24 recherche sur le mot-clé 'competing interests.'

The striatal matrix compartment is expanded in autism spectrum disorder / Jeff L. WAUGH in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : The striatal matrix compartment is expanded in autism spectrum disorder Type de document : texte imprimé Auteurs : Jeff L. WAUGH, Auteur ; Asim O.A. HASSAN, Auteur ; Adrian T. FUNK, Auteur ; Joseph A. MALDJIAN, Auteur Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/diagnostic imaging/pathology  Male  Child  Female  Corpus Striatum/diagnostic imaging/pathology  Adult  Adolescent  Diffusion Tensor Imaging  Young Adult  Cohort Studies  Autism  Connectivity-based Parcellation  Matrix  Striatum  Striosome  Tractography  and supervised by our Institutional Review Board. All analyses were carried out  on de-identified MRI data. Consent was obtained by the studies that originated  that MRI data. Consent for publication: No individually-identifiable data is  presented in this manuscript. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is the second-most common neurodevelopmental disorder in childhood. This complex developmental disorder manifests with restricted interests, repetitive behaviors, and difficulties in communication and social awareness. The inherited and acquired causes of ASD impact many and diverse brain regions, challenging efforts to identify a shared neuroanatomical substrate for this range of symptoms. The striatum and its connections are among the most implicated sites of abnormal structure and/or function in ASD. Striatal projection neurons develop in segregated tissue compartments, the matrix and striosome, that are histochemically, pharmacologically, and functionally distinct. Immunohistochemical assessment of ASD and animal models of autism described abnormal matrix:striosome volume ratios, with an possible shift from striosome to matrix volume. Shifting the matrix:striosome ratio could result from expansion in matrix, reduction in striosome, spatial redistribution of the compartments, or a combination of these changes. Each type of ratio-shifting abnormality may predispose to ASD but yield different combinations of ASD features. METHODS: We developed a cohort of 426 children and adults (213 matched ASD-control pairs) and performed connectivity-based parcellation (diffusion tractography) of the striatum. This identified voxels with matrix-like and striosome-like patterns of structural connectivity. RESULTS: Matrix-like volume was increased in ASD, with no evident change in the volume or organization of the striosome-like compartment. The inter-compartment volume difference (matrix minus striosome) within each individual was 31% larger in ASD. Matrix-like volume was increased in both caudate and putamen, and in somatotopic zones throughout the rostral-caudal extent of the striatum. Subjects with moderate elevations in ADOS (Autism Diagnostic Observation Schedule) scores had increased matrix-like volume, but those with highly elevated ADOS scores had 3.7-fold larger increases in matrix-like volume. CONCLUSIONS: Matrix and striosome are embedded in distinct structural and functional networks, suggesting that compartment-selective injury or maldevelopment may mediate specific and distinct clinical features. Previously, assessing the striatal compartments in humans required post mortem tissue. Striatal parcellation provides a means to assess neuropsychiatric diseases for compartment-specific abnormalities. While this ASD cohort had increased matrix-like volume, other mechanisms that shift the matrix:striosome ratio may also increase the chance of developing the diverse social, sensory, and motor phenotypes of ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09596-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] The striatal matrix compartment is expanded in autism spectrum disorder [texte imprimé] / Jeff L. WAUGH, Auteur ; Asim O.A. HASSAN, Auteur ; Adrian T. FUNK, Auteur ; Joseph A. MALDJIAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Humans  Autism Spectrum Disorder/diagnostic imaging/pathology  Male  Child  Female  Corpus Striatum/diagnostic imaging/pathology  Adult  Adolescent  Diffusion Tensor Imaging  Young Adult  Cohort Studies  Autism  Connectivity-based Parcellation  Matrix  Striatum  Striosome  Tractography  and supervised by our Institutional Review Board. All analyses were carried out  on de-identified MRI data. Consent was obtained by the studies that originated  that MRI data. Consent for publication: No individually-identifiable data is  presented in this manuscript. