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

Identifying comorbid ADHD in autism: Attending to the inattentive presentation / Srishti RAU in Research in Autism Spectrum Disorders, 69 (January 2020)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 69 (January 2020) . - p.101468 Titre : Identifying comorbid ADHD in autism: Attending to the inattentive presentation Type de document : texte imprimé Auteurs : Srishti RAU, Auteur ; Mary F. SKAPEK, Auteur ; Kaitlyn TIPLADY, Auteur ; Sydney SEESE, Auteur ; Alison BURNS, Auteur ; Anna Chelsea ARMOUR, Auteur ; Lauren KENWORTHY, Auteur Article en page(s) : p.101468 Langues : Anglais (eng) Mots-clés : ASD  ADHD  Comorbidity  Assessment Index. décimale : PER Périodiques Résumé : Background There are high rates of comorbidity between ADHD and ASD; however, there has been limited work parsing rates by ADHD presentation. In addition, commonly used questionnaires have demonstrated reduced utility in capturing ADHD symptoms in individuals with ASD. We examined the prevalence of comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) parsed by DSM-5 presentation in clinic-referred youth with Autism Spectrum Disorder (ASD) without intellectual disability (ID). We compared common rating scales to determine which most effectively identified comorbid ADHD. Method We examined comorbid ADHD diagnoses from archival assessment data for 419 youth with ASD without ID. We examined diagnostic discriminability of the parent and teacher ADHD Rating Scale (ADHD R-S), and Attention and ADH Problems Scales of the Child Behavior Checklist and Teacher Report Form using receiver operating characteristic (ROC) curves. Hierarchical logistic regression was used to examine measures’ unique contribution to ADHD diagnosis. Results Sixty-one percent of the study sample met DSM-5 criteria for an attention disorder. ADHD, Combined (ADHD-C) represented the largest proportion of ADHD diagnoses (76.8%), followed by Inattentive (ADHD-I;19.7%), Hyperactive/Impulsive (.02%), and Un-/Other Specified (.02%). Measures provided greater diagnostic discriminability in identifying ADHD-C relative to ADHD-I. The ADHD R-S inattentive symptom count provided the greatest discriminability for both subtypes and was the only scale that provided clinically meaningful differentiation between those with ASD only and ASD + ADHD-I. Conclusions These results support using the ADHD R-S to capture comorbid ADHD symptoms in ASD. The findings underscore the need for more thorough examination of inattentive symptoms to rule out ADHD-I. En ligne : https://doi.org/10.1016/j.rasd.2019.101468 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=412 [article] Identifying comorbid ADHD in autism: Attending to the inattentive presentation [texte imprimé] / Srishti RAU, Auteur ; Mary F. SKAPEK, Auteur ; Kaitlyn TIPLADY, Auteur ; Sydney SEESE, Auteur ; Alison BURNS, Auteur ; Anna Chelsea ARMOUR, Auteur ; Lauren KENWORTHY, Auteur . - p.101468. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 69 (January 2020) . - p.101468 Mots-clés : ASD  ADHD  Comorbidity  Assessment Index. décimale : PER Périodiques Résumé : Background There are high rates of comorbidity between ADHD and ASD; however, there has been limited work parsing rates by ADHD presentation. In addition, commonly used questionnaires have demonstrated reduced utility in capturing ADHD symptoms in individuals with ASD. We examined the prevalence of comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) parsed by DSM-5 presentation in clinic-referred youth with Autism Spectrum Disorder (ASD) without intellectual disability (ID). We compared common rating scales to determine which most effectively identified comorbid ADHD. Method We examined comorbid ADHD diagnoses from archival assessment data for 419 youth with ASD without ID. We examined diagnostic discriminability of the parent and teacher ADHD Rating Scale (ADHD R-S), and Attention and ADH Problems Scales of the Child Behavior Checklist and Teacher Report Form