Atypical maturation of the functional connectome hierarchy in autism / Sunghun KIM ; Shinwon PARK ; Hyoungshin CHOI ; Bo-Yong PARK ; Hyunjin PARK in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 21 Titre : Atypical maturation of the functional connectome hierarchy in autism Type de document : texte imprimé Auteurs : Sunghun KIM, Auteur ; Shinwon PARK, Auteur ; Hyoungshin CHOI, Auteur ; Bo-Yong PARK, Auteur ; Hyunjin PARK, Auteur Article en page(s) : 21 Langues : Anglais (eng) Mots-clés : Humans  Connectome  Adolescent  Child  Male  Young Adult  Female  Magnetic Resonance Imaging  Brain/diagnostic imaging/physiopathology  Child, Preschool  Autism Spectrum Disorder/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology/diagnostic imaging  Adult  Autism spectrum disorder  Cortical hierarchy  Integration and segregation  Normative modeling Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is marked by disruptions in low-level sensory processing and higher-order sociocognitive functions, suggesting a complex interplay between different brain regions across the cortical hierarchy. However, the developmental trajectory of this hierarchical organization in ASD remains underexplored. Herein, we investigated the maturational abnormalities in the cortical hierarchy among individuals with ASD. METHODS: Resting-state functional magnetic resonance imaging data from three large-scale datasets were analyzed: Autism Brain Imaging Data Exchange I and II and Lifespan Human Connectome Project Development (aged 5-22 years). The principal functional connectivity gradient representing cortical hierarchy was estimated using diffusion map embedding. By applying normative modeling with the generalized additive model for location, scale, and shape (GAMLSS), we captured the nonlinear trajectories of the developing functional gradient, as well as the individual-level deviations in ASD from typical development based on centile scores measured as deviations from the normative curves. A whole-brain summary metric, the functional hierarchy score, was derived to measure the extent of abnormal maturation in individuals with ASD. Finally, through a series of mediation analyses, we examined the potential role of network-level connectomic disruptions between the diagnoses and deviations in the cortical hierarchy. RESULTS: The maturation of cortical hierarchy in individuals with ASD followed a non-linear trajectory, showing delayed maturation during childhood compared to that of typically developing individuals, followed by an accelerated "catch-up" phase during adolescence and a subsequent decline in young adulthood. The nature of these deviations varied across networks, with sensory and attention networks displaying the most pronounced abnormalities in childhood, while higher-order networks, particularly the default mode network (DMN), remaining impaired from childhood to adolescence. Mediation analyses revealed that the persistent reduction in DMN segregation throughout development was a key contributor to the atypical development of cortical hierarchy in ASD. LIMITATIONS: The uneven distribution of samples across age groups, particularly in the later stages of development, limited our ability to fully capture developmental trajectories among older individuals. CONCLUSIONS: These findings highlight the importance of understanding the developmental trajectories of cortical organization in ASD, collectively suggesting that early interventions aimed at promoting the normative development of higher-order networks may be critical for improving outcomes in individuals with ASD. En ligne : https://dx.doi.org/10.1186/s13229-025-00641-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Atypical maturation of the functional connectome hierarchy in autism [texte imprimé] / Sunghun KIM, Auteur ; Shinwon PARK, Auteur ; Hyoungshin CHOI, Auteur ; Bo-Yong PARK, Auteur ; Hyunjin PARK, Auteur . - 21. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 21 Mots-clés : Humans  Connectome  Adolescent  Child  Male  Young Adult  Female  Magnetic Resonance Imaging  Brain/diagnostic imaging/physiopathology  Child, Preschool  Autism Spectrum Disorder/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology/diagnostic imaging  Adult  Autism spectrum disorder  Cortical hierarchy  Integration and segregation  Normative modeling Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is marked by disruptions in low-level sensory processing and higher-order sociocognitive functions, suggesting a complex interplay between different brain regions across the cortical hierarchy. However, the developmental trajectory of this hierarchical organization in ASD remains underexplored. Herein, we investigated the maturational abnormalities in the cortical hierarchy among individuals with ASD. METHODS: Resting-state functional magnetic resonance imaging data