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is the second-most common neurodevelopmental disorder in childhood. This complex developmental disorder manifests with restricted interests, repetitive behaviors, and difficulties in communication and social awareness. The inherited and acquired causes of ASD impact many and diverse brain regions, challenging efforts to identify a shared neuroanatomical substrate for this range of symptoms. The striatum and its connections are among the most implicated sites of abnormal structure and/or function in ASD. Striatal projection neurons develop in segregated tissue compartments, the matrix and striosome, that are histochemically, pharmacologically, and functionally distinct. Immunohistochemical assessment of ASD and animal models of autism described abnormal matrix:striosome volume ratios, with an possible shift from striosome to matrix volume. Shifting the matrix:striosome ratio could result from expansion in matrix, reduction in striosome, spatial redistribution of the compartments, or a combination of these changes. Each type of ratio-shifting abnormality may predispose to ASD but yield different combinations of ASD features. METHODS: We developed a cohort of 426 children and adults (213 matched ASD-control pairs) and performed connectivity-based parcellation (diffusion tractography) of the striatum. This identified voxels with matrix-like and striosome-like patterns of structural connectivity. RESULTS: Matrix-like volume was increased in ASD, with no evident change in the volume or organization of the striosome-like compartment. The inter-compartment volume difference (matrix minus striosome) within each individual was 31% larger in ASD. Matrix-like volume was increased in both caudate and putamen, and in somatotopic zones throughout the rostral-caudal extent of the striatum. Subjects with moderate elevations in ADOS (Autism Diagnostic Observation Schedule) scores had increased matrix-like volume, but those with highly elevated ADOS scores had 3.7-fold larger increases in matrix-like volume. CONCLUSIONS: Matrix and striosome are embedded in distinct structural and functional networks, suggesting that compartment-selective injury or maldevelopment may mediate specific and distinct clinical features. Previously, assessing the striatal compartments in humans required post mortem tissue. Striatal parcellation provides a means to assess neuropsychiatric diseases for compartment-specific abnormalities. While this ASD cohort had increased matrix-like volume, other mechanisms that shift the matrix:striosome ratio may also increase the chance of developing the diverse social, sensory, and motor phenotypes of ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09596-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Atypical early neural responses to native and non-native language in infants at high likelihood for developing autism / Megan BANCHIK ; Tawny TSANG ; Nana J. OKADA ; Rebecca ALTSHULER ; Nicole M. MCDONALD ; Susan Y. BOOKHEIMER ; Shafali S. JESTE ; Shulamite A. GREEN ; Mirella DAPRETTO in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 6 Titre : Atypical early neural responses to native and non-native language in infants at high likelihood for developing autism Type de document : texte imprimé Auteurs : Megan BANCHIK, Auteur ; Tawny TSANG, Auteur ; Nana J. OKADA, Auteur ; Rebecca ALTSHULER, Auteur ; Nicole M. MCDONALD, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Shafali S. JESTE, Auteur ; Shulamite A. GREEN, Auteur ; Mirella DAPRETTO, Auteur Article en page(s) : 6 Langues : Anglais (eng) Mots-clés : Humans  Infant  Male  Magnetic Resonance Imaging  Female  Language  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Brain/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology  Brain Mapping  Speech  Autism  Native language  fMRI  obtained from all participants' caregivers and/or legal guardians. All study  protocols were approved by the UCLA Institutional Review Board. Consent for  publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Language difficulties are common in autism spectrum disorder (ASD), a neurodevelopmental condition characterized by impairments in social communication as well as restricted and repetitive behaviors. Amongst infant siblings of children with an ASD diagnosis - who are at higher likelihood for developing ASD - a high proportion also show difficulties and delays in language acquisition. METHODS: In this study, we used functional magnetic resonance imaging (fMRI) to examine differences in language processing in 