Brain abnormalities in a Neuroligin3 R451C knockin mouse model associated with autism / Jacob ELLEGOOD in Autism Research, 4-5 (October 2011)  

Public ISBD [article]  inAutism Research > 4-5 (October 2011) . - p.368-376 Titre : Brain abnormalities in a Neuroligin3 R451C knockin mouse model associated with autism Type de document : Texte imprimé et/ou numérique Auteurs : Jacob ELLEGOOD, Auteur ; Jason LERCH, Auteur ; R. Mark HENKELMAN, Auteur Année de publication : 2011 Article en page(s) : p.368-376 Langues : Anglais (eng) Mots-clés : animal models  magnetic resonance imaging  diffusion tensor imaging  neuroligin3  volume assessment Index. décimale : PER Périodiques Résumé : Magnetic resonance imaging (MRI) has been used quite extensively for examining morphological changes in human and animal brains. One of the many advantages to examining mouse models of human autism is that we are able to examine single gene targets, like that of Neuroligin3 R451C knockin (NL3 KI), which has been directly implicated in human autism. The NL3 KI mouse model has marked volume differences in many different structures in the brain: gray matter structures, such as the hippocampus, the striatum, and the thalamus, were all found to be smaller in the NL3 KI. Further, many white matter structures were found to be significantly smaller, such as the cerebral peduncle, corpus callosum, fornix/fimbria, and internal capsule. Fractional anisotropy measurements in these structures were also measured, and no differences were found. The volume changes in the white matter regions, therefore, are not due to a general breakdown in the microstructure of the tissue and seem to be caused by fewer axons or less mature axons. A larger radial diffusivity was also found in localized regions of the corpus callosum and cerebellum. The corpus callosal changes are particularly interesting as the thinning (or reduced volume) of the corpus callosum is a consistent finding in autism. This suggests that the NL3 KI model may be useful for examining white matter changes associated with autism. Autism Res2011,4:368–376. © 2011 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.215 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=145 [article] Brain abnormalities in a Neuroligin3 R451C knockin mouse model associated with autism [Texte imprimé et/ou numérique] / Jacob ELLEGOOD, Auteur ; Jason LERCH, Auteur ; R. Mark HENKELMAN, Auteur . - 2011 . - p.368-376. Langues : Anglais (eng) in Autism Research > 4-5 (October 2011) . - p.368-376 Mots-clés : animal models  magnetic resonance imaging  diffusion tensor imaging  neuroligin3  volume assessment Index. décimale : PER Périodiques Résumé : Magnetic resonance imaging (MRI) has been used quite extensively for examining morphological changes in human and animal brains. One of the many advantages to examining mouse models of human autism is that we are able to examine single gene targets, like that of Neuroligin3 R451C knockin (NL3 KI), which has been directly implicated in human autism. The NL3 KI mouse model has marked volume differences in many different structures in the brain: gray matter structures, such as the hippocampus, the striatum, and the thalamus, were all found to be smaller in the NL3 KI. Further, many white matter structures were found to be significantly smaller, such as the cerebral peduncle, corpus callosum, fornix/fimbria, and internal capsule. Fractional anisotropy measurements in these structures were also measured, and no differences were found. The volume changes in the white matter regions, therefore, are not due to a general breakdown in the microstructure of the tissue and seem to be caused by fewer axons or less mature axons. A larger radial diffusivity was also found in localized regions of the corpus callosum and cerebellum. The corpus callosal changes are particularly interesting as the thinning (or reduced volume) of the corpus callosum is a consistent finding in autism. This suggests that the NL3 KI model may be useful for examining white matter changes associated with autism. Autism Res2011,4:368–376. © 2011 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.215 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=145

