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

Development and psychometric evaluation of a psychosocial quality-of-life questionnaire for individuals with autism and related developmental disorders / Leslie A MARKOWITZ in Autism, 20-7 (October 2016)  

Public ISBD [article]  inAutism > 20-7 (October 2016) . - p.832-844 Titre : Development and psychometric evaluation of a psychosocial quality-of-life questionnaire for individuals with autism and related developmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : Leslie A MARKOWITZ, Auteur ; Charina REYES, Auteur ; Rebecca A EMBACHER, Auteur ; Leslie L SPEER, Auteur ; Nancy ROIZEN, Auteur ; Thomas W FRAZIER, Auteur Article en page(s) : p.832-844 Langues : Anglais (eng) Mots-clés : autism  behavior problems  child functioning  developmental disabilities  family functioning  quality of life Index. décimale : PER Périodiques Résumé : This study investigated the psychometric properties of the Child and Family Quality of Life scale, a measure of psychosocial quality of life in those with autism and related developmental disorders. Parents of 212 children suspected of autism spectrum disorder completed the Child and Family Quality of Life prior to a diagnostic evaluation. Results indicated that the Child and Family Quality of Life measured six unique quality-of-life constructs (child, family/caregiver, financial, external support, partner relationship, and coping), had good reliability across score ranges and exhibited expected patterns of convergent validity. Caregivers of autism spectrum disorder–affected children reported reduced family quality of life prior to the time of diagnosis relative to caregivers of children with other developmental disabilities. The Child and Family Quality of Life is a brief, reliable measure for assessing psychosocial quality of life in families affected by developmental disability. This study is the first to demonstrate impairments in family quality of life early in the developmental course of autism spectrum disorder, prior to formal diagnosis. In addition to traditional child-focused intervention strategies, families with autism spectrum disorder–affected children require early, broad intervention strategies that positively impact the whole family. En ligne : http://dx.doi.org/10.1177/1362361315611382 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=293 [article] Development and psychometric evaluation of a psychosocial quality-of-life questionnaire for individuals with autism and related developmental disorders [Texte imprimé et/ou numérique] / Leslie A MARKOWITZ, Auteur ; Charina REYES, Auteur ; Rebecca A EMBACHER, Auteur ; Leslie L SPEER, Auteur ; Nancy ROIZEN, Auteur ; Thomas W FRAZIER, Auteur . - p.832-844. Langues : Anglais (eng) in Autism > 20-7 (October 2016) . - p.832-844 Mots-clés : autism  behavior problems  child functioning  developmental disabilities  family functioning  quality of life Index. décimale : PER Périodiques Résumé : This study investigated the psychometric properties of the Child and Family Quality of Life scale, a measure of psychosocial quality of life in those with autism and related developmental disorders. Parents of 212 children suspected of autism spectrum disorder completed the Child and Family Quality of Life prior to a diagnostic evaluation. Results indicated that the Child and Family Quality of Life measured six unique quality-of-life constructs (child, family/caregiver, financial, external support, partner relationship, and coping), had good reliability across score ranges and exhibited expected patterns of convergent validity. Caregivers of autism spectrum disorder–affected children reported reduced family quality of life prior to the time of diagnosis relative to caregivers of children with other developmental disabilities. The Child and Family Quality of Life is a brief, reliable measure for assessing psychosocial quality of life in families affected by developmental disability. This study is the first to demonstrate impairments in family quality of life early in the developmental course of autism spectrum disorder, prior to formal diagnosis. In addition to traditional child-focused intervention strategies, families with autism spectrum disorder–affected children require early, broad intervention strategies that positively impact the whole family. En ligne : http://dx.doi.org/10.1177/1362361315611382 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=293

Exploring Social Subtypes in Autism Spectrum Disorder: A Preliminary Study / Mirko ULJAREVIC in Autism Research, 13-8 (August 2020)  