using receiver operating characteristic (ROC) curves. Hierarchical logistic regression was used to examine measures’ unique contribution to ADHD diagnosis. Results Sixty-one percent of the study sample met DSM-5 criteria for an attention disorder. ADHD, Combined (ADHD-C) represented the largest proportion of ADHD diagnoses (76.8%), followed by Inattentive (ADHD-I;19.7%), Hyperactive/Impulsive (.02%), and Un-/Other Specified (.02%). Measures provided greater diagnostic discriminability in identifying ADHD-C relative to ADHD-I. The ADHD R-S inattentive symptom count provided the greatest discriminability for both subtypes and was the only scale that provided clinically meaningful differentiation between those with ASD only and ASD + ADHD-I. Conclusions These results support using the ADHD R-S to capture comorbid ADHD symptoms in ASD. The findings underscore the need for more thorough examination of inattentive symptoms to rule out ADHD-I. En ligne : https://doi.org/10.1016/j.rasd.2019.101468 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=412

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

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 13 (2021) Titre : Patterns of psychopathology and cognition in sex chromosome aneuploidy Type de document : texte imprimé Auteurs : Srishti RAU, Auteur ; Ethan T. WHITMAN, Auteur ; Kimberly SCHAUDER, Auteur ; Nikhita GOGATE, Auteur ; Nancy Raitano LEE, Auteur ; Lauren KENWORTHY, Auteur ; Armin RAZNAHAN, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Aneuploidy  Child  Cognition  Humans  Mental Disorders  Sex Chromosome Aberrations  Sex Chromosomes/genetics  Neurogenetic conditions  Psychopathology  Sex chromosome aneuploidy  Sex chromosomes Index. décimale : PER Périodiques Résumé : BACKGROUND: Sex chromosome aneuploidies (SCAs) are a collectively common family of genetic disorders that increase the risk for neuropsychiatric and cognitive impairment. Beyond being important medical disorders in their own right, SCAs also offer a unique naturally occurring model for studying X- and Y-chromosome influences on the human brain. However, it remains unclear if (i) different SCAs are associated with different profiles of psychopathology and (ii) the notable interindividual variation in psychopathology is related to co-occurring variation in cognitive ability. METHODS: We examined scores for 11 dimensions of psychopathology [Child/Adult Behavior Checklist (CBCL)] and general cognitive ability [full-scale IQ (FSIQ) from Wechsler tests] in 110 youth with varying SCAs (XXY = 41, XYY = 22, XXX = 27, XXYY = 20) and 131 typically developing controls (XX = 59, XY = 72). RESULTS: All SCAs were associated with elevated CBCL scores across several dimensions of psychopathology (two-sample t tests comparing the euploidic and aneuploidic groups [all |T| > 9, and p < 0.001]). Social and attentional functioning were particularly sensitive to the carriage of a supernumerary Y-chromosome. In particular, the XYY group evidenced significantly more social problems than both extra-X groups (Cohen's d effect size > 0.5, Bonferroni corrected p < .05). There was marked variability in CBCL scores within each SCA group, which generally correlated negatively with IQ, but most strongly so for social and attentional difficulties (standardized β, - 0.3). These correlations showed subtle differences as a function of the SCA group and CBCL scale. CONCLUSIONS: There is domain-specific variation in psychopathology across SCA groups and domain-specific correlation between psychopathology and IQ within SCAs. These findings (i) help to tailor clinical assessment of this common and impactful family of genetic disorders and (ii) suggest that dosage abnormalities of X- and Y-linked genes impart somewhat distinct profiles of neuropsychiatric risk. En ligne : https://dx.doi.org/10.1186/s11689-021-09407-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Patterns of psychopathology and cognition in sex chromosome aneuploidy [texte imprimé] / Srishti RAU, Auteur ; Ethan T. WHITMAN, Auteur ; Kimberly SCHAUDER, Auteur ; Nikhita GOGATE, Auteur ; Nancy Raitano LEE, Auteur ; Lauren KENWORTHY, Auteur ; Armin RAZNAHAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 13 (2021) Mots-clés : Adolescent  Adult  Aneuploidy  Child  Cognition  Humans  Mental Disorders  Sex Chromosome Aberrations  Sex Chromosomes/genetics  Neurogenetic conditions  Psychopathology  Sex chromosome aneuploidy  Sex chromosomes Index. décimale : PER Périodiques Résumé : BACKGROUND: Sex chromosome aneuploidies (SCAs) are a collectively common family of genetic disorders that increase the risk for neuropsychiatric and cognitive impairment. Beyond being important medical disorders in their own right, SCAs also offer a unique naturally occurring model for studying X- and Y-chromosome influences on the human brain. However, it remains unclear if (i) different SCAs are associated with different profiles of psychopathology and (ii) the notable interindividual variation in psychopathology is related to co-occurring variation in cognitive ability. METHODS: We examined scores for 11 dimensions of psychopathology [Child/Adult Behavior Checklist (CBCL)] and general cognitive ability [full-scale IQ (FSIQ) from Wechsler tests] in 110 youth with varying SCAs (XXY = 41, XYY = 22, XXX = 27, XXYY = 20) and 131 typically developing controls (XX = 59, XY = 72). RESULTS: All SCAs were associated with elevated CBCL scores across several dimensions of psychopathology (two-sample t tests comparing the euploidic and aneuploidic groups [all |T| > 9, and p < 0.001]). Social and attentional functioning were particularly sensitive to the carriage of a supernumerary Y-chromosome. In particular, the XYY group evidenced significantly more social problems than both extra-X groups (Cohen's d effect size > 0.5, Bonferroni corrected p < .05). There was marked variability in CBCL scores within each SCA group, which generally correlated negatively with IQ, but most strongly so for social and attentional difficulties (standardized β, - 0.3). These correlations showed subtle differences as a function of the SCA group and CBCL scale. CONCLUSIONS: There is domain-specific variation in psychopathology across SCA groups and domain-specific correlation between psychopathology and IQ within SCAs. These findings (i) help to tailor clinical assessment of this common and impactful family of genetic disorders and (ii) suggest that dosage abnormalities of X- and Y-linked genes impart somewhat distinct profiles of neuropsychiatric risk. En ligne : https://dx.doi.org/10.1186/s11689-021-09407-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

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)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : X- vs. Y-chromosome influences on human behavior: a deep phenotypic comparison of psychopathology in XXY and XYY syndromes Type de document : texte imprimé Auteurs : Lukas SCHAFFER, Auteur ; Srishti RAU, Auteur ; Isabella G. LARSEN, Auteur ; Liv CLASEN, Auteur ; Allysa WARLING, Auteur ; Ethan T. WHITMAN, Auteur ; Ajay NADIG, Auteur ; Cassidy MCDERMOTT, Auteur ; Anastasia XENOPHONTOS, Auteur ; Kathleen WILSON, Auteur ; Jonathan BLUMENTHAL, Auteur ; Erin TORRES, Auteur ; Armin RAZNAHAN, Auteur Langues : Anglais (eng) Mots-clés : Humans  Male  Female  Klinefelter Syndrome/genetics/diagnosis  Adult  Phenotype  XYY Karyotype/genetics  Adolescent  Chromosomes, Human, Y/genetics  Mental Disorders/genetics/diagnosis  Young Adult  Chromosomes, Human, X/genetics  Child  Middle Aged Index. décimale : PER Périodiques Résumé : BACKGROUND: Do different genetic disorders impart different psychiatric risk profiles? This question has major implications for biological and translational aspects of psychiatry, but has been difficult to tackle given limited access to shared batteries of fine-grained clinical data across genetic disorders. METHODS: Using a new suite of generalizable analytic approaches, we examine gold-standard diagnostic ratings, scores on 66 dimensional