Allelic Variation Within the Putative Autism Spectrum Disorder Risk Gene Homeobox A1 and Cerebellar Maturation in Typically Developing Children and Adolescents / Armin RAZNAHAN in Autism Research, 5-2 (April 2012)  

Public ISBD [article]  inAutism Research > 5-2 (April 2012) . - p.93-100 Titre : Allelic Variation Within the Putative Autism Spectrum Disorder Risk Gene Homeobox A1 and Cerebellar Maturation in Typically Developing Children and Adolescents Type de document : texte imprimé Auteurs : Armin RAZNAHAN, Auteur ; Yohan LEE, Auteur ; Catherine VAITUZIS, Auteur ; Lan TRAN, Auteur ; Susan MACKIE, Auteur ; Henning TIEMEIER, Auteur ; Liv S. CLASEN, Auteur ; Francois LALONDE, Auteur ; Deanna GREENSTEIN, Auteur ; Ron PIERSON, Auteur ; Jay N. GIEDD, Auteur Année de publication : 2012 Article en page(s) : p.93-100 Langues : Anglais (eng) Mots-clés : autism  HOXA1  cerebellum  gene  brain  MRI Index. décimale : PER Périodiques Résumé : Homeobox A1 (HOXA1) has been proposed as a candidate gene for autism spectrum disorder (ASD) as it regulates embryological patterning of hind-brain structures implicated in autism neurobiology. In line with this notion, a nonsynonymous single nucleotide polymorphism within a highly conserved domain of HOXA1—A218G (rs10951154)—has been linked to both ASD risk, and cross-sectional differences in superior posterior lobar cerebellar anatomy in late adulthood. Despite evidence for early onset and developmentally dynamic cerebellar involvement in ASD, little is known of the relationship between A218G genotype and maturation of the cerebellum over early development. We addressed this issue using 296 longitudinally acquired structural magnetic resonance imaging brain scans from 116 healthy individuals between 5 and 23 years of age. Mixed models were used to compare the relationship between age and semi-automated measures of cerebellar volume in A-homozygotes (AA) and carriers of the G allele (Gcar). Total cerebellar volume increased between ages of 5 and 23 years in both groups. However, this was accelerated in the Gcar relative to the AA group (Genotype-by-age interaction term, P = 0.03), and driven by genotype-dependent differences in the rate of bilateral superior posterior lobar volume change with age (P = 0.002). Resultantly, although superior posterior lobar volume did not differ significantly between genotype groups at age 5 (P = 0.9), by age 23 it was 12% greater in Gcar than AA (P = 0.002). Our results suggest that common genetic variation within this putative ASD risk gene has the capacity to modify the development of cerebellar systems implicated in ASD neurobiology. En ligne : http://dx.doi.org/10.1002/aur.238 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=155 [article] Allelic Variation Within the Putative Autism Spectrum Disorder Risk Gene Homeobox A1 and Cerebellar Maturation in Typically Developing Children and Adolescents [texte imprimé] / Armin RAZNAHAN, Auteur ; Yohan LEE, Auteur ; Catherine VAITUZIS, Auteur ; Lan TRAN, Auteur ; Susan MACKIE, Auteur ; Henning TIEMEIER, Auteur ; Liv S. CLASEN, Auteur ; Francois LALONDE, Auteur ; Deanna GREENSTEIN, Auteur ; Ron PIERSON, Auteur ; Jay N. GIEDD, Auteur . - 2012 . - p.93-100. Langues : Anglais (eng) in Autism Research > 5-2 (April 2012) . - p.93-100 Mots-clés : autism  HOXA1  cerebellum  gene  brain  MRI Index. décimale : PER Périodiques Résumé : Homeobox A1 (HOXA1) has been proposed as a candidate gene for autism spectrum disorder (ASD) as it regulates embryological patterning of hind-brain structures implicated in autism neurobiology. In line with this notion, a nonsynonymous single nucleotide polymorphism within a highly conserved domain of HOXA1—A218G (rs10951154)—has been linked to both ASD risk, and cross-sectional differences in superior posterior lobar cerebellar anatomy in late adulthood. Despite evidence for early onset and developmentally dynamic cerebellar involvement in ASD, little is known of the relationship between A218G genotype and maturation of the cerebellum over early development. We addressed this issue using 296 longitudinally acquired structural magnetic resonance imaging brain scans from 116 healthy individuals between 5 and 23 years of age. Mixed models were used to compare the relationship between age and semi-automated measures of cerebellar volume in A-homozygotes (AA) and carriers of the G allele (Gcar). Total cerebellar volume increased between ages of 5 and 23 years in both groups. However, this was accelerated in the Gcar relative to the AA group (Genotype-by-age interaction term, P = 0.03), and driven by genotype-dependent differences in the rate of bilateral superior posterior lobar volume change with age (P = 0.002). Resultantly, although superior posterior lobar volume did not differ significantly between genotype groups at age 5 (P = 0.9), by age 23 it was 12% greater in Gcar than AA (P = 0.002). Our results suggest that common genetic variation within this putative ASD risk gene has the capacity to modify the development of cerebellar systems implicated in ASD neurobiology. En ligne : http://dx.doi.org/10.1002/aur.238 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=155