Public ISBD [article]  inAutism Research > 13-8 (August 2020) . - p.1335-1342 Titre : Exploring Social Subtypes in Autism Spectrum Disorder: A Preliminary Study Type de document : Texte imprimé et/ou numérique Auteurs : Mirko ULJAREVIC, Auteur ; Jennifer M. PHILLIPS, Auteur ; Rachel K. SCHUCK, Auteur ; Salena SCHAPP, Auteur ; Elizabeth M. SOLOMON, Auteur ; Emma SALZMAN, Auteur ; Lauren ALLERHAND, Auteur ; Robin A. LIBOVE, Auteur ; Thomas W FRAZIER, Auteur ; Antonio Y. HARDAN, Auteur Article en page(s) : p.1335-1342 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  individual differences  social motivation  social processing Index. décimale : PER Périodiques Résumé : Impairments in social functioning are considered a hallmark diagnostic feature of autism spectrum disorder (ASD). Yet, individuals diagnosed with ASD vary widely with respect to specific presentation, severity, and course across different dimensions of this complex symptom domain. The aim of this investigation was to utilize the Stanford Social Dimensions Scale (SSDS), a newly developed quantitative measure providing parental perspective on their child's social abilities, in order to explore the existence of homogeneous subgroups of ASD individuals who share unique profiles across specific dimensions of the social domain. Parents of 164 individuals with ASD (35 females, 129 males; mean(age) = 7.54?years, SD = 3.85) completed the SSDS, the Social Responsiveness Scale (SRS-2) and the Child Behavior Checklist (CBCL). Data on children's verbal and nonverbal intellectual functioning (FSIQ) were also collected. The Latent Profile Analysis was used to classify participants according to the pattern of SSDS subscale scores (Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach). Five profiles were identified. Profiles did not differ in terms of chronological age nor gender distribution but showed distinct patterns of strengths and weaknesses across different social components rather than simply reflecting a severity gradient. Profiles were further differentiated in terms of cognitive ability, as well as ASD and internalizing symptom severity. The implications of current findings and the necessary further steps toward identifying subgroups of individuals with ASD who share particular constellation of strengths and weaknesses across key social domains as a way of informing personalized interventions are discussed. Autism Res 2020. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism spectrum disorder (ASD) vary greatly in terms of their social abilities and social motivation. However, researchers lack measures that can fully assess different components of social functioning. This paper provides initial evidence for capturing subgroups of individuals with ASD with specific strengths and weakness across different aspects of social functioning. Autism Res 2020, 13: 1335-1342. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2294 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=430 [article] Exploring Social Subtypes in Autism Spectrum Disorder: A Preliminary Study [Texte imprimé et/ou numérique] / Mirko ULJAREVIC, Auteur ; Jennifer M. PHILLIPS, Auteur ; Rachel K. SCHUCK, Auteur ; Salena SCHAPP, Auteur ; Elizabeth M. SOLOMON, Auteur ; Emma SALZMAN, Auteur ; Lauren ALLERHAND, Auteur ; Robin A. LIBOVE, Auteur ; Thomas W FRAZIER, Auteur ; Antonio Y. HARDAN, Auteur . - p.1335-1342. Langues : Anglais (eng) in Autism Research > 13-8 (August 2020) . - p.1335-1342 Mots-clés : autism spectrum disorder  individual differences  social motivation  social processing Index. décimale : PER Périodiques Résumé : Impairments in social functioning are considered a hallmark diagnostic feature of autism spectrum disorder (ASD). Yet, individuals diagnosed with ASD vary widely with respect to specific presentation, severity, and course across different dimensions of this complex symptom domain. The aim of this investigation was to utilize the Stanford Social Dimensions Scale (SSDS), a newly developed quantitative measure providing parental perspective on their child's social abilities, in order to explore the existence of homogeneous subgroups of ASD individuals who share unique profiles across specific dimensions of the social domain. Parents of 164 individuals with ASD (35 females, 129 males; mean(age) = 7.54?years, SD = 3.85) completed the SSDS, the Social Responsiveness Scale (SRS-2) and the Child Behavior Checklist (CBCL). Data on children's verbal and nonverbal intellectual functioning (FSIQ) were also collected. The Latent Profile Analysis was used to classify participants according to the pattern of SSDS subscale scores (Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach). Five profiles were identified. Profiles did not differ in terms of chronological age nor gender distribution but showed distinct patterns of strengths and weaknesses across different social components rather than simply reflecting a severity gradient. Profiles were further differentiated in terms of cognitive ability, as well as ASD and internalizing symptom severity. The implications of current findings and the necessary further steps toward identifying subgroups of individuals with ASD who share particular constellation of strengths and weaknesses across key social domains as a way of informing personalized interventions are discussed. Autism Res 2020. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism spectrum disorder (ASD) vary greatly in terms of their social abilities and social motivation. However, researchers lack measures that can fully assess different components of social functioning. This paper provides initial evidence for capturing subgroups of individuals with ASD with specific strengths and weakness across different aspects of social functioning. Autism Res 2020, 13: 1335-1342. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2294 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=430

The Suicidal Ideation Attributes Scale-Modified (SIDAS-M): Development and preliminary validation of a new scale for the measurement of suicidal ideation in autistic adults / Darren HEDLEY in Autism, 27-4 (May 2023)  