9-month-old infants at high (HL) and typical (TL) familial likelihood for ASD. Infants were presented with native (English) and novel (Japanese) speech while sleeping naturally in the scanner. Whole-brain and a priori region-of-interest analyses were conducted to evaluate neural differences in language processing based on likelihood group and language condition. RESULTS: HL infants showed attenuated responses to speech in general, particularly in left temporal language areas, as well as a lack of neural discrimination between the native and novel languages compared to the TL group. Importantly, we also demonstrate that HL infants show distinctly atypical patterns of lateralization for speech processing, particularly during native speech processing, suggesting a failure to left-lateralize. LIMITATIONS: The sample size, particularly for the TL group, is relatively modest because of the challenges inherent to collecting auditory stimulus-evoked data from sleeping participants, as well as retention and follow-up difficulties posed by the COVID-19 pandemic. The groups were not matched on some demographic variables, but the present findings held even after accounting for these differences. CONCLUSIONS: To our knowledge, this is the first fMRI study to directly measure autism-associated atypicalities in native language uptake during infancy. These findings provide a better understanding of the neurodevelopmental underpinnings of language delay in ASD, which is a prerequisite step for developing earlier and more effective interventions for autistic children and HL siblings who experience language impairments. En ligne : https://dx.doi.org/10.1186/s13229-025-00640-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Atypical early neural responses to native and non-native language in infants at high likelihood for developing autism [texte imprimé] / Megan BANCHIK, Auteur ; Tawny TSANG, Auteur ; Nana J. OKADA, Auteur ; Rebecca ALTSHULER, Auteur ; Nicole M. MCDONALD, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Shafali S. JESTE, Auteur ; Shulamite A. GREEN, Auteur ; Mirella DAPRETTO, Auteur . - 6. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 6 Mots-clés : Humans  Infant  Male  Magnetic Resonance Imaging  Female  Language  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Brain/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology  Brain Mapping  Speech  Autism  Native language  fMRI  obtained from all participants' caregivers and/or legal guardians. All study  protocols were approved by the UCLA Institutional Review Board. Consent for  publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Language difficulties are common in autism spectrum disorder (ASD), a neurodevelopmental condition characterized by impairments in social communication as well as restricted and repetitive behaviors. Amongst infant siblings of children with an ASD diagnosis - who are at higher likelihood for developing ASD - a high proportion also show difficulties and delays in language acquisition. METHODS: In this study, we used functional magnetic resonance imaging (fMRI) to examine differences in language processing in 9-month-old infants at high (HL) and typical (TL) familial likelihood for ASD. Infants were presented with native (English) and novel (Japanese) speech while sleeping naturally in the scanner. Whole-brain and a priori region-of-interest analyses were conducted to evaluate neural differences in language processing based on likelihood group and language condition. RESULTS: HL infants showed attenuated responses to speech in general, particularly in left temporal language areas, as well as a lack of neural discrimination between the native and novel languages compared to the TL group. Importantly, we also demonstrate that HL infants show distinctly atypical patterns of lateralization for speech processing, particularly during native speech processing, suggesting a failure to left-lateralize. LIMITATIONS: The sample size, particularly for the TL group, is relatively modest because of the challenges inherent to collecting auditory stimulus-evoked data from sleeping participants, as well as retention and follow-up difficulties posed by the COVID-19 pandemic. The groups were not matched on some demographic variables, but the present findings held even after accounting for these differences. CONCLUSIONS: To our knowledge, this is the first fMRI study to directly measure autism-associated atypicalities in native language uptake during infancy. These findings provide a better understanding of the neurodevelopmental underpinnings