from three large-scale datasets were analyzed: Autism Brain Imaging Data Exchange I and II and Lifespan Human Connectome Project Development (aged 5-22 years). The principal functional connectivity gradient representing cortical hierarchy was estimated using diffusion map embedding. By applying normative modeling with the generalized additive model for location, scale, and shape (GAMLSS), we captured the nonlinear trajectories of the developing functional gradient, as well as the individual-level deviations in ASD from typical development based on centile scores measured as deviations from the normative curves. A whole-brain summary metric, the functional hierarchy score, was derived to measure the extent of abnormal maturation in individuals with ASD. Finally, through a series of mediation analyses, we examined the potential role of network-level connectomic disruptions between the diagnoses and deviations in the cortical hierarchy. RESULTS: The maturation of cortical hierarchy in individuals with ASD followed a non-linear trajectory, showing delayed maturation during childhood compared to that of typically developing individuals, followed by an accelerated "catch-up" phase during adolescence and a subsequent decline in young adulthood. The nature of these deviations varied across networks, with sensory and attention networks displaying the most pronounced abnormalities in childhood, while higher-order networks, particularly the default mode network (DMN), remaining impaired from childhood to adolescence. Mediation analyses revealed that the persistent reduction in DMN segregation throughout development was a key contributor to the atypical development of cortical hierarchy in ASD. LIMITATIONS: The uneven distribution of samples across age groups, particularly in the later stages of development, limited our ability to fully capture developmental trajectories among older individuals. CONCLUSIONS: These findings highlight the importance of understanding the developmental trajectories of cortical organization in ASD, collectively suggesting that early interventions aimed at promoting the normative development of higher-order networks may be critical for improving outcomes in individuals with ASD. En ligne : https://dx.doi.org/10.1186/s13229-025-00641-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

Contracted functional connectivity profiles in autism / Clara F. WEBER in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 38p. Titre : Contracted functional connectivity profiles in autism Type de document : texte imprimé Auteurs : Clara F. WEBER, Auteur ; Valeria KEBETS, Auteur ; Oualid BENKARIM, Auteur ; Sara LARIVIERE, Auteur ; Yezhou WANG, Auteur ; Alexander NGO, Auteur ; Hongxiu JIANG, Auteur ; Xiaoqian CHAI, Auteur ; Bo-Yong PARK, Auteur ; Michael P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur ; Sofie VALK, Auteur ; Seok-Jun HONG, Auteur ; Boris C. BERNHARDT, Auteur Article en page(s) : 38p. Langues : Anglais (eng) Mots-clés : Humans  Male  Connectome  Young Adult  Adult  Magnetic Resonance Imaging  Adolescent  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Autistic Disorder/physiopathology/diagnostic imaging  Brain/diagnostic imaging/physiopathology  Case-Control Studies  Child  Nerve Net/diagnostic imaging/physiopathology  Neural Pathways/physiopathology/diagnostic imaging  Autism spectrum disorder  Connectivity disruptions  Distance profiling  Functional connectivity  Magnetic resonance imaging  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition that is associated with atypical brain network organization, with prior work suggesting differential connectivity alterations with respect to functional connection length. Here, we tested whether functional connectopathy in ASD specifically relates to disruptions in long- relative to short-range functional connections. Our approach combined functional connectomics with geodesic distance mapping, and we studied associations to macroscale networks, microarchitectural patterns, as well as socio-demographic and clinical phenotypes. METHODS: We studied 211 males from three sites of the ABIDE-I dataset comprising 103 participants with an ASD diagnosis (mean+SD age = 20.8+8.1 years) and 108 neurotypical controls (NT, 19.2+7.2 years). For each participant, we computed cortex-wide connectivity distance (CD) measures by combining geodesic distance mapping with resting-state functional connectivity profiling. We compared CD between ASD and NT participants using surface-based linear models, and studied associations with age, symptom severity, and intelligence scores. We contextualized CD alterations relative to canonical networks and explored spatial associations with functional and microstructural cortical gradients as well as cytoarchitectonic cortical types. RESULTS: Compared to NT, ASD participants presented with widespread