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Cerebrospinal fluid and the early brain development of autism / M. D. SHEN in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)
[article]
Titre : Cerebrospinal fluid and the early brain development of autism Type de document : Texte imprimé et/ou numérique Auteurs : M. D. SHEN, Auteur Année de publication : 2018 Article en page(s) : 39 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Biomarkers Brain development Brain enlargement Cerebrospinal fluid Early risk signs Extra-axial cerebrospinal fluid Glymphatic system Heterogeneity Infancy Lateral ventricles Neural meningeal lymphatic system Neuroinflammation Stratification biomarker Index. décimale : PER Périodiques Résumé : BACKGROUND: There is currently a renaissance of interest in the many functions of cerebrospinal fluid (CSF). Altered flow of CSF, for example, has been shown to impair the clearance of pathogenic inflammatory proteins involved in neurodegenerative diseases, such as amyloid-beta. In addition, the role of CSF in the newly discovered lymphatic system of the brain has become a prominently researched area in clinical neuroscience, as CSF serves as a conduit between the central nervous system and immune system. MAIN BODY: This article will review the importance of CSF in regulating normal brain development and function, from the prenatal period throughout the lifespan, and highlight recent research that CSF abnormalities in autism spectrum disorder (ASD) are present in infancy, are detectable by conventional structural MRI, and could serve as an early indicator of altered neurodevelopment. CONCLUSION: The identification of early CSF abnormalities in children with ASD, along with emerging knowledge of the underlying pathogenic mechanisms, has the potential to serve as early stratification biomarkers that separate children with ASD into biological subtypes that share a common pathophysiology. Such subtypes could help parse the phenotypic heterogeneity of ASD and map on to targeted, biologically based treatments. En ligne : http://dx.doi.org/10.1186/s11689-018-9256-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386
in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 39 p.[article] Cerebrospinal fluid and the early brain development of autism [Texte imprimé et/ou numérique] / M. D. SHEN, Auteur . - 2018 . - 39 p.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 39 p.
Mots-clés : Autism spectrum disorder Biomarkers Brain development Brain enlargement Cerebrospinal fluid Early risk signs Extra-axial cerebrospinal fluid Glymphatic system Heterogeneity Infancy Lateral ventricles Neural meningeal lymphatic system Neuroinflammation Stratification biomarker Index. décimale : PER Périodiques Résumé : BACKGROUND: There is currently a renaissance of interest in the many functions of cerebrospinal fluid (CSF). Altered flow of CSF, for example, has been shown to impair the clearance of pathogenic inflammatory proteins involved in neurodegenerative diseases, such as amyloid-beta. In addition, the role of CSF in the newly discovered lymphatic system of the brain has become a prominently researched area in clinical neuroscience, as CSF serves as a conduit between the central nervous system and immune system. MAIN BODY: This article will review the importance of CSF in regulating normal brain development and function, from the prenatal period throughout the lifespan, and highlight recent research that CSF abnormalities in autism spectrum disorder (ASD) are present in infancy, are detectable by conventional structural MRI, and could serve as an early indicator of altered neurodevelopment. CONCLUSION: The identification of early CSF abnormalities in children with ASD, along with emerging knowledge of the underlying pathogenic mechanisms, has the potential to serve as early stratification biomarkers that separate children with ASD into biological subtypes that share a common pathophysiology. Such subtypes could help parse the phenotypic heterogeneity of ASD and map on to targeted, biologically based treatments. En ligne : http://dx.doi.org/10.1186/s11689-018-9256-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys / O. OZTAN in Molecular Autism, 12 (2021)
[article]
Titre : Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys Type de document : Texte imprimé et/ou numérique Auteurs : O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. 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
in Molecular Autism > 12 (2021) . - 50 p.[article] Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys [Texte imprimé et/ou numérique] / O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. 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 The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study / A. RETICO in Molecular Autism, 7 (2016)
[article]
Titre : The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study Type de document : Texte imprimé et/ou numérique Auteurs : A. RETICO, Auteur ; A. GIULIANO, Auteur ; Raffaella TANCREDI, Auteur ; A. COSENZA, Auteur ; Fabio APICELLA, Auteur ; A. NARZISI, Auteur ; L. BIAGI, Auteur ; M. TOSETTI, Auteur ; F. MURATORI, Auteur ; Sara CALDERONI, Auteur Article en page(s) : 5p. Langues : Anglais (eng) Mots-clés : Area Under Curve Autism Spectrum Disorder/pathology Cerebrospinal Fluid Child Child, Preschool Female Gray Matter/pathology Humans Infant Intelligence Magnetic Resonance Imaging Male Neuroimaging Organ Size Phenotype Research Design Severity of Illness Index Sex Characteristics Support Vector Machine White Matter/pathology Autism spectrum disorders Gender differences Structural MRI Young children Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic, hormonal, and environmental factors contribute since infancy to sexual dimorphism in regional brain structures of subjects with typical development. However, the