Public ISBD [article]  inAutism > 27-4 (May 2023) . - p.1115-1131 Titre : The Suicidal Ideation Attributes Scale-Modified (SIDAS-M): Development and preliminary validation of a new scale for the measurement of suicidal ideation in autistic adults Type de document : Texte imprimé et/ou numérique Auteurs : Darren HEDLEY, Auteur ; Philip J BATTERHAM, Auteur ; Simon M BURY, Auteur ; Angela CLAPPERTON, Auteur ; Kathleen DENNEY, Auteur ; Cheryl DISSANAYAKE, Auteur ; Phoenix FOX, Auteur ; Thomas W FRAZIER, Auteur ; Emma GALLAGHER, Auteur ; Susan M HAYWARD, Auteur ; Jo ROBINSON, Auteur ; Ensu SAHIN, Auteur ; Julian TROLLOR, Auteur ; Mirko ULJAREVI?, Auteur ; Mark A STOKES, Auteur Article en page(s) : p.1115-1131 Langues : Anglais (eng) Mots-clés : adults,assessment,autism spectrum disorder,measurement,risk,screening,suicidal behavior,suicidal ideation,suicide Index. décimale : PER Périodiques Résumé : The study describes the development and preliminary psychometric validation of the Suicidal Ideation Attributes Scale-Modified (SIDAS-M), a five-item assessment of suicidal ideation for use with autistic adults. Participants (n=102 autistic adults; 58% women, 34% men, 8% nonbinary; Mage=41.75, SD=12.89) completed an online survey including the SIDAS-M at Time 1 and participated in follow-up interviews at Time 2 (~111?days later). A single factor solution provided good to excellent fit to the data (comparative fit index=0.961, Tucker-Lewis index=0.921; standardized root mean square residual=0.027), with all items showing good to excellent loadings (0.74-0.91). SIDAS-M total score (?=.930, bias-corrected and accelerated 95% confidence interval (BCa 95% CI) [.90, .95]) demonstrated good convergent validity, correlating significantly with existing suicide specific (?=.442-.698, p<.001) and well-being measures (?=.325.-.505, p?.001), and good divergent validity. Logistic regression controlling for age, gender, and relationship status indicated that SIDAS-M scores at Time 1 significantly predicted suicidal behavior at Time 2, ?=0.462, p En ligne : https://doi.org/10.1177/13623613221131234 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=499 [article] The Suicidal Ideation Attributes Scale-Modified (SIDAS-M): Development and preliminary validation of a new scale for the measurement of suicidal ideation in autistic adults [Texte imprimé et/ou numérique] / Darren HEDLEY, Auteur ; Philip J BATTERHAM, Auteur ; Simon M BURY, Auteur ; Angela CLAPPERTON, Auteur ; Kathleen DENNEY, Auteur ; Cheryl DISSANAYAKE, Auteur ; Phoenix FOX, Auteur ; Thomas W FRAZIER, Auteur ; Emma GALLAGHER, Auteur ; Susan M HAYWARD, Auteur ; Jo ROBINSON, Auteur ; Ensu SAHIN, Auteur ; Julian TROLLOR, Auteur ; Mirko ULJAREVI?, Auteur ; Mark A STOKES, Auteur . - p.1115-1131. Langues : Anglais (eng) in Autism > 27-4 (May 2023) . - p.1115-1131 Mots-clés : adults,assessment,autism spectrum disorder,measurement,risk,screening,suicidal behavior,suicidal ideation,suicide Index. décimale : PER Périodiques Résumé : The study describes the development and preliminary psychometric validation of the Suicidal Ideation Attributes Scale-Modified (SIDAS-M), a five-item assessment of suicidal ideation for use with autistic adults. Participants (n=102 autistic adults; 58% women, 34% men, 8% nonbinary; Mage=41.75, SD=12.89) completed an online survey including the SIDAS-M at Time 1 and participated in follow-up interviews at Time 2 (~111?days later). A single factor solution provided good to excellent fit to the data (comparative fit index=0.961, Tucker-Lewis index=0.921; standardized root mean square residual=0.027), with all items showing good to excellent loadings (0.74-0.91). SIDAS-M total score (?=.930, bias-corrected and accelerated 95% confidence interval (BCa 95% CI) [.90, .95]) demonstrated good convergent validity, correlating significantly with existing suicide specific (?=.442-.698, p<.001) and well-being measures (?=.325.-.505, p?.001), and good divergent validity. Logistic regression controlling for age, gender, and relationship status indicated that SIDAS-M scores at Time 1 significantly predicted suicidal behavior at Time 2, ?=0.462, p En ligne : https://doi.org/10.1177/13623613221131234 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=499

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