reductions in CD, generally indicating shorter average connection length and thus suggesting reduced long-range connectivity but increased short-range connections. Peak reductions were localized in transmodal systems (i.e., heteromodal and paralimbic regions in the prefrontal, temporal, and parietal and temporo-parieto-occipital cortex), and effect sizes correlated with the sensory-transmodal gradient of brain function. ASD-related CD reductions appeared consistent across inter-individual differences in age and symptom severity, and we observed a positive correlation of CD to IQ scores. LIMITATIONS: Despite rigorous harmonization across the three different acquisition sites, heterogeneity in autism poses a potential limitation to the generalizability of our results. Additionally, we focussed male participants, warranting future studies in more balanced cohorts. CONCLUSIONS: Our study showed reductions in CD as a relatively stable imaging phenotype of ASD that preferentially impacted paralimbic and heteromodal association systems. CD reductions in ASD corroborate previous reports of ASD-related imbalance between short-range overconnectivity and long-range underconnectivity. En ligne : https://dx.doi.org/10.1186/s13229-024-00616-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Contracted functional connectivity profiles in autism [texte imprimé] / Clara F. WEBER, Auteur ; Valeria KEBETS, Auteur ; Oualid BENKARIM, Auteur ; Sara LARIVIERE, Auteur ; Yezhou WANG, Auteur ; Alexander NGO, Auteur ; Hongxiu JIANG, Auteur ; Xiaoqian CHAI, Auteur ; Bo-Yong PARK, Auteur ; Michael P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur ; Sofie VALK, Auteur ; Seok-Jun HONG, Auteur ; Boris C. BERNHARDT, Auteur . - 38p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 38p. Mots-clés : Humans  Male  Connectome  Young Adult  Adult  Magnetic Resonance Imaging  Adolescent  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Autistic Disorder/physiopathology/diagnostic imaging  Brain/diagnostic imaging/physiopathology  Case-Control Studies  Child  Nerve Net/diagnostic imaging/physiopathology  Neural Pathways/physiopathology/diagnostic imaging  Autism spectrum disorder  Connectivity disruptions  Distance profiling  Functional connectivity  Magnetic resonance imaging  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition that is associated with atypical brain network organization, with prior work suggesting differential connectivity alterations with respect to functional connection length. Here, we tested whether functional connectopathy in ASD specifically relates to disruptions in long- relative to short-range functional connections. Our approach combined functional connectomics with geodesic distance mapping, and we studied associations to macroscale networks, microarchitectural patterns, as well as socio-demographic and clinical phenotypes. METHODS: We studied 211 males from three sites of the ABIDE-I dataset comprising 103 participants with an ASD diagnosis (mean+SD age = 20.8+8.1 years) and 108 neurotypical controls (NT, 19.2+7.2 years). For each participant, we computed cortex-wide connectivity distance (CD) measures by combining geodesic distance mapping with resting-state functional connectivity profiling. We compared CD between ASD and NT participants using surface-based linear models, and studied associations with age, symptom severity, and intelligence scores. We contextualized CD alterations relative to canonical networks and explored spatial associations with functional and microstructural cortical gradients as well as cytoarchitectonic cortical types. RESULTS: Compared to NT, ASD participants presented with widespread reductions in CD, generally indicating shorter average connection length and thus suggesting reduced long-range connectivity but increased short-range connections. Peak reductions were localized in transmodal systems (i.e., heteromodal and paralimbic regions in the prefrontal, temporal, and parietal and temporo-parieto-occipital cortex), and effect sizes correlated with the sensory-transmodal gradient of brain function. ASD-related CD reductions appeared consistent across inter-individual differences in age and symptom severity, and we observed a positive correlation of CD to IQ scores. LIMITATIONS: Despite rigorous harmonization across the three different acquisition sites, heterogeneity in autism poses a potential limitation to the generalizability of our results. Additionally, we focussed male participants, warranting future studies in more balanced cohorts. CONCLUSIONS: Our study showed reductions in CD as a relatively stable imaging phenotype of ASD that preferentially impacted paralimbic and heteromodal association systems. CD reductions in ASD corroborate previous reports of ASD-related imbalance between short-range overconnectivity and long-range underconnectivity. En ligne : https://dx.doi.org/10.1186/s13229-024-00616-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort / Dina TERLOYEVA in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) Titre : Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort Type de document : texte imprimé Auteurs : Dina TERLOYEVA, Auteur ; Alexander J. FREY, Auteur ; Bo-Yong PARK, Auteur ; Elizabeth M. KAUFFMAN, Auteur ; Leny MATHEW, Auteur ; Anna BOSTWICK, Auteur ; Erika L. VARNER, Auteur ; Brian K. LEE, Auteur ; Lisa A. CROEN, Auteur ; M. Daniele FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur ; Nathaniel W. SNYDER, Auteur Langues : Anglais (eng) Mots-clés : Androgen  Autism-related traits  Meconium  Prenatal exposure  Sex difference  Sibling Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid, cord blood, saliva, and blood with mixed results. METHODS: To provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). One hundred and seventy children had meconium and AOSI, 140 had meconium and SRS, and 137 had meconium and both AOSI and SRS. RESULTS: Separate robust linear regressions between each of the log-transformed androgens and log-transformed SRS scores revealed three-way interaction between sex of the child, sex of the proband, and testosterone concentration. In the adjusted analyses, t-T, u-A4, and u-DHEA (P ≤ 0.01) were positively associated with AOSI scores, while u-T (P = 0.004) and u-DHEA (P = 0.007) were positively associated with SRS total score among females with female probands (n = 10). Additionally, higher concentrations of u-T (P = 0.01) and t-T (P = 0.01) predicted higher SRS total score in males with male probands (n = 63). Limitations Since we explored three-way interactions, this resulted in a limited sample size for some analyses. This study was from an enriched-risk cohort which may limit generalizability, and this study used ASD-assessment scales as outcomes instead of diagnostic categories. Additionally, the novel use of meconium in this study limits the ability to compare the results in this cohort to others due to the paucity of research on meconium. CONCLUSIONS: This study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of older siblings with autism should be considered as a biological variable in relevant studies. En ligne : http://dx.doi.org/10.1186/s13229-020-00395-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 [article] Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort [texte imprimé] / Dina TERLOYEVA, Auteur ; Alexander J. FREY, Auteur ; Bo-Yong PARK, Auteur ; Elizabeth M. KAUFFMAN, Auteur ; Leny MATHEW, Auteur ; Anna BOSTWICK, Auteur ; Erika L. VARNER, Auteur ; Brian K. LEE, Auteur ; Lisa A. CROEN, Auteur ; M. Daniele FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur ; Nathaniel W. SNYDER, Auteur. Langues : Anglais (eng) in Molecular Autism > 11 (2020) Mots-clés : Androgen  Autism-related traits  Meconium  Prenatal exposure  Sex difference  Sibling Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid, cord blood, saliva, and blood with mixed results. METHODS: To provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). One hundred and seventy children had meconium and AOSI, 140 had meconium and SRS, and 137 had meconium and both AOSI and SRS. RESULTS: Separate robust linear regressions between each of the log-transformed androgens and log-transformed SRS scores revealed three-way interaction between sex of the child, sex of the proband, and testosterone concentration. In the adjusted analyses, t-T, u-A4, and u-DHEA (P ≤ 0.01) were positively associated with AOSI scores, while u-T (P = 0.004) and u-DHEA (P = 0.007) were positively associated with SRS total score among females with female probands (n = 10). Additionally, higher concentrations of u-T (P = 0.01) and t-T (P = 0.01) predicted higher SRS total score in males with male probands (n = 63). Limitations Since we explored three-way interactions, this resulted in a limited sample size for some analyses. This study was from an enriched-risk cohort which may limit generalizability, and this study used ASD-assessment scales as outcomes instead of diagnostic categories. Additionally, the novel use of meconium in this study limits the ability to compare the results in this cohort to others due to the paucity of research on meconium. CONCLUSIONS: This study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of older siblings with autism should be considered as a biological variable in relevant studies. En ligne : http://dx.doi.org/10.1186/s13229-020-00395-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438

