrocephalic ASD patients (macro-ASD). Secondarily, associations between protein levels and neurobehavioral functions were examined in the full cohort. METHODS: Patients were recruited at four tertiary medical centers. Peripheral blood-derived protein levels from canonical PTEN pathways (PI3K/AKT and MAPK/ERK) were analyzed using Western blot analyses blinded to genotype and ASD status. Neurobehavioral measures included standardized assessments of global cognitive ability and multiple neurobehavioral domains. Analysis of variance models examined group differences in demographic, neurobehavioral, and protein measures. Bivariate correlations, structural models, and statistical learning procedures estimated associations between molecular and neurobehavioral variables. To complement patient data, Western blots for downstream proteins were generated to evaluate canonical PTEN pathways in the PTEN-m3m4 mouse model. RESULTS: Participants included 61 patients (25 PTEN-ASD, 16 PTEN no-ASD, and 20 macro-ASD). Decreased PTEN and S6 were observed in both PTEN mutation groups. Reductions in MnSOD and increases in P-S6 were observed in ASD groups. Elevated neural P-AKT/AKT and P-S6/S6 from PTEN murine models parallel our patient observations. Patient PTEN and AKT levels were independently associated with global cognitive ability, and p27 expression was associated with frontal sub-cortical functions. As a group, molecular measures added significant predictive value to several neurobehavioral domains over and above PTEN mutation status. LIMITATIONS: Sample sizes were small, precluding within-group analyses. Protein and neurobehavioral data were limited to a single evaluation. A small number of patients were excluded with invalid protein data, and cognitively impaired patients had missing data on some assessments. CONCLUSIONS: Several canonical PTEN pathway molecules appear to influence the presence of ASD and modify neurobehavioral function in PTEN mutation patients. Protein assays of the PTEN pathway may be useful for predicting neurobehavioral outcomes in PTEN patients. Future longitudinal analyses are needed to replicate these findings and evaluate within-group relationships between protein and neurobehavioral measures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02461446. En ligne : http://dx.doi.org/10.1186/s13229-020-00406-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Remote monitoring of social attention in neurogenetic syndromes and idiopathic neurodevelopmental disability / Thomas W. FRAZIER ; Robyn M. BUSCH ; Patricia KLAAS ; Katherine Lachlan ; Shafali JESTE ; Alexander KOLEVZON ; Eva LOTH ; Jacqueline Harris ; Tom Pepper ; Kristin Anthony ; J. Michael Graglia ; Kathryn Helde ; Christal Delagrammatikas ; Sandra Bedrosian-Sermone ; Constance Smith-Hicks ; Mustafa SAHIN ; Eric A. YOUNGSTROM ; Charis ENG ; Lacey CHETCUTI ; Antonio Y. HARDAN ; Mirko ULJAREVIC in Autism Research, 18-2 (February 2025)  

Public ISBD [article]  inAutism Research > 18-2 (February 2025) . - p.334-348 Titre : Remote monitoring of social attention in neurogenetic syndromes and idiopathic neurodevelopmental disability : Autism Research Type de document : Texte imprimé et/ou numérique Auteurs : Thomas W. FRAZIER, Auteur ; Robyn M. BUSCH, Auteur ; Patricia KLAAS, Auteur ; Katherine Lachlan, Auteur ; Shafali JESTE, Auteur ; Alexander KOLEVZON, Auteur ; Eva LOTH, Auteur ; Jacqueline Harris, Auteur ; Tom Pepper, Auteur ; Kristin Anthony, Auteur ; J. Michael Graglia, Auteur ; Kathryn Helde, Auteur ; Christal Delagrammatikas, Auteur ; Sandra Bedrosian-Sermone, Auteur ; Constance Smith-Hicks, Auteur ; Mustafa SAHIN, Auteur ; Eric A. YOUNGSTROM, Auteur ; Charis ENG, Auteur ; Lacey CHETCUTI, Auteur ; Antonio Y. HARDAN, Auteur ; Mirko ULJAREVIC, Auteur Article en page(s) : p.334-348 Langues : Anglais (eng) Mots-clés : autism spectrum disorder online reliability remote monitoring social attention validity Index. décimale : PER Périodiques Résumé : Abstract Social attention is a key aspect of neurodevelopment and is significantly altered in neurodevelopmental genetic syndromes and many individuals with idiopathic autism spectrum disorder (ASD). The primary aim of the present study was to examine the psychometric properties of webcam-collected social attention measurements, including four new specific aspects of social attention, in three genetic syndromes (PTEN Hamartoma Tumor Syndrome?PHTS; Malan Syndrome?NFIX; and SYNGAP1-related disorder?SYNGAP1), a mixed group of other neurodevelopmental genetic syndromes (Other NDGS), and individuals with a range of idiopathic neurodevelopmental disorder (NDD). The secondary aim was to evaluate the construct validity of these social attention measurements, including evaluating known-groups validity across study groups and concurrent validity for separating ASD and non-ASD cases. Participants (N?