measures of psychopathology, and measures of cognition and functioning in two different sex chromosome aneuploidies (SCAs)-Klinefelter (XXY/KS) and XYY syndrome (n = 102 and 64 vs. n = 74 and 60 matched XY controls, total n = 300). We focus on SCAs for their high collective prevalence, informativeness regarding differential X- vs. Y-chromosome effects, and potential relevance for normative sex differences. RESULTS: We show that XXY/KS elevates rates for most psychiatric diagnoses as previously reported for XYY, but disproportionately so for anxiety disorders. Fine-mapping across all 66 traits provides a detailed profile of psychopathology in XXY/KS which is strongly correlated with that of XYY (r = .75 across traits) and robust to ascertainment biases, but reveals: (i) a greater penetrance of XYY than KS/XXY for most traits except mood/anxiety problems, and (ii) a disproportionate impact of XYY vs. XXY/KS on social problems. XXY/KS and XYY showed a similar coupling of psychopathology with adaptive function and caregiver strain, but not IQ. CONCLUSIONS: This work provides new tools for deep-phenotypic comparisons of genetic disorders in psychiatry and uses these to detail unique and shared effects of the X- and Y-chromosome on human behavior. En ligne : https://dx.doi.org/10.1186/s11689-024-09574-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] X- vs. Y-chromosome influences on human behavior: a deep phenotypic comparison of psychopathology in XXY and XYY syndromes [texte imprimé] / Lukas SCHAFFER, Auteur ; Srishti RAU, Auteur ; Isabella G. LARSEN, Auteur ; Liv CLASEN, Auteur ; Allysa WARLING, Auteur ; Ethan T. WHITMAN, Auteur ; Ajay NADIG, Auteur ; Cassidy MCDERMOTT, Auteur ; Anastasia XENOPHONTOS, Auteur ; Kathleen WILSON, Auteur ; Jonathan BLUMENTHAL, Auteur ; Erin TORRES, Auteur ; Armin RAZNAHAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Male  Female  Klinefelter Syndrome/genetics/diagnosis  Adult  Phenotype  XYY Karyotype/genetics  Adolescent  Chromosomes, Human, Y/genetics  Mental Disorders/genetics/diagnosis  Young Adult  Chromosomes, Human, X/genetics  Child  Middle Aged Index. décimale : PER Périodiques Résumé : BACKGROUND: Do different genetic disorders impart different psychiatric risk profiles? This question has major implications for biological and translational aspects of psychiatry, but has been difficult to tackle given limited access to shared batteries of fine-grained clinical data across genetic disorders. METHODS: Using a new suite of generalizable analytic approaches, we examine gold-standard diagnostic ratings, scores on 66 dimensional measures of psychopathology, and measures of cognition and functioning in two different sex chromosome aneuploidies (SCAs)-Klinefelter (XXY/KS) and XYY syndrome (n = 102 and 64 vs. n = 74 and 60 matched XY controls, total n = 300). We focus on SCAs for their high collective prevalence, informativeness regarding differential X- vs. Y-chromosome effects, and potential relevance for normative sex differences. RESULTS: We show that XXY/KS elevates rates for most psychiatric diagnoses as previously reported for XYY, but disproportionately so for anxiety disorders. Fine-mapping across all 66 traits provides a detailed profile of psychopathology in XXY/KS which is strongly correlated with that of XYY (r = .75 across traits) and robust to ascertainment biases, but reveals: (i) a greater penetrance of XYY than KS/XXY for most traits except mood/anxiety problems, and (ii) a disproportionate impact of XYY vs. XXY/KS on social problems. XXY/KS and XYY showed a similar coupling of psychopathology with adaptive function and caregiver strain, but not IQ. CONCLUSIONS: This work provides new tools for deep-phenotypic comparisons of genetic disorders in psychiatry and uses these to detail unique and shared effects of the X- and Y-chromosome on human behavior. En ligne : https://dx.doi.org/10.1186/s11689-024-09574-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

---

1 (1 - 4 / 4) Par page : 25 50 100 200