Childhood onset schizophrenia: cortical brain abnormalities as young adults / Deanna GREENSTEIN in Journal of Child Psychology and Psychiatry, 47-10 (October 2006)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 47-10 (October 2006) . - p.1003–1012 Titre : Childhood onset schizophrenia: cortical brain abnormalities as young adults Type de document : Texte imprimé et/ou numérique Auteurs : Deanna GREENSTEIN, Auteur ; Liv S. CLASEN, Auteur ; Jay N. GIEDD, Auteur ; Jason LERCH, Auteur ; Philip SHAW, Auteur ; Peter GOCHMAN, Auteur ; Judith RAPOPORT, Auteur ; Nitin GOGTAY, Auteur Année de publication : 2007 Article en page(s) : p.1003–1012 Langues : Anglais (eng) Mots-clés : Childhood-onset-schizophrenia MRI cortical-thickness development neurodevelopment schizophrenia Index. décimale : PER Périodiques Résumé : Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset illness. Methods: Neuro-anatomic magnetic resonance scans were obtained prospectively from ages 7 through 26 in 70 children diagnosed with COS and age and sex matched healthy controls. Cortical thickness was measured at 40,962 points across the cerebral hemispheres using a novel, fully automated, validated method. Patterns of patient–control differences in cortical development were compared over a 19-year period. Results: Throughout the age range, the COS group had significantly smaller mean cortical thickness compared to controls. However, the COS brain developmental trajectory appeared to normalize in posterior (parietal) regions, and remained divergent in the anterior regions (frontal and temporal) regions, and the pattern of loss became more like that seen in adults. Conclusions: Cortical thickness loss in COS appears to localize with age to prefrontal and temporal regions that are seen for both medication naïve and medicated adult onset patients. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2006.01658.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=790 [article] Childhood onset schizophrenia: cortical brain abnormalities as young adults [Texte imprimé et/ou numérique] / Deanna GREENSTEIN, Auteur ; Liv S. CLASEN, Auteur ; Jay N. GIEDD, Auteur ; Jason LERCH, Auteur ; Philip SHAW, Auteur ; Peter GOCHMAN, Auteur ; Judith RAPOPORT, Auteur ; Nitin GOGTAY, Auteur . - 2007 . - p.1003–1012. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 47-10 (October 2006) . - p.1003–1012 Mots-clés : Childhood-onset-schizophrenia MRI cortical-thickness development neurodevelopment schizophrenia Index. décimale : PER Périodiques Résumé : Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset illness. Methods: Neuro-anatomic magnetic resonance scans were obtained prospectively from ages 7 through 26 in 70 children diagnosed with COS and age and sex matched healthy controls. Cortical thickness was measured at 40,962 points across the cerebral hemispheres using a novel, fully automated, validated method. Patterns of patient–control differences in cortical development were compared over a 19-year period. Results: Throughout the age range, the COS group had significantly smaller mean cortical thickness compared to controls. However, the COS brain developmental trajectory appeared to normalize in posterior (parietal) regions, and remained divergent in the anterior regions (frontal and temporal) regions, and the pattern of loss became more like that seen in adults. Conclusions: Cortical thickness loss in COS appears to localize with age to prefrontal and temporal regions that are seen for both medication naïve and medicated adult onset patients. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2006.01658.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=790

Effects of age and symptomatology on cortical thickness in autism spectrum disorders / Krissy A. R. DOYLE-THOMAS in Research in Autism Spectrum Disorders, 7-1 (January 2013)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 7-1 (January 2013) . - p.141-50 Titre : Effects of age and symptomatology on cortical thickness in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Krissy A. R. DOYLE-THOMAS, Auteur ; Emma G. DUERDEN, Auteur ; Margot J. TAYLOR, Auteur ; Jason LERCH, Auteur ; Latha V. SOORYA, Auteur ; A. Ting WANG, Auteur ; Jin FAN, Auteur ; Eric HOLLANDER, Auteur ; Evdokia ANAGNOSTOU, Auteur Année de publication : 2013 Article en page(s) : p.141-50 Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  Structural MRI  Cortical thickness  Social impairment  Developmental changes Index. décimale : PER Périodiques Résumé : Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours. En ligne : http://dx.doi.org/10.1016/j.rasd.2012.08.004 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=179 [article] Effects of age and symptomatology on cortical thickness in autism spectrum disorders [Texte imprimé et/ou numérique] / Krissy A. R. DOYLE-THOMAS, Auteur ; Emma G. DUERDEN, Auteur ; Margot J. TAYLOR, Auteur ; Jason LERCH, Auteur ; Latha V. SOORYA, Auteur ; A. Ting WANG, Auteur ; Jin FAN, Auteur ; Eric HOLLANDER, Auteur ; Evdokia ANAGNOSTOU, Auteur . - 2013 . - p.141-50. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 7-1 (January 2013) . - p.141-50 Mots-clés : Autism spectrum disorders  Structural MRI  Cortical thickness  Social impairment  Developmental changes Index. décimale : PER Périodiques Résumé : Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours. En ligne : http://dx.doi.org/10.1016/j.rasd.2012.08.004 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=179