=?467, age 3?45; PHTS n?=?102, NFIX n?=?23, SYNGAP1 n?=?42, other NDGS n?=?63, idiopathic NDD n?=?53, neurotypical siblings n?=?71, and unrelated neurotypical controls n?=?113) completed a 4-min online-administered social attention paradigm that includes a variety of distinct stimuli at three timepoints (baseline, 1-month, and 4-month follow-up). Social attention measures had good scale and test?retest reliability, with the exception of measures of non-social preference and face-specific processing. Unique patterns of social attention emerged across study groups, with near neurotypical levels in PHTS and weaker social attention in NFIX and SYNGAP1 relative to controls. Global social attention had good accuracy in detecting ASD within NDGS participants. Remote monitoring social attention, including distinct aspects of social attention, may be useful for characterizing phenotypic profiles and tracking the natural history of distinct NDGS and idiopathic NDD as well as identifying ASD within NDGS. Given their reproducibility and stability, global social attention and several distinct social attention measures may be useful outcomes for future clinical trials. En ligne : https://doi.org/10.1002/aur.3290 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=547 [article] Remote monitoring of social attention in neurogenetic syndromes and idiopathic neurodevelopmental disability : Autism Research [Texte imprimé et/ou numérique] / Thomas W. FRAZIER, Auteur ; Robyn M. BUSCH, Auteur ; Patricia KLAAS, Auteur ; Katherine Lachlan, Auteur ; Shafali JESTE, Auteur ; Alexander KOLEVZON, Auteur ; Eva LOTH, Auteur ; Jacqueline Harris, Auteur ; Tom Pepper, Auteur ; Kristin Anthony, Auteur ; J. Michael Graglia, Auteur ; Kathryn Helde, Auteur ; Christal Delagrammatikas, Auteur ; Sandra Bedrosian-Sermone, Auteur ; Constance Smith-Hicks, Auteur ; Mustafa SAHIN, Auteur ; Eric A. YOUNGSTROM, Auteur ; Charis ENG, Auteur ; Lacey CHETCUTI, Auteur ; Antonio Y. HARDAN, Auteur ; Mirko ULJAREVIC, Auteur . - p.334-348. Langues : Anglais (eng) in Autism Research > 18-2 (February 2025) . - p.334-348 Mots-clés : autism spectrum disorder online reliability remote monitoring social attention validity Index. décimale : PER Périodiques Résumé : Abstract Social attention is a key aspect of neurodevelopment and is significantly altered in neurodevelopmental genetic syndromes and many individuals with idiopathic autism spectrum disorder (ASD). The primary aim of the present study was to examine the psychometric properties of webcam-collected social attention measurements, including four new specific aspects of social attention, in three genetic syndromes (PTEN Hamartoma Tumor Syndrome?PHTS; Malan Syndrome?NFIX; and SYNGAP1-related disorder?SYNGAP1), a mixed group of other neurodevelopmental genetic syndromes (Other NDGS), and individuals with a range of idiopathic neurodevelopmental disorder (NDD). The secondary aim was to evaluate the construct validity of these social attention measurements, including evaluating known-groups validity across study groups and concurrent validity for separating ASD and non-ASD cases. Participants (N?=?467, age 3?45; PHTS n?=?102, NFIX n?=?23, SYNGAP1 n?=?42, other NDGS n?=?63, idiopathic NDD n?=?53, neurotypical siblings n?=?71, and unrelated neurotypical controls n?=?113) completed a 4-min online-administered social attention paradigm that includes a variety of distinct stimuli at three timepoints (baseline, 1-month, and 4-month follow-up). Social attention measures had good scale and test?retest reliability, with the exception of measures of non-social preference and face-specific processing. Unique patterns of social attention emerged across study groups, with near neurotypical levels in PHTS and weaker social attention in NFIX and SYNGAP1 relative to controls. Global social attention had good accuracy in detecting ASD within NDGS participants. Remote monitoring social attention, including distinct aspects of social attention, may be useful for characterizing phenotypic profiles and tracking the natural history of distinct NDGS and idiopathic NDD as well as identifying ASD within NDGS. Given their reproducibility and stability, global social attention and several distinct social attention measures may be useful outcomes for future clinical trials. En ligne : https://doi.org/10.1002/aur.3290 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=547

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