of language delay in ASD, which is a prerequisite step for developing earlier and more effective interventions for autistic children and HL siblings who experience language impairments. En ligne : https://dx.doi.org/10.1186/s13229-025-00640-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys / Ozge OZTAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 50 p. Titre : Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys Type de document : texte imprimé Auteurs : Ozge OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; Emanuela ARGILLI, Auteur ; Alyssa C. MANESS, Auteur ; Sierra M. SIMMONS, Auteur ; Noreen MOHSIN, Auteur ; Laura A. DEL ROSSO, Auteur ; Joseph P. GARNER, Auteur ; Elliott H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 50 p. Langues : Anglais (eng) Mots-clés : Arginine vasopressin  Autism spectrum disorder  Biomarker  Cerebrospinal fluid  Kinase signaling pathway  Oxytocin  Rhesus macaque  Social responsiveness scale  Social trait variation  the University of California, San Francisco (UCSF) have filed patent applications  related to biological measures studied herein (Stanford University:  PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism  spectrum disorder”  UCSF: PCT/US2016/014623 “Methods of diagnosing and treating  autism spectrum disorders”). These patents have not been granted or licensed, and no  study author is receiving any financial compensation at this time. EHS serves on the  advisory board for Retrophin Inc. All other authors declare that they have no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n = 43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n = 57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys [texte imprimé] / Ozge OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; Emanuela ARGILLI, Auteur ; Alyssa C. MANESS, Auteur ; Sierra M. SIMMONS, Auteur ; Noreen MOHSIN, Auteur ; Laura A. DEL ROSSO, Auteur ; Joseph P. GARNER, Auteur ; Elliott H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - 50 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 50 p. Mots-clés : Arginine vasopressin  Autism spectrum disorder  Biomarker  Cerebrospinal fluid  Kinase signaling pathway  Oxytocin  Rhesus macaque  Social responsiveness scale  Social trait variation  the University of California, San Francisco (UCSF) have filed patent applications  related to biological measures studied herein (Stanford University:  PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism  spectrum disorder”  UCSF: PCT/US2016/014623 “Methods of diagnosing and treating  autism spectrum disorders”). These patents have not been granted or licensed, and no  study author is receiving any financial compensation at this time. EHS serves on the  advisory board for Retrophin Inc. All other authors declare that they have no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n = 43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n = 57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice / Stijn VAN DE SOMPELE ; Clemence LIGNEUL ; Camille CHATELAIN ; Christophe BARREA ; Jason P. LERCH ; Beatrice M. FILIPPI ; Serpil ALKAN ; Elfride DE BAERE ; Jamie JOHNSTON ; Steven J. CLAPCOTE in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 14 Titre : Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice Type de document : texte imprimé Auteurs : Stijn VAN DE SOMPELE, Auteur ; Clemence LIGNEUL, Auteur ; Camille CHATELAIN, Auteur ; Christophe BARREA, Auteur ; Jason P. LERCH, Auteur ; Beatrice M. FILIPPI, Auteur ; Serpil ALKAN, Auteur ; Elfride DE BAERE, Auteur ; Jamie JOHNSTON, Auteur ; Steven J. CLAPCOTE, Auteur Article en page(s) : 14 Langues : Anglais (eng) Mots-clés : Animals  Humans  Male  Female  Mice  Autistic Disorder/genetics  Alleles  Intellectual Disability/genetics  Pedigree  Autism Spectrum Disorder/genetics  Child  Phenotype  Behavior, Animal  Membrane Proteins/genetics  Social Behavior  Mutation  Adult  Child, Preschool  DNA-Binding Proteins  Autism spectrum disorder  Intellectual disability  Olfactory behavior  Pdzd8  Social discrimination  approved by Ghent University Ethical Committee. The affected individuals were  recruited to the study with the informed consent of their mother using a process  that adhered to the tenets of the Declaration of Helsinki. The mouse experiments  were conducted in compliance with the UK Animals (Scientific Procedures) Act 1986  under UK Home Office licences and approved by the Animal Welfare and Ethical  Review Body at the University of Leeds. Consent for publication: Written consent  for publication of case reports and images pertaining to the affected individuals  was obtained from their mother. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intellectual developmental disorder with autism and dysmorphic facies (IDDADF) is a rare syndromic intellectual disability (ID) caused by homozygous disruption of PDZD8 (PDZ domain-containing protein 8), an integral endoplasmic reticulum (ER) protein. All four previously identified IDDADF cases exhibit autistic behavior, with autism spectrum disorder (ASD) diagnosed in three cases. To determine whether autistic behavior is a common outcome of PDZD8 disruption, we studied a third family with biallelic mutation of PDZD8 (family C) and further characterized PDZD8-deficient (Pdzd8(tm1b)) mice that exhibit stereotyped motor behavior relevant to ASD. METHODS: Homozygosity mapping, whole-exome sequencing, and cosegregation analysis were used to identify the PDZD8 variant responsible for IDDADF, including diagnoses of ASD, in consanguineous family C. To assess the in vivo effect of PDZD8 disruption on social responses and related phenotypes, behavioral, structural magnetic resonance imaging, and microscopy analyses were conducted on the Pdzd8(tm1b) mouse line. Metabolic activity was profiled using sealed metabolic cages. RESULTS: The discovery of a third family with IDDADF caused by biallelic disruption of PDZD8 permitted identification of a core clinical phenotype consisting of developmental delay, ID, autism, and facial dysmorphism. In addition to impairments in social recognition and social odor discrimination, Pdzd8(tm1b) mice exhibit increases in locomotor activity (dark phase only) and metabolic rate (both lights-on and dark phases), and decreased plasma triglyceride in males. In the brain, Pdzd8(tm1b) mice exhibit increased levels of accessory olfactory bulb volume, primary olfactory cortex volume, dendritic spine density, and ER stress- and mitochondrial fusion-related transcripts, as well as decreased levels of cerebellar nuclei volume and adult neurogenesis. LIMITATIONS: The total number of known cases of PDZD8-related IDDADF remains low. Some mouse experiments in the study did not use balanced numbers of males and females. The assessment of ER stress and mitochondrial fusion markers did not extend beyond mRNA levels. CONCLUSIONS: Our finding that the Pdzd8(tm1b) mouse model and all six known cases of IDDADF exhibit autistic behavior, with ASD diagnosed in five cases, identifies this trait as a common outcome of biallelic disruption of PDZD8 in humans and mice. Other abnormalities exhibited by Pdzd8(tm1b) mice suggest that the range of comorbidities associated with PDZD8 deficiency may be wider than presently recognized. En ligne : https://dx.doi.org/10.1186/s13229-025-00650-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice [texte imprimé] / Stijn VAN DE SOMPELE, Auteur ; Clemence LIGNEUL, Auteur ; Camille CHATELAIN, Auteur ; Christophe BARREA, Auteur ; Jason P. LERCH, Auteur ; Beatrice M. FILIPPI, Auteur ; Serpil ALKAN, Auteur ; Elfride DE BAERE, Auteur ; Jamie JOHNSTON, Auteur ; Steven J. CLAPCOTE, Auteur . - 14. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 14 Mots-clés : Animals  Humans  Male  Female  Mice  Autistic Disorder/genetics  Alleles  Intellectual Disability/genetics  Pedigree  Autism Spectrum Disorder/genetics  Child  Phenotype  Behavior, Animal  Membrane Proteins/genetics  Social Behavior  Mutation  Adult  Child, Preschool  DNA-Binding Proteins  Autism spectrum disorder  Intellectual disability  Olfactory behavior  Pdzd8  Social discrimination  approved by Ghent University Ethical Committee. The affected individuals were  recruited to the study with the informed consent of their mother using a process  that adhered to the tenets of the Declaration of Helsinki. The mouse experiments  were conducted in compliance with the UK Animals (Scientific Procedures) Act 1986  under UK Home Office licences and approved by the Animal Welfare and Ethical  Review Body at the University of Leeds. Consent for publication: Written consent  for publication of case reports and images pertaining to the affected individuals  was obtained from their mother. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intellectual developmental disorder with autism and dysmorphic facies (IDDADF) is a rare syndromic intellectual disability (ID) caused by homozygous disruption of PDZD8 (PDZ domain-containing protein 8), an integral endoplasmic reticulum (ER) protein. All four previously identified IDDADF cases exhibit autistic behavior, with autism spectrum disorder (ASD) diagnosed in three cases. To determine whether autistic behavior is a common outcome of PDZD8 disruption, we studied a third family with biallelic mutation of PDZD8 (family C) and further characterized PDZD8-deficient (Pdzd8(tm1b)) mice that exhibit stereotyped motor behavior relevant to ASD. METHODS: Homozygosity mapping, whole-exome sequencing, and cosegregation analysis were used to identify the PDZD8 variant responsible for IDDADF, including diagnoses of ASD, in consanguineous family C. To assess the in vivo effect of PDZD8 disruption on social responses and related phenotypes, behavioral, structural magnetic resonance imaging, and microscopy analyses were conducted on the Pdzd8(tm1b) mouse line. Metabolic activity was profiled using sealed metabolic cages. RESULTS: The discovery of a third family with IDDADF caused by biallelic disruption of PDZD8 permitted identification of a core clinical phenotype consisting of developmental delay, ID, autism, and facial dysmorphism. In addition to impairments in social recognition and social odor discrimination, Pdzd8(tm1b) mice exhibit increases in locomotor activity (dark phase only) and metabolic rate (both lights-on and dark phases), and decreased plasma triglyceride in males. In the brain, Pdzd8(tm1b) mice exhibit increased levels of accessory olfactory bulb volume, primary olfactory cortex volume, dendritic spine density, and ER stress- and mitochondrial fusion-related transcripts, as well as decreased levels of cerebellar nuclei volume and adult neurogenesis. LIMITATIONS: The total number of known cases of PDZD8-related IDDADF remains low. Some mouse experiments in the study did not use balanced numbers of males and females. The assessment of ER stress and mitochondrial fusion markers did not extend beyond mRNA levels. CONCLUSIONS: Our finding that the Pdzd8(tm1b) mouse model and all six known cases of IDDADF exhibit autistic behavior, with ASD diagnosed in five cases, identifies this trait as a common outcome of biallelic disruption of PDZD8 in humans and mice. Other abnormalities exhibited by Pdzd8(tm1b) mice suggest that the range of comorbidities associated with PDZD8 deficiency may be wider than presently recognized. En ligne : https://dx.doi.org/10.1186/s13229-025-00650-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

Autistic traits are associated with lower perceived executive function but not poorer executive function task performance in the general population: complementary meta-analytic evidence / Michael K. YEUNG in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 48 Titre : Autistic traits are associated with lower perceived executive function but not poorer executive function task performance in the general population: complementary meta-analytic evidence Type de document : texte imprimé Auteurs : Michael K. YEUNG, Auteur ; Cassie T.Y. LI, Auteur ; Harris C.W. CHUNG, Auteur ; Tsz-Hei AU, Auteur ; Sin-Yue LEE, Auteur ; Jieru BAI, Auteur ; Michael K. YEUNG, Auteur ; Cassie T.Y. LI, Auteur ; Harris C.W. CHUNG, Auteur ; Tsz-Hei AU, Auteur ; Sin-Yue LEE, Auteur ; Jieru BAI, Auteur Article en page(s) : 48 Langues : Anglais (eng) Mots-clés : Humans  Executive Function/physiology  Autistic Disorder/psychology/physiopathology  Male  Adult  Bayes Theorem  Aq  Autism spectrum quotient  Autistic traits  Executive function  Meta-analysis  for publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic individuals generally exhibit real-world executive function (EF) difficulties and perform poorly on EF tasks. However, while autistic traits are distributed continuously throughout the general population, the relationships between autistic traits and EF among nonclinical individuals remain unclear. Here, we conducted complementary meta-analyses to clarify the relationships between autistic traits and various aspects of EF in the general population. METHODS: A literature search was conducted using PubMed, PsycINFO, and Web of Science on July 11, 2025. After screening by two independent reviewers, 39 articles that reported 40 studies were included. These studies either compared EF between groups with high and low autistic traits, based on a cutoff, or investigated the relationships between continuous measures of autistic traits and EF. RESULTS: We found significant negative associations between autistic traits and EF among nonclinical individuals across EF processes. Notably, these relationships were observed only when EFs were measured using questionnaires rather than behavioral tasks. Specifically, random-effects and robust Bayesian meta-analyses revealed significant, strong correlations