Genetic Effects on Cerebellar Structure Across Mouse Models of Autism Using a Magnetic Resonance Imaging Atlas / Patrick E. STEADMAN in Autism Research, 7-1 (February 2014)  

Public ISBD [article]  inAutism Research > 7-1 (February 2014) . - p.124-137 Titre : Genetic Effects on Cerebellar Structure Across Mouse Models of Autism Using a Magnetic Resonance Imaging Atlas Type de document : Texte imprimé et/ou numérique Auteurs : Patrick E. STEADMAN, Auteur ; Jacob ELLEGOOD, Auteur ; Kamila U. SZULC, Auteur ; Daniel H. TURNBULL, Auteur ; Alexandra L. JOYNER, Auteur ; R. Mark HENKELMAN, Auteur ; Jason LERCH, Auteur Article en page(s) : p.124-137 Langues : Anglais (eng) Mots-clés : animal models  neuroimaging  neuroanatomy  structural MRI  genetics Index. décimale : PER Périodiques Résumé : Magnetic resonance imaging (MRI) of autism populations is confounded by the inherent heterogeneity in the individuals' genetics and environment, two factors difficult to control for. Imaging genetic animal models that recapitulate a mutation associated with autism quantify the impact of genetics on brain morphology and mitigate the confounding factors in human studies. Here, we used MRI to image three genetic mouse models with single mutations implicated in autism: Neuroligin-3 R451C knock-in, Methyl-CpG binding protein-2 (MECP2) 308-truncation and integrin ?3 homozygous knockout. This study identified the morphological differences specific to the cerebellum, a structure repeatedly linked to autism in human neuroimaging and postmortem studies. To accomplish a comparative analysis, a segmented cerebellum template was created and used to segment each study image. This template delineated 39 different cerebellar structures. For Neuroligin-3 R451C male mutants, the gray (effect size (ES)?=?1.94, FDR q?=?0.03) and white (ES?=?1.84, q?=?0.037) matter of crus II lobule and the gray matter of the paraflocculus (ES?=?1.45, q?=?0.045) were larger in volume. The MECP2 mutant mice had cerebellar volume changes that increased in scope depending on the genotype: hemizygous males to homozygous females. The integrin ?3 mutant mouse had a drastically smaller cerebellum than controls with 28 out of 39 cerebellar structures smaller. These imaging results are discussed in relation to repetitive behaviors, sociability, and learning in the context of autism. This work further illuminates the cerebellum's role in autism. En ligne : http://dx.doi.org/10.1002/aur.1344 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Genetic Effects on Cerebellar Structure Across Mouse Models of Autism Using a Magnetic Resonance Imaging Atlas [Texte imprimé et/ou numérique] / Patrick E. STEADMAN, Auteur ; Jacob ELLEGOOD, Auteur ; Kamila U. SZULC, Auteur ; Daniel H. TURNBULL, Auteur ; Alexandra L. JOYNER, Auteur ; R. Mark HENKELMAN, Auteur ; Jason LERCH, Auteur . - p.124-137. Langues : Anglais (eng) in Autism Research > 7-1 (February 2014) . - p.124-137 Mots-clés : animal models  neuroimaging  neuroanatomy  structural MRI  genetics Index. décimale : PER Périodiques Résumé : Magnetic resonance imaging (MRI) of autism populations is confounded by the inherent heterogeneity in the individuals' genetics and environment, two factors difficult to control for. Imaging genetic animal models that recapitulate a mutation associated with autism quantify the impact of genetics on brain morphology and mitigate the confounding factors in human studies. Here, we used MRI to image three genetic mouse models with single mutations implicated in autism: Neuroligin-3 R451C knock-in, Methyl-CpG binding protein-2 (MECP2) 308-truncation and integrin ?3 homozygous knockout. This study identified the morphological differences specific to the cerebellum, a structure repeatedly linked to autism in human neuroimaging and postmortem studies. To accomplish a comparative analysis, a segmented cerebellum template was created and used to segment each study image. This template delineated 39 different cerebellar structures. For Neuroligin-3 R451C male mutants, the gray (effect size (ES)?