neuroanatomical differences between male and female children with autism spectrum disorders (ASD) are an intriguing and still poorly investigated issue. This study aims to evaluate whether the brain of young children with ASD exhibits sex-related structural differences and if a correlation exists between clinical ASD features and neuroanatomical underpinnings. METHODS: A total of 152 structural MRI scans were analysed. Specifically, 76 young children with ASD (38 males and 38 females; 2-7 years of age; mean = 53 months, standard deviation = 17 months) were evaluated employing a support vector machine (SVM)-based analysis of the grey matter (GM). Group comparisons consisted of 76 age-, gender- and non-verbal-intelligence quotient-matched children with typical development or idiopathic developmental delay without autism. RESULTS: For both genders combined, SVM showed a significantly increased GM volume in young children with ASD with respect to control subjects, predominantly in the bilateral superior frontal gyrus (Brodmann area -BA- 10), bilateral precuneus (BA 31), bilateral superior temporal gyrus (BA 20/22), whereas less GM in patients with ASD was found in right inferior temporal gyrus (BA 37). For the within gender comparisons (i.e., females with ASD vs. controls and males with ASD vs. controls), two overlapping regions in bilateral precuneus (BA 31) and left superior frontal gyrus (BA 9/10) were detected. Sex-by-group analyses revealed in males with ASD compared to matched controls two male-specific regions of increased GM volume (left middle occipital gyrus-BA 19-and right superior temporal gyrus-BA 22). Comparisons in females with and without ASD demonstrated increased GM volumes predominantly in the bilateral frontal regions. Additional regions of significantly increased GM volume in the right anterior cingulate cortex (BA 32) and right cerebellum were typical only of females with ASD. CONCLUSIONS: Despite the specific behavioural correlates of sex-dimorphism in ASD, brain morphology as yet remains unclear and requires future dedicated investigations. This study provides evidence of structural brain gender differences in young children with ASD that possibly contribute to the different phenotypic disease manifestations in males and females. En ligne : http://dx.doi.org/10.1186/s13229-015-0067-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329
in Molecular Autism > 7 (2016) . - 5p.[article] The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study [Texte imprimé et/ou numérique] / A. RETICO, Auteur ; A. GIULIANO, Auteur ; Raffaella TANCREDI, Auteur ; A. COSENZA, Auteur ; Fabio APICELLA, Auteur ; A. NARZISI, Auteur ; L. BIAGI, Auteur ; M. TOSETTI, Auteur ; F. MURATORI, Auteur ; Sara CALDERONI, Auteur . - 5p.
Langues : Anglais (eng)
in Molecular Autism > 7 (2016) . - 5p.
Mots-clés : Area Under Curve Autism Spectrum Disorder/pathology Cerebrospinal Fluid Child Child, Preschool Female Gray Matter/pathology Humans Infant Intelligence Magnetic Resonance Imaging Male Neuroimaging Organ Size Phenotype Research Design Severity of Illness Index Sex Characteristics Support Vector Machine White Matter/pathology Autism spectrum disorders Gender differences Structural MRI Young children Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic, hormonal, and environmental factors contribute since infancy to sexual dimorphism in regional brain structures of subjects with typical development. However, the neuroanatomical differences between male and female children with autism spectrum disorders (ASD) are an intriguing and still poorly investigated issue. This study aims to evaluate whether the brain of young children with ASD exhibits sex-related structural differences and if a correlation exists between clinical ASD features and neuroanatomical underpinnings. METHODS: A total of 152 structural MRI scans were analysed. Specifically, 76 young children with ASD (38 males and 38 females; 2-7 years of age; mean = 53 months, standard deviation = 17 months) were evaluated employing a support vector machine (SVM)-based analysis of the grey matter (GM). Group comparisons consisted of 76 age-, gender- and non-verbal-intelligence quotient-matched children with typical development or idiopathic developmental delay without autism. RESULTS: For both genders combined, SVM showed a significantly increased GM volume in young children with ASD with respect to control subjects, predominantly in the bilateral superior frontal gyrus (Brodmann area -BA- 10), bilateral precuneus (BA 31), bilateral superior temporal gyrus (BA 20/22), whereas less GM in patients with ASD was found in right inferior temporal gyrus (BA 37). For the within gender comparisons (i.e., females with ASD vs. controls and males with ASD vs. controls), two overlapping regions in bilateral precuneus (BA 31) and left superior frontal gyrus (BA 9/10) were detected. Sex-by-group analyses revealed in males with ASD compared to matched controls two male-specific regions of increased GM volume (left middle occipital gyrus-BA 19-and right superior temporal gyrus-BA 22). Comparisons in females with and without ASD demonstrated increased GM volumes predominantly in the bilateral frontal regions. Additional regions of significantly increased GM volume in the right anterior cingulate cortex (BA 32) and right cerebellum were typical only of females with ASD. CONCLUSIONS: Despite the specific behavioural correlates of sex-dimorphism in ASD, brain morphology as yet remains unclear and requires future dedicated investigations. This study provides evidence of structural brain gender differences in young children with ASD that possibly contribute to the different phenotypic disease manifestations in males and females. En ligne : http://dx.doi.org/10.1186/s13229-015-0067-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329