Autism Risk Gene MET Variation and Cortical Thickness in Typically Developing Children and Adolescents / Alexis HEDRICK in Autism Research, 5-6 (December 2012)  

Public ISBD [article]  inAutism Research > 5-6 (December 2012) . - p.434-439 Titre : Autism Risk Gene MET Variation and Cortical Thickness in Typically Developing Children and Adolescents Type de document : texte imprimé Auteurs : Alexis HEDRICK, Auteur ; Yohan LEE, Auteur ; Gregory L. WALLACE, Auteur ; Deanna GREENSTEIN, Auteur ; Liv S. CLASEN, Auteur ; Jay N. GIEDD, Auteur ; Armin RAZNAHAN, Auteur Article en page(s) : p.434-439 Mots-clés : MET receptor tyrosine kinase  cortex  autism  development  MRI Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.1256 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=187 [article] Autism Risk Gene MET Variation and Cortical Thickness in Typically Developing Children and Adolescents [texte imprimé] / Alexis HEDRICK, Auteur ; Yohan LEE, Auteur ; Gregory L. WALLACE, Auteur ; Deanna GREENSTEIN, Auteur ; Liv S. CLASEN, Auteur ; Jay N. GIEDD, Auteur ; Armin RAZNAHAN, Auteur . - p.434-439. in Autism Research > 5-6 (December 2012) . - p.434-439 Mots-clés : MET receptor tyrosine kinase  cortex  autism  development  MRI Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.1256 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=187

Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome / Lisa JOSEPH in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 30 p. Titre : Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome Type de document : texte imprimé Auteurs : Lisa JOSEPH, Auteur ; Cristan FARMER, Auteur ; Colby CHLEBOWSKI, Auteur ; Laura HENRY, Auteur ; Ari FISH, Auteur ; Catherine MANKIW, Auteur ; Anastasia XENOPHONTOS, Auteur ; Liv S. CLASEN, Auteur ; Bethany SAULS, Auteur ; Jakob SEIDLITZ, Auteur ; Jonathan D. BLUMENTHAL, Auteur ; Erin TORRES, Auteur ; Audrey THURM, Auteur ; Armin RAZNAHAN, Auteur Année de publication : 2018 Article en page(s) : 30 p. Langues : Anglais (eng) Mots-clés : Adaptive behavior  Autism spectrum disorder symptoms  Cognitive functioning  Learning disabilities  Sex chromosome aneuploidies Index. décimale : PER Périodiques Résumé : BACKGROUND: XYY syndrome is a sex chromosome aneuploidy that occurs in ~ 1/850 male births and is associated with increased risk for neurodevelopmental difficulties. However, the profile of neurodevelopmental impairments, including symptoms of autism spectrum disorder (ASD) in XYY remains poorly understood. This gap in knowledge has persisted in part due to lack of access to patient cohorts with dense and homogeneous phenotypic data. METHODS: We evaluated a single-center cohort of 64 individuals with XYY aged 5-25 years, using a standardized battery of cognitive and behavioral assessments spanning developmental milestones, IQ, adaptive behavior, academic achievement, behavioral problems, and gold-standard diagnostic instruments for ASD. Our goals were to (i) detail the neurodevelopmental profile of XYY with a focus on ASD diagnostic rates and symptom profiles, (ii) screen phenotypes for potential ascertainment bias effects by contrasting pre- vs. postnatally diagnosed XYY subgroups, and (iii) define major modules of phenotypic variation using graph-theoretical analysis. RESULTS: Although there was marked inter-individual variability, the average profile was characterized by some degree of developmental delay, and decreased IQ and adaptive behavior. Impairments were most pronounced for language and socio-communicative functioning. The rate of ASD was 14%, and these individuals exhibited autism symptom profiles resembling those observed in ASD without XYY. Most neurodevelopmental dimensions showed milder impairment among pre- vs. postnatally diagnosed individuals, with clinically meaningful differences in verbal IQ. Feature network analysis revealed three reliably separable modules comprising (i) cognition and academic achievement, (ii) broad domain psychopathology and adaptive behavior, and (iii) ASD-related features. CONCLUSIONS: By adding granularity to our understanding of neurodevelopmental difficulties in XYY, these findings assist targeted clinical assessment of newly identified cases, motivate greater provision of specialized multidisciplinary support, and inform future efforts to integrate behavioral phenotypes in XYY with neurobiology. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls." En ligne : http://dx.doi.org/10.1186/s11689-018-9248-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome [texte imprimé] / Lisa JOSEPH, Auteur ; Cristan FARMER, Auteur ; Colby CHLEBOWSKI, Auteur ; Laura HENRY, Auteur ; Ari FISH, Auteur ; Catherine MANKIW, Auteur ; Anastasia XENOPHONTOS, Auteur ; Liv S. CLASEN, Auteur ; Bethany SAULS, Auteur ; Jakob SEIDLITZ, Auteur ; Jonathan D. BLUMENTHAL, Auteur ; Erin TORRES, Auteur ; Audrey THURM, Auteur ; Armin RAZNAHAN, Auteur . - 2018 . - 30 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 30 p. Mots-clés : Adaptive behavior  Autism spectrum disorder symptoms  Cognitive functioning  Learning disabilities  Sex chromosome aneuploidies Index. décimale : PER Périodiques Résumé : BACKGROUND: XYY syndrome is a sex chromosome aneuploidy that occurs in ~ 1/850 male births and is associated with increased risk for neurodevelopmental difficulties. However, the profile of neurodevelopmental impairments, including symptoms of autism spectrum disorder (ASD) in XYY remains poorly understood. This gap in knowledge has persisted in part due to lack of access to patient cohorts with dense and homogeneous phenotypic data. METHODS: We evaluated a single-center cohort of 64 individuals with XYY aged 5-25 years, using a standardized battery of cognitive and behavioral assessments spanning developmental milestones, IQ, adaptive behavior, academic achievement, behavioral problems, and gold-standard diagnostic instruments for ASD. Our goals were to (i) detail the neurodevelopmental profile of XYY with a focus on ASD diagnostic rates and symptom profiles, (ii) screen phenotypes for potential ascertainment bias effects by contrasting pre- vs. postnatally diagnosed XYY subgroups, and (iii) define major modules of phenotypic variation using graph-theoretical analysis. RESULTS: Although there was marked inter-individual variability, the average profile was characterized by some degree of developmental delay, and decreased IQ and adaptive behavior. Impairments were most pronounced for language and socio-communicative functioning. The rate of ASD was 14%, and these individuals exhibited autism symptom profiles resembling those observed in ASD without XYY. Most neurodevelopmental dimensions showed milder impairment among pre- vs. postnatally diagnosed individuals, with clinically meaningful differences in verbal IQ. Feature network analysis revealed three reliably separable modules comprising (i) cognition and academic achievement, (ii) broad domain psychopathology and adaptive behavior, and (iii) ASD-related features. CONCLUSIONS: By adding granularity to our understanding of neurodevelopmental difficulties in XYY, these findings assist targeted clinical assessment of newly identified cases, motivate greater provision of specialized multidisciplinary support, and inform future efforts to integrate behavioral phenotypes in XYY with neurobiology. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls." En ligne : http://dx.doi.org/10.1186/s11689-018-9248-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Deep phenotypic analysis of psychiatric features in genetically defined cohorts: application to XYY syndrome / Armin RAZNAHAN in Journal of Neurodevelopmental Disorders, 15 (2023)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 15 (2023) Titre : Deep phenotypic analysis of psychiatric features in genetically defined cohorts: application to XYY syndrome Type de document : texte imprimé Auteurs : Armin RAZNAHAN, Auteur ; Srishti RAU, Auteur ; Luke SCHAFFER, Auteur ; Siyuan LIU, Auteur ; Ari M. FISH, Auteur ; Catherine MANKIW, Auteur ; Anastasia XENOPHONTOS, Auteur ; Liv S. CLASEN, Auteur ; Lisa JOSEPH, Auteur ; Audrey THURM, Auteur ; Jonathan D. BLUMENTHAL, Auteur ; Dani S. BASSETT, Auteur ; Erin N. TORRES, Auteur Langues : Anglais (eng) Mots-clés : Humans  Male  XYY Karyotype  Sex Chromosome Disorders/diagnosis  Cognition  Phenotype  Adaptive function  Behavioral phenotyping  Deep phenotyping  Neurogenetics  Sex chromosomes  Symptom networks Index. décimale : PER Périodiques Résumé : BACKGROUND: Recurrent gene dosage disorders impart substantial risk for psychopathology. Yet, understanding that risk is hampered by complex presentations that challenge classical diagnostic systems. Here, we present a suite of generalizable analytic approaches for parsing this clinical complexity, which we illustrate through application to XYY syndrome. METHOD: We gathered high-dimensional measures of psychopathology in 64 XYY individuals and 60 XY controls, plus additional interviewer-based diagnostic data in the XYY group. We provide the first comprehensive diagnostic description of psychiatric morbidity in XYY syndrome and show how diagnostic morbidity relates to functioning, subthreshold symptoms, and ascertainment bias. We then map behavioral vulnerabilities and resilience across 67 behavioral dimensions before borrowing techniques from network science to resolve the mesoscale architecture of these dimensions and links to observable functional outcomes. RESULTS: Carriage of an extra Y-chromosome increases risk for diverse psychiatric diagnoses, with clinically impactful subthreshold symptomatology. Highest rates are seen for neurodevelopmental and affective disorders. A lower bound of < 25% of carriers are free of any diagnosis. Dimensional analysis of 67 scales details the profile of psychopathology in XYY, which survives control for ascertainment bias, specifies attentional and social domains as the most impacted, and refutes stigmatizing historical associations between XYY and violence. Network modeling compresses all measured symptom scales into 8 modules with dissociable links to cognitive ability, adaptive function, and caregiver strain. Hub modules offer efficient proxies for the full symptom network. CONCLUSIONS: This study parses the complex behavioral phenotype of XYY syndrome by applying new and generalizable analytic approaches for analysis of deep-phenotypic psychiatric data in neurogenetic disorders. En ligne : https://dx.doi.org/10.1186/s11689-023-09476-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Deep phenotypic analysis of psychiatric features in genetically defined cohorts: application to XYY syndrome [texte imprimé] / Armin RAZNAHAN, Auteur ; Srishti RAU, Auteur ; Luke SCHAFFER, Auteur ; Siyuan LIU, Auteur ; Ari M. FISH, Auteur ; Catherine MANKIW, Auteur ; Anastasia XENOPHONTOS, Auteur ; Liv S. CLASEN, Auteur ; Lisa JOSEPH, Auteur ; Audrey THURM, Auteur ; Jonathan D. BLUMENTHAL, Auteur ; Dani S. BASSETT, Auteur ; Erin N. TORRES, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 15 (2023) Mots-clés : Humans  Male  XYY Karyotype  Sex Chromosome Disorders/diagnosis  Cognition  Phenotype  Adaptive function  Behavioral phenotyping  Deep phenotyping  Neurogenetics  Sex chromosomes  Symptom networks Index. décimale : PER Périodiques Résumé : BACKGROUND: Recurrent gene dosage disorders impart substantial risk for psychopathology. Yet, understanding that risk is hampered by complex presentations that challenge classical diagnostic systems. Here, we present a suite of generalizable analytic approaches for parsing this clinical complexity, which we illustrate through application to XYY syndrome. METHOD: We gathered high-dimensional measures of psychopathology in 64 XYY individuals and 60 XY controls, plus additional interviewer-based diagnostic data in the XYY group. We provide the first comprehensive diagnostic description of psychiatric morbidity in XYY syndrome and show how diagnostic morbidity relates to functioning, subthreshold symptoms, and ascertainment bias. We then map behavioral vulnerabilities and resilience across 67 behavioral dimensions before borrowing techniques from network science to resolve the mesoscale architecture of these dimensions and links to observable functional outcomes. RESULTS: Carriage of an extra Y-chromosome increases risk for diverse psychiatric diagnoses, with clinically impactful subthreshold symptomatology. Highest rates are seen for neurodevelopmental and affective