=?1.94, FDR q?=?0.03) and white (ES?=?1.84, q?=?0.037) matter of crus II lobule and the gray matter of the paraflocculus (ES?=?1.45, q?=?0.045) were larger in volume. The MECP2 mutant mice had cerebellar volume changes that increased in scope depending on the genotype: hemizygous males to homozygous females. The integrin ?3 mutant mouse had a drastically smaller cerebellum than controls with 28 out of 39 cerebellar structures smaller. These imaging results are discussed in relation to repetitive behaviors, sociability, and learning in the context of autism. This work further illuminates the cerebellum's role in autism. En ligne : http://dx.doi.org/10.1002/aur.1344 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Measures of Cortical Grey Matter Structure and Development in Children with Autism Spectrum Disorder / Kathleen M. MAK-FAN in Journal of Autism and Developmental Disorders, 42-3 (March 2012)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 42-3 (March 2012) . - p.419-427 Titre : Measures of Cortical Grey Matter Structure and Development in Children with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Kathleen M. MAK-FAN, Auteur ; Margot J. TAYLOR, Auteur ; Wendy ROBERTS, Auteur ; Jason LERCH, Auteur Année de publication : 2012 Article en page(s) : p.419-427 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Brain structure  Volume  Surface area  Cortical thickness  Development Index. décimale : PER Périodiques Résumé : The current study examined group differences in cortical volume, surface area, and thickness with age, in a group of typically developing children and a group of children with ASD aged 6–15 years. Results showed evidence of age by group interactions, suggesting atypicalities in the relation between these measures and age in the ASD group. Additional vertex-based analyses of cortical thickness revealed that specific regions in the left inferior frontal gyrus (BA 44) and left precuneus showed thicker cortex for the ASD group at younger ages only. These data support the hypothesis of an abnormal developmental trajectory of the cortex in ASD, which could have profound effects on other aspects of neural development in children with ASD. En ligne : http://dx.doi.org/10.1007/s10803-011-1261-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=152 [article] Measures of Cortical Grey Matter Structure and Development in Children with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Kathleen M. MAK-FAN, Auteur ; Margot J. TAYLOR, Auteur ; Wendy ROBERTS, Auteur ; Jason LERCH, Auteur . - 2012 . - p.419-427. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 42-3 (March 2012) . - p.419-427 Mots-clés : Autism spectrum disorder  Brain structure  Volume  Surface area  Cortical thickness  Development Index. décimale : PER Périodiques Résumé : The current study examined group differences in cortical volume, surface area, and thickness with age, in a group of typically developing children and a group of children with ASD aged 6–15 years. Results showed evidence of age by group interactions, suggesting atypicalities in the relation between these measures and age in the ASD group. Additional vertex-based analyses of cortical thickness revealed that specific regions in the left inferior frontal gyrus (BA 44) and left precuneus showed thicker cortex for the ASD group at younger ages only. These data support the hypothesis of an abnormal developmental trajectory of the cortex in ASD, which could have profound effects on other aspects of neural development in children with ASD. En ligne : http://dx.doi.org/10.1007/s10803-011-1261-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=152

Neuroanatomical Phenotypes Are Consistent With Autism-Like Behavioral Phenotypes in the 15q11-13 Duplication Mouse Model / Jacob ELLEGOOD in Autism Research, 8-5 (October 2015)  

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