between higher autistic traits and poorer ratings on EF questionnaires, with primarily substantial evidence supporting the presence than absence of relationships. In contrast, the meta-analyses indicated nonsignificant, very weak correlations between higher autistic traits and poorer performances on EF tasks, with primarily substantial evidence supporting the absence than presence of relationships. LIMITATIONS: These findings were mainly based on self-reported measures of autistic traits in adults and derived from single studies without follow up or replication. CONCLUSIONS: Autistic traits are associated with lower perceived real-world EF behavior rather than poorer EF task performance in the general population. These findings underscore the importance of paying closer attention to addressing the concerns of individuals with high autistic traits and their parents regarding their own and their children's EF behavior. Based on the available evidence, we construct a picture of the relationships between autistic traits and EF across the trait's continuum. REGISTRATION: This study was preregistered at https://osf.io/zncv3 . En ligne : https://dx.doi.org/10.1186/s13229-025-00680-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=569 [article] Autistic traits are associated with lower perceived executive function but not poorer executive function task performance in the general population: complementary meta-analytic evidence [texte imprimé] / Michael K. YEUNG, Auteur ; Cassie T.Y. LI, Auteur ; Harris C.W. CHUNG, Auteur ; Tsz-Hei AU, Auteur ; Sin-Yue LEE, Auteur ; Jieru BAI, Auteur ; Michael K. YEUNG, Auteur ; Cassie T.Y. LI, Auteur ; Harris C.W. CHUNG, Auteur ; Tsz-Hei AU, Auteur ; Sin-Yue LEE, Auteur ; Jieru BAI, Auteur . - 48. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 48 Mots-clés : Humans  Executive Function/physiology  Autistic Disorder/psychology/physiopathology  Male  Adult  Bayes Theorem  Aq  Autism spectrum quotient  Autistic traits  Executive function  Meta-analysis  for publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic individuals generally exhibit real-world executive function (EF) difficulties and perform poorly on EF tasks. However, while autistic traits are distributed continuously throughout the general population, the relationships between autistic traits and EF among nonclinical individuals remain unclear. Here, we conducted complementary meta-analyses to clarify the relationships between autistic traits and various aspects of EF in the general population. METHODS: A literature search was conducted using PubMed, PsycINFO, and Web of Science on July 11, 2025. After screening by two independent reviewers, 39 articles that reported 40 studies were included. These studies either compared EF between groups with high and low autistic traits, based on a cutoff, or investigated the relationships between continuous measures of autistic traits and EF. RESULTS: We found significant negative associations between autistic traits and EF among nonclinical individuals across EF processes. Notably, these relationships were observed only when EFs were measured using questionnaires rather than behavioral tasks. Specifically, random-effects and robust Bayesian meta-analyses revealed significant, strong correlations between higher autistic traits and poorer ratings on EF questionnaires, with primarily substantial evidence supporting the presence than absence of relationships. In contrast, the meta-analyses indicated nonsignificant, very weak correlations between higher autistic traits and poorer performances on EF tasks, with primarily substantial evidence supporting the absence than presence of relationships. LIMITATIONS: These findings were mainly based on self-reported measures of autistic traits in adults and derived from single studies without follow up or replication. CONCLUSIONS: Autistic traits are associated with lower perceived real-world EF behavior rather than poorer EF task performance in the general population. These findings underscore the importance of paying closer attention to addressing the concerns of individuals with high autistic traits and their parents regarding their own and their children's EF behavior. Based on the available evidence, we construct a picture of the relationships between autistic traits and EF across the trait's continuum. REGISTRATION: This study was preregistered at https://osf.io/zncv3 . En ligne : https://dx.doi.org/10.1186/s13229-025-00680-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=569

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