A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood / Charles E. MORDAUNT in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 36 p. Titre : A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood Type de document : texte imprimé Auteurs : Charles E. MORDAUNT, Auteur ; Bo-Yong PARK, Auteur ; Kelly M. BAKULSKI, Auteur ; Jason I. FEINBERG, Auteur ; Lisa A. CROEN, Auteur ; Christine LADD-ACOSTA, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Heather E. VOLK, Auteur ; Sally OZONOFF, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Janine M. LASALLE, Auteur ; Rebecca J. SCHMIDT, Auteur ; M. Daniele FALLIN, Auteur Article en page(s) : 36 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Chromatin  Environment  Gene expression  Meta-analysis  Microarray  Neurodevelopment  Perinatal  Prospective study  Umbilical cord blood Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Methods: Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. Results: While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. Limitations: ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. Conclusions: This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology. En ligne : http://dx.doi.org/10.1186/s13229-019-0287-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood [texte imprimé] / Charles E. MORDAUNT, Auteur ; Bo-Yong PARK, Auteur ; Kelly M. BAKULSKI, Auteur ; Jason I. FEINBERG, Auteur ; Lisa A. CROEN, Auteur ; Christine LADD-ACOSTA, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Heather E. VOLK, Auteur ; Sally OZONOFF, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Janine M. LASALLE, Auteur ; Rebecca J. SCHMIDT, Auteur ; M. Daniele FALLIN, Auteur . - 36 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 36 p. Mots-clés : Autism spectrum disorder  Chromatin  Environment  Gene expression  Meta-analysis  Microarray  Neurodevelopment  Perinatal  Prospective study  Umbilical cord blood Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Methods: Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. Results: While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. Limitations: ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. Conclusions: This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology. En ligne : http://dx.doi.org/10.1186/s13229-019-0287-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study / Bo-Yong PARK in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 3p. Titre : Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study Type de document : texte imprimé Auteurs : Bo-Yong PARK, Auteur ; Brian K. LEE, Auteur ; Igor BURSTYN, Auteur ; Loni P. TABB, Auteur ; Jeff A. KEELAN, Auteur ; Andrew J.O. WHITEHOUSE, Auteur ; Lisa A. CROEN, Auteur ; M. Daniele FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Owen MONTGOMERY, Auteur ; Craig J. NEWSCHAFFER, Auteur Article en page(s) : 3p. Langues : Anglais (eng) Mots-clés : Adult  Androstenedione/*metabolism  Autism Spectrum Disorder/metabolism/*psychology  Chromatography, Liquid  Cohort Studies  Dehydroepiandrosterone/*metabolism  Female  Fetal Blood/*metabolism  Humans  Infant  Linear Models  Longitudinal Studies  Male  Pregnancy  Prospective Studies  Risk Assessment  Severity of Illness Index  Siblings/*psychology  Tandem Mass Spectrometry  Testosterone/*metabolism  *Autism  *Sex difference  *Sibling  *Testosterone  *Umbilical cord blood Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. METHODS: We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. RESULTS: Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P = 0.006) than in subjects whose older affected sibling was male. CONCLUSIONS: While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution. En ligne : http://dx.doi.org/10.1186/s13229-017-0118-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study [texte imprimé] / Bo-Yong PARK, Auteur ; Brian K. LEE, Auteur ; Igor BURSTYN, Auteur ; Loni P. TABB, Auteur ; Jeff A. KEELAN, Auteur ; Andrew J.O. WHITEHOUSE, Auteur ; Lisa A. CROEN, Auteur ; M. Daniele FALLIN, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Owen MONTGOMERY, Auteur ; Craig J. NEWSCHAFFER, Auteur . - 3p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 3p. Mots-clés : Adult  Androstenedione/*metabolism  Autism Spectrum Disorder/metabolism/*psychology  Chromatography, Liquid  Cohort Studies  Dehydroepiandrosterone/*metabolism  Female  Fetal Blood/*metabolism  Humans  Infant  Linear Models  Longitudinal Studies  Male  Pregnancy  Prospective Studies  Risk Assessment  Severity of Illness Index  Siblings/*psychology  Tandem Mass Spectrometry  Testosterone/*metabolism  *Autism  *Sex difference  *Sibling  *Testosterone  *Umbilical cord blood Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. METHODS: We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. RESULTS: Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P = 0.006) than in subjects whose older affected sibling was male. CONCLUSIONS: While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution. En ligne : http://dx.doi.org/10.1186/s13229-017-0118-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

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