disorders. A lower bound of < 25% of carriers are free of any diagnosis. Dimensional analysis of 67 scales details the profile of psychopathology in XYY, which survives control for ascertainment bias, specifies attentional and social domains as the most impacted, and refutes stigmatizing historical associations between XYY and violence. Network modeling compresses all measured symptom scales into 8 modules with dissociable links to cognitive ability, adaptive function, and caregiver strain. Hub modules offer efficient proxies for the full symptom network. CONCLUSIONS: This study parses the complex behavioral phenotype of XYY syndrome by applying new and generalizable analytic approaches for analysis of deep-phenotypic psychiatric data in neurogenetic disorders. En ligne : https://dx.doi.org/10.1186/s11689-023-09476-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Divergence of Age-Related Differences in Social-Communication: Improvements for Typically Developing Youth but Declines for Youth with Autism Spectrum Disorder / Gregory L. WALLACE in Journal of Autism and Developmental Disorders, 47-2 (February 2017)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 47-2 (February 2017) . - p.472-479 Titre : Divergence of Age-Related Differences in Social-Communication: Improvements for Typically Developing Youth but Declines for Youth with Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Gregory L. WALLACE, Auteur ; Katerina DUDLEY, Auteur ; Laura G. ANTHONY, Auteur ; Cara E. PUGLIESE, Auteur ; Bako ORIONZI, Auteur ; Liv S. CLASEN, Auteur ; Nancy R. LEE, Auteur ; Jay N. GIEDD, Auteur ; Alex MARTIN, Auteur ; Armin RAZNAHAN, Auteur ; Lauren KENWORTHY, Auteur Article en page(s) : p.472-479 Langues : Anglais (eng) Mots-clés : Autism  Social  Communication  Repetitive behavior  Age  Social Responsiveness Scale Index. décimale : PER Périodiques Résumé : Although social-communication difficulties and repetitive behaviors are hallmark features of autism spectrum disorder (ASD) and persist across the lifespan, very few studies have compared age-related differences in these behaviors between youth with ASD and same-age typically developing (TD) peers. We examined this issue using SRS-2 (Social Responsiveness Scale-Second Edition) measures of social-communicative functioning and repetitive behaviors in a stratified cross-sectional sample of 324 youth with ASD in the absence of intellectual disability, and 438 TD youth (aged 4–29 years). An age-by-group interaction emerged indicating that TD youth exhibited age-related improvements in social-communication scores while the ASD group demonstrated age-related declines in these scores. This suggests that adolescents/adults with ASD may fall increasingly behind their same-age peers in social-communicative skills. En ligne : http://dx.doi.org/10.1007/s10803-016-2972-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303 [article] Divergence of Age-Related Differences in Social-Communication: Improvements for Typically Developing Youth but Declines for Youth with Autism Spectrum Disorder [texte imprimé] / Gregory L. WALLACE, Auteur ; Katerina DUDLEY, Auteur ; Laura G. ANTHONY, Auteur ; Cara E. PUGLIESE, Auteur ; Bako ORIONZI, Auteur ; Liv S. CLASEN, Auteur ; Nancy R. LEE, Auteur ; Jay N. GIEDD, Auteur ; Alex MARTIN, Auteur ; Armin RAZNAHAN, Auteur ; Lauren KENWORTHY, Auteur . - p.472-479. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 47-2 (February 2017) . - p.472-479 Mots-clés : Autism  Social  Communication  Repetitive behavior  Age  Social Responsiveness Scale Index. décimale : PER Périodiques Résumé : Although social-communication difficulties and repetitive behaviors are hallmark features of autism spectrum disorder (ASD) and persist across the lifespan, very few studies have compared age-related differences in these behaviors between youth with ASD and same-age typically developing (TD) peers. We examined this issue using SRS-2 (Social Responsiveness Scale-Second Edition) measures of social-communicative functioning and repetitive behaviors in a stratified cross-sectional sample of 324 youth with ASD in the absence of intellectual disability, and 438 TD youth (aged 4–29 years). An age-by-group interaction emerged indicating that TD youth exhibited age-related improvements in social-communication scores while the ASD group demonstrated age-related declines in these scores. This suggests that adolescents/adults with ASD may fall increasingly behind their same-age peers in social-communicative skills. En ligne : http://dx.doi.org/10.1007/s10803-016-2972-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303

A functional polymorphism of the brain derived neurotrophic factor gene and cortical anatomy in autism spectrum disorder / Armin RAZNAHAN in Journal of Neurodevelopmental Disorders, 1-3 (September 2009)  

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Modeling familial predictors of proband outcomes in neurogenetic disorders: initial application in XYY syndrome / Kathleen E. WILSON in Journal of Neurodevelopmental Disorders, 13 (2021)  

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Patterns of psychopathology and cognition in sex chromosome aneuploidy / Srishti RAU in Journal of Neurodevelopmental Disorders, 13 (2021)  

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X- vs. Y-chromosome influences on human behavior: a deep phenotypic comparison of psychopathology in XXY and XYY syndromes / Lukas SCHAFFER in Journal of Neurodevelopmental Disorders, 16 (2024)  

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